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FDA OKs symplicity renal denervation system for hypertension
the company has announced.
The Symplicity Spyral system, also known as the Symplicity blood pressure procedure, provides a catheter-based approach to denervate the renal arteries using radiofrequency energy.
Back in August, the FDA’s Circulatory System Devices Panel unanimously agreed that the Symplicity Spyral system is safe, but the panel was split on its efficacy and whether the benefits outweighed the risks associated with its use.
As part of the Medtronic SPYRAL HTN Global Clinical Program, more than 25,000 patients have been treated worldwide, both in the presence and absence of medication, and in patients with high baseline cardiovascular risk.
The SPYRAL HTN-OFF study enrolled patients with hypertension whose medications could be stopped at the start of the trial.
The primary effectiveness endpoint was the mean difference in the baseline adjusted 24-hour ambulatory systolic blood pressure (ASBP) from baseline to 3 months after renal denervation or sham procedure. The study showed a statistically significant reduction of 3.9 mm Hg ASBP in patients who received the device, compared with sham-control patients.
The SPYRAL HTN-ON study evaluated patients with uncontrolled hypertension who continued taking their BP medications during treatment with either the Spyral renal denervation device or a sham device.
The primary endpoint was the mean difference in the baseline adjusted 24-hour ambulatory systolic blood pressure at 6 months. The study showed a nonsignificant 24-hour 0.03 mm Hg reduction in ASBP in active-treatment patients, compared with sham-control patients.
“The Symplicity blood pressure procedure is safe and effective, providing significant ‘always-on’ blood pressure reductions for patients,” David Kandzari, MD, chief, Piedmont Heart Institute, Atlanta, and co–principal investigator of the SPYRAL clinical program, said in the news release.
“This approval paves the way for a transformation in hypertension treatment, offering a solution that complements medication and lifestyle changes,” added co–principal investigator Raymond Townsend, MD, with University of Pennsylvania, Philadelphia.
Medtronic notes that patient preference and shared decision-making are key components when considering the Symplicity blood pressure procedure.
In a patient preference study led by Medtronic, when presented with an interventional treatment with BP reduction and potential risks in line with those of the Symplicity blood pressure procedure, approximately one-third of patients were likely to choose the interventional treatment.
Earlier in November, the FDA also approved the Paradise Ultrasound Renal Denervation system (Recor Medical, Otsuka Medical Devices) for the treatment of hypertension.
A version of this article first appeared on Medscape.com.
the company has announced.
The Symplicity Spyral system, also known as the Symplicity blood pressure procedure, provides a catheter-based approach to denervate the renal arteries using radiofrequency energy.
Back in August, the FDA’s Circulatory System Devices Panel unanimously agreed that the Symplicity Spyral system is safe, but the panel was split on its efficacy and whether the benefits outweighed the risks associated with its use.
As part of the Medtronic SPYRAL HTN Global Clinical Program, more than 25,000 patients have been treated worldwide, both in the presence and absence of medication, and in patients with high baseline cardiovascular risk.
The SPYRAL HTN-OFF study enrolled patients with hypertension whose medications could be stopped at the start of the trial.
The primary effectiveness endpoint was the mean difference in the baseline adjusted 24-hour ambulatory systolic blood pressure (ASBP) from baseline to 3 months after renal denervation or sham procedure. The study showed a statistically significant reduction of 3.9 mm Hg ASBP in patients who received the device, compared with sham-control patients.
The SPYRAL HTN-ON study evaluated patients with uncontrolled hypertension who continued taking their BP medications during treatment with either the Spyral renal denervation device or a sham device.
The primary endpoint was the mean difference in the baseline adjusted 24-hour ambulatory systolic blood pressure at 6 months. The study showed a nonsignificant 24-hour 0.03 mm Hg reduction in ASBP in active-treatment patients, compared with sham-control patients.
“The Symplicity blood pressure procedure is safe and effective, providing significant ‘always-on’ blood pressure reductions for patients,” David Kandzari, MD, chief, Piedmont Heart Institute, Atlanta, and co–principal investigator of the SPYRAL clinical program, said in the news release.
“This approval paves the way for a transformation in hypertension treatment, offering a solution that complements medication and lifestyle changes,” added co–principal investigator Raymond Townsend, MD, with University of Pennsylvania, Philadelphia.
Medtronic notes that patient preference and shared decision-making are key components when considering the Symplicity blood pressure procedure.
In a patient preference study led by Medtronic, when presented with an interventional treatment with BP reduction and potential risks in line with those of the Symplicity blood pressure procedure, approximately one-third of patients were likely to choose the interventional treatment.
Earlier in November, the FDA also approved the Paradise Ultrasound Renal Denervation system (Recor Medical, Otsuka Medical Devices) for the treatment of hypertension.
A version of this article first appeared on Medscape.com.
the company has announced.
The Symplicity Spyral system, also known as the Symplicity blood pressure procedure, provides a catheter-based approach to denervate the renal arteries using radiofrequency energy.
Back in August, the FDA’s Circulatory System Devices Panel unanimously agreed that the Symplicity Spyral system is safe, but the panel was split on its efficacy and whether the benefits outweighed the risks associated with its use.
As part of the Medtronic SPYRAL HTN Global Clinical Program, more than 25,000 patients have been treated worldwide, both in the presence and absence of medication, and in patients with high baseline cardiovascular risk.
The SPYRAL HTN-OFF study enrolled patients with hypertension whose medications could be stopped at the start of the trial.
The primary effectiveness endpoint was the mean difference in the baseline adjusted 24-hour ambulatory systolic blood pressure (ASBP) from baseline to 3 months after renal denervation or sham procedure. The study showed a statistically significant reduction of 3.9 mm Hg ASBP in patients who received the device, compared with sham-control patients.
The SPYRAL HTN-ON study evaluated patients with uncontrolled hypertension who continued taking their BP medications during treatment with either the Spyral renal denervation device or a sham device.
The primary endpoint was the mean difference in the baseline adjusted 24-hour ambulatory systolic blood pressure at 6 months. The study showed a nonsignificant 24-hour 0.03 mm Hg reduction in ASBP in active-treatment patients, compared with sham-control patients.
“The Symplicity blood pressure procedure is safe and effective, providing significant ‘always-on’ blood pressure reductions for patients,” David Kandzari, MD, chief, Piedmont Heart Institute, Atlanta, and co–principal investigator of the SPYRAL clinical program, said in the news release.
“This approval paves the way for a transformation in hypertension treatment, offering a solution that complements medication and lifestyle changes,” added co–principal investigator Raymond Townsend, MD, with University of Pennsylvania, Philadelphia.
Medtronic notes that patient preference and shared decision-making are key components when considering the Symplicity blood pressure procedure.
In a patient preference study led by Medtronic, when presented with an interventional treatment with BP reduction and potential risks in line with those of the Symplicity blood pressure procedure, approximately one-third of patients were likely to choose the interventional treatment.
Earlier in November, the FDA also approved the Paradise Ultrasound Renal Denervation system (Recor Medical, Otsuka Medical Devices) for the treatment of hypertension.
A version of this article first appeared on Medscape.com.
Single injection reduces blood pressure for 6 months: KARDIA-1
with what appeared to be an encouraging side-effect profile, in the phase 2 dose-ranging KARDIA-1 study.
“Our study demonstrates that either quarterly or biannual doses of zilebesiran can effectively and safely lower blood pressure in patients with uncontrolled hypertension,” said senior study investigator George Bakris, MD.
“Based on these results, zilebesiran has the potential to improve medication adherence, which will, in turn, reduce cardiovascular risk in people with hypertension,” added Dr. Bakris, who is professor of medicine and director of the Comprehensive Hypertension Center at the University of Chicago Medicine.
The KARDIA-1 study was presented at the American Heart Association scientific sessions.
Dr. Bakris noted that uncontrolled hypertension is a leading cause of morbidity and mortality, and despite availability of effective antihypertensives, many adults with hypertension are untreated, and up to 80% have uncontrolled disease, both globally and in the United States.
Zilebesiran is a subcutaneous RNA interference therapeutic that binds with high affinity to the hepatic asialoglycoprotein receptor, bringing about a reduction in the synthesis of angiotensinogen, the sole precursor of all angiotensin peptides. It is hoped that its hepatocyte-targeted delivery may allow extrahepatic angiotensinogen expression to be preserved, which could limit off-target effects in the kidney and other tissues.
The KARDIA-1 trial investigated the safety and efficacy of different doses of zilebesiran in patients with mild to moderate hypertension (systolic BP of 135-160 mm Hg), who are untreated or on stable therapy with up to two antihypertensive medications.
The study included 394 such patients (average baseline systolic BP was 142 mm Hg) who were randomly assigned to receive one of four different zilebesiran doses (150 mg, 300 mg, or 600 mg once every 6 months or 300 mg once every 2 months) or a placebo. The final analysis included 377 patients (56% men, 25% Black).
Results showed sustained reductions in serum angiotensinogen (between 88% and 98%) over the 6-month follow-up period.
Ambulatory systolic BP measured over 24 hours was significantly decreased with all zilebesiran regimens, with a mean reduction from baseline to month 6 of around 10 mm Hg in the three top doses studied and by around 14 mm Hg compared with placebo.
Patients receiving zilebesiran were more likely to achieve 24-hour average systolic BP measurements of 130 mm Hg or less at 6 months.
In addition, participants in all four zilebesiran groups consistently experienced significantly greater reductions in both daytime and nighttime systolic BP.
There were four nonserious adverse reactions leading to discontinuation in the zilebesiran groups: two instances of orthostatic hypotension, one of BP elevation, and one of injection site reaction.
Most hyperkalemia adverse events, which occurred in 6% of patients, were mild, did not require intervention, and generally resolved with repeat measurement; none were associated with acute kidney injury or led to study drug discontinuation. The incidence of hypotension events was low, and no clinically relevant changes in renal or hepatic function were observed, Dr. Bakris reported.
There was one death caused by cardiopulmonary arrest in a patient receiving zilebesiran 300 mg every 3 months, but this was not classified as drug related.
Zilebesiran is being further evaluated as an add-on therapy for treatment of hypertension in the ongoing KARDIA-2 phase 2 study.
Moderator of an AHA press conference at which the study was discussed, Sandra Taler, MD, professor of medicine at the Mayo Clinic, Rochester, Minn., said that “to have an injectable medicine that gives long-term blood pressure lowering is extremely exciting.”
Dr. Taler raised the point that some patients may not return for subsequent doses, but added that with subcutaneous dosing, administration at home may be a possibility.
Also commenting at the press conference, Keith Ferdinand, MD, professor of clinical medicine at Tulane University, New Orleans, said that this study “suggests we can now target the first step in the renin-angiotensin system – angiotensinogen – which then appears to lead to robust and continued blood pressure lowering for up to 6 months, which should improve adherence.”
Noting that only 50% of patients continue to take antihypertensive drugs after 1 year, Dr. Ferdinand added: “If we can increase adherence, we will increase efficacy and perhaps protect against some of the target organ damage.”
Designated discussant of the KARDIA-1 study at the AHA late-breaking clinical trial session, Anna Dominiczak, MD, University of Glasgow, noted that hypertension affects one in three adults worldwide, but only around 20% of people have it under control.
“An increase in the number of patients effectively treated for hypertension to levels observed in high-performing countries could prevent 76 million deaths, 120 million strokes, 79 million heart attacks, and 17 million cases of heart failure between now and 2050,” she said.
Dr. Bakris has received consulting fees from Alnylam Pharmaceuticals.
A version of this article first appeared on Medscape.com.
with what appeared to be an encouraging side-effect profile, in the phase 2 dose-ranging KARDIA-1 study.
“Our study demonstrates that either quarterly or biannual doses of zilebesiran can effectively and safely lower blood pressure in patients with uncontrolled hypertension,” said senior study investigator George Bakris, MD.
“Based on these results, zilebesiran has the potential to improve medication adherence, which will, in turn, reduce cardiovascular risk in people with hypertension,” added Dr. Bakris, who is professor of medicine and director of the Comprehensive Hypertension Center at the University of Chicago Medicine.
The KARDIA-1 study was presented at the American Heart Association scientific sessions.
Dr. Bakris noted that uncontrolled hypertension is a leading cause of morbidity and mortality, and despite availability of effective antihypertensives, many adults with hypertension are untreated, and up to 80% have uncontrolled disease, both globally and in the United States.
Zilebesiran is a subcutaneous RNA interference therapeutic that binds with high affinity to the hepatic asialoglycoprotein receptor, bringing about a reduction in the synthesis of angiotensinogen, the sole precursor of all angiotensin peptides. It is hoped that its hepatocyte-targeted delivery may allow extrahepatic angiotensinogen expression to be preserved, which could limit off-target effects in the kidney and other tissues.
The KARDIA-1 trial investigated the safety and efficacy of different doses of zilebesiran in patients with mild to moderate hypertension (systolic BP of 135-160 mm Hg), who are untreated or on stable therapy with up to two antihypertensive medications.
The study included 394 such patients (average baseline systolic BP was 142 mm Hg) who were randomly assigned to receive one of four different zilebesiran doses (150 mg, 300 mg, or 600 mg once every 6 months or 300 mg once every 2 months) or a placebo. The final analysis included 377 patients (56% men, 25% Black).
Results showed sustained reductions in serum angiotensinogen (between 88% and 98%) over the 6-month follow-up period.
Ambulatory systolic BP measured over 24 hours was significantly decreased with all zilebesiran regimens, with a mean reduction from baseline to month 6 of around 10 mm Hg in the three top doses studied and by around 14 mm Hg compared with placebo.
Patients receiving zilebesiran were more likely to achieve 24-hour average systolic BP measurements of 130 mm Hg or less at 6 months.
In addition, participants in all four zilebesiran groups consistently experienced significantly greater reductions in both daytime and nighttime systolic BP.
There were four nonserious adverse reactions leading to discontinuation in the zilebesiran groups: two instances of orthostatic hypotension, one of BP elevation, and one of injection site reaction.
Most hyperkalemia adverse events, which occurred in 6% of patients, were mild, did not require intervention, and generally resolved with repeat measurement; none were associated with acute kidney injury or led to study drug discontinuation. The incidence of hypotension events was low, and no clinically relevant changes in renal or hepatic function were observed, Dr. Bakris reported.
There was one death caused by cardiopulmonary arrest in a patient receiving zilebesiran 300 mg every 3 months, but this was not classified as drug related.
Zilebesiran is being further evaluated as an add-on therapy for treatment of hypertension in the ongoing KARDIA-2 phase 2 study.
Moderator of an AHA press conference at which the study was discussed, Sandra Taler, MD, professor of medicine at the Mayo Clinic, Rochester, Minn., said that “to have an injectable medicine that gives long-term blood pressure lowering is extremely exciting.”
Dr. Taler raised the point that some patients may not return for subsequent doses, but added that with subcutaneous dosing, administration at home may be a possibility.
Also commenting at the press conference, Keith Ferdinand, MD, professor of clinical medicine at Tulane University, New Orleans, said that this study “suggests we can now target the first step in the renin-angiotensin system – angiotensinogen – which then appears to lead to robust and continued blood pressure lowering for up to 6 months, which should improve adherence.”
Noting that only 50% of patients continue to take antihypertensive drugs after 1 year, Dr. Ferdinand added: “If we can increase adherence, we will increase efficacy and perhaps protect against some of the target organ damage.”
Designated discussant of the KARDIA-1 study at the AHA late-breaking clinical trial session, Anna Dominiczak, MD, University of Glasgow, noted that hypertension affects one in three adults worldwide, but only around 20% of people have it under control.
“An increase in the number of patients effectively treated for hypertension to levels observed in high-performing countries could prevent 76 million deaths, 120 million strokes, 79 million heart attacks, and 17 million cases of heart failure between now and 2050,” she said.
Dr. Bakris has received consulting fees from Alnylam Pharmaceuticals.
A version of this article first appeared on Medscape.com.
with what appeared to be an encouraging side-effect profile, in the phase 2 dose-ranging KARDIA-1 study.
“Our study demonstrates that either quarterly or biannual doses of zilebesiran can effectively and safely lower blood pressure in patients with uncontrolled hypertension,” said senior study investigator George Bakris, MD.
“Based on these results, zilebesiran has the potential to improve medication adherence, which will, in turn, reduce cardiovascular risk in people with hypertension,” added Dr. Bakris, who is professor of medicine and director of the Comprehensive Hypertension Center at the University of Chicago Medicine.
The KARDIA-1 study was presented at the American Heart Association scientific sessions.
Dr. Bakris noted that uncontrolled hypertension is a leading cause of morbidity and mortality, and despite availability of effective antihypertensives, many adults with hypertension are untreated, and up to 80% have uncontrolled disease, both globally and in the United States.
Zilebesiran is a subcutaneous RNA interference therapeutic that binds with high affinity to the hepatic asialoglycoprotein receptor, bringing about a reduction in the synthesis of angiotensinogen, the sole precursor of all angiotensin peptides. It is hoped that its hepatocyte-targeted delivery may allow extrahepatic angiotensinogen expression to be preserved, which could limit off-target effects in the kidney and other tissues.
The KARDIA-1 trial investigated the safety and efficacy of different doses of zilebesiran in patients with mild to moderate hypertension (systolic BP of 135-160 mm Hg), who are untreated or on stable therapy with up to two antihypertensive medications.
The study included 394 such patients (average baseline systolic BP was 142 mm Hg) who were randomly assigned to receive one of four different zilebesiran doses (150 mg, 300 mg, or 600 mg once every 6 months or 300 mg once every 2 months) or a placebo. The final analysis included 377 patients (56% men, 25% Black).
Results showed sustained reductions in serum angiotensinogen (between 88% and 98%) over the 6-month follow-up period.
Ambulatory systolic BP measured over 24 hours was significantly decreased with all zilebesiran regimens, with a mean reduction from baseline to month 6 of around 10 mm Hg in the three top doses studied and by around 14 mm Hg compared with placebo.
Patients receiving zilebesiran were more likely to achieve 24-hour average systolic BP measurements of 130 mm Hg or less at 6 months.
In addition, participants in all four zilebesiran groups consistently experienced significantly greater reductions in both daytime and nighttime systolic BP.
There were four nonserious adverse reactions leading to discontinuation in the zilebesiran groups: two instances of orthostatic hypotension, one of BP elevation, and one of injection site reaction.
Most hyperkalemia adverse events, which occurred in 6% of patients, were mild, did not require intervention, and generally resolved with repeat measurement; none were associated with acute kidney injury or led to study drug discontinuation. The incidence of hypotension events was low, and no clinically relevant changes in renal or hepatic function were observed, Dr. Bakris reported.
There was one death caused by cardiopulmonary arrest in a patient receiving zilebesiran 300 mg every 3 months, but this was not classified as drug related.
Zilebesiran is being further evaluated as an add-on therapy for treatment of hypertension in the ongoing KARDIA-2 phase 2 study.
Moderator of an AHA press conference at which the study was discussed, Sandra Taler, MD, professor of medicine at the Mayo Clinic, Rochester, Minn., said that “to have an injectable medicine that gives long-term blood pressure lowering is extremely exciting.”
Dr. Taler raised the point that some patients may not return for subsequent doses, but added that with subcutaneous dosing, administration at home may be a possibility.
Also commenting at the press conference, Keith Ferdinand, MD, professor of clinical medicine at Tulane University, New Orleans, said that this study “suggests we can now target the first step in the renin-angiotensin system – angiotensinogen – which then appears to lead to robust and continued blood pressure lowering for up to 6 months, which should improve adherence.”
Noting that only 50% of patients continue to take antihypertensive drugs after 1 year, Dr. Ferdinand added: “If we can increase adherence, we will increase efficacy and perhaps protect against some of the target organ damage.”
Designated discussant of the KARDIA-1 study at the AHA late-breaking clinical trial session, Anna Dominiczak, MD, University of Glasgow, noted that hypertension affects one in three adults worldwide, but only around 20% of people have it under control.
“An increase in the number of patients effectively treated for hypertension to levels observed in high-performing countries could prevent 76 million deaths, 120 million strokes, 79 million heart attacks, and 17 million cases of heart failure between now and 2050,” she said.
Dr. Bakris has received consulting fees from Alnylam Pharmaceuticals.
A version of this article first appeared on Medscape.com.
FROM AHA 2023
A better way to control blood pressure
My Bing AI engine, when prompted, tells me that there are about 87 journals, 45 conferences, and 53 workshops presently dedicated exclusively to hypertension. All of that attention, and yet ...
What is going on?
The top killers of Americans remain coronary artery heart disease (26%), cancer (22%), and stroke (6%). The precursors and attributable risk factors for coronary artery heart disease include hypertension (40%), obesity (20%), diabetes (15%), and combustible tobacco use (15%). The key precursors and attributable risk factors for stroke are hypertension (53%), obesity (37%), diabetes (9%), and combustible tobacco use (11%). Obviously, these are estimates, with substantial overlap.
It’s pretty obvious that
We have addressed improving tobacco control and preventing obesity and diabetes on these pages many times, and lamented the medical, public health, and societal failings. Today we turn our attention to the control of hypertension. That is much easier and far less expensive.
All physicians and medical organizations know that hypertension is a major attributable cause of many serious, expensive, and fatal illnesses. As many as 119 million (48%) of American adults have hypertension. The American Heart Association (AHA), American Medical Association (AMA), American College of Cardiology (ACC), and hundreds of other organizations have set a new target of 130/80 (revised from 140/90) for blood pressure control and have launched a major initiative, Target: BP, to reach it.
That is just great. We all wish this massive effort to succeed where few others have. But do AHA, AMA, ACC, and others understand why most efforts to this point have failed? The blame is typically aimed at patients failing to adhere to their instructions. Maybe, but why? And how does Target: BP intend to convert chronic failure into success if it just continues to do everything they have been trying to do that doesn’t work?
At this point, the Centers for Disease Control and Prevention reports that fewer than 48% of American patients with hypertension meet even the less stringent historical 140/90 goal.
A group practice in Ohio, PriMed Physicians, has consistently exceeded 90% or even 95% blood pressure control for its patients with hypertension for more than 10 years. Exemplary. How do they do it? This video of the 13th annual Lundberg Institute lecture describes this unique and successful program.
PriMed’s clinicians use the MedsEngine AI tool from MediSync and the NICaS (noninvasive cardiac system with impedance cardiography) to determine each patient’s unique blood pressure pathophysiology. Clinicians and patients understand that the simplest explanation of this pathophysiology encompasses three factors: (1) the volume of “water” (blood) in the system; (2) the strength of the pumping (pulsatile) process; and (3) the tightness (resistance) of the tubes that carry the blood. Patients “get it” when it is explained this way, and they cooperate.
At the first patient encounter, the Food and Drug Administration–approved PhysioFlow is employed to assess those three vital hemodynamic factors. The individual patient’s data are loaded into a tightly programed EHR-based algorithm with 37 clinical factors and five classes of drugs, providing multiple ways to influence the three key pathophysiologic processes. In this way, they arrive at the precise drug(s) and dosages for that patient. During the second visit, most patients are already showing improvement. By the third visit, the blood pressures of most patients have reached target control. After that, it is maintenance and tweaking.
These factors summarize why it works:
- Senior management belief, commitment, and leadership
- Informed buy-in from clinicians and patients
- A test that determines root causes of too much fluid, too strong pump action, or too tight pipes, and their proportionality
- An AI tool that matches those three pathophysiologic factors and 35 other clinical factors with the best drug or drugs (of many, not just a few) and dosages
- Persistent clinician-patient follow-up
- Refusal to accept failure
Since this approach is so successful, why is its use not everywhere?
It is not as if nobody noticed, even if you and many organizations have not. The American Medical Group Association recognized the program’s success by giving its top award to PriMed in 2015.
Klepper and Rodis wrote about this approach for managing multiple chronic conditions in 2021. Here’s a background article and an explainer, Clinical use of impedance cardiography for hemodynamic assessment of early cardiovascular disease and management of hypertension.
I found one pragmatic controlled clinical trial of impedance cardiography with a decision-support system from Beijing that did demonstrate clinical and statistical significance.
Frankly, we do need more rigorous, unbiased, large, controlled clinical trials assessing the MedsEngine and NICaS approach to managing blood pressure to facilitate a massive switch from the old and established (but failing) approach to a starkly better way.
Almost no one ever “completes a database.” All decision makers must act based upon the best data to which they have access. Data are often incomplete. The difference between success and mediocrity is often the ability of an individual or system to decide when enough information is enough and act accordingly.
Cost-effectiveness studies in three countries (United Kingdom, United States, and China) confirm sharply lower lifelong costs when blood pressure is well controlled. Of course.
For the American medical-industrial complex, lowered costs for managing common serious diseases may be an undesired rather than a good thing. In money-driven medicine, lower costs to the payer and purchaser translate to less revenue for the providers. Imagine all of those invasive and noninvasive diagnostic and therapeutic procedures forgone by prevention of hypertension. Is it possible that such an underlying truth is the real reason why American medicine is habitually unsuccessful at controlling blood pressure?
Right now, if my blood pressure were not well controlled (it is), I would find my way to Cincinnati, to give PriMed physicians, MediSync, and MedsEngine a crack at prolonging my useful life.
Dr. Lundberg is editor in chief of Cancer Commons. He disclosed no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
My Bing AI engine, when prompted, tells me that there are about 87 journals, 45 conferences, and 53 workshops presently dedicated exclusively to hypertension. All of that attention, and yet ...
What is going on?
The top killers of Americans remain coronary artery heart disease (26%), cancer (22%), and stroke (6%). The precursors and attributable risk factors for coronary artery heart disease include hypertension (40%), obesity (20%), diabetes (15%), and combustible tobacco use (15%). The key precursors and attributable risk factors for stroke are hypertension (53%), obesity (37%), diabetes (9%), and combustible tobacco use (11%). Obviously, these are estimates, with substantial overlap.
It’s pretty obvious that
We have addressed improving tobacco control and preventing obesity and diabetes on these pages many times, and lamented the medical, public health, and societal failings. Today we turn our attention to the control of hypertension. That is much easier and far less expensive.
All physicians and medical organizations know that hypertension is a major attributable cause of many serious, expensive, and fatal illnesses. As many as 119 million (48%) of American adults have hypertension. The American Heart Association (AHA), American Medical Association (AMA), American College of Cardiology (ACC), and hundreds of other organizations have set a new target of 130/80 (revised from 140/90) for blood pressure control and have launched a major initiative, Target: BP, to reach it.
That is just great. We all wish this massive effort to succeed where few others have. But do AHA, AMA, ACC, and others understand why most efforts to this point have failed? The blame is typically aimed at patients failing to adhere to their instructions. Maybe, but why? And how does Target: BP intend to convert chronic failure into success if it just continues to do everything they have been trying to do that doesn’t work?
At this point, the Centers for Disease Control and Prevention reports that fewer than 48% of American patients with hypertension meet even the less stringent historical 140/90 goal.
A group practice in Ohio, PriMed Physicians, has consistently exceeded 90% or even 95% blood pressure control for its patients with hypertension for more than 10 years. Exemplary. How do they do it? This video of the 13th annual Lundberg Institute lecture describes this unique and successful program.
PriMed’s clinicians use the MedsEngine AI tool from MediSync and the NICaS (noninvasive cardiac system with impedance cardiography) to determine each patient’s unique blood pressure pathophysiology. Clinicians and patients understand that the simplest explanation of this pathophysiology encompasses three factors: (1) the volume of “water” (blood) in the system; (2) the strength of the pumping (pulsatile) process; and (3) the tightness (resistance) of the tubes that carry the blood. Patients “get it” when it is explained this way, and they cooperate.
At the first patient encounter, the Food and Drug Administration–approved PhysioFlow is employed to assess those three vital hemodynamic factors. The individual patient’s data are loaded into a tightly programed EHR-based algorithm with 37 clinical factors and five classes of drugs, providing multiple ways to influence the three key pathophysiologic processes. In this way, they arrive at the precise drug(s) and dosages for that patient. During the second visit, most patients are already showing improvement. By the third visit, the blood pressures of most patients have reached target control. After that, it is maintenance and tweaking.
These factors summarize why it works:
- Senior management belief, commitment, and leadership
- Informed buy-in from clinicians and patients
- A test that determines root causes of too much fluid, too strong pump action, or too tight pipes, and their proportionality
- An AI tool that matches those three pathophysiologic factors and 35 other clinical factors with the best drug or drugs (of many, not just a few) and dosages
- Persistent clinician-patient follow-up
- Refusal to accept failure
Since this approach is so successful, why is its use not everywhere?
It is not as if nobody noticed, even if you and many organizations have not. The American Medical Group Association recognized the program’s success by giving its top award to PriMed in 2015.
Klepper and Rodis wrote about this approach for managing multiple chronic conditions in 2021. Here’s a background article and an explainer, Clinical use of impedance cardiography for hemodynamic assessment of early cardiovascular disease and management of hypertension.
I found one pragmatic controlled clinical trial of impedance cardiography with a decision-support system from Beijing that did demonstrate clinical and statistical significance.
Frankly, we do need more rigorous, unbiased, large, controlled clinical trials assessing the MedsEngine and NICaS approach to managing blood pressure to facilitate a massive switch from the old and established (but failing) approach to a starkly better way.
Almost no one ever “completes a database.” All decision makers must act based upon the best data to which they have access. Data are often incomplete. The difference between success and mediocrity is often the ability of an individual or system to decide when enough information is enough and act accordingly.
Cost-effectiveness studies in three countries (United Kingdom, United States, and China) confirm sharply lower lifelong costs when blood pressure is well controlled. Of course.
For the American medical-industrial complex, lowered costs for managing common serious diseases may be an undesired rather than a good thing. In money-driven medicine, lower costs to the payer and purchaser translate to less revenue for the providers. Imagine all of those invasive and noninvasive diagnostic and therapeutic procedures forgone by prevention of hypertension. Is it possible that such an underlying truth is the real reason why American medicine is habitually unsuccessful at controlling blood pressure?
Right now, if my blood pressure were not well controlled (it is), I would find my way to Cincinnati, to give PriMed physicians, MediSync, and MedsEngine a crack at prolonging my useful life.
Dr. Lundberg is editor in chief of Cancer Commons. He disclosed no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
My Bing AI engine, when prompted, tells me that there are about 87 journals, 45 conferences, and 53 workshops presently dedicated exclusively to hypertension. All of that attention, and yet ...
What is going on?
The top killers of Americans remain coronary artery heart disease (26%), cancer (22%), and stroke (6%). The precursors and attributable risk factors for coronary artery heart disease include hypertension (40%), obesity (20%), diabetes (15%), and combustible tobacco use (15%). The key precursors and attributable risk factors for stroke are hypertension (53%), obesity (37%), diabetes (9%), and combustible tobacco use (11%). Obviously, these are estimates, with substantial overlap.
It’s pretty obvious that
We have addressed improving tobacco control and preventing obesity and diabetes on these pages many times, and lamented the medical, public health, and societal failings. Today we turn our attention to the control of hypertension. That is much easier and far less expensive.
All physicians and medical organizations know that hypertension is a major attributable cause of many serious, expensive, and fatal illnesses. As many as 119 million (48%) of American adults have hypertension. The American Heart Association (AHA), American Medical Association (AMA), American College of Cardiology (ACC), and hundreds of other organizations have set a new target of 130/80 (revised from 140/90) for blood pressure control and have launched a major initiative, Target: BP, to reach it.
That is just great. We all wish this massive effort to succeed where few others have. But do AHA, AMA, ACC, and others understand why most efforts to this point have failed? The blame is typically aimed at patients failing to adhere to their instructions. Maybe, but why? And how does Target: BP intend to convert chronic failure into success if it just continues to do everything they have been trying to do that doesn’t work?
At this point, the Centers for Disease Control and Prevention reports that fewer than 48% of American patients with hypertension meet even the less stringent historical 140/90 goal.
A group practice in Ohio, PriMed Physicians, has consistently exceeded 90% or even 95% blood pressure control for its patients with hypertension for more than 10 years. Exemplary. How do they do it? This video of the 13th annual Lundberg Institute lecture describes this unique and successful program.
PriMed’s clinicians use the MedsEngine AI tool from MediSync and the NICaS (noninvasive cardiac system with impedance cardiography) to determine each patient’s unique blood pressure pathophysiology. Clinicians and patients understand that the simplest explanation of this pathophysiology encompasses three factors: (1) the volume of “water” (blood) in the system; (2) the strength of the pumping (pulsatile) process; and (3) the tightness (resistance) of the tubes that carry the blood. Patients “get it” when it is explained this way, and they cooperate.
At the first patient encounter, the Food and Drug Administration–approved PhysioFlow is employed to assess those three vital hemodynamic factors. The individual patient’s data are loaded into a tightly programed EHR-based algorithm with 37 clinical factors and five classes of drugs, providing multiple ways to influence the three key pathophysiologic processes. In this way, they arrive at the precise drug(s) and dosages for that patient. During the second visit, most patients are already showing improvement. By the third visit, the blood pressures of most patients have reached target control. After that, it is maintenance and tweaking.
These factors summarize why it works:
- Senior management belief, commitment, and leadership
- Informed buy-in from clinicians and patients
- A test that determines root causes of too much fluid, too strong pump action, or too tight pipes, and their proportionality
- An AI tool that matches those three pathophysiologic factors and 35 other clinical factors with the best drug or drugs (of many, not just a few) and dosages
- Persistent clinician-patient follow-up
- Refusal to accept failure
Since this approach is so successful, why is its use not everywhere?
It is not as if nobody noticed, even if you and many organizations have not. The American Medical Group Association recognized the program’s success by giving its top award to PriMed in 2015.
Klepper and Rodis wrote about this approach for managing multiple chronic conditions in 2021. Here’s a background article and an explainer, Clinical use of impedance cardiography for hemodynamic assessment of early cardiovascular disease and management of hypertension.
I found one pragmatic controlled clinical trial of impedance cardiography with a decision-support system from Beijing that did demonstrate clinical and statistical significance.
Frankly, we do need more rigorous, unbiased, large, controlled clinical trials assessing the MedsEngine and NICaS approach to managing blood pressure to facilitate a massive switch from the old and established (but failing) approach to a starkly better way.
Almost no one ever “completes a database.” All decision makers must act based upon the best data to which they have access. Data are often incomplete. The difference between success and mediocrity is often the ability of an individual or system to decide when enough information is enough and act accordingly.
Cost-effectiveness studies in three countries (United Kingdom, United States, and China) confirm sharply lower lifelong costs when blood pressure is well controlled. Of course.
For the American medical-industrial complex, lowered costs for managing common serious diseases may be an undesired rather than a good thing. In money-driven medicine, lower costs to the payer and purchaser translate to less revenue for the providers. Imagine all of those invasive and noninvasive diagnostic and therapeutic procedures forgone by prevention of hypertension. Is it possible that such an underlying truth is the real reason why American medicine is habitually unsuccessful at controlling blood pressure?
Right now, if my blood pressure were not well controlled (it is), I would find my way to Cincinnati, to give PriMed physicians, MediSync, and MedsEngine a crack at prolonging my useful life.
Dr. Lundberg is editor in chief of Cancer Commons. He disclosed no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
Albuminuria reduction fuels finerenone’s kidney benefits
PHILADELPHIA – Reducing albuminuria is a key mediator of the way finerenone (Kerendia, Bayer) reduces adverse renal and cardiovascular events in people with type 2 diabetes and chronic kidney disease (CKD), based on findings from two novel mediation analyses run on data from more than 12,000 people included in the two finerenone pivotal trials.
Results from these analyses showed that that finerenone treatment produced in the FIDELIO-DKD and FIGARO-DKD phase 3 trials. FIDELIO-DKD, which had protection against adverse kidney outcomes as its primary endpoint, supplied the data that led to finerenone’s approval in 2021 by the U.S. Food and Drug Administration for treating people with type 2 diabetes and CKD.
The findings of the mediation analyses underscore the important role that albuminuria plays in the nephropathy and related comorbidities associated with type 2 diabetes and CKD and highlight the importance of ongoing monitoring of albuminuria to guide treatments aimed at minimizing this pathology, said Rajiv Agarwal, MD, who presented a poster on the mediation analyses at Kidney Week 2023, organized by the American Society of Nephrology.
“My hope is that this [report] heightens awareness of UACR” as an important marker of both CKD and of the response by patients with CKD to their treatment, said Dr. Agarwal, a nephrologist and professor at Indiana University in Indianapolis.
“Only about half of people with type 2 diabetes get their UACR measured even though every guideline says measure UACR in people with diabetes. Our findings say that UACR is important not just for CKD diagnosis but also to give feedback” on whether management is working, Dr. Agarwal said in an interview.
Incorporate UACR into clinical decision-making
“My hope is that clinicians will look at UACR as something they should incorporate into clinical decision-making. I measure UACR in my patients [with CKD and type 2 diabetes] at every visit; it’s so inexpensive. Albuminuria is not a good sign. If it’s not reduced in a patient by at least 30% [the recommended minimum reduction by the American Diabetes Association for people who start with a UACR of at least 300 mg/g] clinicians should think of what else they could do to lower albuminuria”: Reduce salt intake, improve blood pressure control, make sure the patient is adherent to treatments, and add additional treatments, Dr. Agarwal advised.
Multiple efforts are now underway or will soon start to boost the rate at which at-risk people get their UACR measured, noted Leslie A. Inker, MD, in a separate talk during Kidney Week. These efforts include the National Kidney Foundation’s CKD Learning Collaborative, which aims to improve clinician awareness of CKD and improve routine testing for CKD. Early results during 2023 from this program in Missouri showed a nearly 8–percentage point increase in the screening rate for UACR levels in at-risk people, said Dr. Inker, professor and director of the Kidney and Blood Pressure Center at Tufts Medical Center in Boston.
A second advance was introduction in 2018 of the “kidney profile” lab order by the American College of Clinical Pathology that allows clinicians to order as a single test both an estimated glomerular filtration rate (eGFR) and a UACR.
Also, the Centers for Medicare & Medicaid Services and the National Committee for Quality Assurance have both taken steps to encourage UACR ordering. The NCQA established a new Healthcare Effectiveness Data and Information Set performance measure for U.S. physicians starting in 2023 that will track measurement of UACR and eGFR in people with diabetes. CMS also has made assessment of kidney health a measure of care quality in programs effective in 2023 and 2024, Dr. Inker noted.
Most subjects had elevated UACRs
The study run by Dr. Agarwal and his associates used data from 12,512 of the more than 13,000 people enrolled in either FIDELITY-DKD or FIGARO-DKD who had UACR measurements recorded at baseline, at 4 months into either study, or both. Their median UACR at the time they began on finerenone or placebo was 514 mg/g, with 67% having a UACR of at least 300 mg/g (macroalbuminuria) and 31% having a UACR of 30-299 mg/g (microalbuminuria). By design, virtually all patients in these two trials were on a renin-angiotensin system inhibitor (either an angiotensin-converting enzyme inhibitor or an angiotensin-receptor blocker), but given the time period when the two trials enrolled participants (during 2015-2018) only 7% of those enrolled were on a sodium-glucose cotransporter 2 inhibitor and only 7% were on a glucagonlike peptide–1 receptor agonist.
Four months after treatment began, 53% of those randomized to finerenone treatment and 27% of those in the placebo arm had their UACR reduced by at least 30% from baseline, the cutpoint chosen by Dr. Agarwal based on the American Diabetes Association guideline.
Kaplan-Meier analyses showed that the incidence of the primary kidney outcome – kidney failure, a sustained ≥ 57% decrease in eGFR from baseline, or kidney death – showed close correlation with at least a 30% reduction in UACR regardless of whether the patients in this subgroup received finerenone or placebo.
A different correlation was found in those with a less than 30% reduction in their UACR from baseline to 4 months, regardless of whether this happened on finerenone or placebo. People in the two finerenone trials who had a lesser reduction from baseline in their UACR also had a significantly higher rate of adverse kidney outcomes whether they received finerenone or placebo.
84% of finerenone’s kidney benefit linked to lowering of UACR
The causal-mediation analysis run by Dr. Agarwal quantified this observation, showing that 84% of finerenone’s effect on the kidney outcome was mediated by the reduction in UACR.
“It seems like the kidney benefit [from finerenone] travels through the level of albuminuria. This has broad implications for treatment of people with type 2 diabetes and CKD,” he said.
The link with reduction in albuminuria was weaker for the primary cardiovascular disease outcome: CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. The strongest effect on this outcome was only seen in Kaplan-Meier analysis in those on finerenone who had at least a 30% reduction in their UACR. Those on placebo and with a similarly robust 4-month reduction in UACR showed a much more modest cardiovascular benefit that resembled those on either finerenone or placebo who had a smaller, less than 30% UACR reduction. The mediation analysis of these data showed that UACR reduction accounted for about 37% of the observed cardiovascular benefit seen during the trials.
“The effect of UACR is much stronger for the kidney outcomes,” summed up Dr. Agarwal. The results suggest that for cardiovascular outcomes finerenone works through factors other than lowering of UACR, but he admitted that no one currently knows what those other factors might be.
Treat aggressively to lower UACR by 30%
“I wouldn’t stop finerenone treatment in people who do not get a 30% reduction in their UACR” because these analyses suggest that a portion of the overall benefits from finerenone occurs via other mechanisms, he said. But in patients whose UACR is not reduced by at least 30% “be more aggressive on other measures to reduce UACR,” he advised.
The mediation analyses he ran are “the first time this has been done in nephrology,” producing a “groundbreaking” analysis and finding, Dr. Agarwal said. He also highlighted that the findings primarily relate to the importance of controlling UACR rather than an endorsement of finerenone as the best way to achieve this.
“All I care about is that people think about UACR as a modifiable risk factor. It doesn’t have to be treated with finerenone. It could be a renin-angiotensin system inhibitor, it could be chlorthalidone [a thiazide diuretic]. It just happened that we had a large dataset of people treated with finerenone or placebo.”
He said that future mediation analyses should look at the link between outcomes and UACR reductions produced by agents from the classes of sodium-glucose cotransporter 2 inhibitors and the glucagonlike peptide–1 receptor agonists.
FIDELIO-DKD and FIGARO-DKD were both sponsored by Bayer, the company that markets finerenone. Dr. Agarwal has received personal fees and nonfinancial support from Bayer. He has also received personal fees and nonfinancial support from Akebia Therapeutics, AstraZeneca, Boehringer Ingelheim, Eli Lilly, and Vifor Pharma, and he is a member of data safety monitoring committees for Chinook and Vertex. Dr. Inker is a consultant to Diamtrix, and her department receives research funding from Chinook, Omeros, Reata, and Tricida.
PHILADELPHIA – Reducing albuminuria is a key mediator of the way finerenone (Kerendia, Bayer) reduces adverse renal and cardiovascular events in people with type 2 diabetes and chronic kidney disease (CKD), based on findings from two novel mediation analyses run on data from more than 12,000 people included in the two finerenone pivotal trials.
Results from these analyses showed that that finerenone treatment produced in the FIDELIO-DKD and FIGARO-DKD phase 3 trials. FIDELIO-DKD, which had protection against adverse kidney outcomes as its primary endpoint, supplied the data that led to finerenone’s approval in 2021 by the U.S. Food and Drug Administration for treating people with type 2 diabetes and CKD.
The findings of the mediation analyses underscore the important role that albuminuria plays in the nephropathy and related comorbidities associated with type 2 diabetes and CKD and highlight the importance of ongoing monitoring of albuminuria to guide treatments aimed at minimizing this pathology, said Rajiv Agarwal, MD, who presented a poster on the mediation analyses at Kidney Week 2023, organized by the American Society of Nephrology.
“My hope is that this [report] heightens awareness of UACR” as an important marker of both CKD and of the response by patients with CKD to their treatment, said Dr. Agarwal, a nephrologist and professor at Indiana University in Indianapolis.
“Only about half of people with type 2 diabetes get their UACR measured even though every guideline says measure UACR in people with diabetes. Our findings say that UACR is important not just for CKD diagnosis but also to give feedback” on whether management is working, Dr. Agarwal said in an interview.
Incorporate UACR into clinical decision-making
“My hope is that clinicians will look at UACR as something they should incorporate into clinical decision-making. I measure UACR in my patients [with CKD and type 2 diabetes] at every visit; it’s so inexpensive. Albuminuria is not a good sign. If it’s not reduced in a patient by at least 30% [the recommended minimum reduction by the American Diabetes Association for people who start with a UACR of at least 300 mg/g] clinicians should think of what else they could do to lower albuminuria”: Reduce salt intake, improve blood pressure control, make sure the patient is adherent to treatments, and add additional treatments, Dr. Agarwal advised.
Multiple efforts are now underway or will soon start to boost the rate at which at-risk people get their UACR measured, noted Leslie A. Inker, MD, in a separate talk during Kidney Week. These efforts include the National Kidney Foundation’s CKD Learning Collaborative, which aims to improve clinician awareness of CKD and improve routine testing for CKD. Early results during 2023 from this program in Missouri showed a nearly 8–percentage point increase in the screening rate for UACR levels in at-risk people, said Dr. Inker, professor and director of the Kidney and Blood Pressure Center at Tufts Medical Center in Boston.
A second advance was introduction in 2018 of the “kidney profile” lab order by the American College of Clinical Pathology that allows clinicians to order as a single test both an estimated glomerular filtration rate (eGFR) and a UACR.
Also, the Centers for Medicare & Medicaid Services and the National Committee for Quality Assurance have both taken steps to encourage UACR ordering. The NCQA established a new Healthcare Effectiveness Data and Information Set performance measure for U.S. physicians starting in 2023 that will track measurement of UACR and eGFR in people with diabetes. CMS also has made assessment of kidney health a measure of care quality in programs effective in 2023 and 2024, Dr. Inker noted.
Most subjects had elevated UACRs
The study run by Dr. Agarwal and his associates used data from 12,512 of the more than 13,000 people enrolled in either FIDELITY-DKD or FIGARO-DKD who had UACR measurements recorded at baseline, at 4 months into either study, or both. Their median UACR at the time they began on finerenone or placebo was 514 mg/g, with 67% having a UACR of at least 300 mg/g (macroalbuminuria) and 31% having a UACR of 30-299 mg/g (microalbuminuria). By design, virtually all patients in these two trials were on a renin-angiotensin system inhibitor (either an angiotensin-converting enzyme inhibitor or an angiotensin-receptor blocker), but given the time period when the two trials enrolled participants (during 2015-2018) only 7% of those enrolled were on a sodium-glucose cotransporter 2 inhibitor and only 7% were on a glucagonlike peptide–1 receptor agonist.
Four months after treatment began, 53% of those randomized to finerenone treatment and 27% of those in the placebo arm had their UACR reduced by at least 30% from baseline, the cutpoint chosen by Dr. Agarwal based on the American Diabetes Association guideline.
Kaplan-Meier analyses showed that the incidence of the primary kidney outcome – kidney failure, a sustained ≥ 57% decrease in eGFR from baseline, or kidney death – showed close correlation with at least a 30% reduction in UACR regardless of whether the patients in this subgroup received finerenone or placebo.
A different correlation was found in those with a less than 30% reduction in their UACR from baseline to 4 months, regardless of whether this happened on finerenone or placebo. People in the two finerenone trials who had a lesser reduction from baseline in their UACR also had a significantly higher rate of adverse kidney outcomes whether they received finerenone or placebo.
84% of finerenone’s kidney benefit linked to lowering of UACR
The causal-mediation analysis run by Dr. Agarwal quantified this observation, showing that 84% of finerenone’s effect on the kidney outcome was mediated by the reduction in UACR.
“It seems like the kidney benefit [from finerenone] travels through the level of albuminuria. This has broad implications for treatment of people with type 2 diabetes and CKD,” he said.
The link with reduction in albuminuria was weaker for the primary cardiovascular disease outcome: CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. The strongest effect on this outcome was only seen in Kaplan-Meier analysis in those on finerenone who had at least a 30% reduction in their UACR. Those on placebo and with a similarly robust 4-month reduction in UACR showed a much more modest cardiovascular benefit that resembled those on either finerenone or placebo who had a smaller, less than 30% UACR reduction. The mediation analysis of these data showed that UACR reduction accounted for about 37% of the observed cardiovascular benefit seen during the trials.
“The effect of UACR is much stronger for the kidney outcomes,” summed up Dr. Agarwal. The results suggest that for cardiovascular outcomes finerenone works through factors other than lowering of UACR, but he admitted that no one currently knows what those other factors might be.
Treat aggressively to lower UACR by 30%
“I wouldn’t stop finerenone treatment in people who do not get a 30% reduction in their UACR” because these analyses suggest that a portion of the overall benefits from finerenone occurs via other mechanisms, he said. But in patients whose UACR is not reduced by at least 30% “be more aggressive on other measures to reduce UACR,” he advised.
The mediation analyses he ran are “the first time this has been done in nephrology,” producing a “groundbreaking” analysis and finding, Dr. Agarwal said. He also highlighted that the findings primarily relate to the importance of controlling UACR rather than an endorsement of finerenone as the best way to achieve this.
“All I care about is that people think about UACR as a modifiable risk factor. It doesn’t have to be treated with finerenone. It could be a renin-angiotensin system inhibitor, it could be chlorthalidone [a thiazide diuretic]. It just happened that we had a large dataset of people treated with finerenone or placebo.”
He said that future mediation analyses should look at the link between outcomes and UACR reductions produced by agents from the classes of sodium-glucose cotransporter 2 inhibitors and the glucagonlike peptide–1 receptor agonists.
FIDELIO-DKD and FIGARO-DKD were both sponsored by Bayer, the company that markets finerenone. Dr. Agarwal has received personal fees and nonfinancial support from Bayer. He has also received personal fees and nonfinancial support from Akebia Therapeutics, AstraZeneca, Boehringer Ingelheim, Eli Lilly, and Vifor Pharma, and he is a member of data safety monitoring committees for Chinook and Vertex. Dr. Inker is a consultant to Diamtrix, and her department receives research funding from Chinook, Omeros, Reata, and Tricida.
PHILADELPHIA – Reducing albuminuria is a key mediator of the way finerenone (Kerendia, Bayer) reduces adverse renal and cardiovascular events in people with type 2 diabetes and chronic kidney disease (CKD), based on findings from two novel mediation analyses run on data from more than 12,000 people included in the two finerenone pivotal trials.
Results from these analyses showed that that finerenone treatment produced in the FIDELIO-DKD and FIGARO-DKD phase 3 trials. FIDELIO-DKD, which had protection against adverse kidney outcomes as its primary endpoint, supplied the data that led to finerenone’s approval in 2021 by the U.S. Food and Drug Administration for treating people with type 2 diabetes and CKD.
The findings of the mediation analyses underscore the important role that albuminuria plays in the nephropathy and related comorbidities associated with type 2 diabetes and CKD and highlight the importance of ongoing monitoring of albuminuria to guide treatments aimed at minimizing this pathology, said Rajiv Agarwal, MD, who presented a poster on the mediation analyses at Kidney Week 2023, organized by the American Society of Nephrology.
“My hope is that this [report] heightens awareness of UACR” as an important marker of both CKD and of the response by patients with CKD to their treatment, said Dr. Agarwal, a nephrologist and professor at Indiana University in Indianapolis.
“Only about half of people with type 2 diabetes get their UACR measured even though every guideline says measure UACR in people with diabetes. Our findings say that UACR is important not just for CKD diagnosis but also to give feedback” on whether management is working, Dr. Agarwal said in an interview.
Incorporate UACR into clinical decision-making
“My hope is that clinicians will look at UACR as something they should incorporate into clinical decision-making. I measure UACR in my patients [with CKD and type 2 diabetes] at every visit; it’s so inexpensive. Albuminuria is not a good sign. If it’s not reduced in a patient by at least 30% [the recommended minimum reduction by the American Diabetes Association for people who start with a UACR of at least 300 mg/g] clinicians should think of what else they could do to lower albuminuria”: Reduce salt intake, improve blood pressure control, make sure the patient is adherent to treatments, and add additional treatments, Dr. Agarwal advised.
Multiple efforts are now underway or will soon start to boost the rate at which at-risk people get their UACR measured, noted Leslie A. Inker, MD, in a separate talk during Kidney Week. These efforts include the National Kidney Foundation’s CKD Learning Collaborative, which aims to improve clinician awareness of CKD and improve routine testing for CKD. Early results during 2023 from this program in Missouri showed a nearly 8–percentage point increase in the screening rate for UACR levels in at-risk people, said Dr. Inker, professor and director of the Kidney and Blood Pressure Center at Tufts Medical Center in Boston.
A second advance was introduction in 2018 of the “kidney profile” lab order by the American College of Clinical Pathology that allows clinicians to order as a single test both an estimated glomerular filtration rate (eGFR) and a UACR.
Also, the Centers for Medicare & Medicaid Services and the National Committee for Quality Assurance have both taken steps to encourage UACR ordering. The NCQA established a new Healthcare Effectiveness Data and Information Set performance measure for U.S. physicians starting in 2023 that will track measurement of UACR and eGFR in people with diabetes. CMS also has made assessment of kidney health a measure of care quality in programs effective in 2023 and 2024, Dr. Inker noted.
Most subjects had elevated UACRs
The study run by Dr. Agarwal and his associates used data from 12,512 of the more than 13,000 people enrolled in either FIDELITY-DKD or FIGARO-DKD who had UACR measurements recorded at baseline, at 4 months into either study, or both. Their median UACR at the time they began on finerenone or placebo was 514 mg/g, with 67% having a UACR of at least 300 mg/g (macroalbuminuria) and 31% having a UACR of 30-299 mg/g (microalbuminuria). By design, virtually all patients in these two trials were on a renin-angiotensin system inhibitor (either an angiotensin-converting enzyme inhibitor or an angiotensin-receptor blocker), but given the time period when the two trials enrolled participants (during 2015-2018) only 7% of those enrolled were on a sodium-glucose cotransporter 2 inhibitor and only 7% were on a glucagonlike peptide–1 receptor agonist.
Four months after treatment began, 53% of those randomized to finerenone treatment and 27% of those in the placebo arm had their UACR reduced by at least 30% from baseline, the cutpoint chosen by Dr. Agarwal based on the American Diabetes Association guideline.
Kaplan-Meier analyses showed that the incidence of the primary kidney outcome – kidney failure, a sustained ≥ 57% decrease in eGFR from baseline, or kidney death – showed close correlation with at least a 30% reduction in UACR regardless of whether the patients in this subgroup received finerenone or placebo.
A different correlation was found in those with a less than 30% reduction in their UACR from baseline to 4 months, regardless of whether this happened on finerenone or placebo. People in the two finerenone trials who had a lesser reduction from baseline in their UACR also had a significantly higher rate of adverse kidney outcomes whether they received finerenone or placebo.
84% of finerenone’s kidney benefit linked to lowering of UACR
The causal-mediation analysis run by Dr. Agarwal quantified this observation, showing that 84% of finerenone’s effect on the kidney outcome was mediated by the reduction in UACR.
“It seems like the kidney benefit [from finerenone] travels through the level of albuminuria. This has broad implications for treatment of people with type 2 diabetes and CKD,” he said.
The link with reduction in albuminuria was weaker for the primary cardiovascular disease outcome: CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. The strongest effect on this outcome was only seen in Kaplan-Meier analysis in those on finerenone who had at least a 30% reduction in their UACR. Those on placebo and with a similarly robust 4-month reduction in UACR showed a much more modest cardiovascular benefit that resembled those on either finerenone or placebo who had a smaller, less than 30% UACR reduction. The mediation analysis of these data showed that UACR reduction accounted for about 37% of the observed cardiovascular benefit seen during the trials.
“The effect of UACR is much stronger for the kidney outcomes,” summed up Dr. Agarwal. The results suggest that for cardiovascular outcomes finerenone works through factors other than lowering of UACR, but he admitted that no one currently knows what those other factors might be.
Treat aggressively to lower UACR by 30%
“I wouldn’t stop finerenone treatment in people who do not get a 30% reduction in their UACR” because these analyses suggest that a portion of the overall benefits from finerenone occurs via other mechanisms, he said. But in patients whose UACR is not reduced by at least 30% “be more aggressive on other measures to reduce UACR,” he advised.
The mediation analyses he ran are “the first time this has been done in nephrology,” producing a “groundbreaking” analysis and finding, Dr. Agarwal said. He also highlighted that the findings primarily relate to the importance of controlling UACR rather than an endorsement of finerenone as the best way to achieve this.
“All I care about is that people think about UACR as a modifiable risk factor. It doesn’t have to be treated with finerenone. It could be a renin-angiotensin system inhibitor, it could be chlorthalidone [a thiazide diuretic]. It just happened that we had a large dataset of people treated with finerenone or placebo.”
He said that future mediation analyses should look at the link between outcomes and UACR reductions produced by agents from the classes of sodium-glucose cotransporter 2 inhibitors and the glucagonlike peptide–1 receptor agonists.
FIDELIO-DKD and FIGARO-DKD were both sponsored by Bayer, the company that markets finerenone. Dr. Agarwal has received personal fees and nonfinancial support from Bayer. He has also received personal fees and nonfinancial support from Akebia Therapeutics, AstraZeneca, Boehringer Ingelheim, Eli Lilly, and Vifor Pharma, and he is a member of data safety monitoring committees for Chinook and Vertex. Dr. Inker is a consultant to Diamtrix, and her department receives research funding from Chinook, Omeros, Reata, and Tricida.
AT KIDNEY WEEK 2023
‘Love more’: Why doctors should promote social connection
Those who embrace lifestyle medicine are familiar with the slogan Dean Ornish, MD, likes to use: Eat well, move more, stress less, love more.
That last one, love, was the renowned physician and author’s focus at the recent American College of Lifestyle Medicine Conference in Denver. That’s because love – essentially the support, connectedness, and caring that patients feel when they join a lifestyle-change program – is “where healing occurs at the deepest level.”
Indeed, social connectedness is emerging as a vital pillar in the burgeoning field of lifestyle medicine, a specialty that uses lifestyle interventions to treat chronic conditions. About 300 lifestyle medicine programs are now integrated into residencies in medical schools across the country, up from a handful just 5 years ago, said Meagan Grega, MD, the conference chair.
“The energy and growth in American lifestyle medicine is unparalleled by anything else I see in the health care world right now,” said Dr. Grega, a family physician for 25 years in eastern Pennsylvania.
The field applies volumes of research, from the 1990s to today, demonstrating the healing effects of lifestyle changes. Dr. Ornish’s Preventive Medicine Research Institute has published research on small changes (like pomegranate juice helping blood flow in the heart) and huge ones: Coronary heart patients reversed the narrowing of arteries without lipid-lowering drugs after 1 year of lifestyle changes, including a vegetarian diet, aerobic exercise, stress management, and group support.
Ranking alongside bedrocks such as healthy diet, sleep, exercise, and stress management is positive social connection. That part, the “love more” part, often draws skepticism but is vital, said Dr. Ornish, who is sometimes referred to as the father of lifestyle medicine.
It’s “invariably the part that’s the most meaningful – that sense of connection to community that can come when you bring total strangers together,” Dr. Ornish said. “The ‘love more’ part, in many ways, is not only as important, but in some ways even more because everything really flows from that.”
Patients in a support group, who can “let down their emotional defenses and talk openly and authentically,” are much more likely to make and maintain healthy changes, Dr. Ornish said.
Love as medicine
Mounting evidence links loneliness and isolation with a range of health issues, from mood disorders such as depression to chronic conditions such as cardiovascular disease. What’s more, data suggest that loneliness and social isolation in the United States are on the rise, and the COVID pandemic made that more clear. In May 2023, Surgeon General Vivek Murthy, MD, called loneliness, isolation, and lack of connection in the United States a “public health crisis.”
“Good relationships keep us happier and healthier,” said Robert Waldinger, MD, a psychiatrist at Massachusetts General Hospital, Boston.
Dr. Waldinger, who was not affiliated with the conference, is head of the Harvard Study of Adult Development, one of the longest studies of adult life. Beginning in 1938, the study has tracked 724 people plus more than 1,300 of their descendants and found that embracing community and close relationships helps us live longer and be happier.
In the study, the people who were most satisfied with their relationships at age 50 years were the healthiest at age 80 years. Knowing you have someone to rely on protects the brain: “Those people’s memories stay sharper longer,” Dr. Waldinger said.
He draws a distinction between connection and love. “Love is, I think, more of a feeling,” Dr. Waldinger noted. “Connection is a feeling, but it’s also an activity.”
One in five Americans say they’re lonely, he said, “and loneliness is a stressor.” People who are isolated don’t sleep as well, he added. Their health declines earlier in midlife, brain function slips sooner, and their lives are shorter.
“You don’t have anyone to complain to,” he said. If you do, “you can feel your body start to calm down.” Those without social connections may stay in a low-level “fight-or-flight mode.”
“What we think happens is that you have low levels of inflammation chronically, and those can gradually break down body systems.” Moreover, higher rates of cardiac reactivity, for instance, a racing heartbeat when upset, can lead to high blood pressure and lower immune function.
In his talk, Dr. Ornish said, “Anger is that one emotion that has consistently been shown to make heart disease worse.”
Helping people in those straits is gratifying, Dr. Ornish said. “If we can work with people as lifestyle medicine practitioners when they’re suffering, there’s an opportunity for transformation.”
Future
Of course, that can be easier said than done. Dr. Ornish relayed a patient’s typical reaction to a lifestyle program: “This is kind of weird stuff. Like, I get diet. But a plant-based diet, really? Meditation? Loving more? Really?”
He told the conference, “Part of our job as lifestyle medicine practitioners is to spend a little extra time with them. It doesn’t even take that much time. And to really help them understand what brings them a sense of hope and meaning and purpose.”
The results can be motivating. “Most people feel so much better so quickly,” Dr. Ornish said. “It reframes the reason for change from fear of dying to joy of living.”
Dr. Grega, for one, is optimistic for the future, citing survey results showing that 95% of medical students think that they›d be better counselors with lifestyle training. ‘They passionately want this type of thing,” she said.
A version of this article first appeared on Medscape.com.
Those who embrace lifestyle medicine are familiar with the slogan Dean Ornish, MD, likes to use: Eat well, move more, stress less, love more.
That last one, love, was the renowned physician and author’s focus at the recent American College of Lifestyle Medicine Conference in Denver. That’s because love – essentially the support, connectedness, and caring that patients feel when they join a lifestyle-change program – is “where healing occurs at the deepest level.”
Indeed, social connectedness is emerging as a vital pillar in the burgeoning field of lifestyle medicine, a specialty that uses lifestyle interventions to treat chronic conditions. About 300 lifestyle medicine programs are now integrated into residencies in medical schools across the country, up from a handful just 5 years ago, said Meagan Grega, MD, the conference chair.
“The energy and growth in American lifestyle medicine is unparalleled by anything else I see in the health care world right now,” said Dr. Grega, a family physician for 25 years in eastern Pennsylvania.
The field applies volumes of research, from the 1990s to today, demonstrating the healing effects of lifestyle changes. Dr. Ornish’s Preventive Medicine Research Institute has published research on small changes (like pomegranate juice helping blood flow in the heart) and huge ones: Coronary heart patients reversed the narrowing of arteries without lipid-lowering drugs after 1 year of lifestyle changes, including a vegetarian diet, aerobic exercise, stress management, and group support.
Ranking alongside bedrocks such as healthy diet, sleep, exercise, and stress management is positive social connection. That part, the “love more” part, often draws skepticism but is vital, said Dr. Ornish, who is sometimes referred to as the father of lifestyle medicine.
It’s “invariably the part that’s the most meaningful – that sense of connection to community that can come when you bring total strangers together,” Dr. Ornish said. “The ‘love more’ part, in many ways, is not only as important, but in some ways even more because everything really flows from that.”
Patients in a support group, who can “let down their emotional defenses and talk openly and authentically,” are much more likely to make and maintain healthy changes, Dr. Ornish said.
Love as medicine
Mounting evidence links loneliness and isolation with a range of health issues, from mood disorders such as depression to chronic conditions such as cardiovascular disease. What’s more, data suggest that loneliness and social isolation in the United States are on the rise, and the COVID pandemic made that more clear. In May 2023, Surgeon General Vivek Murthy, MD, called loneliness, isolation, and lack of connection in the United States a “public health crisis.”
“Good relationships keep us happier and healthier,” said Robert Waldinger, MD, a psychiatrist at Massachusetts General Hospital, Boston.
Dr. Waldinger, who was not affiliated with the conference, is head of the Harvard Study of Adult Development, one of the longest studies of adult life. Beginning in 1938, the study has tracked 724 people plus more than 1,300 of their descendants and found that embracing community and close relationships helps us live longer and be happier.
In the study, the people who were most satisfied with their relationships at age 50 years were the healthiest at age 80 years. Knowing you have someone to rely on protects the brain: “Those people’s memories stay sharper longer,” Dr. Waldinger said.
He draws a distinction between connection and love. “Love is, I think, more of a feeling,” Dr. Waldinger noted. “Connection is a feeling, but it’s also an activity.”
One in five Americans say they’re lonely, he said, “and loneliness is a stressor.” People who are isolated don’t sleep as well, he added. Their health declines earlier in midlife, brain function slips sooner, and their lives are shorter.
“You don’t have anyone to complain to,” he said. If you do, “you can feel your body start to calm down.” Those without social connections may stay in a low-level “fight-or-flight mode.”
“What we think happens is that you have low levels of inflammation chronically, and those can gradually break down body systems.” Moreover, higher rates of cardiac reactivity, for instance, a racing heartbeat when upset, can lead to high blood pressure and lower immune function.
In his talk, Dr. Ornish said, “Anger is that one emotion that has consistently been shown to make heart disease worse.”
Helping people in those straits is gratifying, Dr. Ornish said. “If we can work with people as lifestyle medicine practitioners when they’re suffering, there’s an opportunity for transformation.”
Future
Of course, that can be easier said than done. Dr. Ornish relayed a patient’s typical reaction to a lifestyle program: “This is kind of weird stuff. Like, I get diet. But a plant-based diet, really? Meditation? Loving more? Really?”
He told the conference, “Part of our job as lifestyle medicine practitioners is to spend a little extra time with them. It doesn’t even take that much time. And to really help them understand what brings them a sense of hope and meaning and purpose.”
The results can be motivating. “Most people feel so much better so quickly,” Dr. Ornish said. “It reframes the reason for change from fear of dying to joy of living.”
Dr. Grega, for one, is optimistic for the future, citing survey results showing that 95% of medical students think that they›d be better counselors with lifestyle training. ‘They passionately want this type of thing,” she said.
A version of this article first appeared on Medscape.com.
Those who embrace lifestyle medicine are familiar with the slogan Dean Ornish, MD, likes to use: Eat well, move more, stress less, love more.
That last one, love, was the renowned physician and author’s focus at the recent American College of Lifestyle Medicine Conference in Denver. That’s because love – essentially the support, connectedness, and caring that patients feel when they join a lifestyle-change program – is “where healing occurs at the deepest level.”
Indeed, social connectedness is emerging as a vital pillar in the burgeoning field of lifestyle medicine, a specialty that uses lifestyle interventions to treat chronic conditions. About 300 lifestyle medicine programs are now integrated into residencies in medical schools across the country, up from a handful just 5 years ago, said Meagan Grega, MD, the conference chair.
“The energy and growth in American lifestyle medicine is unparalleled by anything else I see in the health care world right now,” said Dr. Grega, a family physician for 25 years in eastern Pennsylvania.
The field applies volumes of research, from the 1990s to today, demonstrating the healing effects of lifestyle changes. Dr. Ornish’s Preventive Medicine Research Institute has published research on small changes (like pomegranate juice helping blood flow in the heart) and huge ones: Coronary heart patients reversed the narrowing of arteries without lipid-lowering drugs after 1 year of lifestyle changes, including a vegetarian diet, aerobic exercise, stress management, and group support.
Ranking alongside bedrocks such as healthy diet, sleep, exercise, and stress management is positive social connection. That part, the “love more” part, often draws skepticism but is vital, said Dr. Ornish, who is sometimes referred to as the father of lifestyle medicine.
It’s “invariably the part that’s the most meaningful – that sense of connection to community that can come when you bring total strangers together,” Dr. Ornish said. “The ‘love more’ part, in many ways, is not only as important, but in some ways even more because everything really flows from that.”
Patients in a support group, who can “let down their emotional defenses and talk openly and authentically,” are much more likely to make and maintain healthy changes, Dr. Ornish said.
Love as medicine
Mounting evidence links loneliness and isolation with a range of health issues, from mood disorders such as depression to chronic conditions such as cardiovascular disease. What’s more, data suggest that loneliness and social isolation in the United States are on the rise, and the COVID pandemic made that more clear. In May 2023, Surgeon General Vivek Murthy, MD, called loneliness, isolation, and lack of connection in the United States a “public health crisis.”
“Good relationships keep us happier and healthier,” said Robert Waldinger, MD, a psychiatrist at Massachusetts General Hospital, Boston.
Dr. Waldinger, who was not affiliated with the conference, is head of the Harvard Study of Adult Development, one of the longest studies of adult life. Beginning in 1938, the study has tracked 724 people plus more than 1,300 of their descendants and found that embracing community and close relationships helps us live longer and be happier.
In the study, the people who were most satisfied with their relationships at age 50 years were the healthiest at age 80 years. Knowing you have someone to rely on protects the brain: “Those people’s memories stay sharper longer,” Dr. Waldinger said.
He draws a distinction between connection and love. “Love is, I think, more of a feeling,” Dr. Waldinger noted. “Connection is a feeling, but it’s also an activity.”
One in five Americans say they’re lonely, he said, “and loneliness is a stressor.” People who are isolated don’t sleep as well, he added. Their health declines earlier in midlife, brain function slips sooner, and their lives are shorter.
“You don’t have anyone to complain to,” he said. If you do, “you can feel your body start to calm down.” Those without social connections may stay in a low-level “fight-or-flight mode.”
“What we think happens is that you have low levels of inflammation chronically, and those can gradually break down body systems.” Moreover, higher rates of cardiac reactivity, for instance, a racing heartbeat when upset, can lead to high blood pressure and lower immune function.
In his talk, Dr. Ornish said, “Anger is that one emotion that has consistently been shown to make heart disease worse.”
Helping people in those straits is gratifying, Dr. Ornish said. “If we can work with people as lifestyle medicine practitioners when they’re suffering, there’s an opportunity for transformation.”
Future
Of course, that can be easier said than done. Dr. Ornish relayed a patient’s typical reaction to a lifestyle program: “This is kind of weird stuff. Like, I get diet. But a plant-based diet, really? Meditation? Loving more? Really?”
He told the conference, “Part of our job as lifestyle medicine practitioners is to spend a little extra time with them. It doesn’t even take that much time. And to really help them understand what brings them a sense of hope and meaning and purpose.”
The results can be motivating. “Most people feel so much better so quickly,” Dr. Ornish said. “It reframes the reason for change from fear of dying to joy of living.”
Dr. Grega, for one, is optimistic for the future, citing survey results showing that 95% of medical students think that they›d be better counselors with lifestyle training. ‘They passionately want this type of thing,” she said.
A version of this article first appeared on Medscape.com.
Low-salt diet cut BP by 6 mm Hg in 1 week: CARDIA-SSBP
The CARDIA-SSBP trial involved 213 individuals aged 50-75 years, including those with and those without hypertension, and showed that the decline in blood pressure brought about by a low-salt diet was independent of hypertension status and antihypertensive medication use. It was also generally consistent across subgroups and did not result in excess adverse events.
“The blood pressure reduction we see here is meaningful, and comparable to that produced by one antihypertensive medication,” lead investigator Deepak Gupta, MD, Vanderbilt University Medical Center, Nashville, Tenn., said in an interview.
Dr. Gupta presented the CARDIA-SSBP study on Nov. 11 at the American Heart Association scientific sessions, held in Philadelphia. The study was published online in JAMA. The exact menus used in the study are available in a supplement to the JAMA paper.
“In order to live a healthy lifestyle, understanding what we eat has important health effects. Raised blood pressure contributes to one out of every eight deaths worldwide,” Dr. Gupta noted. “If people want to lower their blood pressure, attention to dietary sodium is one part of that. If individuals can stick with a low sodium diet, they may be able to stop taking one of their antihypertensive medications, and those who are normotensive will be less likely to develop hypertension.”
Commentators said the study had significant implications for public health, but they pointed out that maintaining a low-sodium diet over the long term is challenging, given the high salt content of generally available foods.
Dr. Gupta noted that the study did use commercially available products in the low-sodium diets and the menus are available for people to follow, making it more accessible than some diets used in previous studies.
“What may also be attractive to people is that you don’t have to wait for months to see an effect. If you start to consume a low-sodium diet, you can see results on blood pressure rapidly, within a week,” he said.
The diet in this study brought about a large reduction in dietary sodium, but Dr. Gupta says any reduction in dietary sodium is likely to be beneficial.
“If you go to the level that we got to, you could expect to see a reduction of around 6 mm Hg. But it’s like walking – you don’t necessarily need to get to 10,000 steps every day. Any amount of walking or physical activity is of benefit. The same is probably true for salt: Any reduction that you can make is probably of benefit.”
For the study, participants had their blood pressure measured by 24-hour ambulatory monitoring while on their usual diets. They were then randomly assigned to either a high-sodium diet or a low-sodium diet for 1 week. Participants then crossed over to the opposite diet for 1 week, with blood pressure measured over a 24-hour period on the last day of each diet.
As assessed by 24-hour urine excretion, the usual diet of participants was found to already be high in sodium (median, 4.45 g/d). This increased to a median of 5.00 g/d when on the high-sodium diet in the study and decreased to 1.27 g/d while on the low-sodium diet.
Results found participants had a median systolic blood pressure of 125 mm Hg on their usual diets. This was raised to 126 mm Hg on the high-sodium diet and lowered to 119 mm Hg on the low-sodium diet.
The researchers also reported that 75% of individuals showed a blood pressure reduction on the low-sodium diet and are thus defined as “salt-sensitive.” This is a higher percentage than found in previous studies.
“Of those that didn’t show a blood pressure reduction with a low-sodium diet in this study, it appears that they may not have been so adherent to the diet as those who did show a blood pressure reduction,” Dr. Gupta said.
He noted that hypertension is the most common chronic disease condition worldwide, with about 1.3 billion people affected, and although it has been known for some time that dietary sodium affects blood pressure, there have been some gaps in previous studies.
For example, many studies have excluded individuals who were already taking antihypertensive medications and people with diabetes, and they have generally not included many older individuals. The current study found that all of these groups showed significant blood pressure reductions by reducing dietary sodium.
Large effect in people with diabetes
Subgroup analysis largely showed consistent results across the population, regardless of age, sex, race, and body mass index and whether participants were taking antihypertensive medication or not, but there were a couple of exceptions. Individuals with higher blood pressure at baseline seemed to have a greater effect of lowering dietary sodium, although those who were normotensive at baseline still showed significant blood pressure reduction, Dr. Gupta reported.
The researchers found a particularly large reduction in blood pressure from lowering sodium intake in people with diabetes, who made up about 21% of the overall cohort. Their average reduction in systolic blood pressure between the high and low sodium diet was close to 17 mm Hg rather than the 7-8 mm Hg in the whole cohort.
Dr. Gupta said that the results are applicable to most of the population.
“The people who will be most motivated to follow a low-sodium diet are those with hypertension. But even in normotensive individuals, there is likely to be benefit.”
To help people follow a low-sodium diet, Dr. Gupta says education campaigns are needed “to show people that they can do it and make it work.” But there are bigger structural issues that need to be addressed at policy and governmental levels.
“Most of our food available in grocery stores and restaurants is high in salt. We now have a preponderance of evidence showing us that we need to change what’s available in the food supply,” he said. “There is a push going on for this now, and the U.S. has introduced some guidelines for the food industry on sodium content of foods. These are voluntary at this point, but it’s a start.”
Difficult to maintain long term
Commenting on the study, Paul Whelton, MD, chair in global public health at Tulane University, New Orleans, noted that sodium reduction is known to reduce blood pressure, with greater sodium reductions giving greater blood pressure decreases, and that some people are more sensitive to the effects of sodium than others.
He described CARDIA-SSBP as a “well-done study.”
“They managed to get a very low sodium intake and a large difference between the two groups, which translated into a big reduction in systolic blood pressure,” Dr. Whelton said. “However, the problem with these sorts of trials where the diets are provided to the participants is that although they show proof of concept, it is difficult to generalize because we can’t normally provide patients with their meals. In this type of ‘feeding’ study, we find it difficult to maintain people on their behavioral intervention over the long term.”
Dr. Whelton said that he was more excited about this trial knowing that the food given was commercially available. “That makes it more practical, but you still have to be quite motivated to follow a diet like this. Buying low-sodium products in the supermarket does require quite a lot of work to read the labels, and sometimes the low-sodium foods are specialty products and are more expensive.”
He pointed out that older people in higher socioeconomic classes are more likely to attempt this and do better from behavioral interventions in general. “Unfortunately, people who don’t do well from behavioral interventions like this are those from lower socioeconomic groups, who are ones at most at risk for cardiovascular disease.”
Dr. Whelton noted that the food industry has been reluctant to lower sodium content because high-salt foods sell better. “Unfortunately, foods high in saturated fat and salt taste good to most people. We are generally attuned to a high salt intake. But when people have been following a low-salt diet for a while, they generally don’t like high-salt foods anymore. They become attuned to lower-sodium diet,” he added.
New U.S. sodium reduction guidelines
Discussant of the CARDIA-SSBP study at the AHA meeting, Cheryl Anderson, MD, University of California, San Diego, said that the findings were important and consistent with prior studies.
“These studies have global implications because salt is ubiquitous in the food supply in much of the world,” she noted, adding that, “Americans consume almost 50% more sodium than recommended, and there has been a persistent lack of adherence to healthy diet recommendations for reductions in salt, sugar, and fats.”
Dr. Anderson pointed out that in 2021, the Food and Drug Administration issued guidance for voluntary sodium reduction, which uses a gradual approach, with targets to reach a population goal of 3,000 mg/d of sodium by 2023 and 2,300 mg/d by 2031.
“These targets apply to 150 categories of food that are sales-weighted to focus on dominant sellers in each category. They apply to food manufacturers, restaurants and food service operations,” she concluded. “These targets serve as a basis for continued dialogue. The research community eagerly awaits the review of population-based data to help refine this approach and goals.”
This study was supported by grants from the National Heart, Lung, and Blood Institute, the National Institutes of Health, the American Heart Association, and the National Center for Advancing Translational Sciences. The authors report no disclosures.
A version of this article appeared on Medscape.com.
The CARDIA-SSBP trial involved 213 individuals aged 50-75 years, including those with and those without hypertension, and showed that the decline in blood pressure brought about by a low-salt diet was independent of hypertension status and antihypertensive medication use. It was also generally consistent across subgroups and did not result in excess adverse events.
“The blood pressure reduction we see here is meaningful, and comparable to that produced by one antihypertensive medication,” lead investigator Deepak Gupta, MD, Vanderbilt University Medical Center, Nashville, Tenn., said in an interview.
Dr. Gupta presented the CARDIA-SSBP study on Nov. 11 at the American Heart Association scientific sessions, held in Philadelphia. The study was published online in JAMA. The exact menus used in the study are available in a supplement to the JAMA paper.
“In order to live a healthy lifestyle, understanding what we eat has important health effects. Raised blood pressure contributes to one out of every eight deaths worldwide,” Dr. Gupta noted. “If people want to lower their blood pressure, attention to dietary sodium is one part of that. If individuals can stick with a low sodium diet, they may be able to stop taking one of their antihypertensive medications, and those who are normotensive will be less likely to develop hypertension.”
Commentators said the study had significant implications for public health, but they pointed out that maintaining a low-sodium diet over the long term is challenging, given the high salt content of generally available foods.
Dr. Gupta noted that the study did use commercially available products in the low-sodium diets and the menus are available for people to follow, making it more accessible than some diets used in previous studies.
“What may also be attractive to people is that you don’t have to wait for months to see an effect. If you start to consume a low-sodium diet, you can see results on blood pressure rapidly, within a week,” he said.
The diet in this study brought about a large reduction in dietary sodium, but Dr. Gupta says any reduction in dietary sodium is likely to be beneficial.
“If you go to the level that we got to, you could expect to see a reduction of around 6 mm Hg. But it’s like walking – you don’t necessarily need to get to 10,000 steps every day. Any amount of walking or physical activity is of benefit. The same is probably true for salt: Any reduction that you can make is probably of benefit.”
For the study, participants had their blood pressure measured by 24-hour ambulatory monitoring while on their usual diets. They were then randomly assigned to either a high-sodium diet or a low-sodium diet for 1 week. Participants then crossed over to the opposite diet for 1 week, with blood pressure measured over a 24-hour period on the last day of each diet.
As assessed by 24-hour urine excretion, the usual diet of participants was found to already be high in sodium (median, 4.45 g/d). This increased to a median of 5.00 g/d when on the high-sodium diet in the study and decreased to 1.27 g/d while on the low-sodium diet.
Results found participants had a median systolic blood pressure of 125 mm Hg on their usual diets. This was raised to 126 mm Hg on the high-sodium diet and lowered to 119 mm Hg on the low-sodium diet.
The researchers also reported that 75% of individuals showed a blood pressure reduction on the low-sodium diet and are thus defined as “salt-sensitive.” This is a higher percentage than found in previous studies.
“Of those that didn’t show a blood pressure reduction with a low-sodium diet in this study, it appears that they may not have been so adherent to the diet as those who did show a blood pressure reduction,” Dr. Gupta said.
He noted that hypertension is the most common chronic disease condition worldwide, with about 1.3 billion people affected, and although it has been known for some time that dietary sodium affects blood pressure, there have been some gaps in previous studies.
For example, many studies have excluded individuals who were already taking antihypertensive medications and people with diabetes, and they have generally not included many older individuals. The current study found that all of these groups showed significant blood pressure reductions by reducing dietary sodium.
Large effect in people with diabetes
Subgroup analysis largely showed consistent results across the population, regardless of age, sex, race, and body mass index and whether participants were taking antihypertensive medication or not, but there were a couple of exceptions. Individuals with higher blood pressure at baseline seemed to have a greater effect of lowering dietary sodium, although those who were normotensive at baseline still showed significant blood pressure reduction, Dr. Gupta reported.
The researchers found a particularly large reduction in blood pressure from lowering sodium intake in people with diabetes, who made up about 21% of the overall cohort. Their average reduction in systolic blood pressure between the high and low sodium diet was close to 17 mm Hg rather than the 7-8 mm Hg in the whole cohort.
Dr. Gupta said that the results are applicable to most of the population.
“The people who will be most motivated to follow a low-sodium diet are those with hypertension. But even in normotensive individuals, there is likely to be benefit.”
To help people follow a low-sodium diet, Dr. Gupta says education campaigns are needed “to show people that they can do it and make it work.” But there are bigger structural issues that need to be addressed at policy and governmental levels.
“Most of our food available in grocery stores and restaurants is high in salt. We now have a preponderance of evidence showing us that we need to change what’s available in the food supply,” he said. “There is a push going on for this now, and the U.S. has introduced some guidelines for the food industry on sodium content of foods. These are voluntary at this point, but it’s a start.”
Difficult to maintain long term
Commenting on the study, Paul Whelton, MD, chair in global public health at Tulane University, New Orleans, noted that sodium reduction is known to reduce blood pressure, with greater sodium reductions giving greater blood pressure decreases, and that some people are more sensitive to the effects of sodium than others.
He described CARDIA-SSBP as a “well-done study.”
“They managed to get a very low sodium intake and a large difference between the two groups, which translated into a big reduction in systolic blood pressure,” Dr. Whelton said. “However, the problem with these sorts of trials where the diets are provided to the participants is that although they show proof of concept, it is difficult to generalize because we can’t normally provide patients with their meals. In this type of ‘feeding’ study, we find it difficult to maintain people on their behavioral intervention over the long term.”
Dr. Whelton said that he was more excited about this trial knowing that the food given was commercially available. “That makes it more practical, but you still have to be quite motivated to follow a diet like this. Buying low-sodium products in the supermarket does require quite a lot of work to read the labels, and sometimes the low-sodium foods are specialty products and are more expensive.”
He pointed out that older people in higher socioeconomic classes are more likely to attempt this and do better from behavioral interventions in general. “Unfortunately, people who don’t do well from behavioral interventions like this are those from lower socioeconomic groups, who are ones at most at risk for cardiovascular disease.”
Dr. Whelton noted that the food industry has been reluctant to lower sodium content because high-salt foods sell better. “Unfortunately, foods high in saturated fat and salt taste good to most people. We are generally attuned to a high salt intake. But when people have been following a low-salt diet for a while, they generally don’t like high-salt foods anymore. They become attuned to lower-sodium diet,” he added.
New U.S. sodium reduction guidelines
Discussant of the CARDIA-SSBP study at the AHA meeting, Cheryl Anderson, MD, University of California, San Diego, said that the findings were important and consistent with prior studies.
“These studies have global implications because salt is ubiquitous in the food supply in much of the world,” she noted, adding that, “Americans consume almost 50% more sodium than recommended, and there has been a persistent lack of adherence to healthy diet recommendations for reductions in salt, sugar, and fats.”
Dr. Anderson pointed out that in 2021, the Food and Drug Administration issued guidance for voluntary sodium reduction, which uses a gradual approach, with targets to reach a population goal of 3,000 mg/d of sodium by 2023 and 2,300 mg/d by 2031.
“These targets apply to 150 categories of food that are sales-weighted to focus on dominant sellers in each category. They apply to food manufacturers, restaurants and food service operations,” she concluded. “These targets serve as a basis for continued dialogue. The research community eagerly awaits the review of population-based data to help refine this approach and goals.”
This study was supported by grants from the National Heart, Lung, and Blood Institute, the National Institutes of Health, the American Heart Association, and the National Center for Advancing Translational Sciences. The authors report no disclosures.
A version of this article appeared on Medscape.com.
The CARDIA-SSBP trial involved 213 individuals aged 50-75 years, including those with and those without hypertension, and showed that the decline in blood pressure brought about by a low-salt diet was independent of hypertension status and antihypertensive medication use. It was also generally consistent across subgroups and did not result in excess adverse events.
“The blood pressure reduction we see here is meaningful, and comparable to that produced by one antihypertensive medication,” lead investigator Deepak Gupta, MD, Vanderbilt University Medical Center, Nashville, Tenn., said in an interview.
Dr. Gupta presented the CARDIA-SSBP study on Nov. 11 at the American Heart Association scientific sessions, held in Philadelphia. The study was published online in JAMA. The exact menus used in the study are available in a supplement to the JAMA paper.
“In order to live a healthy lifestyle, understanding what we eat has important health effects. Raised blood pressure contributes to one out of every eight deaths worldwide,” Dr. Gupta noted. “If people want to lower their blood pressure, attention to dietary sodium is one part of that. If individuals can stick with a low sodium diet, they may be able to stop taking one of their antihypertensive medications, and those who are normotensive will be less likely to develop hypertension.”
Commentators said the study had significant implications for public health, but they pointed out that maintaining a low-sodium diet over the long term is challenging, given the high salt content of generally available foods.
Dr. Gupta noted that the study did use commercially available products in the low-sodium diets and the menus are available for people to follow, making it more accessible than some diets used in previous studies.
“What may also be attractive to people is that you don’t have to wait for months to see an effect. If you start to consume a low-sodium diet, you can see results on blood pressure rapidly, within a week,” he said.
The diet in this study brought about a large reduction in dietary sodium, but Dr. Gupta says any reduction in dietary sodium is likely to be beneficial.
“If you go to the level that we got to, you could expect to see a reduction of around 6 mm Hg. But it’s like walking – you don’t necessarily need to get to 10,000 steps every day. Any amount of walking or physical activity is of benefit. The same is probably true for salt: Any reduction that you can make is probably of benefit.”
For the study, participants had their blood pressure measured by 24-hour ambulatory monitoring while on their usual diets. They were then randomly assigned to either a high-sodium diet or a low-sodium diet for 1 week. Participants then crossed over to the opposite diet for 1 week, with blood pressure measured over a 24-hour period on the last day of each diet.
As assessed by 24-hour urine excretion, the usual diet of participants was found to already be high in sodium (median, 4.45 g/d). This increased to a median of 5.00 g/d when on the high-sodium diet in the study and decreased to 1.27 g/d while on the low-sodium diet.
Results found participants had a median systolic blood pressure of 125 mm Hg on their usual diets. This was raised to 126 mm Hg on the high-sodium diet and lowered to 119 mm Hg on the low-sodium diet.
The researchers also reported that 75% of individuals showed a blood pressure reduction on the low-sodium diet and are thus defined as “salt-sensitive.” This is a higher percentage than found in previous studies.
“Of those that didn’t show a blood pressure reduction with a low-sodium diet in this study, it appears that they may not have been so adherent to the diet as those who did show a blood pressure reduction,” Dr. Gupta said.
He noted that hypertension is the most common chronic disease condition worldwide, with about 1.3 billion people affected, and although it has been known for some time that dietary sodium affects blood pressure, there have been some gaps in previous studies.
For example, many studies have excluded individuals who were already taking antihypertensive medications and people with diabetes, and they have generally not included many older individuals. The current study found that all of these groups showed significant blood pressure reductions by reducing dietary sodium.
Large effect in people with diabetes
Subgroup analysis largely showed consistent results across the population, regardless of age, sex, race, and body mass index and whether participants were taking antihypertensive medication or not, but there were a couple of exceptions. Individuals with higher blood pressure at baseline seemed to have a greater effect of lowering dietary sodium, although those who were normotensive at baseline still showed significant blood pressure reduction, Dr. Gupta reported.
The researchers found a particularly large reduction in blood pressure from lowering sodium intake in people with diabetes, who made up about 21% of the overall cohort. Their average reduction in systolic blood pressure between the high and low sodium diet was close to 17 mm Hg rather than the 7-8 mm Hg in the whole cohort.
Dr. Gupta said that the results are applicable to most of the population.
“The people who will be most motivated to follow a low-sodium diet are those with hypertension. But even in normotensive individuals, there is likely to be benefit.”
To help people follow a low-sodium diet, Dr. Gupta says education campaigns are needed “to show people that they can do it and make it work.” But there are bigger structural issues that need to be addressed at policy and governmental levels.
“Most of our food available in grocery stores and restaurants is high in salt. We now have a preponderance of evidence showing us that we need to change what’s available in the food supply,” he said. “There is a push going on for this now, and the U.S. has introduced some guidelines for the food industry on sodium content of foods. These are voluntary at this point, but it’s a start.”
Difficult to maintain long term
Commenting on the study, Paul Whelton, MD, chair in global public health at Tulane University, New Orleans, noted that sodium reduction is known to reduce blood pressure, with greater sodium reductions giving greater blood pressure decreases, and that some people are more sensitive to the effects of sodium than others.
He described CARDIA-SSBP as a “well-done study.”
“They managed to get a very low sodium intake and a large difference between the two groups, which translated into a big reduction in systolic blood pressure,” Dr. Whelton said. “However, the problem with these sorts of trials where the diets are provided to the participants is that although they show proof of concept, it is difficult to generalize because we can’t normally provide patients with their meals. In this type of ‘feeding’ study, we find it difficult to maintain people on their behavioral intervention over the long term.”
Dr. Whelton said that he was more excited about this trial knowing that the food given was commercially available. “That makes it more practical, but you still have to be quite motivated to follow a diet like this. Buying low-sodium products in the supermarket does require quite a lot of work to read the labels, and sometimes the low-sodium foods are specialty products and are more expensive.”
He pointed out that older people in higher socioeconomic classes are more likely to attempt this and do better from behavioral interventions in general. “Unfortunately, people who don’t do well from behavioral interventions like this are those from lower socioeconomic groups, who are ones at most at risk for cardiovascular disease.”
Dr. Whelton noted that the food industry has been reluctant to lower sodium content because high-salt foods sell better. “Unfortunately, foods high in saturated fat and salt taste good to most people. We are generally attuned to a high salt intake. But when people have been following a low-salt diet for a while, they generally don’t like high-salt foods anymore. They become attuned to lower-sodium diet,” he added.
New U.S. sodium reduction guidelines
Discussant of the CARDIA-SSBP study at the AHA meeting, Cheryl Anderson, MD, University of California, San Diego, said that the findings were important and consistent with prior studies.
“These studies have global implications because salt is ubiquitous in the food supply in much of the world,” she noted, adding that, “Americans consume almost 50% more sodium than recommended, and there has been a persistent lack of adherence to healthy diet recommendations for reductions in salt, sugar, and fats.”
Dr. Anderson pointed out that in 2021, the Food and Drug Administration issued guidance for voluntary sodium reduction, which uses a gradual approach, with targets to reach a population goal of 3,000 mg/d of sodium by 2023 and 2,300 mg/d by 2031.
“These targets apply to 150 categories of food that are sales-weighted to focus on dominant sellers in each category. They apply to food manufacturers, restaurants and food service operations,” she concluded. “These targets serve as a basis for continued dialogue. The research community eagerly awaits the review of population-based data to help refine this approach and goals.”
This study was supported by grants from the National Heart, Lung, and Blood Institute, the National Institutes of Health, the American Heart Association, and the National Center for Advancing Translational Sciences. The authors report no disclosures.
A version of this article appeared on Medscape.com.
FROM AHA 2023
Better postpartum BP control with self-monitoring: POP-HT
, new research suggests.
In a randomized trial of 220 women with preeclampsia or gestational hypertension, those who took daily postpartum BP readings and received clinician-guided advice for titrating antihypertensives had a 5 mm Hg–lower average diastolic BP at 9 months, compared with those receiving usual care.
Jamie Kitt, DPhil, from the University of Oxford (England) presented these findings from the Physicians Optimized Postpartum Hypertension Treatment (POP-HT, NCT04273854) clinical trial at the American Heart Association scientific sessions. The study was simultaneously published online in JAMA, and a cardiac imaging substudy was published online in Circulation.
“This trial identifies a potential need for a paradigm shift in the way women affected by hypertensive pregnancy are managed postnatally,” Dr. Kitt said. “If a 5–mm Hg improvement in BP is maintained longer term, it can result in about a 20% reduction in lifetime cardiovascular risk.”
The imaging substudy suggests that short-term postnatal optimization of BP control following hypertensive pregnancy through self-monitoring and physician-guided antihypertensive titration is linked with better cardiac remodeling changes seen by cardiovascular magnetic resonance and echocardiography.
POP-HT “proves for the first time that the first few weeks after delivery are a critical time that can determine the long-term cardiovascular health of the mother,” senior author Paul Leeson, PhD, also from the University of Oxford, who presented the findings in a press briefing, said in an interview.
“Interventions during this period can have long-term beneficial impacts on cardiovascular health,” he said. “These findings rewrite the textbook on our understanding of how and why hypertensive pregnancies associate with later cardiovascular disease in the mother.”
Next, Dr. Leeson said, “We need to work out the best ways to implement these interventions “at scale. Then we can ensure all women who have hypertensive pregnancies can get access to the long-term cardiovascular benefits we have demonstrated are possible through improving postpartum cardiac care,” he said, adding that “this is entirely achievable using current available technologies.”
Hypertension in pregnancy
About 1 in 10 pregnant women develop hypertension in pregnancy (preeclampsia or gestational hypertension), and 1 in 3 such women go on to develop chronic hypertension within 10 years, “when they are usually still in their 30s or 40s,” Dr. Leeson said.
During pregnancy, the heart remodels to cope with pregnancy, and it undergoes more severe changes if BP is high. Then during the 6 weeks after giving birth, this remodeling rapidly reverses.
Higher blood pressure in young adulthood is associated with a twofold higher risk of subsequent myocardial infarction and stroke. And abnormal cardiac remodeling postpartum is also linked with higher cardiovascular risk.
Self-monitoring blood pressure during the postpartum period may be a “critical window” for intervention.
Previously, the research group performed a pilot study, the Self-Management of Postnatal Antihypertensive Treatment (SNAP-HT) trial and the SNAP-extension trial, which compared a BP self-monitoring intervention with usual care in 91 women with gestational hypertension or preeclampsia requiring postnatal antihypertensive treatment.
Diastolic BP, which drives cardiovascular risk in younger populations, was 4.5–mm Hg lower at 6 months postpartum and 7–mm Hg lower at 4 years post partum in patients randomly assigned to BP self-management vs. usual care – even after they were no longer taking antihypertensives.
Building on these findings, the POP-HT trial enrolled 220 pregnant women seen at Oxford University Hospitals in the United Kingdom who were age 18 years or older, had either gestational hypertension or preeclampsia, and still required antihypertensives when they were being discharged from hospital after giving birth.
Following a baseline visit at day 1-6 after delivery, while in the postnatal ward, the patients were randomly assigned 1:1 to the intervention group (112 women) or usual-care group (108 women).
They had an average age of 32.6 years; 40% had gestational hypertension, and 60% had preeclampsia.
Women in the usual-care group typically received a BP review at 7-10 days after hospital discharge with a community midwife, and another at 6-8 weeks with their general practitioner.
The women in the intervention group were given and taught to use a Bluetooth-enabled OMRON Evolv BP monitor (Omron Healthcare Europe) while on the postnatal ward, and they installed a smartphone app on their mobile phones that transmitted self-monitored BP readings to a National Health Service-hosted, web-based platform.
They were instructed to take daily BP measurements (twice daily if out of target range). Dose titration of antihypertensives after hospital discharge was guided remotely by research clinicians, according to a guideline-based algorithm.
Patients in both groups had four study visits when their BP was measured: visit 1 (baseline) between days 1 and 6 post partum; visit 2 at week 1; visit 3 at week 6; and visit 4 between months 6 and 9 post partum.
Similar antihypertensive classes were prescribed in each group (enalapril 57%, nifedipine 27%, and labetalol 30% for intervention vs. enalapril 43%, nifedipine 30%, and labetalol 27% for control).
At 6 weeks, approximately 30% of participants in each group were still taking medication; this dropped to approximately 12% by visit 4.
The primary outcome – the mean 24-hour diastolic BP at visit 4 (roughly 9 months post partum), adjusted for baseline postnatal diastolic blood pressure – was 5.8–mm Hg lower in the intervention group than in the control group (71.2 mm Hg vs. 76.6 mm Hg; P < .001).
Secondary outcomes – between-group differences in systolic BP at 9 months, BP-related postnatal admission, and cardiac remodeling assessed by cardiac magnetic resonance – were all better in the intervention group.
The mean 24-hour average systolic BP at 9 months post partum, adjusted for baseline postnatal systolic BP was 6.5–mm Hg lower in the intervention group than in the control group (114.0 mm Hg vs. 120.3 mm Hg; P < .001).
There was an absolute risk reduction of 20% and a relative risk reduction of 73.5% in postnatal readmission. The number needed to treat to avoid one postnatal readmission was five, which “has potential for big cost savings,” said Dr. Leeson.
Blood pressure post partum can be improved with self-monitoring and physician-guided medication adjustment, Dr. Leeson summarized. The blood pressure remains low for at least 9 months, even when medication is stopped, and the intervention leads to beneficial cardiac remodeling.
U.S. pilot study
Non-Hispanic Black adults have a high hypertension and cardiovascular disease burden, and a related small U.S. study showed benefits of BP self-monitoring in a population comprising mainly Black women, Keith Ferdinand, MD, discussant of the POP-HT trial in the press briefing, said in an interview.
Dr. Ferdinand, from Tulane University, New Orleans, Louisiana, was lead author of the Text My Hypertension BP Meds NOLA pilot study that was published in February in the American Heart Journal Plus: Cardiology Research and Practice.
The study showed that text-messaging and social support increased hypertension medication adherence.
They enrolled 36 individuals, of whom 32 (89%) were non-Hispanic Black, and 23 (64%) were women. The participants received validated Bluetooth-enabled BP-monitoring devices that were synced to smartphones via a secured cloud-based application. The participants could send and receive messages to health care practitioners.
This intervention significantly improved medication adherence and systolic BP without modifying pharmacotherapy.
‘Need to be passionate about monitoring BP’
“The take-home messages from these exciting findings is that physicians and women who have had high BP during pregnancy need to be passionate about monitoring and controlling their blood pressure and not ignore it,” Anastasia Mihailidou, PhD, Royal North Shore Hospital, Sydney, the assigned discussant in the late-breaking trial session, said in an interview.
“It also resulted in fewer postpartum hospital readmissions for high blood pressure and benefit at 9 months in the structure and function of the heart and blood vessels of the women,” she said.
“While we need to see further studies in ethnically diverse women to see that they are reproducible, there are simple measures that clinicians can implement, and women can ask to have their BP monitored more frequently than the current practice. In the U.K. it is 5-10 days after delivery and then at 6-8 weeks after giving birth when changes in heart structure have already started,” Dr. Mihailidou noted.
“The procedure will need to be modified if there are no telemedicine facilities, but that should not stop having close monitoring of BP and treating it adequately. Monitoring requires an accurate BP monitor. There also has to be monitoring BP for the children.”
The trial was funded by a BHF Clinical Research Training Fellowship to Dr. Kitt, with additional support from the NIHR Oxford Biomedical Research Centre and Oxford BHF Centre for Research Excellence.
A version of this article first appeared on Medscape.com.
, new research suggests.
In a randomized trial of 220 women with preeclampsia or gestational hypertension, those who took daily postpartum BP readings and received clinician-guided advice for titrating antihypertensives had a 5 mm Hg–lower average diastolic BP at 9 months, compared with those receiving usual care.
Jamie Kitt, DPhil, from the University of Oxford (England) presented these findings from the Physicians Optimized Postpartum Hypertension Treatment (POP-HT, NCT04273854) clinical trial at the American Heart Association scientific sessions. The study was simultaneously published online in JAMA, and a cardiac imaging substudy was published online in Circulation.
“This trial identifies a potential need for a paradigm shift in the way women affected by hypertensive pregnancy are managed postnatally,” Dr. Kitt said. “If a 5–mm Hg improvement in BP is maintained longer term, it can result in about a 20% reduction in lifetime cardiovascular risk.”
The imaging substudy suggests that short-term postnatal optimization of BP control following hypertensive pregnancy through self-monitoring and physician-guided antihypertensive titration is linked with better cardiac remodeling changes seen by cardiovascular magnetic resonance and echocardiography.
POP-HT “proves for the first time that the first few weeks after delivery are a critical time that can determine the long-term cardiovascular health of the mother,” senior author Paul Leeson, PhD, also from the University of Oxford, who presented the findings in a press briefing, said in an interview.
“Interventions during this period can have long-term beneficial impacts on cardiovascular health,” he said. “These findings rewrite the textbook on our understanding of how and why hypertensive pregnancies associate with later cardiovascular disease in the mother.”
Next, Dr. Leeson said, “We need to work out the best ways to implement these interventions “at scale. Then we can ensure all women who have hypertensive pregnancies can get access to the long-term cardiovascular benefits we have demonstrated are possible through improving postpartum cardiac care,” he said, adding that “this is entirely achievable using current available technologies.”
Hypertension in pregnancy
About 1 in 10 pregnant women develop hypertension in pregnancy (preeclampsia or gestational hypertension), and 1 in 3 such women go on to develop chronic hypertension within 10 years, “when they are usually still in their 30s or 40s,” Dr. Leeson said.
During pregnancy, the heart remodels to cope with pregnancy, and it undergoes more severe changes if BP is high. Then during the 6 weeks after giving birth, this remodeling rapidly reverses.
Higher blood pressure in young adulthood is associated with a twofold higher risk of subsequent myocardial infarction and stroke. And abnormal cardiac remodeling postpartum is also linked with higher cardiovascular risk.
Self-monitoring blood pressure during the postpartum period may be a “critical window” for intervention.
Previously, the research group performed a pilot study, the Self-Management of Postnatal Antihypertensive Treatment (SNAP-HT) trial and the SNAP-extension trial, which compared a BP self-monitoring intervention with usual care in 91 women with gestational hypertension or preeclampsia requiring postnatal antihypertensive treatment.
Diastolic BP, which drives cardiovascular risk in younger populations, was 4.5–mm Hg lower at 6 months postpartum and 7–mm Hg lower at 4 years post partum in patients randomly assigned to BP self-management vs. usual care – even after they were no longer taking antihypertensives.
Building on these findings, the POP-HT trial enrolled 220 pregnant women seen at Oxford University Hospitals in the United Kingdom who were age 18 years or older, had either gestational hypertension or preeclampsia, and still required antihypertensives when they were being discharged from hospital after giving birth.
Following a baseline visit at day 1-6 after delivery, while in the postnatal ward, the patients were randomly assigned 1:1 to the intervention group (112 women) or usual-care group (108 women).
They had an average age of 32.6 years; 40% had gestational hypertension, and 60% had preeclampsia.
Women in the usual-care group typically received a BP review at 7-10 days after hospital discharge with a community midwife, and another at 6-8 weeks with their general practitioner.
The women in the intervention group were given and taught to use a Bluetooth-enabled OMRON Evolv BP monitor (Omron Healthcare Europe) while on the postnatal ward, and they installed a smartphone app on their mobile phones that transmitted self-monitored BP readings to a National Health Service-hosted, web-based platform.
They were instructed to take daily BP measurements (twice daily if out of target range). Dose titration of antihypertensives after hospital discharge was guided remotely by research clinicians, according to a guideline-based algorithm.
Patients in both groups had four study visits when their BP was measured: visit 1 (baseline) between days 1 and 6 post partum; visit 2 at week 1; visit 3 at week 6; and visit 4 between months 6 and 9 post partum.
Similar antihypertensive classes were prescribed in each group (enalapril 57%, nifedipine 27%, and labetalol 30% for intervention vs. enalapril 43%, nifedipine 30%, and labetalol 27% for control).
At 6 weeks, approximately 30% of participants in each group were still taking medication; this dropped to approximately 12% by visit 4.
The primary outcome – the mean 24-hour diastolic BP at visit 4 (roughly 9 months post partum), adjusted for baseline postnatal diastolic blood pressure – was 5.8–mm Hg lower in the intervention group than in the control group (71.2 mm Hg vs. 76.6 mm Hg; P < .001).
Secondary outcomes – between-group differences in systolic BP at 9 months, BP-related postnatal admission, and cardiac remodeling assessed by cardiac magnetic resonance – were all better in the intervention group.
The mean 24-hour average systolic BP at 9 months post partum, adjusted for baseline postnatal systolic BP was 6.5–mm Hg lower in the intervention group than in the control group (114.0 mm Hg vs. 120.3 mm Hg; P < .001).
There was an absolute risk reduction of 20% and a relative risk reduction of 73.5% in postnatal readmission. The number needed to treat to avoid one postnatal readmission was five, which “has potential for big cost savings,” said Dr. Leeson.
Blood pressure post partum can be improved with self-monitoring and physician-guided medication adjustment, Dr. Leeson summarized. The blood pressure remains low for at least 9 months, even when medication is stopped, and the intervention leads to beneficial cardiac remodeling.
U.S. pilot study
Non-Hispanic Black adults have a high hypertension and cardiovascular disease burden, and a related small U.S. study showed benefits of BP self-monitoring in a population comprising mainly Black women, Keith Ferdinand, MD, discussant of the POP-HT trial in the press briefing, said in an interview.
Dr. Ferdinand, from Tulane University, New Orleans, Louisiana, was lead author of the Text My Hypertension BP Meds NOLA pilot study that was published in February in the American Heart Journal Plus: Cardiology Research and Practice.
The study showed that text-messaging and social support increased hypertension medication adherence.
They enrolled 36 individuals, of whom 32 (89%) were non-Hispanic Black, and 23 (64%) were women. The participants received validated Bluetooth-enabled BP-monitoring devices that were synced to smartphones via a secured cloud-based application. The participants could send and receive messages to health care practitioners.
This intervention significantly improved medication adherence and systolic BP without modifying pharmacotherapy.
‘Need to be passionate about monitoring BP’
“The take-home messages from these exciting findings is that physicians and women who have had high BP during pregnancy need to be passionate about monitoring and controlling their blood pressure and not ignore it,” Anastasia Mihailidou, PhD, Royal North Shore Hospital, Sydney, the assigned discussant in the late-breaking trial session, said in an interview.
“It also resulted in fewer postpartum hospital readmissions for high blood pressure and benefit at 9 months in the structure and function of the heart and blood vessels of the women,” she said.
“While we need to see further studies in ethnically diverse women to see that they are reproducible, there are simple measures that clinicians can implement, and women can ask to have their BP monitored more frequently than the current practice. In the U.K. it is 5-10 days after delivery and then at 6-8 weeks after giving birth when changes in heart structure have already started,” Dr. Mihailidou noted.
“The procedure will need to be modified if there are no telemedicine facilities, but that should not stop having close monitoring of BP and treating it adequately. Monitoring requires an accurate BP monitor. There also has to be monitoring BP for the children.”
The trial was funded by a BHF Clinical Research Training Fellowship to Dr. Kitt, with additional support from the NIHR Oxford Biomedical Research Centre and Oxford BHF Centre for Research Excellence.
A version of this article first appeared on Medscape.com.
, new research suggests.
In a randomized trial of 220 women with preeclampsia or gestational hypertension, those who took daily postpartum BP readings and received clinician-guided advice for titrating antihypertensives had a 5 mm Hg–lower average diastolic BP at 9 months, compared with those receiving usual care.
Jamie Kitt, DPhil, from the University of Oxford (England) presented these findings from the Physicians Optimized Postpartum Hypertension Treatment (POP-HT, NCT04273854) clinical trial at the American Heart Association scientific sessions. The study was simultaneously published online in JAMA, and a cardiac imaging substudy was published online in Circulation.
“This trial identifies a potential need for a paradigm shift in the way women affected by hypertensive pregnancy are managed postnatally,” Dr. Kitt said. “If a 5–mm Hg improvement in BP is maintained longer term, it can result in about a 20% reduction in lifetime cardiovascular risk.”
The imaging substudy suggests that short-term postnatal optimization of BP control following hypertensive pregnancy through self-monitoring and physician-guided antihypertensive titration is linked with better cardiac remodeling changes seen by cardiovascular magnetic resonance and echocardiography.
POP-HT “proves for the first time that the first few weeks after delivery are a critical time that can determine the long-term cardiovascular health of the mother,” senior author Paul Leeson, PhD, also from the University of Oxford, who presented the findings in a press briefing, said in an interview.
“Interventions during this period can have long-term beneficial impacts on cardiovascular health,” he said. “These findings rewrite the textbook on our understanding of how and why hypertensive pregnancies associate with later cardiovascular disease in the mother.”
Next, Dr. Leeson said, “We need to work out the best ways to implement these interventions “at scale. Then we can ensure all women who have hypertensive pregnancies can get access to the long-term cardiovascular benefits we have demonstrated are possible through improving postpartum cardiac care,” he said, adding that “this is entirely achievable using current available technologies.”
Hypertension in pregnancy
About 1 in 10 pregnant women develop hypertension in pregnancy (preeclampsia or gestational hypertension), and 1 in 3 such women go on to develop chronic hypertension within 10 years, “when they are usually still in their 30s or 40s,” Dr. Leeson said.
During pregnancy, the heart remodels to cope with pregnancy, and it undergoes more severe changes if BP is high. Then during the 6 weeks after giving birth, this remodeling rapidly reverses.
Higher blood pressure in young adulthood is associated with a twofold higher risk of subsequent myocardial infarction and stroke. And abnormal cardiac remodeling postpartum is also linked with higher cardiovascular risk.
Self-monitoring blood pressure during the postpartum period may be a “critical window” for intervention.
Previously, the research group performed a pilot study, the Self-Management of Postnatal Antihypertensive Treatment (SNAP-HT) trial and the SNAP-extension trial, which compared a BP self-monitoring intervention with usual care in 91 women with gestational hypertension or preeclampsia requiring postnatal antihypertensive treatment.
Diastolic BP, which drives cardiovascular risk in younger populations, was 4.5–mm Hg lower at 6 months postpartum and 7–mm Hg lower at 4 years post partum in patients randomly assigned to BP self-management vs. usual care – even after they were no longer taking antihypertensives.
Building on these findings, the POP-HT trial enrolled 220 pregnant women seen at Oxford University Hospitals in the United Kingdom who were age 18 years or older, had either gestational hypertension or preeclampsia, and still required antihypertensives when they were being discharged from hospital after giving birth.
Following a baseline visit at day 1-6 after delivery, while in the postnatal ward, the patients were randomly assigned 1:1 to the intervention group (112 women) or usual-care group (108 women).
They had an average age of 32.6 years; 40% had gestational hypertension, and 60% had preeclampsia.
Women in the usual-care group typically received a BP review at 7-10 days after hospital discharge with a community midwife, and another at 6-8 weeks with their general practitioner.
The women in the intervention group were given and taught to use a Bluetooth-enabled OMRON Evolv BP monitor (Omron Healthcare Europe) while on the postnatal ward, and they installed a smartphone app on their mobile phones that transmitted self-monitored BP readings to a National Health Service-hosted, web-based platform.
They were instructed to take daily BP measurements (twice daily if out of target range). Dose titration of antihypertensives after hospital discharge was guided remotely by research clinicians, according to a guideline-based algorithm.
Patients in both groups had four study visits when their BP was measured: visit 1 (baseline) between days 1 and 6 post partum; visit 2 at week 1; visit 3 at week 6; and visit 4 between months 6 and 9 post partum.
Similar antihypertensive classes were prescribed in each group (enalapril 57%, nifedipine 27%, and labetalol 30% for intervention vs. enalapril 43%, nifedipine 30%, and labetalol 27% for control).
At 6 weeks, approximately 30% of participants in each group were still taking medication; this dropped to approximately 12% by visit 4.
The primary outcome – the mean 24-hour diastolic BP at visit 4 (roughly 9 months post partum), adjusted for baseline postnatal diastolic blood pressure – was 5.8–mm Hg lower in the intervention group than in the control group (71.2 mm Hg vs. 76.6 mm Hg; P < .001).
Secondary outcomes – between-group differences in systolic BP at 9 months, BP-related postnatal admission, and cardiac remodeling assessed by cardiac magnetic resonance – were all better in the intervention group.
The mean 24-hour average systolic BP at 9 months post partum, adjusted for baseline postnatal systolic BP was 6.5–mm Hg lower in the intervention group than in the control group (114.0 mm Hg vs. 120.3 mm Hg; P < .001).
There was an absolute risk reduction of 20% and a relative risk reduction of 73.5% in postnatal readmission. The number needed to treat to avoid one postnatal readmission was five, which “has potential for big cost savings,” said Dr. Leeson.
Blood pressure post partum can be improved with self-monitoring and physician-guided medication adjustment, Dr. Leeson summarized. The blood pressure remains low for at least 9 months, even when medication is stopped, and the intervention leads to beneficial cardiac remodeling.
U.S. pilot study
Non-Hispanic Black adults have a high hypertension and cardiovascular disease burden, and a related small U.S. study showed benefits of BP self-monitoring in a population comprising mainly Black women, Keith Ferdinand, MD, discussant of the POP-HT trial in the press briefing, said in an interview.
Dr. Ferdinand, from Tulane University, New Orleans, Louisiana, was lead author of the Text My Hypertension BP Meds NOLA pilot study that was published in February in the American Heart Journal Plus: Cardiology Research and Practice.
The study showed that text-messaging and social support increased hypertension medication adherence.
They enrolled 36 individuals, of whom 32 (89%) were non-Hispanic Black, and 23 (64%) were women. The participants received validated Bluetooth-enabled BP-monitoring devices that were synced to smartphones via a secured cloud-based application. The participants could send and receive messages to health care practitioners.
This intervention significantly improved medication adherence and systolic BP without modifying pharmacotherapy.
‘Need to be passionate about monitoring BP’
“The take-home messages from these exciting findings is that physicians and women who have had high BP during pregnancy need to be passionate about monitoring and controlling their blood pressure and not ignore it,” Anastasia Mihailidou, PhD, Royal North Shore Hospital, Sydney, the assigned discussant in the late-breaking trial session, said in an interview.
“It also resulted in fewer postpartum hospital readmissions for high blood pressure and benefit at 9 months in the structure and function of the heart and blood vessels of the women,” she said.
“While we need to see further studies in ethnically diverse women to see that they are reproducible, there are simple measures that clinicians can implement, and women can ask to have their BP monitored more frequently than the current practice. In the U.K. it is 5-10 days after delivery and then at 6-8 weeks after giving birth when changes in heart structure have already started,” Dr. Mihailidou noted.
“The procedure will need to be modified if there are no telemedicine facilities, but that should not stop having close monitoring of BP and treating it adequately. Monitoring requires an accurate BP monitor. There also has to be monitoring BP for the children.”
The trial was funded by a BHF Clinical Research Training Fellowship to Dr. Kitt, with additional support from the NIHR Oxford Biomedical Research Centre and Oxford BHF Centre for Research Excellence.
A version of this article first appeared on Medscape.com.
FROM AHA 2023
Blood pressure lowering reduces dementia risk
Results of a trial using an intensive, 4-year program aimed at blood pressure lowering showed that intervention reduced not only blood pressure, but also significantly reduced the risk of total dementia over that period.
and cognitive impairment no dementia (CIND), a secondary outcome, was also significantly reduced by 16%.
“Blood pressure reduction is effective in reducing the risk of dementia in patients with hypertension,” concluded Jiang He, MD, PhD, professor of epidemiology and medicine and director of Tulane University’s Translational Science Institute, New Orleans. “This proven, effective intervention should be widely scaled up to reduce the global burden of dementia.”
He presented these results from the China Rural Hypertension Control Project (CRHCP) at the annual scientific sessions of the American Heart Association.
Target organ damage
Keith Ferdinand, MD, also from Tulane University, commented on the findings during a press conference at the meeting, noting that the result “opens our opportunity to recognize that the target organ damage of hypertension also now includes dementia.”
The researchers were able to “rigorously lower blood pressure from 157 to 127.6 in the intervention, 155 to 147 in the controls – 22 mg Hg – and if you look at the P values for all the various outcomes, they were very robust,” Dr. Ferdinand said.
Another interesting feature about the strategy used in this trial is that “this was true team-based care,” he pointed out. The trained interventionists in the study, called village doctors, collaborated with primary care physicians and initiated medications. “They stayed on a simple treatment protocol, and they were able to assist patients to ensure they had free medications, health coaching for lifestyle, home blood pressure measurement, and ensuring adherence.”
So, Dr. Ferdinand added, “one of the questions is whether this is a model we can use in other places around the globe, in places with low resources, and in the United States in disadvantaged populations.”
Public health priority
It’s estimated that the global number of those living with dementia will increase from 57.4 million in 2019 to 152.8 million by 2050, Dr. He said. “In the absence of curative treatment, the primary prevention of dementia through risk factor reduction, such as blood pressure lowering, becomes a public health priority.”
Previous randomized trials have lacked sample size and duration but have reported a nonsignificant reduction in dementia associated with antihypertensive treatment in patients with hypertension or a history of stroke, Dr. He noted.
This new trial aimed to test the effectiveness of intensive BP intervention to reduce the risk of all-cause dementia and cognitive impairment over a 48-month intervention period versus usual care.
It was an open-label, blinded-endpoint, cluster-randomized trial, and included 33,995 individual patients from 325 villages in China, aged 40 years and older, with untreated hypertension. The villages were randomly assigned to an intervention group or usual care, stratified by province, county, and township.
Patients were eligible if they had mean untreated systolic BP greater than 140 mm Hg and/or diastolic BP greater than 90 mm Hg or mean treated systolic BP of greater than 130 and/or diastolic greater than 80 mm Hg. Patients with a history of cardiovascular disease, chronic kidney disease, or diabetes and a mean systolic BP greater than 130 mm Hg and/or diastolic BP greater than 80 mm Hg from six measures on two different days were also eligible.
All were enrolled in the China New Rural Cooperative Medical Scheme, which covers 99% of rural residents for health care services, Dr. He noted.
The intervention was a simple stepped-care protocol for hypertension treatment, aimed at achieving a target systolic BP of less than 130 mm Hg and diastolic of less than 80 mm Hg.
Village doctors started and titrated antihypertensive treatment based on a protocol and were able to deliver discounted and free medications to patients. They also did health coaching on lifestyle modification and adherence to medication, and instructed patients on home BP monitoring.
Patients were provided training, supervision, and consultation by primary care physicians and hypertension specialists.
At the month 48 follow-up visit, the participants were assessed by neurologists who were blinded to randomization assignments. Neurologists did a variety of tests and assessments including collecting data on the patient’s medical and psychiatric history and risk factors for dementia, as well as neurologic assessment using the Mini-Mental State Examination, the Functional Activities Questionnaire, and the Quick Dementia Rating System.
The primary outcome was all-cause dementia, defined according to recommendations from the National Institute on Aging–Alzheimer’s Association work groups on diagnostic guidelines for Alzheimer’s disease.
Secondary outcomes included CIND, a composite outcome of dementia or CIND, and a composite of dementia or deaths.
The final diagnosis of all-cause dementia or CIND was made by an expert adjudication panel blinded to the intervention assignment.
At 48 months, 91.3% of patients completed the follow-up for clinical outcomes. Participants were an average of 63 years of age, 61% were female, and 23% had less than a primary school education, Dr. He noted.
The net group differences in systolic and diastolic BP reduction were 22 and 9.3 mm Hg, respectively (P < .0001).
Significant differences were also seen between the groups in the primary outcome of all-cause dementia, as well as secondary outcomes of CIND, dementia or cognitive impairment, or dementia or deaths.
Serious adverse events were more common in the usual care group, and there was no difference between groups in the occurrence of falls or syncope.
The effect was consistent across subgroups, Dr. He said, including age, sex, education, cigarette smoking, body mass index, systolic BP, and fasting plasma glucose at baseline.
First definitive evidence
Invited discussant for the trial, Daniel W. Jones, MD, University of Mississippi Medical Center, Jackson, and past president of the AHA, pointed out that previous results from CRHCP on cardiovascular outcomes, reported earlier in 2023 in The Lancet, showed that, similar to results of the large SPRINT trial, lowering systolic BP to a goal of less than 130 mm Hg reduced a composite endpoint of MI, stroke, heart failure requiring hospitalization, and cardiovascular disease death over the 36-month follow-up.
The SPRINT findings also suggested a possible reduction in dementia, Dr. Jones said.
Now, in these new CRHCP results, “there was a clear benefit for intensive BP control in reducing risk for dementia and cognitive dysfunction,” he said. “This is, importantly, the first definitive evidence of dementia risk reduction demonstrated in a randomized controlled clinical trial. This outcome supports observational data that shows a strong relationship between BP and dementia.”
Since it is the first of its kind though, replication of the results will be important, he noted.
The study also showed that the intervention, using minimally trained village doctors, sustained BP control for 48 months. “This model could be used in any setting with modifications, including in the United States,” Dr. Jones said.
The study was supported by the Ministry of Science and Technology of China; U.S. investigators did not receive financial support from this study. The researchers and Dr. Jones disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Results of a trial using an intensive, 4-year program aimed at blood pressure lowering showed that intervention reduced not only blood pressure, but also significantly reduced the risk of total dementia over that period.
and cognitive impairment no dementia (CIND), a secondary outcome, was also significantly reduced by 16%.
“Blood pressure reduction is effective in reducing the risk of dementia in patients with hypertension,” concluded Jiang He, MD, PhD, professor of epidemiology and medicine and director of Tulane University’s Translational Science Institute, New Orleans. “This proven, effective intervention should be widely scaled up to reduce the global burden of dementia.”
He presented these results from the China Rural Hypertension Control Project (CRHCP) at the annual scientific sessions of the American Heart Association.
Target organ damage
Keith Ferdinand, MD, also from Tulane University, commented on the findings during a press conference at the meeting, noting that the result “opens our opportunity to recognize that the target organ damage of hypertension also now includes dementia.”
The researchers were able to “rigorously lower blood pressure from 157 to 127.6 in the intervention, 155 to 147 in the controls – 22 mg Hg – and if you look at the P values for all the various outcomes, they were very robust,” Dr. Ferdinand said.
Another interesting feature about the strategy used in this trial is that “this was true team-based care,” he pointed out. The trained interventionists in the study, called village doctors, collaborated with primary care physicians and initiated medications. “They stayed on a simple treatment protocol, and they were able to assist patients to ensure they had free medications, health coaching for lifestyle, home blood pressure measurement, and ensuring adherence.”
So, Dr. Ferdinand added, “one of the questions is whether this is a model we can use in other places around the globe, in places with low resources, and in the United States in disadvantaged populations.”
Public health priority
It’s estimated that the global number of those living with dementia will increase from 57.4 million in 2019 to 152.8 million by 2050, Dr. He said. “In the absence of curative treatment, the primary prevention of dementia through risk factor reduction, such as blood pressure lowering, becomes a public health priority.”
Previous randomized trials have lacked sample size and duration but have reported a nonsignificant reduction in dementia associated with antihypertensive treatment in patients with hypertension or a history of stroke, Dr. He noted.
This new trial aimed to test the effectiveness of intensive BP intervention to reduce the risk of all-cause dementia and cognitive impairment over a 48-month intervention period versus usual care.
It was an open-label, blinded-endpoint, cluster-randomized trial, and included 33,995 individual patients from 325 villages in China, aged 40 years and older, with untreated hypertension. The villages were randomly assigned to an intervention group or usual care, stratified by province, county, and township.
Patients were eligible if they had mean untreated systolic BP greater than 140 mm Hg and/or diastolic BP greater than 90 mm Hg or mean treated systolic BP of greater than 130 and/or diastolic greater than 80 mm Hg. Patients with a history of cardiovascular disease, chronic kidney disease, or diabetes and a mean systolic BP greater than 130 mm Hg and/or diastolic BP greater than 80 mm Hg from six measures on two different days were also eligible.
All were enrolled in the China New Rural Cooperative Medical Scheme, which covers 99% of rural residents for health care services, Dr. He noted.
The intervention was a simple stepped-care protocol for hypertension treatment, aimed at achieving a target systolic BP of less than 130 mm Hg and diastolic of less than 80 mm Hg.
Village doctors started and titrated antihypertensive treatment based on a protocol and were able to deliver discounted and free medications to patients. They also did health coaching on lifestyle modification and adherence to medication, and instructed patients on home BP monitoring.
Patients were provided training, supervision, and consultation by primary care physicians and hypertension specialists.
At the month 48 follow-up visit, the participants were assessed by neurologists who were blinded to randomization assignments. Neurologists did a variety of tests and assessments including collecting data on the patient’s medical and psychiatric history and risk factors for dementia, as well as neurologic assessment using the Mini-Mental State Examination, the Functional Activities Questionnaire, and the Quick Dementia Rating System.
The primary outcome was all-cause dementia, defined according to recommendations from the National Institute on Aging–Alzheimer’s Association work groups on diagnostic guidelines for Alzheimer’s disease.
Secondary outcomes included CIND, a composite outcome of dementia or CIND, and a composite of dementia or deaths.
The final diagnosis of all-cause dementia or CIND was made by an expert adjudication panel blinded to the intervention assignment.
At 48 months, 91.3% of patients completed the follow-up for clinical outcomes. Participants were an average of 63 years of age, 61% were female, and 23% had less than a primary school education, Dr. He noted.
The net group differences in systolic and diastolic BP reduction were 22 and 9.3 mm Hg, respectively (P < .0001).
Significant differences were also seen between the groups in the primary outcome of all-cause dementia, as well as secondary outcomes of CIND, dementia or cognitive impairment, or dementia or deaths.
Serious adverse events were more common in the usual care group, and there was no difference between groups in the occurrence of falls or syncope.
The effect was consistent across subgroups, Dr. He said, including age, sex, education, cigarette smoking, body mass index, systolic BP, and fasting plasma glucose at baseline.
First definitive evidence
Invited discussant for the trial, Daniel W. Jones, MD, University of Mississippi Medical Center, Jackson, and past president of the AHA, pointed out that previous results from CRHCP on cardiovascular outcomes, reported earlier in 2023 in The Lancet, showed that, similar to results of the large SPRINT trial, lowering systolic BP to a goal of less than 130 mm Hg reduced a composite endpoint of MI, stroke, heart failure requiring hospitalization, and cardiovascular disease death over the 36-month follow-up.
The SPRINT findings also suggested a possible reduction in dementia, Dr. Jones said.
Now, in these new CRHCP results, “there was a clear benefit for intensive BP control in reducing risk for dementia and cognitive dysfunction,” he said. “This is, importantly, the first definitive evidence of dementia risk reduction demonstrated in a randomized controlled clinical trial. This outcome supports observational data that shows a strong relationship between BP and dementia.”
Since it is the first of its kind though, replication of the results will be important, he noted.
The study also showed that the intervention, using minimally trained village doctors, sustained BP control for 48 months. “This model could be used in any setting with modifications, including in the United States,” Dr. Jones said.
The study was supported by the Ministry of Science and Technology of China; U.S. investigators did not receive financial support from this study. The researchers and Dr. Jones disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Results of a trial using an intensive, 4-year program aimed at blood pressure lowering showed that intervention reduced not only blood pressure, but also significantly reduced the risk of total dementia over that period.
and cognitive impairment no dementia (CIND), a secondary outcome, was also significantly reduced by 16%.
“Blood pressure reduction is effective in reducing the risk of dementia in patients with hypertension,” concluded Jiang He, MD, PhD, professor of epidemiology and medicine and director of Tulane University’s Translational Science Institute, New Orleans. “This proven, effective intervention should be widely scaled up to reduce the global burden of dementia.”
He presented these results from the China Rural Hypertension Control Project (CRHCP) at the annual scientific sessions of the American Heart Association.
Target organ damage
Keith Ferdinand, MD, also from Tulane University, commented on the findings during a press conference at the meeting, noting that the result “opens our opportunity to recognize that the target organ damage of hypertension also now includes dementia.”
The researchers were able to “rigorously lower blood pressure from 157 to 127.6 in the intervention, 155 to 147 in the controls – 22 mg Hg – and if you look at the P values for all the various outcomes, they were very robust,” Dr. Ferdinand said.
Another interesting feature about the strategy used in this trial is that “this was true team-based care,” he pointed out. The trained interventionists in the study, called village doctors, collaborated with primary care physicians and initiated medications. “They stayed on a simple treatment protocol, and they were able to assist patients to ensure they had free medications, health coaching for lifestyle, home blood pressure measurement, and ensuring adherence.”
So, Dr. Ferdinand added, “one of the questions is whether this is a model we can use in other places around the globe, in places with low resources, and in the United States in disadvantaged populations.”
Public health priority
It’s estimated that the global number of those living with dementia will increase from 57.4 million in 2019 to 152.8 million by 2050, Dr. He said. “In the absence of curative treatment, the primary prevention of dementia through risk factor reduction, such as blood pressure lowering, becomes a public health priority.”
Previous randomized trials have lacked sample size and duration but have reported a nonsignificant reduction in dementia associated with antihypertensive treatment in patients with hypertension or a history of stroke, Dr. He noted.
This new trial aimed to test the effectiveness of intensive BP intervention to reduce the risk of all-cause dementia and cognitive impairment over a 48-month intervention period versus usual care.
It was an open-label, blinded-endpoint, cluster-randomized trial, and included 33,995 individual patients from 325 villages in China, aged 40 years and older, with untreated hypertension. The villages were randomly assigned to an intervention group or usual care, stratified by province, county, and township.
Patients were eligible if they had mean untreated systolic BP greater than 140 mm Hg and/or diastolic BP greater than 90 mm Hg or mean treated systolic BP of greater than 130 and/or diastolic greater than 80 mm Hg. Patients with a history of cardiovascular disease, chronic kidney disease, or diabetes and a mean systolic BP greater than 130 mm Hg and/or diastolic BP greater than 80 mm Hg from six measures on two different days were also eligible.
All were enrolled in the China New Rural Cooperative Medical Scheme, which covers 99% of rural residents for health care services, Dr. He noted.
The intervention was a simple stepped-care protocol for hypertension treatment, aimed at achieving a target systolic BP of less than 130 mm Hg and diastolic of less than 80 mm Hg.
Village doctors started and titrated antihypertensive treatment based on a protocol and were able to deliver discounted and free medications to patients. They also did health coaching on lifestyle modification and adherence to medication, and instructed patients on home BP monitoring.
Patients were provided training, supervision, and consultation by primary care physicians and hypertension specialists.
At the month 48 follow-up visit, the participants were assessed by neurologists who were blinded to randomization assignments. Neurologists did a variety of tests and assessments including collecting data on the patient’s medical and psychiatric history and risk factors for dementia, as well as neurologic assessment using the Mini-Mental State Examination, the Functional Activities Questionnaire, and the Quick Dementia Rating System.
The primary outcome was all-cause dementia, defined according to recommendations from the National Institute on Aging–Alzheimer’s Association work groups on diagnostic guidelines for Alzheimer’s disease.
Secondary outcomes included CIND, a composite outcome of dementia or CIND, and a composite of dementia or deaths.
The final diagnosis of all-cause dementia or CIND was made by an expert adjudication panel blinded to the intervention assignment.
At 48 months, 91.3% of patients completed the follow-up for clinical outcomes. Participants were an average of 63 years of age, 61% were female, and 23% had less than a primary school education, Dr. He noted.
The net group differences in systolic and diastolic BP reduction were 22 and 9.3 mm Hg, respectively (P < .0001).
Significant differences were also seen between the groups in the primary outcome of all-cause dementia, as well as secondary outcomes of CIND, dementia or cognitive impairment, or dementia or deaths.
Serious adverse events were more common in the usual care group, and there was no difference between groups in the occurrence of falls or syncope.
The effect was consistent across subgroups, Dr. He said, including age, sex, education, cigarette smoking, body mass index, systolic BP, and fasting plasma glucose at baseline.
First definitive evidence
Invited discussant for the trial, Daniel W. Jones, MD, University of Mississippi Medical Center, Jackson, and past president of the AHA, pointed out that previous results from CRHCP on cardiovascular outcomes, reported earlier in 2023 in The Lancet, showed that, similar to results of the large SPRINT trial, lowering systolic BP to a goal of less than 130 mm Hg reduced a composite endpoint of MI, stroke, heart failure requiring hospitalization, and cardiovascular disease death over the 36-month follow-up.
The SPRINT findings also suggested a possible reduction in dementia, Dr. Jones said.
Now, in these new CRHCP results, “there was a clear benefit for intensive BP control in reducing risk for dementia and cognitive dysfunction,” he said. “This is, importantly, the first definitive evidence of dementia risk reduction demonstrated in a randomized controlled clinical trial. This outcome supports observational data that shows a strong relationship between BP and dementia.”
Since it is the first of its kind though, replication of the results will be important, he noted.
The study also showed that the intervention, using minimally trained village doctors, sustained BP control for 48 months. “This model could be used in any setting with modifications, including in the United States,” Dr. Jones said.
The study was supported by the Ministry of Science and Technology of China; U.S. investigators did not receive financial support from this study. The researchers and Dr. Jones disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
FROM AHA 2023
Two biomarkers promising for preeclampsia prediction
Two biomarkers – pregnancy-associated plasma protein A2 (PAPP-A2) and activin A – when added to relevant clinical information have a better positive predictive value than and a comparable negative predictive value to the currently used ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF), new research suggests.
The third-trimester sFlt-1:PlGF ratio can predict short-term absence of preeclampsia. By contrast, , according to the authors.
Preeclampsia has “potentially devastating maternal and fetal complications, [including] significantly increased cardiovascular risk for affected women later in life,” study author Stella S. Daskalopoulou, MD, PhD, associate professor of medicine at McGill University Health Centre in Montreal, said in an interview.
“A more accurate prediction of preeclampsia is expected to improve risk stratification and clinical care and shape clinical practice guidelines,” she said.
The study was published online in the Canadian Journal of Cardiology.
Better predictive value
For a prospective cohort study, the investigators recruited 192 women with first-trimester high-risk singleton pregnancies from tertiary obstetric clinics in Montreal.
At baseline, they collected clinical information, including height, prepregnancy weight, personal and family medical history, and medication use.
At each trimester, blood pressure was measured, and blood samples were collected to quantify sFlt-1, PlGF, PAPP-A2, PAPP-A, activin A, inhibin A, follistatin, and glycosylated fibronectin. For the sFlt-1:PlGF ratio, the researchers used a cutoff point of 38, based on prior evidence. Because there are no agreed-upon cutoff points for the other biomarkers, they chose cutoff points that maximized sensitivity and specificity.
Pregnancies were considered high risk if the mother had any of the following conditions: prepregnancy BMI ≥ 25, maternal age ≥ 35 years, chronic hypertension, diabetes, renal disease, conception via in vitro fertilization, or maternal or first-degree family history of preeclampsia.
The primary outcome was preeclampsia, which was defined according to the Society of Obstetrics and Gynecology guidelines as systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure of ≥ mm Hg together with either proteinuria or maternal end-organ dysfunction.
A total of 18 women (9.38%) developed preeclampsia. Those women had higher blood pressure at baseline (although it was within normal limits) and were more likely to have preexisting diabetes or a previous pregnancy with preeclampsia. They were also more likely to report Black race. Serum levels of PAPP-A, PAPP-A2, activin A, and inhibin A were significantly different between patients who developed preeclampsia and those who did not. These levels were increased throughout pregnancy.
Alongside the sFlt-1:PlGF ratio, two biomarkers, PAPP-A2 (odds ratio, 1.78) and activin A (OR, 1.84), were significantly associated with the primary outcome after adjustment for age, prepregnancy BMI, race, and mean arterial pressure.
When added to a model that included those clinical factors, a positive third-trimester result for both PAPP-A2 and activin A had a better positive predictive value than the sFlt-1:PlGF ratio added to the clinical model (91.67% vs. 66.67%). The two biomarkers also had a negative predictive value that was comparable to that of the sFlt-1:PlGF ratio (97.69% vs. 96%).
Study limitations include the small sample size and missing covariates for some participants. Furthermore, the findings cannot be generalized to low-risk populations.
“Whereas the third-trimester sFlt-1:PlGF ratio can predict short-term absence of preeclampsia, PAPP-A2 and activin A had both high positive and negative predictive values and thus could serve as biomarkers to predict the occurrence (and absence) of preeclampsia; these findings will be validated in future studies,” the authors concluded.
Dr. Daskalopoulou said that her group is currently performing a large multinational study, PULSE, “which will be the ideal platform to validate and extend our findings. The aim of the study is to predict preeclampsia using a multimodal approach that includes arterial stiffness measurements and blood biomarkers.”
She expanded on the potential benefits of this research. “Finding an accurate predictive tool would not only help design appropriate early care plans for truly high-risk pregnant women, including monitoring and delivery planning, but also facilitate the development of novel strategies for the prevention and treatment of preeclampsia, improving the life of millions of young mothers and their offspring around the world.”
Promising biomarkers
Commenting on the study, Nieca Goldberg, MD, clinical associate professor of medicine at NYU Langone Health and medical director of Atria, both in New York, said, “These biomarkers are promising, as the current biomarker, sFlt-1:PlGF, is good at ruling out preeclampsia in the short term, while the new biomarkers show that they are better at ruling in preeclampsia” as well as ruling it out. Dr. Goldberg was not involved in the research.
“The current study is small, some participant data points are missing, and the researchers only studied high-risk pregnancies,” she added. “We need larger studies of all the risk markers, in both high- and low-risk pregnancies that are followed throughout pregnancy.”
This work was supported by the Fonds de recherche du Québec Santé (FRQS), Heart and Stroke Foundation of Canada, McGill University Department of Obstetrics and Gynecology Academic Enrichment Fund, and Canadian Foundation for Women›s Health. Dr. Daskalopoulou is a senior clinician-scientist supported by a FRQS Clinician Scientist-Senior salary award. Dr. Daskalopoulou and Dr. Goldberg disclosed no conflicts of interest.
A version of this article appeared on Medscape.com.
Two biomarkers – pregnancy-associated plasma protein A2 (PAPP-A2) and activin A – when added to relevant clinical information have a better positive predictive value than and a comparable negative predictive value to the currently used ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF), new research suggests.
The third-trimester sFlt-1:PlGF ratio can predict short-term absence of preeclampsia. By contrast, , according to the authors.
Preeclampsia has “potentially devastating maternal and fetal complications, [including] significantly increased cardiovascular risk for affected women later in life,” study author Stella S. Daskalopoulou, MD, PhD, associate professor of medicine at McGill University Health Centre in Montreal, said in an interview.
“A more accurate prediction of preeclampsia is expected to improve risk stratification and clinical care and shape clinical practice guidelines,” she said.
The study was published online in the Canadian Journal of Cardiology.
Better predictive value
For a prospective cohort study, the investigators recruited 192 women with first-trimester high-risk singleton pregnancies from tertiary obstetric clinics in Montreal.
At baseline, they collected clinical information, including height, prepregnancy weight, personal and family medical history, and medication use.
At each trimester, blood pressure was measured, and blood samples were collected to quantify sFlt-1, PlGF, PAPP-A2, PAPP-A, activin A, inhibin A, follistatin, and glycosylated fibronectin. For the sFlt-1:PlGF ratio, the researchers used a cutoff point of 38, based on prior evidence. Because there are no agreed-upon cutoff points for the other biomarkers, they chose cutoff points that maximized sensitivity and specificity.
Pregnancies were considered high risk if the mother had any of the following conditions: prepregnancy BMI ≥ 25, maternal age ≥ 35 years, chronic hypertension, diabetes, renal disease, conception via in vitro fertilization, or maternal or first-degree family history of preeclampsia.
The primary outcome was preeclampsia, which was defined according to the Society of Obstetrics and Gynecology guidelines as systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure of ≥ mm Hg together with either proteinuria or maternal end-organ dysfunction.
A total of 18 women (9.38%) developed preeclampsia. Those women had higher blood pressure at baseline (although it was within normal limits) and were more likely to have preexisting diabetes or a previous pregnancy with preeclampsia. They were also more likely to report Black race. Serum levels of PAPP-A, PAPP-A2, activin A, and inhibin A were significantly different between patients who developed preeclampsia and those who did not. These levels were increased throughout pregnancy.
Alongside the sFlt-1:PlGF ratio, two biomarkers, PAPP-A2 (odds ratio, 1.78) and activin A (OR, 1.84), were significantly associated with the primary outcome after adjustment for age, prepregnancy BMI, race, and mean arterial pressure.
When added to a model that included those clinical factors, a positive third-trimester result for both PAPP-A2 and activin A had a better positive predictive value than the sFlt-1:PlGF ratio added to the clinical model (91.67% vs. 66.67%). The two biomarkers also had a negative predictive value that was comparable to that of the sFlt-1:PlGF ratio (97.69% vs. 96%).
Study limitations include the small sample size and missing covariates for some participants. Furthermore, the findings cannot be generalized to low-risk populations.
“Whereas the third-trimester sFlt-1:PlGF ratio can predict short-term absence of preeclampsia, PAPP-A2 and activin A had both high positive and negative predictive values and thus could serve as biomarkers to predict the occurrence (and absence) of preeclampsia; these findings will be validated in future studies,” the authors concluded.
Dr. Daskalopoulou said that her group is currently performing a large multinational study, PULSE, “which will be the ideal platform to validate and extend our findings. The aim of the study is to predict preeclampsia using a multimodal approach that includes arterial stiffness measurements and blood biomarkers.”
She expanded on the potential benefits of this research. “Finding an accurate predictive tool would not only help design appropriate early care plans for truly high-risk pregnant women, including monitoring and delivery planning, but also facilitate the development of novel strategies for the prevention and treatment of preeclampsia, improving the life of millions of young mothers and their offspring around the world.”
Promising biomarkers
Commenting on the study, Nieca Goldberg, MD, clinical associate professor of medicine at NYU Langone Health and medical director of Atria, both in New York, said, “These biomarkers are promising, as the current biomarker, sFlt-1:PlGF, is good at ruling out preeclampsia in the short term, while the new biomarkers show that they are better at ruling in preeclampsia” as well as ruling it out. Dr. Goldberg was not involved in the research.
“The current study is small, some participant data points are missing, and the researchers only studied high-risk pregnancies,” she added. “We need larger studies of all the risk markers, in both high- and low-risk pregnancies that are followed throughout pregnancy.”
This work was supported by the Fonds de recherche du Québec Santé (FRQS), Heart and Stroke Foundation of Canada, McGill University Department of Obstetrics and Gynecology Academic Enrichment Fund, and Canadian Foundation for Women›s Health. Dr. Daskalopoulou is a senior clinician-scientist supported by a FRQS Clinician Scientist-Senior salary award. Dr. Daskalopoulou and Dr. Goldberg disclosed no conflicts of interest.
A version of this article appeared on Medscape.com.
Two biomarkers – pregnancy-associated plasma protein A2 (PAPP-A2) and activin A – when added to relevant clinical information have a better positive predictive value than and a comparable negative predictive value to the currently used ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF), new research suggests.
The third-trimester sFlt-1:PlGF ratio can predict short-term absence of preeclampsia. By contrast, , according to the authors.
Preeclampsia has “potentially devastating maternal and fetal complications, [including] significantly increased cardiovascular risk for affected women later in life,” study author Stella S. Daskalopoulou, MD, PhD, associate professor of medicine at McGill University Health Centre in Montreal, said in an interview.
“A more accurate prediction of preeclampsia is expected to improve risk stratification and clinical care and shape clinical practice guidelines,” she said.
The study was published online in the Canadian Journal of Cardiology.
Better predictive value
For a prospective cohort study, the investigators recruited 192 women with first-trimester high-risk singleton pregnancies from tertiary obstetric clinics in Montreal.
At baseline, they collected clinical information, including height, prepregnancy weight, personal and family medical history, and medication use.
At each trimester, blood pressure was measured, and blood samples were collected to quantify sFlt-1, PlGF, PAPP-A2, PAPP-A, activin A, inhibin A, follistatin, and glycosylated fibronectin. For the sFlt-1:PlGF ratio, the researchers used a cutoff point of 38, based on prior evidence. Because there are no agreed-upon cutoff points for the other biomarkers, they chose cutoff points that maximized sensitivity and specificity.
Pregnancies were considered high risk if the mother had any of the following conditions: prepregnancy BMI ≥ 25, maternal age ≥ 35 years, chronic hypertension, diabetes, renal disease, conception via in vitro fertilization, or maternal or first-degree family history of preeclampsia.
The primary outcome was preeclampsia, which was defined according to the Society of Obstetrics and Gynecology guidelines as systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure of ≥ mm Hg together with either proteinuria or maternal end-organ dysfunction.
A total of 18 women (9.38%) developed preeclampsia. Those women had higher blood pressure at baseline (although it was within normal limits) and were more likely to have preexisting diabetes or a previous pregnancy with preeclampsia. They were also more likely to report Black race. Serum levels of PAPP-A, PAPP-A2, activin A, and inhibin A were significantly different between patients who developed preeclampsia and those who did not. These levels were increased throughout pregnancy.
Alongside the sFlt-1:PlGF ratio, two biomarkers, PAPP-A2 (odds ratio, 1.78) and activin A (OR, 1.84), were significantly associated with the primary outcome after adjustment for age, prepregnancy BMI, race, and mean arterial pressure.
When added to a model that included those clinical factors, a positive third-trimester result for both PAPP-A2 and activin A had a better positive predictive value than the sFlt-1:PlGF ratio added to the clinical model (91.67% vs. 66.67%). The two biomarkers also had a negative predictive value that was comparable to that of the sFlt-1:PlGF ratio (97.69% vs. 96%).
Study limitations include the small sample size and missing covariates for some participants. Furthermore, the findings cannot be generalized to low-risk populations.
“Whereas the third-trimester sFlt-1:PlGF ratio can predict short-term absence of preeclampsia, PAPP-A2 and activin A had both high positive and negative predictive values and thus could serve as biomarkers to predict the occurrence (and absence) of preeclampsia; these findings will be validated in future studies,” the authors concluded.
Dr. Daskalopoulou said that her group is currently performing a large multinational study, PULSE, “which will be the ideal platform to validate and extend our findings. The aim of the study is to predict preeclampsia using a multimodal approach that includes arterial stiffness measurements and blood biomarkers.”
She expanded on the potential benefits of this research. “Finding an accurate predictive tool would not only help design appropriate early care plans for truly high-risk pregnant women, including monitoring and delivery planning, but also facilitate the development of novel strategies for the prevention and treatment of preeclampsia, improving the life of millions of young mothers and their offspring around the world.”
Promising biomarkers
Commenting on the study, Nieca Goldberg, MD, clinical associate professor of medicine at NYU Langone Health and medical director of Atria, both in New York, said, “These biomarkers are promising, as the current biomarker, sFlt-1:PlGF, is good at ruling out preeclampsia in the short term, while the new biomarkers show that they are better at ruling in preeclampsia” as well as ruling it out. Dr. Goldberg was not involved in the research.
“The current study is small, some participant data points are missing, and the researchers only studied high-risk pregnancies,” she added. “We need larger studies of all the risk markers, in both high- and low-risk pregnancies that are followed throughout pregnancy.”
This work was supported by the Fonds de recherche du Québec Santé (FRQS), Heart and Stroke Foundation of Canada, McGill University Department of Obstetrics and Gynecology Academic Enrichment Fund, and Canadian Foundation for Women›s Health. Dr. Daskalopoulou is a senior clinician-scientist supported by a FRQS Clinician Scientist-Senior salary award. Dr. Daskalopoulou and Dr. Goldberg disclosed no conflicts of interest.
A version of this article appeared on Medscape.com.
FROM THE CANADIAN JOURNAL OF CARDIOLOGY
Risk calculator for early-stage CKD may soon enter U.S. market
PHILADELPHIA – The analyses offer the possibility of focusing intensified medical management of early-stage CKD on those patients who could potentially receive the most benefit.
The Klinrisk model predicts the risk of an adult with early-stage CKD developing either a 40% or greater drop in estimated glomerular filtration rate or kidney failure. It calculates risk based on 20 lab-measured variables that include serum creatinine, urine albumin-to-creatinine ratio, and other values taken from routinely ordered tests such as complete blood cell counts, chemistry panels, comprehensive metabolic panels, and urinalysis.
In the most recent and largest external validation study using data from 4.6 million American adults enrolled in commercial and Medicare insurance plans, the results showed Klinrisk correctly predicted CKD progression in 80%-83% of individuals over 2 years and in 78%-83% of individuals over 5 years, depending on the insurance provider, Navdeep Tangri, MD, PhD, reported at the annual meeting of the American Society of Nephrology. When urinalysis data were available, the model correctly predicted CKD progression in 81%-87% of individuals over 2 years and in 80%-87% of individuals over 5 years. These results follow prior reports of several other successful validations of Klinrisk.
‘Ready to implement’
“The Klinrisk model is ready to implement by any payer, health system, or clinic where the needed lab data are available,” said Dr. Tangri, a nephrologist and professor at the University of Manitoba, Winnipeg, and founder of Klinrisk Inc., the company developing and commercializing the Klinrisk assessment tool.
For the time being, Dr. Tangri sees Klinrisk as a population health device that can allow insurers and health systems to track management quality and quality improvement and to target patients who stand to benefit most from relatively expensive resources. This includes prescriptions for finerenone (Kerendia, Bayer) for people who also have type 2 diabetes, and agents from the class of sodium-glucose cotransporter 2 (SGLT2) inhibitors such as dapagliflozin (Farxiga, AstraZeneca) and empagliflozin (Jardiance, Boehringer Ingelheim and Lilly).
He has also begun discussions with the Food and Drug Administration about the data the agency will need to consider Klinrisk for potential approval as a new medical device, perhaps in 2025. That’s how he envisions getting a Klinrisk assessment into the hands of caregivers that they could use with individual patients to create an appropriate treatment plan.
Results from his new analysis showed that “all the kidney disease action is in the 10%-20% of people with the highest risk on Klinrisk, while not much happens in those in the bottom half,” Dr. Tangri said during his presentation.
“We’re trying to find the patients who get the largest [absolute] benefit from intensified treatment,” he added in an interview. “Klinrisk finds people with high-risk kidney disease early on, when kidney function is still normal or near normal. High-risk patients are often completely unrecognized. Risk-based management” that identifies the early-stage CKD patients who would benefit most from treatment with an SGLT2 inhibitor, finerenone, and other foundational treatments to slow CKD progression “is better than the free-for-all that occurs today.”
Simplified data collection
“Klinrisk is very effective,” but requires follow-up by clinicians and health systems to implement its findings, commented Josef Coresh, MD, a professor of clinical epidemiology at Johns Hopkins Bloomberg, Baltimore. Dr. Coresh compared it with a free equation that estimates a person’s risk for a 40% drop in kidney function over the next 3 years developed by Dr. Tangri, Dr. Coresh, and many collaborators led by Morgan C. Grams, MD, PhD, of New York University that they published in 2022, and posted on a website of the CKD Prognosis Consortium.
The CKD Prognosis Consortium formula “takes a different approach” from Klinrisk. The commercial formula “is simpler, only using lab measures, and avoids inputs taken from physical examination such as systolic blood pressure and body mass index and health history data such as smoking, noted Dr. Coresh. He also speculated that “a commercial formula that must be paid for may counterintuitively result in better follow-up for making management changes if it uses some of the resources for education and system changes.”
Using data from multiple sources, like the CKD Prognosis Consortium equation, can create implementation challenges, said Dr. Tangri. “Lab results don’t vary much,” which makes Klinrisk “quite an improvement for implementation. It’s easier to implement.”
Other findings from the newest validation study that Dr. Tangri presented were that the people studied with Klinrisk scores in the top 10% had, over the next 2 years of follow-up and compared with people in the bottom half for Klinrisk staging, a 3- to 5-fold higher rate of all-cause medical costs, a 13-30-fold increase in CKD-related costs, and a 5- to 10-fold increase in hospitalizations and ED visits.
Early identification of CKD and early initiation of intensified treatment for high-risk patients can reduce the rate of progression to dialysis, reduce hospitalizations for heart failure, and lower the cost of care, Dr. Tangri said.
The validation study in 4.6 million Americans was sponsored by Boehringer Ingelheim. Dr. Tangri founded and has an ownership interest in Klinrisk. He has also received honoraria from, has ownership interests in, and has been a consultant to multiple pharmaceutical companies. Dr. Coresh had no disclosures.
PHILADELPHIA – The analyses offer the possibility of focusing intensified medical management of early-stage CKD on those patients who could potentially receive the most benefit.
The Klinrisk model predicts the risk of an adult with early-stage CKD developing either a 40% or greater drop in estimated glomerular filtration rate or kidney failure. It calculates risk based on 20 lab-measured variables that include serum creatinine, urine albumin-to-creatinine ratio, and other values taken from routinely ordered tests such as complete blood cell counts, chemistry panels, comprehensive metabolic panels, and urinalysis.
In the most recent and largest external validation study using data from 4.6 million American adults enrolled in commercial and Medicare insurance plans, the results showed Klinrisk correctly predicted CKD progression in 80%-83% of individuals over 2 years and in 78%-83% of individuals over 5 years, depending on the insurance provider, Navdeep Tangri, MD, PhD, reported at the annual meeting of the American Society of Nephrology. When urinalysis data were available, the model correctly predicted CKD progression in 81%-87% of individuals over 2 years and in 80%-87% of individuals over 5 years. These results follow prior reports of several other successful validations of Klinrisk.
‘Ready to implement’
“The Klinrisk model is ready to implement by any payer, health system, or clinic where the needed lab data are available,” said Dr. Tangri, a nephrologist and professor at the University of Manitoba, Winnipeg, and founder of Klinrisk Inc., the company developing and commercializing the Klinrisk assessment tool.
For the time being, Dr. Tangri sees Klinrisk as a population health device that can allow insurers and health systems to track management quality and quality improvement and to target patients who stand to benefit most from relatively expensive resources. This includes prescriptions for finerenone (Kerendia, Bayer) for people who also have type 2 diabetes, and agents from the class of sodium-glucose cotransporter 2 (SGLT2) inhibitors such as dapagliflozin (Farxiga, AstraZeneca) and empagliflozin (Jardiance, Boehringer Ingelheim and Lilly).
He has also begun discussions with the Food and Drug Administration about the data the agency will need to consider Klinrisk for potential approval as a new medical device, perhaps in 2025. That’s how he envisions getting a Klinrisk assessment into the hands of caregivers that they could use with individual patients to create an appropriate treatment plan.
Results from his new analysis showed that “all the kidney disease action is in the 10%-20% of people with the highest risk on Klinrisk, while not much happens in those in the bottom half,” Dr. Tangri said during his presentation.
“We’re trying to find the patients who get the largest [absolute] benefit from intensified treatment,” he added in an interview. “Klinrisk finds people with high-risk kidney disease early on, when kidney function is still normal or near normal. High-risk patients are often completely unrecognized. Risk-based management” that identifies the early-stage CKD patients who would benefit most from treatment with an SGLT2 inhibitor, finerenone, and other foundational treatments to slow CKD progression “is better than the free-for-all that occurs today.”
Simplified data collection
“Klinrisk is very effective,” but requires follow-up by clinicians and health systems to implement its findings, commented Josef Coresh, MD, a professor of clinical epidemiology at Johns Hopkins Bloomberg, Baltimore. Dr. Coresh compared it with a free equation that estimates a person’s risk for a 40% drop in kidney function over the next 3 years developed by Dr. Tangri, Dr. Coresh, and many collaborators led by Morgan C. Grams, MD, PhD, of New York University that they published in 2022, and posted on a website of the CKD Prognosis Consortium.
The CKD Prognosis Consortium formula “takes a different approach” from Klinrisk. The commercial formula “is simpler, only using lab measures, and avoids inputs taken from physical examination such as systolic blood pressure and body mass index and health history data such as smoking, noted Dr. Coresh. He also speculated that “a commercial formula that must be paid for may counterintuitively result in better follow-up for making management changes if it uses some of the resources for education and system changes.”
Using data from multiple sources, like the CKD Prognosis Consortium equation, can create implementation challenges, said Dr. Tangri. “Lab results don’t vary much,” which makes Klinrisk “quite an improvement for implementation. It’s easier to implement.”
Other findings from the newest validation study that Dr. Tangri presented were that the people studied with Klinrisk scores in the top 10% had, over the next 2 years of follow-up and compared with people in the bottom half for Klinrisk staging, a 3- to 5-fold higher rate of all-cause medical costs, a 13-30-fold increase in CKD-related costs, and a 5- to 10-fold increase in hospitalizations and ED visits.
Early identification of CKD and early initiation of intensified treatment for high-risk patients can reduce the rate of progression to dialysis, reduce hospitalizations for heart failure, and lower the cost of care, Dr. Tangri said.
The validation study in 4.6 million Americans was sponsored by Boehringer Ingelheim. Dr. Tangri founded and has an ownership interest in Klinrisk. He has also received honoraria from, has ownership interests in, and has been a consultant to multiple pharmaceutical companies. Dr. Coresh had no disclosures.
PHILADELPHIA – The analyses offer the possibility of focusing intensified medical management of early-stage CKD on those patients who could potentially receive the most benefit.
The Klinrisk model predicts the risk of an adult with early-stage CKD developing either a 40% or greater drop in estimated glomerular filtration rate or kidney failure. It calculates risk based on 20 lab-measured variables that include serum creatinine, urine albumin-to-creatinine ratio, and other values taken from routinely ordered tests such as complete blood cell counts, chemistry panels, comprehensive metabolic panels, and urinalysis.
In the most recent and largest external validation study using data from 4.6 million American adults enrolled in commercial and Medicare insurance plans, the results showed Klinrisk correctly predicted CKD progression in 80%-83% of individuals over 2 years and in 78%-83% of individuals over 5 years, depending on the insurance provider, Navdeep Tangri, MD, PhD, reported at the annual meeting of the American Society of Nephrology. When urinalysis data were available, the model correctly predicted CKD progression in 81%-87% of individuals over 2 years and in 80%-87% of individuals over 5 years. These results follow prior reports of several other successful validations of Klinrisk.
‘Ready to implement’
“The Klinrisk model is ready to implement by any payer, health system, or clinic where the needed lab data are available,” said Dr. Tangri, a nephrologist and professor at the University of Manitoba, Winnipeg, and founder of Klinrisk Inc., the company developing and commercializing the Klinrisk assessment tool.
For the time being, Dr. Tangri sees Klinrisk as a population health device that can allow insurers and health systems to track management quality and quality improvement and to target patients who stand to benefit most from relatively expensive resources. This includes prescriptions for finerenone (Kerendia, Bayer) for people who also have type 2 diabetes, and agents from the class of sodium-glucose cotransporter 2 (SGLT2) inhibitors such as dapagliflozin (Farxiga, AstraZeneca) and empagliflozin (Jardiance, Boehringer Ingelheim and Lilly).
He has also begun discussions with the Food and Drug Administration about the data the agency will need to consider Klinrisk for potential approval as a new medical device, perhaps in 2025. That’s how he envisions getting a Klinrisk assessment into the hands of caregivers that they could use with individual patients to create an appropriate treatment plan.
Results from his new analysis showed that “all the kidney disease action is in the 10%-20% of people with the highest risk on Klinrisk, while not much happens in those in the bottom half,” Dr. Tangri said during his presentation.
“We’re trying to find the patients who get the largest [absolute] benefit from intensified treatment,” he added in an interview. “Klinrisk finds people with high-risk kidney disease early on, when kidney function is still normal or near normal. High-risk patients are often completely unrecognized. Risk-based management” that identifies the early-stage CKD patients who would benefit most from treatment with an SGLT2 inhibitor, finerenone, and other foundational treatments to slow CKD progression “is better than the free-for-all that occurs today.”
Simplified data collection
“Klinrisk is very effective,” but requires follow-up by clinicians and health systems to implement its findings, commented Josef Coresh, MD, a professor of clinical epidemiology at Johns Hopkins Bloomberg, Baltimore. Dr. Coresh compared it with a free equation that estimates a person’s risk for a 40% drop in kidney function over the next 3 years developed by Dr. Tangri, Dr. Coresh, and many collaborators led by Morgan C. Grams, MD, PhD, of New York University that they published in 2022, and posted on a website of the CKD Prognosis Consortium.
The CKD Prognosis Consortium formula “takes a different approach” from Klinrisk. The commercial formula “is simpler, only using lab measures, and avoids inputs taken from physical examination such as systolic blood pressure and body mass index and health history data such as smoking, noted Dr. Coresh. He also speculated that “a commercial formula that must be paid for may counterintuitively result in better follow-up for making management changes if it uses some of the resources for education and system changes.”
Using data from multiple sources, like the CKD Prognosis Consortium equation, can create implementation challenges, said Dr. Tangri. “Lab results don’t vary much,” which makes Klinrisk “quite an improvement for implementation. It’s easier to implement.”
Other findings from the newest validation study that Dr. Tangri presented were that the people studied with Klinrisk scores in the top 10% had, over the next 2 years of follow-up and compared with people in the bottom half for Klinrisk staging, a 3- to 5-fold higher rate of all-cause medical costs, a 13-30-fold increase in CKD-related costs, and a 5- to 10-fold increase in hospitalizations and ED visits.
Early identification of CKD and early initiation of intensified treatment for high-risk patients can reduce the rate of progression to dialysis, reduce hospitalizations for heart failure, and lower the cost of care, Dr. Tangri said.
The validation study in 4.6 million Americans was sponsored by Boehringer Ingelheim. Dr. Tangri founded and has an ownership interest in Klinrisk. He has also received honoraria from, has ownership interests in, and has been a consultant to multiple pharmaceutical companies. Dr. Coresh had no disclosures.
AT KIDNEY WEEK 2023