Hypertension

As inclisiran, a first-in-class LDL-cholesterol lowering drug, enters the U.S. market following Food and Drug Administration approval in December 2021, several issues muddy how popular inclisiran will be in actual practice. That’s despite stellar phase 3 trial evidence for safety, tolerability, and a potent lipid-lowering effect.

The active ingredient of inclisiran (Leqvio) is a small interfering RNA (siRNA) molecule that shuts down production of the PCSK9 (proprotein convertase subtilisin/kexin type 9) protein, an enzyme that’s made and functions primarily in the liver and degrades cellular receptors for LDL cholesterol. Inhibiting PCSK9 production means LDL-cholesterol receptors accumulate and boost the ability of liver cells to pull more LDL cholesterol out of blood.

PCSK9 inhibition is the most potent LDL-cholesterol lowering method now available, and it works well in patients who have maxed out LDL reduction by diet and statin treatment. The siRNA of inclisiran is tweaked to target the molecule to the surface of liver cells following subcutaneous injection. Other modifications of the siRNA give it stability that allows twice-a-year dosing, although patients receive a third injection during their first year to hasten a maximum treatment effect.

Inclisiran’s FDA approval relied on results from three pivotal trials that together enrolled 3,660 patients with either atherosclerotic cardiovascular disease (ASCVD), ASCVD risk equivalents, or heterozygous familial hypercholesterolemia (HeFH), and LDL-cholesterol levels of at least 70 mg/dL in those with established ASCVD, or at least 100 mg/dL in other patients. (HeFH and ASCVD are the drug’s approved indications.) Pooled data from the three trials showed that inclisiran was safe and well tolerated during 18 months and produced an average LDL-cholesterol reduction after 510 days (1.4 years) of about 51% compared to baseline after correction for placebo effects (J Am Coll Cardiol. 2021 Mar 9;77 [9]:1182-93).

These data showed inclisiran was about as safe and effective for reducing LDL-cholesterol as agents from another class of PCSK9 inhibitors that rely on injected antibodies to inactivate PCSK9. Two agents from this class, alirocumab (Praluent) and evolocumab (Repatha), both came on the U.S. market in 2015. Although their performance in routine practice during the ensuing 6-plus years has been as safe and effective as what they showed in their respective registration trials, they have faced a rocky uptake road that’s been primarily hindered by the hefty price tag that both drugs carry.
 

Prior-authorization blues

When they first came out, evolocumab and alirocumab were burdened by annual drug costs of roughly $14,000, a fact that led to widespread prior-authorization and copay barriers set up by U.S. insurers. Although these barriers gradually lessened over time, in part aided by a substantial price cut for both drugs that led to annual drug costs more in the range of $6,000/year, they remain relatively pricey and are still not easy to start in patients because of prior-authorization requirements, said clinicians.

Recent penetration of the older PCSK9 inhibitors into eligible U.S. patients “is only about 1%-2%, based on the latest data,” said Michael H. Davidson, MD, a lipid specialist and director of Preventive Cardiology at the University of Chicago.

“We have these great, effective drugs, but they haven’t really made an impact over the past 5 years,” because of very limited uptake, a situation Dr. Davidson called “very disappointing,” during an interview.

Given this recent history, inclisiran, another expensive PCSK9 inhibitor, may face similar coverage pushback as it hits the U.S. market with a retail price, announced by its manufacturer Novartis, of $3,250/dose. This means that patients who start the drug and receive their initial dose, a second dose after 3 months, and then additional doses every 6 months, rack up a drug cost of close to $10,000 the first year on the drug and $6,500 each subsequent year.

This treatment schedule highlights the major logistical difference that distinguishes inclisiran from the antibody-based PCSK9 inhibitors, which are given by repeated subcutaneous injection every 2 or 4 weeks, usually with patients self-injecting the drugs at home. The less-frequent dosing schedule for inclisiran prompted the drug’s developers to schedule injections by a clinician in an office setting in the pivotal trials, which led to labeling for inclisiran that specifies administration only by a health care professional.
 

The ‘buy-and-bill’ coverage model

This difference in drug administration between inclisiran and the antibody-based PCSK9 inhibitors set up Novartis to promote insurance reimbursement for inclisiran using a “buy-and-bill” paradigm that was first developed for oncology drugs and which may provide a loophole around the prior-authorization roadblocks that hindered early uptake of the antibody-based PCSK9 inhibitors.

It’s also an approach that has made U.S. clinicians unsure how it will play out in practice. Infrequent inclisiran dosing may also boost patient compliance.

“Adherence is the greatest challenge in preventive cardiology, and thus inclisiran has the potential to be a game changer,” commented Christie M. Ballantyne, MD, professor and chief of cardiology at Baylor College of Medicine, Houston.

“Will it be easier for physicians to write a prescription and for patients to get the medication without a demanding and frustrating prior-authorization process?” he wondered during an interview. “I’m waiting to see how this unfolds, especially in systems where pharmacy is not fully integrated with the outpatient setting. In some ways, this is as big of an experiment as was development of the drug,” Dr. Ballantyne said.

Although the prior-authorization hoops for evolocumab and alirocumab have become easier to jump through, “most physicians don’t have the resources to handle it and don’t bother,” noted Dr. Davidson, and he’s concerned that infrastructure challenges will also hamper the buy-and-bill strategy for inclisiran.

He also expressed skepticism that the prior-authorization barrier will disappear. “Payers don’t want to open a large population to a very expensive drug without some gatekeeping,” he said, while acknowledging that in late January 2022 he did not yet have personal experience administering inclisiran or navigating its insurance reimbursement.
 

Boosting patient compliance

Dr. Davidson agreed that the prospect for enhanced patient compliance with inclisiran was intriguing and had already drawn the interest of some of his patients.

“There is a lot of appeal” to a treatment that’s only given once every 6 months, he said. “Compliance is a major issue, and this is less work for patients.”

“The biggest possible attraction of inclisiran is that it is given twice a year, but whether this plays out as anticipated in the real world need to be seen,” cautioned Vijay Nambi, MD, a cardiologist at the Michael E. DeBakey VA Hospital, Houston, and at Baylor College of Medicine who has written about inclisiran. He noted that while two doses a year is “on paper very attractive,” this scheme opens the door to missed or delayed appointments because of vacations, other patient travel, or events like a pandemic.

“The biggest pro for inclisiran is the dosing schedule,” said Chandni Bardolia, PharmD, a drug information specialist at Tabula Rasa Healthcare, Moorestown, N.J., who has analyzed and written about inclisiran and other lipid-lowering medications. “Twice yearly dosing following initiation will be a huge benefit to improve adherence and reduce the number of injections.”

However, inclisiran’s attractive dosing schedule as well as its safety and potent efficacy do not tell the whole story, she highlighted in an interview.

Inclisiran’s clinical evidence still cooking

“I see inclisiran as a last-line drug, mainly because the current alternatives have more safety and efficacy data,” Dr. Bardolia said.

Inclisiran’s “cost and the fact that there are other agents with clinical outcome data already available [alirocumab and evolocumab] means inclisiran is not a first-line agent after statins,” agreed Dr. Nambi.

The FDA based its inclisiran approval entirely on the drug’s demonstrated safety and LDL-lowering efficacy. The cardiovascular outcomes trial for inclisiran, ORION-4, with about 15,000 enrolled patients, started in 2018 and remains in progress with full results expected in 2026.

The lack of clinical outcomes data for inclisiran is a major limitation, said Neil J. Stone, MD, a cardiologist and professor at Northwestern University, Chicago, and vice chair of the panel that wrote the most recent cholesterol guideline for the American College of Cardiology and American Heart Association.

“My greatest concern is the lack of outcome trial data. That’s very important,” Dr. Stone said in an interview.

But others minimize this limitation given the overwhelming evidence that links lower levels of LDL-cholesterol to reduced clinical events.

Most clinicians “support lower LDL as a surrogate” for reduced clinical events, “just like blood pressure and hemoglobin A1c,” noted Dr. Davidson, although he conceded that a “substantial minority wants to wait to see inclisiran’s outcome benefits.”
 

It’s all about price

While opinions are mixed on the need for clinical outcomes data, experts are more uniform in seeing drug prices that run to several thousands per year as the main uptake issue.

“We need to look at the cost-efficacy with inclisiran, and we need benefit data to determine this,” said Dr. Stone.

“Outcomes data are central to characterizing value. I imagine that costs will impact adoption and dissemination” of inclisiran, commented Paul L. Hess, MD, a cardiologist at the Rocky Mountain Regional VA Medical Center, Denver.

Patient interest in less frequent dosing will be important for driving use, but “ultimately cost will be the most important driving factor,” for inclisiran uptake, commented Robert H. Eckel, MD, an endocrinologist affiliated with the University of Colorado School of Medicine, Aurora.

Dr. Davidson has ties to New Amsterdam Pharma and Amgen, which markets evolocumab (Repatha). Dr. Ballantyne is a consultant to numerous companies, including Amgen and Regeneron, which market alirocumab (Praluent). Dr. Nambi has been a site investigator for studies sponsored by Amgen, and by Merck, which markets the LDL-cholesterol drug ezetimibe (Zetia) and is developing an oral PCSK9 inhibitor (he said that the views he expressed are his own and don’t represent that of the department of Veterans Affairs or Baylor.) Dr. Bardolia had no disclosures beyond her employment at Tabula Rasa Healthcare. Dr. Stone, Dr. Hess, and Dr. Eckel had no relevant disclosures.


 

As inclisiran, a first-in-class LDL-cholesterol lowering drug, enters the U.S. market following Food and Drug Administration approval in December 2021, several issues muddy how popular inclisiran will be in actual practice. That’s despite stellar phase 3 trial evidence for safety, tolerability, and a potent lipid-lowering effect.

The active ingredient of inclisiran (Leqvio) is a small interfering RNA (siRNA) molecule that shuts down production of the PCSK9 (proprotein convertase subtilisin/kexin type 9) protein, an enzyme that’s made and functions primarily in the liver and degrades cellular receptors for LDL cholesterol. Inhibiting PCSK9 production means LDL-cholesterol receptors accumulate and boost the ability of liver cells to pull more LDL cholesterol out of blood.

PCSK9 inhibition is the most potent LDL-cholesterol lowering method now available, and it works well in patients who have maxed out LDL reduction by diet and statin treatment. The siRNA of inclisiran is tweaked to target the molecule to the surface of liver cells following subcutaneous injection. Other modifications of the siRNA give it stability that allows twice-a-year dosing, although patients receive a third injection during their first year to hasten a maximum treatment effect.

Inclisiran’s FDA approval relied on results from three pivotal trials that together enrolled 3,660 patients with either atherosclerotic cardiovascular disease (ASCVD), ASCVD risk equivalents, or heterozygous familial hypercholesterolemia (HeFH), and LDL-cholesterol levels of at least 70 mg/dL in those with established ASCVD, or at least 100 mg/dL in other patients. (HeFH and ASCVD are the drug’s approved indications.) Pooled data from the three trials showed that inclisiran was safe and well tolerated during 18 months and produced an average LDL-cholesterol reduction after 510 days (1.4 years) of about 51% compared to baseline after correction for placebo effects (J Am Coll Cardiol. 2021 Mar 9;77 [9]:1182-93).

These data showed inclisiran was about as safe and effective for reducing LDL-cholesterol as agents from another class of PCSK9 inhibitors that rely on injected antibodies to inactivate PCSK9. Two agents from this class, alirocumab (Praluent) and evolocumab (Repatha), both came on the U.S. market in 2015. Although their performance in routine practice during the ensuing 6-plus years has been as safe and effective as what they showed in their respective registration trials, they have faced a rocky uptake road that’s been primarily hindered by the hefty price tag that both drugs carry.
 

Prior-authorization blues

When they first came out, evolocumab and alirocumab were burdened by annual drug costs of roughly $14,000, a fact that led to widespread prior-authorization and copay barriers set up by U.S. insurers. Although these barriers gradually lessened over time, in part aided by a substantial price cut for both drugs that led to annual drug costs more in the range of $6,000/year, they remain relatively pricey and are still not easy to start in patients because of prior-authorization requirements, said clinicians.

Recent penetration of the older PCSK9 inhibitors into eligible U.S. patients “is only about 1%-2%, based on the latest data,” said Michael H. Davidson, MD, a lipid specialist and director of Preventive Cardiology at the University of Chicago.

“We have these great, effective drugs, but they haven’t really made an impact over the past 5 years,” because of very limited uptake, a situation Dr. Davidson called “very disappointing,” during an interview.

Given this recent history, inclisiran, another expensive PCSK9 inhibitor, may face similar coverage pushback as it hits the U.S. market with a retail price, announced by its manufacturer Novartis, of $3,250/dose. This means that patients who start the drug and receive their initial dose, a second dose after 3 months, and then additional doses every 6 months, rack up a drug cost of close to $10,000 the first year on the drug and $6,500 each subsequent year.

This treatment schedule highlights the major logistical difference that distinguishes inclisiran from the antibody-based PCSK9 inhibitors, which are given by repeated subcutaneous injection every 2 or 4 weeks, usually with patients self-injecting the drugs at home. The less-frequent dosing schedule for inclisiran prompted the drug’s developers to schedule injections by a clinician in an office setting in the pivotal trials, which led to labeling for inclisiran that specifies administration only by a health care professional.
 

The ‘buy-and-bill’ coverage model

This difference in drug administration between inclisiran and the antibody-based PCSK9 inhibitors set up Novartis to promote insurance reimbursement for inclisiran using a “buy-and-bill” paradigm that was first developed for oncology drugs and which may provide a loophole around the prior-authorization roadblocks that hindered early uptake of the antibody-based PCSK9 inhibitors.

It’s also an approach that has made U.S. clinicians unsure how it will play out in practice. Infrequent inclisiran dosing may also boost patient compliance.

“Adherence is the greatest challenge in preventive cardiology, and thus inclisiran has the potential to be a game changer,” commented Christie M. Ballantyne, MD, professor and chief of cardiology at Baylor College of Medicine, Houston.

“Will it be easier for physicians to write a prescription and for patients to get the medication without a demanding and frustrating prior-authorization process?” he wondered during an interview. “I’m waiting to see how this unfolds, especially in systems where pharmacy is not fully integrated with the outpatient setting. In some ways, this is as big of an experiment as was development of the drug,” Dr. Ballantyne said.

Although the prior-authorization hoops for evolocumab and alirocumab have become easier to jump through, “most physicians don’t have the resources to handle it and don’t bother,” noted Dr. Davidson, and he’s concerned that infrastructure challenges will also hamper the buy-and-bill strategy for inclisiran.

He also expressed skepticism that the prior-authorization barrier will disappear. “Payers don’t want to open a large population to a very expensive drug without some gatekeeping,” he said, while acknowledging that in late January 2022 he did not yet have personal experience administering inclisiran or navigating its insurance reimbursement.
 

Boosting patient compliance

Dr. Davidson agreed that the prospect for enhanced patient compliance with inclisiran was intriguing and had already drawn the interest of some of his patients.

“There is a lot of appeal” to a treatment that’s only given once every 6 months, he said. “Compliance is a major issue, and this is less work for patients.”

“The biggest possible attraction of inclisiran is that it is given twice a year, but whether this plays out as anticipated in the real world need to be seen,” cautioned Vijay Nambi, MD, a cardiologist at the Michael E. DeBakey VA Hospital, Houston, and at Baylor College of Medicine who has written about inclisiran. He noted that while two doses a year is “on paper very attractive,” this scheme opens the door to missed or delayed appointments because of vacations, other patient travel, or events like a pandemic.

“The biggest pro for inclisiran is the dosing schedule,” said Chandni Bardolia, PharmD, a drug information specialist at Tabula Rasa Healthcare, Moorestown, N.J., who has analyzed and written about inclisiran and other lipid-lowering medications. “Twice yearly dosing following initiation will be a huge benefit to improve adherence and reduce the number of injections.”

However, inclisiran’s attractive dosing schedule as well as its safety and potent efficacy do not tell the whole story, she highlighted in an interview.

Inclisiran’s clinical evidence still cooking

“I see inclisiran as a last-line drug, mainly because the current alternatives have more safety and efficacy data,” Dr. Bardolia said.

Inclisiran’s “cost and the fact that there are other agents with clinical outcome data already available [alirocumab and evolocumab] means inclisiran is not a first-line agent after statins,” agreed Dr. Nambi.

The FDA based its inclisiran approval entirely on the drug’s demonstrated safety and LDL-lowering efficacy. The cardiovascular outcomes trial for inclisiran, ORION-4, with about 15,000 enrolled patients, started in 2018 and remains in progress with full results expected in 2026.

The lack of clinical outcomes data for inclisiran is a major limitation, said Neil J. Stone, MD, a cardiologist and professor at Northwestern University, Chicago, and vice chair of the panel that wrote the most recent cholesterol guideline for the American College of Cardiology and American Heart Association.

“My greatest concern is the lack of outcome trial data. That’s very important,” Dr. Stone said in an interview.

But others minimize this limitation given the overwhelming evidence that links lower levels of LDL-cholesterol to reduced clinical events.

Most clinicians “support lower LDL as a surrogate” for reduced clinical events, “just like blood pressure and hemoglobin A1c,” noted Dr. Davidson, although he conceded that a “substantial minority wants to wait to see inclisiran’s outcome benefits.”
 

It’s all about price

While opinions are mixed on the need for clinical outcomes data, experts are more uniform in seeing drug prices that run to several thousands per year as the main uptake issue.

“We need to look at the cost-efficacy with inclisiran, and we need benefit data to determine this,” said Dr. Stone.

“Outcomes data are central to characterizing value. I imagine that costs will impact adoption and dissemination” of inclisiran, commented Paul L. Hess, MD, a cardiologist at the Rocky Mountain Regional VA Medical Center, Denver.

Patient interest in less frequent dosing will be important for driving use, but “ultimately cost will be the most important driving factor,” for inclisiran uptake, commented Robert H. Eckel, MD, an endocrinologist affiliated with the University of Colorado School of Medicine, Aurora.

Dr. Davidson has ties to New Amsterdam Pharma and Amgen, which markets evolocumab (Repatha). Dr. Ballantyne is a consultant to numerous companies, including Amgen and Regeneron, which market alirocumab (Praluent). Dr. Nambi has been a site investigator for studies sponsored by Amgen, and by Merck, which markets the LDL-cholesterol drug ezetimibe (Zetia) and is developing an oral PCSK9 inhibitor (he said that the views he expressed are his own and don’t represent that of the department of Veterans Affairs or Baylor.) Dr. Bardolia had no disclosures beyond her employment at Tabula Rasa Healthcare. Dr. Stone, Dr. Hess, and Dr. Eckel had no relevant disclosures.


 

As inclisiran, a first-in-class LDL-cholesterol lowering drug, enters the U.S. market following Food and Drug Administration approval in December 2021, several issues muddy how popular inclisiran will be in actual practice. That’s despite stellar phase 3 trial evidence for safety, tolerability, and a potent lipid-lowering effect.

The active ingredient of inclisiran (Leqvio) is a small interfering RNA (siRNA) molecule that shuts down production of the PCSK9 (proprotein convertase subtilisin/kexin type 9) protein, an enzyme that’s made and functions primarily in the liver and degrades cellular receptors for LDL cholesterol. Inhibiting PCSK9 production means LDL-cholesterol receptors accumulate and boost the ability of liver cells to pull more LDL cholesterol out of blood.

PCSK9 inhibition is the most potent LDL-cholesterol lowering method now available, and it works well in patients who have maxed out LDL reduction by diet and statin treatment. The siRNA of inclisiran is tweaked to target the molecule to the surface of liver cells following subcutaneous injection. Other modifications of the siRNA give it stability that allows twice-a-year dosing, although patients receive a third injection during their first year to hasten a maximum treatment effect.

Inclisiran’s FDA approval relied on results from three pivotal trials that together enrolled 3,660 patients with either atherosclerotic cardiovascular disease (ASCVD), ASCVD risk equivalents, or heterozygous familial hypercholesterolemia (HeFH), and LDL-cholesterol levels of at least 70 mg/dL in those with established ASCVD, or at least 100 mg/dL in other patients. (HeFH and ASCVD are the drug’s approved indications.) Pooled data from the three trials showed that inclisiran was safe and well tolerated during 18 months and produced an average LDL-cholesterol reduction after 510 days (1.4 years) of about 51% compared to baseline after correction for placebo effects (J Am Coll Cardiol. 2021 Mar 9;77 [9]:1182-93).

These data showed inclisiran was about as safe and effective for reducing LDL-cholesterol as agents from another class of PCSK9 inhibitors that rely on injected antibodies to inactivate PCSK9. Two agents from this class, alirocumab (Praluent) and evolocumab (Repatha), both came on the U.S. market in 2015. Although their performance in routine practice during the ensuing 6-plus years has been as safe and effective as what they showed in their respective registration trials, they have faced a rocky uptake road that’s been primarily hindered by the hefty price tag that both drugs carry.
 

Prior-authorization blues

When they first came out, evolocumab and alirocumab were burdened by annual drug costs of roughly $14,000, a fact that led to widespread prior-authorization and copay barriers set up by U.S. insurers. Although these barriers gradually lessened over time, in part aided by a substantial price cut for both drugs that led to annual drug costs more in the range of $6,000/year, they remain relatively pricey and are still not easy to start in patients because of prior-authorization requirements, said clinicians.

Recent penetration of the older PCSK9 inhibitors into eligible U.S. patients “is only about 1%-2%, based on the latest data,” said Michael H. Davidson, MD, a lipid specialist and director of Preventive Cardiology at the University of Chicago.

“We have these great, effective drugs, but they haven’t really made an impact over the past 5 years,” because of very limited uptake, a situation Dr. Davidson called “very disappointing,” during an interview.

Given this recent history, inclisiran, another expensive PCSK9 inhibitor, may face similar coverage pushback as it hits the U.S. market with a retail price, announced by its manufacturer Novartis, of $3,250/dose. This means that patients who start the drug and receive their initial dose, a second dose after 3 months, and then additional doses every 6 months, rack up a drug cost of close to $10,000 the first year on the drug and $6,500 each subsequent year.

This treatment schedule highlights the major logistical difference that distinguishes inclisiran from the antibody-based PCSK9 inhibitors, which are given by repeated subcutaneous injection every 2 or 4 weeks, usually with patients self-injecting the drugs at home. The less-frequent dosing schedule for inclisiran prompted the drug’s developers to schedule injections by a clinician in an office setting in the pivotal trials, which led to labeling for inclisiran that specifies administration only by a health care professional.
 

The ‘buy-and-bill’ coverage model

This difference in drug administration between inclisiran and the antibody-based PCSK9 inhibitors set up Novartis to promote insurance reimbursement for inclisiran using a “buy-and-bill” paradigm that was first developed for oncology drugs and which may provide a loophole around the prior-authorization roadblocks that hindered early uptake of the antibody-based PCSK9 inhibitors.

It’s also an approach that has made U.S. clinicians unsure how it will play out in practice. Infrequent inclisiran dosing may also boost patient compliance.

“Adherence is the greatest challenge in preventive cardiology, and thus inclisiran has the potential to be a game changer,” commented Christie M. Ballantyne, MD, professor and chief of cardiology at Baylor College of Medicine, Houston.

“Will it be easier for physicians to write a prescription and for patients to get the medication without a demanding and frustrating prior-authorization process?” he wondered during an interview. “I’m waiting to see how this unfolds, especially in systems where pharmacy is not fully integrated with the outpatient setting. In some ways, this is as big of an experiment as was development of the drug,” Dr. Ballantyne said.

Although the prior-authorization hoops for evolocumab and alirocumab have become easier to jump through, “most physicians don’t have the resources to handle it and don’t bother,” noted Dr. Davidson, and he’s concerned that infrastructure challenges will also hamper the buy-and-bill strategy for inclisiran.

He also expressed skepticism that the prior-authorization barrier will disappear. “Payers don’t want to open a large population to a very expensive drug without some gatekeeping,” he said, while acknowledging that in late January 2022 he did not yet have personal experience administering inclisiran or navigating its insurance reimbursement.
 

Boosting patient compliance

Dr. Davidson agreed that the prospect for enhanced patient compliance with inclisiran was intriguing and had already drawn the interest of some of his patients.

“There is a lot of appeal” to a treatment that’s only given once every 6 months, he said. “Compliance is a major issue, and this is less work for patients.”

“The biggest possible attraction of inclisiran is that it is given twice a year, but whether this plays out as anticipated in the real world need to be seen,” cautioned Vijay Nambi, MD, a cardiologist at the Michael E. DeBakey VA Hospital, Houston, and at Baylor College of Medicine who has written about inclisiran. He noted that while two doses a year is “on paper very attractive,” this scheme opens the door to missed or delayed appointments because of vacations, other patient travel, or events like a pandemic.

“The biggest pro for inclisiran is the dosing schedule,” said Chandni Bardolia, PharmD, a drug information specialist at Tabula Rasa Healthcare, Moorestown, N.J., who has analyzed and written about inclisiran and other lipid-lowering medications. “Twice yearly dosing following initiation will be a huge benefit to improve adherence and reduce the number of injections.”

However, inclisiran’s attractive dosing schedule as well as its safety and potent efficacy do not tell the whole story, she highlighted in an interview.

Inclisiran’s clinical evidence still cooking

“I see inclisiran as a last-line drug, mainly because the current alternatives have more safety and efficacy data,” Dr. Bardolia said.

Inclisiran’s “cost and the fact that there are other agents with clinical outcome data already available [alirocumab and evolocumab] means inclisiran is not a first-line agent after statins,” agreed Dr. Nambi.

The FDA based its inclisiran approval entirely on the drug’s demonstrated safety and LDL-lowering efficacy. The cardiovascular outcomes trial for inclisiran, ORION-4, with about 15,000 enrolled patients, started in 2018 and remains in progress with full results expected in 2026.

The lack of clinical outcomes data for inclisiran is a major limitation, said Neil J. Stone, MD, a cardiologist and professor at Northwestern University, Chicago, and vice chair of the panel that wrote the most recent cholesterol guideline for the American College of Cardiology and American Heart Association.

“My greatest concern is the lack of outcome trial data. That’s very important,” Dr. Stone said in an interview.

But others minimize this limitation given the overwhelming evidence that links lower levels of LDL-cholesterol to reduced clinical events.

Most clinicians “support lower LDL as a surrogate” for reduced clinical events, “just like blood pressure and hemoglobin A1c,” noted Dr. Davidson, although he conceded that a “substantial minority wants to wait to see inclisiran’s outcome benefits.”
 

It’s all about price

While opinions are mixed on the need for clinical outcomes data, experts are more uniform in seeing drug prices that run to several thousands per year as the main uptake issue.

“We need to look at the cost-efficacy with inclisiran, and we need benefit data to determine this,” said Dr. Stone.

“Outcomes data are central to characterizing value. I imagine that costs will impact adoption and dissemination” of inclisiran, commented Paul L. Hess, MD, a cardiologist at the Rocky Mountain Regional VA Medical Center, Denver.

Patient interest in less frequent dosing will be important for driving use, but “ultimately cost will be the most important driving factor,” for inclisiran uptake, commented Robert H. Eckel, MD, an endocrinologist affiliated with the University of Colorado School of Medicine, Aurora.

Dr. Davidson has ties to New Amsterdam Pharma and Amgen, which markets evolocumab (Repatha). Dr. Ballantyne is a consultant to numerous companies, including Amgen and Regeneron, which market alirocumab (Praluent). Dr. Nambi has been a site investigator for studies sponsored by Amgen, and by Merck, which markets the LDL-cholesterol drug ezetimibe (Zetia) and is developing an oral PCSK9 inhibitor (he said that the views he expressed are his own and don’t represent that of the department of Veterans Affairs or Baylor.) Dr. Bardolia had no disclosures beyond her employment at Tabula Rasa Healthcare. Dr. Stone, Dr. Hess, and Dr. Eckel had no relevant disclosures.


 

The widely held notion that consuming small to moderate amounts of alcohol is good for cardiovascular health is not supported by the data, the World Heart Federation says in a new policy brief.

In fact, the evidence is clear that any level of drinking can contribute to loss of a healthy life, the organization says.

“Over the past several decades, the prevalence of cardiovascular disease has nearly doubled, and alcohol has played a major role in the incidence of much of it,” the WHF said in the brief.

“The portrayal of alcohol as necessary for a vibrant social life has diverted attention from the harms of alcohol use, as have the frequent and widely publicized claims that moderate drinking, such as a glass of red wine a day, can offer protection against cardiovascular disease,” Monika Arora, PhD, member of the WHF advocacy committee and coauthor of the brief, said in a news release.

“These claims are at best misinformed and at worst an attempt by the alcohol industry to mislead the public about the danger of their product,” Dr. Arora added.

The WHF conclusions follow a report in the Lancet based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), which found that there is no safe level of alcohol consumption.

In 2019, nearly 2.4 million deaths were attributed to alcohol, accounting for 4.3% of all deaths globally and 12.6% of deaths in men 15 to 49 years of age.

Even small amounts of alcohol have been shown to raise the risk for cardiovascular disease, including coronary disease, stroke, heart failure, hypertensive heart disease, cardiomyopathy, atrial fibrillation, and aneurysm, the WHF notes.

Studies that claim otherwise are largely based on purely observational research, which fails to account for relevant cofactors, the organization writes.

Based on their summary of the evidence to date, there is no reliable correlation between moderate alcohol consumption and a lower risk for cardiovascular disease.

Alcohol use is also a “major avoidable risk factor” for cancer, digestive diseases, intentional and unintentional injuries, and several infectious diseases, the WHF says.

Alcohol use also has significant economic and social costs, which include costs to individuals and health systems, productivity losses, as well as the increased risk for violence, homelessness, and criminal activity.

The WHF policy brief calls for “urgent and decisive action” to tackle the unprecedented rise in alcohol-related death and disability worldwide.

Recommended actions include boosting restrictions on alcohol availability; advancing and enforcing drinking and driving countermeasures; increasing access to screening, brief interventions, and treatment for alcohol use disorder; enforcing bans on alcohol advertising; establishing a uniform minimum legal drinking age; and mandating health warnings on alcohol products.

A version of this article first appeared on Medscape.com.

The widely held notion that consuming small to moderate amounts of alcohol is good for cardiovascular health is not supported by the data, the World Heart Federation says in a new policy brief.

In fact, the evidence is clear that any level of drinking can contribute to loss of a healthy life, the organization says.

“Over the past several decades, the prevalence of cardiovascular disease has nearly doubled, and alcohol has played a major role in the incidence of much of it,” the WHF said in the brief.

“The portrayal of alcohol as necessary for a vibrant social life has diverted attention from the harms of alcohol use, as have the frequent and widely publicized claims that moderate drinking, such as a glass of red wine a day, can offer protection against cardiovascular disease,” Monika Arora, PhD, member of the WHF advocacy committee and coauthor of the brief, said in a news release.

“These claims are at best misinformed and at worst an attempt by the alcohol industry to mislead the public about the danger of their product,” Dr. Arora added.

The WHF conclusions follow a report in the Lancet based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), which found that there is no safe level of alcohol consumption.

In 2019, nearly 2.4 million deaths were attributed to alcohol, accounting for 4.3% of all deaths globally and 12.6% of deaths in men 15 to 49 years of age.

Even small amounts of alcohol have been shown to raise the risk for cardiovascular disease, including coronary disease, stroke, heart failure, hypertensive heart disease, cardiomyopathy, atrial fibrillation, and aneurysm, the WHF notes.

Studies that claim otherwise are largely based on purely observational research, which fails to account for relevant cofactors, the organization writes.

Based on their summary of the evidence to date, there is no reliable correlation between moderate alcohol consumption and a lower risk for cardiovascular disease.

Alcohol use is also a “major avoidable risk factor” for cancer, digestive diseases, intentional and unintentional injuries, and several infectious diseases, the WHF says.

Alcohol use also has significant economic and social costs, which include costs to individuals and health systems, productivity losses, as well as the increased risk for violence, homelessness, and criminal activity.

The WHF policy brief calls for “urgent and decisive action” to tackle the unprecedented rise in alcohol-related death and disability worldwide.

Recommended actions include boosting restrictions on alcohol availability; advancing and enforcing drinking and driving countermeasures; increasing access to screening, brief interventions, and treatment for alcohol use disorder; enforcing bans on alcohol advertising; establishing a uniform minimum legal drinking age; and mandating health warnings on alcohol products.

A version of this article first appeared on Medscape.com.

The widely held notion that consuming small to moderate amounts of alcohol is good for cardiovascular health is not supported by the data, the World Heart Federation says in a new policy brief.

In fact, the evidence is clear that any level of drinking can contribute to loss of a healthy life, the organization says.

“Over the past several decades, the prevalence of cardiovascular disease has nearly doubled, and alcohol has played a major role in the incidence of much of it,” the WHF said in the brief.

“The portrayal of alcohol as necessary for a vibrant social life has diverted attention from the harms of alcohol use, as have the frequent and widely publicized claims that moderate drinking, such as a glass of red wine a day, can offer protection against cardiovascular disease,” Monika Arora, PhD, member of the WHF advocacy committee and coauthor of the brief, said in a news release.

“These claims are at best misinformed and at worst an attempt by the alcohol industry to mislead the public about the danger of their product,” Dr. Arora added.

The WHF conclusions follow a report in the Lancet based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), which found that there is no safe level of alcohol consumption.

In 2019, nearly 2.4 million deaths were attributed to alcohol, accounting for 4.3% of all deaths globally and 12.6% of deaths in men 15 to 49 years of age.

Even small amounts of alcohol have been shown to raise the risk for cardiovascular disease, including coronary disease, stroke, heart failure, hypertensive heart disease, cardiomyopathy, atrial fibrillation, and aneurysm, the WHF notes.

Studies that claim otherwise are largely based on purely observational research, which fails to account for relevant cofactors, the organization writes.

Based on their summary of the evidence to date, there is no reliable correlation between moderate alcohol consumption and a lower risk for cardiovascular disease.

Alcohol use is also a “major avoidable risk factor” for cancer, digestive diseases, intentional and unintentional injuries, and several infectious diseases, the WHF says.

Alcohol use also has significant economic and social costs, which include costs to individuals and health systems, productivity losses, as well as the increased risk for violence, homelessness, and criminal activity.

The WHF policy brief calls for “urgent and decisive action” to tackle the unprecedented rise in alcohol-related death and disability worldwide.

Recommended actions include boosting restrictions on alcohol availability; advancing and enforcing drinking and driving countermeasures; increasing access to screening, brief interventions, and treatment for alcohol use disorder; enforcing bans on alcohol advertising; establishing a uniform minimum legal drinking age; and mandating health warnings on alcohol products.

A version of this article first appeared on Medscape.com.

Creators of a pilot program that educates preschoolers about good heart health have validated a template for successful early childhood intervention that, they claim, provides a pathway for translating scientific evidence into the community and classroom for educational purposes to encourage long-lasting lifestyle changes.

That validation supports the creators' plans to take the program into more schools.

They reported key lessons in crafting the program, known as the SI! Program (for Salud Integral-Comprehensive Health), online in the Journal of the American College of Cardiology.

Mount Sinai Hospital

“This is a research-based program that uses randomized clinical trial evidence with implementation strategies to design educational health promotion programs,” senior author Valentin Fuster, MD, PhD, founder and trustees chairman of the Foundation for Science, Health, and Education (SHE) based in Barcelona, under whose aegis the SI! Program was implemented, said in an interview. Dr. Fuster is also director of Mount Sinai Heart and physician-in-chief at Mount Sinai Hospital in New York, and general director of the National Center for Cardiovascular Investigation (CNIC) in Madrid, Spain’s equivalent of the National Heart, Lung, and Blood Institute.

“There are specific times in a child’s life when improvements can be made to enhance long-term cardiovascular health status,” said Rodrigo Fernández-Jiménez, MD, PhD, group leader of the cardiovascular health and imaging lab at CNIC and study coauthor. “Our review, and previous studies, suggest that 4-5 years of age is the most favorable time to start a school-based intervention focused on healthy habits.”

A key piece of the SI! Program used a Sesame Street character, known as Dr. Ruster, a Muppet based on Dr. Fuster, to introduce and convey most messages and activities to the preschool children. The program also used a heart-shaped mascot named “Cardio” to teach about healthy behaviors. Other components include video segments, a colorful storybook, an interactive board game, flash cards, and a teacher’s guide. The activities and messages were tailored based on the country in which the program was implemented.
 

A decade of experience

The review evaluated 10 years of experience with the preschool-based program, drawing upon cluster-randomized clinical trials of the program in three countries with different socioeconomic conditions: Colombia, Spain, and the United States. The studies randomized schools to receive the SI! Program for 4 months or to a control group and included more than 3,800 children from 50 schools, along with their parents or caregivers and teachers. The studies found significant increases in preschoolers’ knowledge, attitudes, and habits toward healthy eating and living an active lifestyle. Now, the SI! Program is expanding into more than 250 schools in Spain and more than 40 schools in all five boroughs of New York City.

“This is a multidimensional program,” Dr. Fuster said. The review identified five stages for implementing the program: dissemination; adoption; implementation; evaluation; and institutionalization.

Dissemination involves three substages for intervention: components, design, and strategy. With regard to the components, said Dr. Fuster, “We’re targeting children to educate them in four topics: how the body works; nutritional and dietary requirements; physical activity; and the need to control emotions – to say no in the future when they’re confronted with alcohol, drugs, and tobacco.”

Design involved a multidisciplinary team of experts to develop the intervention, Dr. Fuster said. The strategy itself enlists parents and teachers in the implementation, but goes beyond that. “This is a community,” Dr. Fuster said. Hence, the school environment and classroom itself are also engaged to support the message of the four topics.

Dr. Fuster said future research should look at knowledge, attitude, and habits and biological outcomes in children who’ve been in the SI! Program when they reach adolescence. “Our hypothesis is that we can do this in older children, but when they reach age 10 we want to reintervene in them,” Dr. Fuster said. “Humans need reintervention. Our findings don’t get into sustainability.” He added that further research should also identify socioeconomic factors that influence child health.

Expanding the program across the New York City’s five boroughs “offers a unique opportunity to explore which socioeconomic factors, at both the family and borough level, and may eventually affect children’s health, how they are implicated in the intervention’s effectiveness, and how they can be addressed to reduce the gap in health inequalities,” he said. 

Karalyn Kinsella, MD, a pediatrician affiliated with Yale New Haven (Conn.) Medical Center, noted the program’s multidimensional nature is an important element. “I think what is so important about this intervention is that it is not one single intervention but a curriculum that takes a significant amount of time (up to 50 hours) that allows for repetition of the information, which allows it to become remembered,” she said in an interview. “I also think incorporating families in the intervention is key as that is where change often has to happen.”

While she said the program may provide a template for a mental health curriculum, she added, “My concern is that teachers are already feeling overwhelmed and this may be viewed as another burden.”

The American Heart Association provided funding for the study in the United States. Dr Fernández-Jiménez has received funding from the Fondo de Investigación Sanitaria–Instituto de Salud Carlos III, which is cofunded by the European Regional Development Fund/European Social Fund. Dr. Fuster and Dr. Kinsella have no relevant disclosures.

Creators of a pilot program that educates preschoolers about good heart health have validated a template for successful early childhood intervention that, they claim, provides a pathway for translating scientific evidence into the community and classroom for educational purposes to encourage long-lasting lifestyle changes.

That validation supports the creators' plans to take the program into more schools.

They reported key lessons in crafting the program, known as the SI! Program (for Salud Integral-Comprehensive Health), online in the Journal of the American College of Cardiology.

Mount Sinai Hospital

“This is a research-based program that uses randomized clinical trial evidence with implementation strategies to design educational health promotion programs,” senior author Valentin Fuster, MD, PhD, founder and trustees chairman of the Foundation for Science, Health, and Education (SHE) based in Barcelona, under whose aegis the SI! Program was implemented, said in an interview. Dr. Fuster is also director of Mount Sinai Heart and physician-in-chief at Mount Sinai Hospital in New York, and general director of the National Center for Cardiovascular Investigation (CNIC) in Madrid, Spain’s equivalent of the National Heart, Lung, and Blood Institute.

“There are specific times in a child’s life when improvements can be made to enhance long-term cardiovascular health status,” said Rodrigo Fernández-Jiménez, MD, PhD, group leader of the cardiovascular health and imaging lab at CNIC and study coauthor. “Our review, and previous studies, suggest that 4-5 years of age is the most favorable time to start a school-based intervention focused on healthy habits.”

A key piece of the SI! Program used a Sesame Street character, known as Dr. Ruster, a Muppet based on Dr. Fuster, to introduce and convey most messages and activities to the preschool children. The program also used a heart-shaped mascot named “Cardio” to teach about healthy behaviors. Other components include video segments, a colorful storybook, an interactive board game, flash cards, and a teacher’s guide. The activities and messages were tailored based on the country in which the program was implemented.
 

A decade of experience

The review evaluated 10 years of experience with the preschool-based program, drawing upon cluster-randomized clinical trials of the program in three countries with different socioeconomic conditions: Colombia, Spain, and the United States. The studies randomized schools to receive the SI! Program for 4 months or to a control group and included more than 3,800 children from 50 schools, along with their parents or caregivers and teachers. The studies found significant increases in preschoolers’ knowledge, attitudes, and habits toward healthy eating and living an active lifestyle. Now, the SI! Program is expanding into more than 250 schools in Spain and more than 40 schools in all five boroughs of New York City.

“This is a multidimensional program,” Dr. Fuster said. The review identified five stages for implementing the program: dissemination; adoption; implementation; evaluation; and institutionalization.

Dissemination involves three substages for intervention: components, design, and strategy. With regard to the components, said Dr. Fuster, “We’re targeting children to educate them in four topics: how the body works; nutritional and dietary requirements; physical activity; and the need to control emotions – to say no in the future when they’re confronted with alcohol, drugs, and tobacco.”

Design involved a multidisciplinary team of experts to develop the intervention, Dr. Fuster said. The strategy itself enlists parents and teachers in the implementation, but goes beyond that. “This is a community,” Dr. Fuster said. Hence, the school environment and classroom itself are also engaged to support the message of the four topics.

Dr. Fuster said future research should look at knowledge, attitude, and habits and biological outcomes in children who’ve been in the SI! Program when they reach adolescence. “Our hypothesis is that we can do this in older children, but when they reach age 10 we want to reintervene in them,” Dr. Fuster said. “Humans need reintervention. Our findings don’t get into sustainability.” He added that further research should also identify socioeconomic factors that influence child health.

Expanding the program across the New York City’s five boroughs “offers a unique opportunity to explore which socioeconomic factors, at both the family and borough level, and may eventually affect children’s health, how they are implicated in the intervention’s effectiveness, and how they can be addressed to reduce the gap in health inequalities,” he said. 

Karalyn Kinsella, MD, a pediatrician affiliated with Yale New Haven (Conn.) Medical Center, noted the program’s multidimensional nature is an important element. “I think what is so important about this intervention is that it is not one single intervention but a curriculum that takes a significant amount of time (up to 50 hours) that allows for repetition of the information, which allows it to become remembered,” she said in an interview. “I also think incorporating families in the intervention is key as that is where change often has to happen.”

While she said the program may provide a template for a mental health curriculum, she added, “My concern is that teachers are already feeling overwhelmed and this may be viewed as another burden.”

The American Heart Association provided funding for the study in the United States. Dr Fernández-Jiménez has received funding from the Fondo de Investigación Sanitaria–Instituto de Salud Carlos III, which is cofunded by the European Regional Development Fund/European Social Fund. Dr. Fuster and Dr. Kinsella have no relevant disclosures.

Creators of a pilot program that educates preschoolers about good heart health have validated a template for successful early childhood intervention that, they claim, provides a pathway for translating scientific evidence into the community and classroom for educational purposes to encourage long-lasting lifestyle changes.

That validation supports the creators' plans to take the program into more schools.

They reported key lessons in crafting the program, known as the SI! Program (for Salud Integral-Comprehensive Health), online in the Journal of the American College of Cardiology.

Mount Sinai Hospital

“This is a research-based program that uses randomized clinical trial evidence with implementation strategies to design educational health promotion programs,” senior author Valentin Fuster, MD, PhD, founder and trustees chairman of the Foundation for Science, Health, and Education (SHE) based in Barcelona, under whose aegis the SI! Program was implemented, said in an interview. Dr. Fuster is also director of Mount Sinai Heart and physician-in-chief at Mount Sinai Hospital in New York, and general director of the National Center for Cardiovascular Investigation (CNIC) in Madrid, Spain’s equivalent of the National Heart, Lung, and Blood Institute.

“There are specific times in a child’s life when improvements can be made to enhance long-term cardiovascular health status,” said Rodrigo Fernández-Jiménez, MD, PhD, group leader of the cardiovascular health and imaging lab at CNIC and study coauthor. “Our review, and previous studies, suggest that 4-5 years of age is the most favorable time to start a school-based intervention focused on healthy habits.”

A key piece of the SI! Program used a Sesame Street character, known as Dr. Ruster, a Muppet based on Dr. Fuster, to introduce and convey most messages and activities to the preschool children. The program also used a heart-shaped mascot named “Cardio” to teach about healthy behaviors. Other components include video segments, a colorful storybook, an interactive board game, flash cards, and a teacher’s guide. The activities and messages were tailored based on the country in which the program was implemented.
 

A decade of experience

The review evaluated 10 years of experience with the preschool-based program, drawing upon cluster-randomized clinical trials of the program in three countries with different socioeconomic conditions: Colombia, Spain, and the United States. The studies randomized schools to receive the SI! Program for 4 months or to a control group and included more than 3,800 children from 50 schools, along with their parents or caregivers and teachers. The studies found significant increases in preschoolers’ knowledge, attitudes, and habits toward healthy eating and living an active lifestyle. Now, the SI! Program is expanding into more than 250 schools in Spain and more than 40 schools in all five boroughs of New York City.

“This is a multidimensional program,” Dr. Fuster said. The review identified five stages for implementing the program: dissemination; adoption; implementation; evaluation; and institutionalization.

Dissemination involves three substages for intervention: components, design, and strategy. With regard to the components, said Dr. Fuster, “We’re targeting children to educate them in four topics: how the body works; nutritional and dietary requirements; physical activity; and the need to control emotions – to say no in the future when they’re confronted with alcohol, drugs, and tobacco.”

Design involved a multidisciplinary team of experts to develop the intervention, Dr. Fuster said. The strategy itself enlists parents and teachers in the implementation, but goes beyond that. “This is a community,” Dr. Fuster said. Hence, the school environment and classroom itself are also engaged to support the message of the four topics.

Dr. Fuster said future research should look at knowledge, attitude, and habits and biological outcomes in children who’ve been in the SI! Program when they reach adolescence. “Our hypothesis is that we can do this in older children, but when they reach age 10 we want to reintervene in them,” Dr. Fuster said. “Humans need reintervention. Our findings don’t get into sustainability.” He added that further research should also identify socioeconomic factors that influence child health.

Expanding the program across the New York City’s five boroughs “offers a unique opportunity to explore which socioeconomic factors, at both the family and borough level, and may eventually affect children’s health, how they are implicated in the intervention’s effectiveness, and how they can be addressed to reduce the gap in health inequalities,” he said. 

Karalyn Kinsella, MD, a pediatrician affiliated with Yale New Haven (Conn.) Medical Center, noted the program’s multidimensional nature is an important element. “I think what is so important about this intervention is that it is not one single intervention but a curriculum that takes a significant amount of time (up to 50 hours) that allows for repetition of the information, which allows it to become remembered,” she said in an interview. “I also think incorporating families in the intervention is key as that is where change often has to happen.”

While she said the program may provide a template for a mental health curriculum, she added, “My concern is that teachers are already feeling overwhelmed and this may be viewed as another burden.”

The American Heart Association provided funding for the study in the United States. Dr Fernández-Jiménez has received funding from the Fondo de Investigación Sanitaria–Instituto de Salud Carlos III, which is cofunded by the European Regional Development Fund/European Social Fund. Dr. Fuster and Dr. Kinsella have no relevant disclosures.

Therapeutic inertia regarding intensification of blood pressure treatment has been shown to be more of an issue in Black patients, but this was not the case in the SPRINT trial, which involved a strict standardized approach to blood pressure management, a new analysis shows.

Ingram Publishing/ThinkStock

“Overall, we found that therapeutic inertia was similar in different races in the SPRINT trial. We did not see disparities that have been reported in previous observational studies,” lead author, Alexander Zheutlin, MD, University of Utah School of Medicine, Salt Lake City, told this news organization.

“These results show that a well-resourced approach in which a standardized approach to blood pressure measurement and treatment intensification is followed can overcome the racial disparity that is seen in therapeutic inertia and the treatment of blood pressure,” he added.

The study was published online in JAMA Network Open on Jan. 10.

The authors explain that hypertension remains a leading modifiable cause of racial disparities in cardiovascular disease. Despite similar treatment rates and increased availability of safe, effective, and affordable antihypertensive medications, blood pressure control rates among Black and Hispanic adults remain significantly lower than among White adults in the United States, and one of the factors contributing to this is thought to be therapeutic inertia – the phenomenon of clinicians not initiating or up-titrating clinically indicated therapy in the setting of unmet treatment goals.

The current analysis of the SPRINT trial was conducted to investigate whether racial and ethnic differences in therapeutic inertia in hypertension were present when blood pressure care was standardized and protocolized.

The landmark SPRINT trial compared intensive (<120 mm Hg) with standard (<140 mm Hg) systolic blood pressure treatment goals in adults 50 years and older at high risk for cardiovascular disease. The present analysis was restricted to participant visits with measured blood pressure above the target goal and included 4,141 patients in the standard group and 4,415 patients in the intensive group.

Results showed that the overall prevalence of therapeutic inertia – defined as no antihypertensive medication intensification at each study visit where the blood pressure was above target goal – was either similar or lower for Black and Hispanic participants than for White participants. This pattern was observed whether participants were randomized to the standard or intensive treatment group.

“These findings support the idea that a standardized approach to blood pressure management, as implemented in SPRINT, may help ensure equitable care is provided to all patients and could reduce the contribution of therapeutic inertia to disparities in uncontrolled blood pressure,” the authors say.

They point out that therapeutic inertia has been identified as a key clinician-level barrier to blood pressure control and is estimated to be present in more than 80% of clinic visits in community practice, whereas in the current analysis of the SPRINT trial, therapeutic inertia was present in 50% to 60% of participant visits with uncontrolled blood pressure.

“In SPRINT, blood pressure had to be measured at defined intervals with a specific method, and there were clear instructions on intensifying treatment if blood pressure was above a certain goal,” Dr. Zheutlin noted. “Our results show that within such strict confines, therapeutic inertia does not seem to be different between different racial groups. This suggests that we could make better gains in blood pressure control and more equitable treatment if we adopted a standardized approach to hypertension management.”

He added: “Many guidelines have been published on when to start treatment and the targets for blood pressure, but there is a lot of variation in how we turn these guidelines into protocols. We need to bring in more consistent protocols on blood pressure measurement and intensification and ensure they are followed. In practice, if the BP is 5 or 10 mm Hg above target, a clinician may defer a decision to intensify treatment and intensification never gets done. But if there was a strict protocol to follow, there would be less chance of this happening.”
 

Therapeutic inertia still high

In an accompanying commentary, Matthew Rivara, MD, Nisha Bansal, MD, and Bessie Young, MD, University of Washington, Seattle, say the current SPRINT analysis has broad implications for reducing racial and ethnic disparities in achievement of evidence-based treatment targets in the general population.

“In hypertension management, standardized protocols for medication adjustments may limit clinician practice heterogeneity to ultimately reduce differences in blood pressure control among racial and ethnic minority populations,” they write. But they add that such protocols must be implemented thoughtfully to incorporate individualized clinical assessment and clinician-patient shared decision-making.

Dr. Rivara et al. point out that the rates of therapeutic inertia in SPRINT, while lower than community-based estimates, were still very high. They suggest reasons for this could include clinician concerns about medication efficacy, adverse effects, and patient mistrust of medical professionals. Outside the clinical trial environment, additional considerations may include prescription drug and laboratory test costs, pharmacy access, and competing demands during busy clinic visits.

To address these challenges, they say that clinicians need education on current clinical practice guidelines, managing complications of intensified antihypertensive therapies, and shared decisionmaking, including culturally sensitive collaborative care. Similarly, care systems must support patients on how to address concerns about treatments.

Finally, further research is needed to better define the specific factors associated with therapeutic inertia to allow tailored interventions to overcome this inertia.

“In designing and performing such research, it is vital that investigators engage with racial and ethnic minority groups to better explore the intersection of race, ethnicity, therapeutic decision-making, trust, and shared decisionmaking,” they add.

The SPRINT trial was funded with federal funds from the National Institutes of Health. Dr. Zheutlin reported receiving grants from the NIH during the conduct of the study.

A version of this article first appeared on Medscape.com.

Therapeutic inertia regarding intensification of blood pressure treatment has been shown to be more of an issue in Black patients, but this was not the case in the SPRINT trial, which involved a strict standardized approach to blood pressure management, a new analysis shows.

Ingram Publishing/ThinkStock

“Overall, we found that therapeutic inertia was similar in different races in the SPRINT trial. We did not see disparities that have been reported in previous observational studies,” lead author, Alexander Zheutlin, MD, University of Utah School of Medicine, Salt Lake City, told this news organization.

“These results show that a well-resourced approach in which a standardized approach to blood pressure measurement and treatment intensification is followed can overcome the racial disparity that is seen in therapeutic inertia and the treatment of blood pressure,” he added.

The study was published online in JAMA Network Open on Jan. 10.

The authors explain that hypertension remains a leading modifiable cause of racial disparities in cardiovascular disease. Despite similar treatment rates and increased availability of safe, effective, and affordable antihypertensive medications, blood pressure control rates among Black and Hispanic adults remain significantly lower than among White adults in the United States, and one of the factors contributing to this is thought to be therapeutic inertia – the phenomenon of clinicians not initiating or up-titrating clinically indicated therapy in the setting of unmet treatment goals.

The current analysis of the SPRINT trial was conducted to investigate whether racial and ethnic differences in therapeutic inertia in hypertension were present when blood pressure care was standardized and protocolized.

The landmark SPRINT trial compared intensive (<120 mm Hg) with standard (<140 mm Hg) systolic blood pressure treatment goals in adults 50 years and older at high risk for cardiovascular disease. The present analysis was restricted to participant visits with measured blood pressure above the target goal and included 4,141 patients in the standard group and 4,415 patients in the intensive group.

Results showed that the overall prevalence of therapeutic inertia – defined as no antihypertensive medication intensification at each study visit where the blood pressure was above target goal – was either similar or lower for Black and Hispanic participants than for White participants. This pattern was observed whether participants were randomized to the standard or intensive treatment group.

“These findings support the idea that a standardized approach to blood pressure management, as implemented in SPRINT, may help ensure equitable care is provided to all patients and could reduce the contribution of therapeutic inertia to disparities in uncontrolled blood pressure,” the authors say.

They point out that therapeutic inertia has been identified as a key clinician-level barrier to blood pressure control and is estimated to be present in more than 80% of clinic visits in community practice, whereas in the current analysis of the SPRINT trial, therapeutic inertia was present in 50% to 60% of participant visits with uncontrolled blood pressure.

“In SPRINT, blood pressure had to be measured at defined intervals with a specific method, and there were clear instructions on intensifying treatment if blood pressure was above a certain goal,” Dr. Zheutlin noted. “Our results show that within such strict confines, therapeutic inertia does not seem to be different between different racial groups. This suggests that we could make better gains in blood pressure control and more equitable treatment if we adopted a standardized approach to hypertension management.”

He added: “Many guidelines have been published on when to start treatment and the targets for blood pressure, but there is a lot of variation in how we turn these guidelines into protocols. We need to bring in more consistent protocols on blood pressure measurement and intensification and ensure they are followed. In practice, if the BP is 5 or 10 mm Hg above target, a clinician may defer a decision to intensify treatment and intensification never gets done. But if there was a strict protocol to follow, there would be less chance of this happening.”
 

Therapeutic inertia still high

In an accompanying commentary, Matthew Rivara, MD, Nisha Bansal, MD, and Bessie Young, MD, University of Washington, Seattle, say the current SPRINT analysis has broad implications for reducing racial and ethnic disparities in achievement of evidence-based treatment targets in the general population.

“In hypertension management, standardized protocols for medication adjustments may limit clinician practice heterogeneity to ultimately reduce differences in blood pressure control among racial and ethnic minority populations,” they write. But they add that such protocols must be implemented thoughtfully to incorporate individualized clinical assessment and clinician-patient shared decision-making.

Dr. Rivara et al. point out that the rates of therapeutic inertia in SPRINT, while lower than community-based estimates, were still very high. They suggest reasons for this could include clinician concerns about medication efficacy, adverse effects, and patient mistrust of medical professionals. Outside the clinical trial environment, additional considerations may include prescription drug and laboratory test costs, pharmacy access, and competing demands during busy clinic visits.

To address these challenges, they say that clinicians need education on current clinical practice guidelines, managing complications of intensified antihypertensive therapies, and shared decisionmaking, including culturally sensitive collaborative care. Similarly, care systems must support patients on how to address concerns about treatments.

Finally, further research is needed to better define the specific factors associated with therapeutic inertia to allow tailored interventions to overcome this inertia.

“In designing and performing such research, it is vital that investigators engage with racial and ethnic minority groups to better explore the intersection of race, ethnicity, therapeutic decision-making, trust, and shared decisionmaking,” they add.

The SPRINT trial was funded with federal funds from the National Institutes of Health. Dr. Zheutlin reported receiving grants from the NIH during the conduct of the study.

A version of this article first appeared on Medscape.com.

Therapeutic inertia regarding intensification of blood pressure treatment has been shown to be more of an issue in Black patients, but this was not the case in the SPRINT trial, which involved a strict standardized approach to blood pressure management, a new analysis shows.

Ingram Publishing/ThinkStock

“Overall, we found that therapeutic inertia was similar in different races in the SPRINT trial. We did not see disparities that have been reported in previous observational studies,” lead author, Alexander Zheutlin, MD, University of Utah School of Medicine, Salt Lake City, told this news organization.

“These results show that a well-resourced approach in which a standardized approach to blood pressure measurement and treatment intensification is followed can overcome the racial disparity that is seen in therapeutic inertia and the treatment of blood pressure,” he added.

The study was published online in JAMA Network Open on Jan. 10.

The authors explain that hypertension remains a leading modifiable cause of racial disparities in cardiovascular disease. Despite similar treatment rates and increased availability of safe, effective, and affordable antihypertensive medications, blood pressure control rates among Black and Hispanic adults remain significantly lower than among White adults in the United States, and one of the factors contributing to this is thought to be therapeutic inertia – the phenomenon of clinicians not initiating or up-titrating clinically indicated therapy in the setting of unmet treatment goals.

The current analysis of the SPRINT trial was conducted to investigate whether racial and ethnic differences in therapeutic inertia in hypertension were present when blood pressure care was standardized and protocolized.

The landmark SPRINT trial compared intensive (<120 mm Hg) with standard (<140 mm Hg) systolic blood pressure treatment goals in adults 50 years and older at high risk for cardiovascular disease. The present analysis was restricted to participant visits with measured blood pressure above the target goal and included 4,141 patients in the standard group and 4,415 patients in the intensive group.

Results showed that the overall prevalence of therapeutic inertia – defined as no antihypertensive medication intensification at each study visit where the blood pressure was above target goal – was either similar or lower for Black and Hispanic participants than for White participants. This pattern was observed whether participants were randomized to the standard or intensive treatment group.

“These findings support the idea that a standardized approach to blood pressure management, as implemented in SPRINT, may help ensure equitable care is provided to all patients and could reduce the contribution of therapeutic inertia to disparities in uncontrolled blood pressure,” the authors say.

They point out that therapeutic inertia has been identified as a key clinician-level barrier to blood pressure control and is estimated to be present in more than 80% of clinic visits in community practice, whereas in the current analysis of the SPRINT trial, therapeutic inertia was present in 50% to 60% of participant visits with uncontrolled blood pressure.

“In SPRINT, blood pressure had to be measured at defined intervals with a specific method, and there were clear instructions on intensifying treatment if blood pressure was above a certain goal,” Dr. Zheutlin noted. “Our results show that within such strict confines, therapeutic inertia does not seem to be different between different racial groups. This suggests that we could make better gains in blood pressure control and more equitable treatment if we adopted a standardized approach to hypertension management.”

He added: “Many guidelines have been published on when to start treatment and the targets for blood pressure, but there is a lot of variation in how we turn these guidelines into protocols. We need to bring in more consistent protocols on blood pressure measurement and intensification and ensure they are followed. In practice, if the BP is 5 or 10 mm Hg above target, a clinician may defer a decision to intensify treatment and intensification never gets done. But if there was a strict protocol to follow, there would be less chance of this happening.”
 

Therapeutic inertia still high

In an accompanying commentary, Matthew Rivara, MD, Nisha Bansal, MD, and Bessie Young, MD, University of Washington, Seattle, say the current SPRINT analysis has broad implications for reducing racial and ethnic disparities in achievement of evidence-based treatment targets in the general population.

“In hypertension management, standardized protocols for medication adjustments may limit clinician practice heterogeneity to ultimately reduce differences in blood pressure control among racial and ethnic minority populations,” they write. But they add that such protocols must be implemented thoughtfully to incorporate individualized clinical assessment and clinician-patient shared decision-making.

Dr. Rivara et al. point out that the rates of therapeutic inertia in SPRINT, while lower than community-based estimates, were still very high. They suggest reasons for this could include clinician concerns about medication efficacy, adverse effects, and patient mistrust of medical professionals. Outside the clinical trial environment, additional considerations may include prescription drug and laboratory test costs, pharmacy access, and competing demands during busy clinic visits.

To address these challenges, they say that clinicians need education on current clinical practice guidelines, managing complications of intensified antihypertensive therapies, and shared decisionmaking, including culturally sensitive collaborative care. Similarly, care systems must support patients on how to address concerns about treatments.

Finally, further research is needed to better define the specific factors associated with therapeutic inertia to allow tailored interventions to overcome this inertia.

“In designing and performing such research, it is vital that investigators engage with racial and ethnic minority groups to better explore the intersection of race, ethnicity, therapeutic decision-making, trust, and shared decisionmaking,” they add.

The SPRINT trial was funded with federal funds from the National Institutes of Health. Dr. Zheutlin reported receiving grants from the NIH during the conduct of the study.

A version of this article first appeared on Medscape.com.

A new document from the American Heart Association summarizes the latest research on cardiovascular risk factor management in type 2 diabetes, including medications, lifestyle, and social determinants of health.

Despite the availability of effective therapies for improving cardiovascular risk, in the United States fewer than one in five people with type 2 diabetes and without known cardiovascular disease meet control targets for a combination of A1c, blood pressure, LDL cholesterol, and nonsmoking status.

Volkan Ünalan/Thinkstock

That proportion drops to less than 1 in 10 if body mass index less than 30 kg/m² is included among the targets, and even less than that among individuals with established atherosclerotic cardiovascular disease, Joshua J. Joseph, MD, and colleagues point out in their paper, published online Jan. 10 in Circulation.

“This new scientific statement is an urgent call to action to follow the latest evidence-based approaches and to develop new best practices to advance type 2 diabetes treatment and care and reduce cardiovascular disease risk,” wrote Dr. Joseph, assistant professor of medicine in the division of endocrinology, diabetes, and metabolism at The Ohio State University, Columbus, Ohio, and coauthors.

The statement is not a guideline but an expert analysis that may inform future clinical practice guidelines, according to a press release from the AHA.

The new statement reviews evidence through June 2020 for lifestyle management of diabetes and weight, glycemic targets and control, blood pressure management, lipid management, antithrombotic therapy, and screening for cardiovascular and renal complications, including imaging. It also discusses the clinical implications of recent cardiovascular outcomes trials of newer glucose-lowering medications.

However, Dr. Joseph and colleagues point out, clinical care and treatment account for just 10%-20% of modifiable contributors to health outcomes. The other 80%-90% relate to social determinants of health, including health-related behaviors, socioeconomic factors, environmental factors, and racism.

“If we are to continue to advance the management of cardiovascular risk factors, we must also address the [social determinants of health] in the delivery of health care,” they noted.

Overall, they advise a patient-centered approach, meaning “reframing our clinical encounters to think about patients as people who live in families, communities, and societies that must be considered in their cardiovascular risk management.”

“People with [type 2 diabetes] face numerous barriers to health including access to care and equitable care, which must be considered when developing individualized care plans with our patients,” Dr. Joseph said in the AHA press release.
 

Lifestyle, medications for lowering A1c, BP, lipids

For lifestyle management, the authors say, “culturally appropriate recommendations through diabetes self-management education and support and medical nutrition therapy are key to meeting individualized goals for behavioral change and diabetes self-management.”

The document summarizes recommendations from other professional societies regarding glycemic targets and glucose lowering medications, i.e., target A1c levels of either < 7% or < 6.5% for the majority, with adjustments based on individual factors, such as life expectancy. It advises on use of metformin as first-line therapy followed by a sodium-glucose cotransporter-2 inhibitor or a glucagon-like peptide-1 agonist for those with established cardiovascular disease or risk factors.

“Cost may be a barrier to taking some [type 2 diabetes] medications as prescribed; however, many of these medications are now more commonly covered by more health insurance plans,” Dr. Joseph said.

“Another barrier is recognition by patients that these newer [type 2 diabetes] medications are also effective in reducing the risk of heart disease, stroke, heart failure, and kidney disease.”

Blood pressure treatment guidelines differ between those of the AHA/American College of Cardiology (ACC) and the American Diabetes Association (ADA), most notably that the AHA/ACC guidelines advise a general target of < 130/80 mm Hg, whereas ADA advises < 140/90 mm Hg or < 130/80 mm Hg for those with high risk if it can be safely achieved.

The decision should be “patient-centered with shared decision-making,” Dr. Joseph and colleagues advised.

For lipid-lowering, the document cites the 2018 ACC/AHA cholesterol guidelines, which include advising statins as first-line therapy for both primary and secondary prevention in diabetes, with highest intensity statins used in those at highest risk. But again, treatment should be individualized, and other agents should be used for patients in whom statins don’t work or aren’t tolerated.

And while use of antiplatelets – that is, aspirin – is well established as secondary prevention in type 2 diabetes, given new data suggesting that the risk for major bleeding could outweigh the benefits for primary prevention, “the relative benefits of antithrombotic approaches need to be weighed carefully against risks using a patient-centered approach,” the authors advised.

Among the many imaging tests available to facilitate cardiovascular risk stratification in type 2 diabetes, coronary artery calcification (CAC) CT screening is one of the few with sufficient data to support routine use in selected patients. The National Lipid Association, for example, recommends escalation to high-intensity statin for CAC > 100.

“One avenue to continue to address and advance diabetes management is through breaking down the four walls of the clinic or hospital through community engagement, clinic-to-community connections, and academic-community-government partnerships that may help address and support modifiable lifestyle behaviors such as physical activity, nutrition, smoking cessation and stress management,” Dr. Joseph concluded.

The AHA receives funding primarily from individuals. Foundations and corporations, including pharmaceutical, device manufacturers, and other companies, also make donations and fund AHA programs and events. The AHA’s strict policies prevent these relationships from influencing the science content. Revenues from pharmaceutical and biotech companies, device manufacturers, and health insurance providers and the AHA’s financial information are available on the association’s website. Dr. Joseph has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new document from the American Heart Association summarizes the latest research on cardiovascular risk factor management in type 2 diabetes, including medications, lifestyle, and social determinants of health.

Despite the availability of effective therapies for improving cardiovascular risk, in the United States fewer than one in five people with type 2 diabetes and without known cardiovascular disease meet control targets for a combination of A1c, blood pressure, LDL cholesterol, and nonsmoking status.

Volkan Ünalan/Thinkstock

That proportion drops to less than 1 in 10 if body mass index less than 30 kg/m² is included among the targets, and even less than that among individuals with established atherosclerotic cardiovascular disease, Joshua J. Joseph, MD, and colleagues point out in their paper, published online Jan. 10 in Circulation.

“This new scientific statement is an urgent call to action to follow the latest evidence-based approaches and to develop new best practices to advance type 2 diabetes treatment and care and reduce cardiovascular disease risk,” wrote Dr. Joseph, assistant professor of medicine in the division of endocrinology, diabetes, and metabolism at The Ohio State University, Columbus, Ohio, and coauthors.

The statement is not a guideline but an expert analysis that may inform future clinical practice guidelines, according to a press release from the AHA.

The new statement reviews evidence through June 2020 for lifestyle management of diabetes and weight, glycemic targets and control, blood pressure management, lipid management, antithrombotic therapy, and screening for cardiovascular and renal complications, including imaging. It also discusses the clinical implications of recent cardiovascular outcomes trials of newer glucose-lowering medications.

However, Dr. Joseph and colleagues point out, clinical care and treatment account for just 10%-20% of modifiable contributors to health outcomes. The other 80%-90% relate to social determinants of health, including health-related behaviors, socioeconomic factors, environmental factors, and racism.

“If we are to continue to advance the management of cardiovascular risk factors, we must also address the [social determinants of health] in the delivery of health care,” they noted.

Overall, they advise a patient-centered approach, meaning “reframing our clinical encounters to think about patients as people who live in families, communities, and societies that must be considered in their cardiovascular risk management.”

“People with [type 2 diabetes] face numerous barriers to health including access to care and equitable care, which must be considered when developing individualized care plans with our patients,” Dr. Joseph said in the AHA press release.
 

Lifestyle, medications for lowering A1c, BP, lipids

For lifestyle management, the authors say, “culturally appropriate recommendations through diabetes self-management education and support and medical nutrition therapy are key to meeting individualized goals for behavioral change and diabetes self-management.”

The document summarizes recommendations from other professional societies regarding glycemic targets and glucose lowering medications, i.e., target A1c levels of either < 7% or < 6.5% for the majority, with adjustments based on individual factors, such as life expectancy. It advises on use of metformin as first-line therapy followed by a sodium-glucose cotransporter-2 inhibitor or a glucagon-like peptide-1 agonist for those with established cardiovascular disease or risk factors.

“Cost may be a barrier to taking some [type 2 diabetes] medications as prescribed; however, many of these medications are now more commonly covered by more health insurance plans,” Dr. Joseph said.

“Another barrier is recognition by patients that these newer [type 2 diabetes] medications are also effective in reducing the risk of heart disease, stroke, heart failure, and kidney disease.”

Blood pressure treatment guidelines differ between those of the AHA/American College of Cardiology (ACC) and the American Diabetes Association (ADA), most notably that the AHA/ACC guidelines advise a general target of < 130/80 mm Hg, whereas ADA advises < 140/90 mm Hg or < 130/80 mm Hg for those with high risk if it can be safely achieved.

The decision should be “patient-centered with shared decision-making,” Dr. Joseph and colleagues advised.

For lipid-lowering, the document cites the 2018 ACC/AHA cholesterol guidelines, which include advising statins as first-line therapy for both primary and secondary prevention in diabetes, with highest intensity statins used in those at highest risk. But again, treatment should be individualized, and other agents should be used for patients in whom statins don’t work or aren’t tolerated.

And while use of antiplatelets – that is, aspirin – is well established as secondary prevention in type 2 diabetes, given new data suggesting that the risk for major bleeding could outweigh the benefits for primary prevention, “the relative benefits of antithrombotic approaches need to be weighed carefully against risks using a patient-centered approach,” the authors advised.

Among the many imaging tests available to facilitate cardiovascular risk stratification in type 2 diabetes, coronary artery calcification (CAC) CT screening is one of the few with sufficient data to support routine use in selected patients. The National Lipid Association, for example, recommends escalation to high-intensity statin for CAC > 100.

“One avenue to continue to address and advance diabetes management is through breaking down the four walls of the clinic or hospital through community engagement, clinic-to-community connections, and academic-community-government partnerships that may help address and support modifiable lifestyle behaviors such as physical activity, nutrition, smoking cessation and stress management,” Dr. Joseph concluded.

The AHA receives funding primarily from individuals. Foundations and corporations, including pharmaceutical, device manufacturers, and other companies, also make donations and fund AHA programs and events. The AHA’s strict policies prevent these relationships from influencing the science content. Revenues from pharmaceutical and biotech companies, device manufacturers, and health insurance providers and the AHA’s financial information are available on the association’s website. Dr. Joseph has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new document from the American Heart Association summarizes the latest research on cardiovascular risk factor management in type 2 diabetes, including medications, lifestyle, and social determinants of health.

Despite the availability of effective therapies for improving cardiovascular risk, in the United States fewer than one in five people with type 2 diabetes and without known cardiovascular disease meet control targets for a combination of A1c, blood pressure, LDL cholesterol, and nonsmoking status.

Volkan Ünalan/Thinkstock

That proportion drops to less than 1 in 10 if body mass index less than 30 kg/m² is included among the targets, and even less than that among individuals with established atherosclerotic cardiovascular disease, Joshua J. Joseph, MD, and colleagues point out in their paper, published online Jan. 10 in Circulation.

“This new scientific statement is an urgent call to action to follow the latest evidence-based approaches and to develop new best practices to advance type 2 diabetes treatment and care and reduce cardiovascular disease risk,” wrote Dr. Joseph, assistant professor of medicine in the division of endocrinology, diabetes, and metabolism at The Ohio State University, Columbus, Ohio, and coauthors.

The statement is not a guideline but an expert analysis that may inform future clinical practice guidelines, according to a press release from the AHA.

The new statement reviews evidence through June 2020 for lifestyle management of diabetes and weight, glycemic targets and control, blood pressure management, lipid management, antithrombotic therapy, and screening for cardiovascular and renal complications, including imaging. It also discusses the clinical implications of recent cardiovascular outcomes trials of newer glucose-lowering medications.

However, Dr. Joseph and colleagues point out, clinical care and treatment account for just 10%-20% of modifiable contributors to health outcomes. The other 80%-90% relate to social determinants of health, including health-related behaviors, socioeconomic factors, environmental factors, and racism.

“If we are to continue to advance the management of cardiovascular risk factors, we must also address the [social determinants of health] in the delivery of health care,” they noted.

Overall, they advise a patient-centered approach, meaning “reframing our clinical encounters to think about patients as people who live in families, communities, and societies that must be considered in their cardiovascular risk management.”

“People with [type 2 diabetes] face numerous barriers to health including access to care and equitable care, which must be considered when developing individualized care plans with our patients,” Dr. Joseph said in the AHA press release.
 

Lifestyle, medications for lowering A1c, BP, lipids

For lifestyle management, the authors say, “culturally appropriate recommendations through diabetes self-management education and support and medical nutrition therapy are key to meeting individualized goals for behavioral change and diabetes self-management.”

The document summarizes recommendations from other professional societies regarding glycemic targets and glucose lowering medications, i.e., target A1c levels of either < 7% or < 6.5% for the majority, with adjustments based on individual factors, such as life expectancy. It advises on use of metformin as first-line therapy followed by a sodium-glucose cotransporter-2 inhibitor or a glucagon-like peptide-1 agonist for those with established cardiovascular disease or risk factors.

“Cost may be a barrier to taking some [type 2 diabetes] medications as prescribed; however, many of these medications are now more commonly covered by more health insurance plans,” Dr. Joseph said.

“Another barrier is recognition by patients that these newer [type 2 diabetes] medications are also effective in reducing the risk of heart disease, stroke, heart failure, and kidney disease.”

Blood pressure treatment guidelines differ between those of the AHA/American College of Cardiology (ACC) and the American Diabetes Association (ADA), most notably that the AHA/ACC guidelines advise a general target of < 130/80 mm Hg, whereas ADA advises < 140/90 mm Hg or < 130/80 mm Hg for those with high risk if it can be safely achieved.

The decision should be “patient-centered with shared decision-making,” Dr. Joseph and colleagues advised.

For lipid-lowering, the document cites the 2018 ACC/AHA cholesterol guidelines, which include advising statins as first-line therapy for both primary and secondary prevention in diabetes, with highest intensity statins used in those at highest risk. But again, treatment should be individualized, and other agents should be used for patients in whom statins don’t work or aren’t tolerated.

And while use of antiplatelets – that is, aspirin – is well established as secondary prevention in type 2 diabetes, given new data suggesting that the risk for major bleeding could outweigh the benefits for primary prevention, “the relative benefits of antithrombotic approaches need to be weighed carefully against risks using a patient-centered approach,” the authors advised.

Among the many imaging tests available to facilitate cardiovascular risk stratification in type 2 diabetes, coronary artery calcification (CAC) CT screening is one of the few with sufficient data to support routine use in selected patients. The National Lipid Association, for example, recommends escalation to high-intensity statin for CAC > 100.

“One avenue to continue to address and advance diabetes management is through breaking down the four walls of the clinic or hospital through community engagement, clinic-to-community connections, and academic-community-government partnerships that may help address and support modifiable lifestyle behaviors such as physical activity, nutrition, smoking cessation and stress management,” Dr. Joseph concluded.

The AHA receives funding primarily from individuals. Foundations and corporations, including pharmaceutical, device manufacturers, and other companies, also make donations and fund AHA programs and events. The AHA’s strict policies prevent these relationships from influencing the science content. Revenues from pharmaceutical and biotech companies, device manufacturers, and health insurance providers and the AHA’s financial information are available on the association’s website. Dr. Joseph has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity. The transcript and an accompanying video first appeared on Medscape.com.

Justin L. Berk, MD, MPH, MBA: Welcome back to The Cribsiders, our video recap of our pediatric medicine podcast. We interview leading experts in the field to bring clinical pearls and practice-changing knowledge, and answer lingering questions about core topics in pediatric medicine. Chris, what is our topic today?

Christopher J. Chiu, MD: I was really happy to be able to talk about our recent episode with Dr. Carissa Baker-Smith, a pediatric cardiologist and director of the Nemours preventive cardiology program. She helped us review the pediatric screening guidelines for blood pressure, including initial workup and treatment.

Dr. Berk: This was a really great episode that a lot of people found really helpful. What were some of the key takeaway pearls that you think listeners would be interested in?

Dr. Chiu: We talked about when and how we should be checking blood pressures in children. Blood pressure should be checked at every well-child visit starting at age 3. But if they have other risk factors like kidney disease or a condition such as coarctation of the aorta, then blood pressure should be checked at every visit.

Dr. Berk: One thing she spoke about was how blood pressures should be measured. How should we be checking blood pressures in the clinic?

Dr. Chiu: Clinic blood pressures are usually checked with oscillometric devices. They can differ by manufacturer, but basically they find a mean arterial pressure and then each device has a method of calculating systolic and diastolic pressures. Now after that, if the child’s blood pressure is maybe abnormal, you want to double-check a manual blood pressure using Korotkoff sounds to confirm the blood pressure.

She reminded us that blood pressure should be measured with the child sitting with their back supported, feet flat on the floor, and arm at the level of the heart. Make sure you use the right size cuff. The bladder of the cuff should be 40% of the width of the arm, and about 80%-100% of the arm circumference. She recommends sizing up if you have to.

Dr. Berk: Accuracy of blood pressure management was a really important point, especially for diagnosis at this stage. Can you walk us through what we learned about diagnosis of hypertension?

Dr. Chiu: The definitions of hypertension come from the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents. Up until the age of 13, they define prehypertension as systolic and diastolic blood pressures between the 90th and 95th percentile, or if the blood pressure exceeds 120/80 mm Hg. Hypertension is defined when blood pressure reaches the 95th percentile. Now age 13 is when it gets a little hazy. Many changes in the guidelines happen at age 13, when hypertension starts being defined by adult guidelines. The 2017 adult hypertension guidelines define stage 1 hypertension as 130/89 to 139/89, and stage 2 hypertension as greater than 140/90.

Dr. Berk: How about workup of hypertension? The work of pediatric hypertension is always a little bit complex. What are some of the pearls you took away?

Dr. Chui: She talked about tailoring the workup to the child. So when we’re doing our workup, obviously physical exam should be the first thing we do. You have to assess and compare pulses, which is one of the most important parts of the initial evaluation. Obviously, looking at coarctation of the aorta, but also looking for things like a cushingoid appearance. If the child is less than 6 years of age, she recommends a referral to nephrology for more comprehensive renovascular workup, which probably will include renal ultrasound, urinalysis, metabolic panel, and thyroid studies.

We have to be cognizant of secondary causes of hypertension, such as endocrine tumors, hyperthyroidism, aortic disease, or even medication-induced hypertension. She told us that in the majority of these cases, especially with our obese older children, primary hypertension or essential hypertension is the most likely cause.

Dr. Berk: That was my big takeaway. If they’re really young, they need a big workup, but otherwise it is likely primary hypertension. What did we learn about treatment?

Dr. Chui: Just as we tailor our assessment to the child, we also have to tailor treatment. We know that lifestyle modification is usually the first line of treatment, especially for primary hypertension, and Dr. Baker-Smith tells us that we really need to perform counseling that meets the patient where they are. So if they like dancing to the newest TikTok trends or music videos, maybe we can encourage them to move more that way. Using our motivational interviewing skills is really key here.

If you want to start medication, Dr. Baker-Smith uses things like low-dose ACE inhibitors or calcium channel blockers, but obviously it’ll be tailored to the patient and any underlying conditions.

Dr. Berk: That’s great – a lot of wonderful pearls on the diagnosis and management of pediatric hypertension. Thank you for joining us for another video recap of The Cribsiders pediatric podcast. You can download the full podcast, Off the Cuff: Managing Pediatric Hypertension in Your Primary Care Clinic, on any podcast player, or check out our website at www.theCribsiders.com.

Christopher J. Chiu, MD, is assistant professor, department of internal medicine, division of general internal medicine, Ohio State University, Columbus; lead physician, general internal medicine, OSU Outpatient Care East; department of internal medicine, division of general internal medicine, Ohio State University Wexner Medical Center. Dr. Chiu has disclosed no relevant financial relationships. Justin L. Berk, MD, MPH, MBA, is assistant professor, department of medicine; assistant professor, department of pediatrics, Brown University, Providence, R.I.

This transcript has been edited for clarity. The transcript and an accompanying video first appeared on Medscape.com.

Justin L. Berk, MD, MPH, MBA: Welcome back to The Cribsiders, our video recap of our pediatric medicine podcast. We interview leading experts in the field to bring clinical pearls and practice-changing knowledge, and answer lingering questions about core topics in pediatric medicine. Chris, what is our topic today?

Christopher J. Chiu, MD: I was really happy to be able to talk about our recent episode with Dr. Carissa Baker-Smith, a pediatric cardiologist and director of the Nemours preventive cardiology program. She helped us review the pediatric screening guidelines for blood pressure, including initial workup and treatment.

Dr. Berk: This was a really great episode that a lot of people found really helpful. What were some of the key takeaway pearls that you think listeners would be interested in?

Dr. Chiu: We talked about when and how we should be checking blood pressures in children. Blood pressure should be checked at every well-child visit starting at age 3. But if they have other risk factors like kidney disease or a condition such as coarctation of the aorta, then blood pressure should be checked at every visit.

Dr. Berk: One thing she spoke about was how blood pressures should be measured. How should we be checking blood pressures in the clinic?

Dr. Chiu: Clinic blood pressures are usually checked with oscillometric devices. They can differ by manufacturer, but basically they find a mean arterial pressure and then each device has a method of calculating systolic and diastolic pressures. Now after that, if the child’s blood pressure is maybe abnormal, you want to double-check a manual blood pressure using Korotkoff sounds to confirm the blood pressure.

She reminded us that blood pressure should be measured with the child sitting with their back supported, feet flat on the floor, and arm at the level of the heart. Make sure you use the right size cuff. The bladder of the cuff should be 40% of the width of the arm, and about 80%-100% of the arm circumference. She recommends sizing up if you have to.

Dr. Berk: Accuracy of blood pressure management was a really important point, especially for diagnosis at this stage. Can you walk us through what we learned about diagnosis of hypertension?

Dr. Chiu: The definitions of hypertension come from the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents. Up until the age of 13, they define prehypertension as systolic and diastolic blood pressures between the 90th and 95th percentile, or if the blood pressure exceeds 120/80 mm Hg. Hypertension is defined when blood pressure reaches the 95th percentile. Now age 13 is when it gets a little hazy. Many changes in the guidelines happen at age 13, when hypertension starts being defined by adult guidelines. The 2017 adult hypertension guidelines define stage 1 hypertension as 130/89 to 139/89, and stage 2 hypertension as greater than 140/90.

Dr. Berk: How about workup of hypertension? The work of pediatric hypertension is always a little bit complex. What are some of the pearls you took away?

Dr. Chui: She talked about tailoring the workup to the child. So when we’re doing our workup, obviously physical exam should be the first thing we do. You have to assess and compare pulses, which is one of the most important parts of the initial evaluation. Obviously, looking at coarctation of the aorta, but also looking for things like a cushingoid appearance. If the child is less than 6 years of age, she recommends a referral to nephrology for more comprehensive renovascular workup, which probably will include renal ultrasound, urinalysis, metabolic panel, and thyroid studies.

We have to be cognizant of secondary causes of hypertension, such as endocrine tumors, hyperthyroidism, aortic disease, or even medication-induced hypertension. She told us that in the majority of these cases, especially with our obese older children, primary hypertension or essential hypertension is the most likely cause.

Dr. Berk: That was my big takeaway. If they’re really young, they need a big workup, but otherwise it is likely primary hypertension. What did we learn about treatment?

Dr. Chui: Just as we tailor our assessment to the child, we also have to tailor treatment. We know that lifestyle modification is usually the first line of treatment, especially for primary hypertension, and Dr. Baker-Smith tells us that we really need to perform counseling that meets the patient where they are. So if they like dancing to the newest TikTok trends or music videos, maybe we can encourage them to move more that way. Using our motivational interviewing skills is really key here.

If you want to start medication, Dr. Baker-Smith uses things like low-dose ACE inhibitors or calcium channel blockers, but obviously it’ll be tailored to the patient and any underlying conditions.

Dr. Berk: That’s great – a lot of wonderful pearls on the diagnosis and management of pediatric hypertension. Thank you for joining us for another video recap of The Cribsiders pediatric podcast. You can download the full podcast, Off the Cuff: Managing Pediatric Hypertension in Your Primary Care Clinic, on any podcast player, or check out our website at www.theCribsiders.com.

Christopher J. Chiu, MD, is assistant professor, department of internal medicine, division of general internal medicine, Ohio State University, Columbus; lead physician, general internal medicine, OSU Outpatient Care East; department of internal medicine, division of general internal medicine, Ohio State University Wexner Medical Center. Dr. Chiu has disclosed no relevant financial relationships. Justin L. Berk, MD, MPH, MBA, is assistant professor, department of medicine; assistant professor, department of pediatrics, Brown University, Providence, R.I.

This transcript has been edited for clarity. The transcript and an accompanying video first appeared on Medscape.com.

Justin L. Berk, MD, MPH, MBA: Welcome back to The Cribsiders, our video recap of our pediatric medicine podcast. We interview leading experts in the field to bring clinical pearls and practice-changing knowledge, and answer lingering questions about core topics in pediatric medicine. Chris, what is our topic today?

Christopher J. Chiu, MD: I was really happy to be able to talk about our recent episode with Dr. Carissa Baker-Smith, a pediatric cardiologist and director of the Nemours preventive cardiology program. She helped us review the pediatric screening guidelines for blood pressure, including initial workup and treatment.

Dr. Berk: This was a really great episode that a lot of people found really helpful. What were some of the key takeaway pearls that you think listeners would be interested in?

Dr. Chiu: We talked about when and how we should be checking blood pressures in children. Blood pressure should be checked at every well-child visit starting at age 3. But if they have other risk factors like kidney disease or a condition such as coarctation of the aorta, then blood pressure should be checked at every visit.

Dr. Berk: One thing she spoke about was how blood pressures should be measured. How should we be checking blood pressures in the clinic?

Dr. Chiu: Clinic blood pressures are usually checked with oscillometric devices. They can differ by manufacturer, but basically they find a mean arterial pressure and then each device has a method of calculating systolic and diastolic pressures. Now after that, if the child’s blood pressure is maybe abnormal, you want to double-check a manual blood pressure using Korotkoff sounds to confirm the blood pressure.

She reminded us that blood pressure should be measured with the child sitting with their back supported, feet flat on the floor, and arm at the level of the heart. Make sure you use the right size cuff. The bladder of the cuff should be 40% of the width of the arm, and about 80%-100% of the arm circumference. She recommends sizing up if you have to.

Dr. Berk: Accuracy of blood pressure management was a really important point, especially for diagnosis at this stage. Can you walk us through what we learned about diagnosis of hypertension?

Dr. Chiu: The definitions of hypertension come from the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents. Up until the age of 13, they define prehypertension as systolic and diastolic blood pressures between the 90th and 95th percentile, or if the blood pressure exceeds 120/80 mm Hg. Hypertension is defined when blood pressure reaches the 95th percentile. Now age 13 is when it gets a little hazy. Many changes in the guidelines happen at age 13, when hypertension starts being defined by adult guidelines. The 2017 adult hypertension guidelines define stage 1 hypertension as 130/89 to 139/89, and stage 2 hypertension as greater than 140/90.

Dr. Berk: How about workup of hypertension? The work of pediatric hypertension is always a little bit complex. What are some of the pearls you took away?

Dr. Chui: She talked about tailoring the workup to the child. So when we’re doing our workup, obviously physical exam should be the first thing we do. You have to assess and compare pulses, which is one of the most important parts of the initial evaluation. Obviously, looking at coarctation of the aorta, but also looking for things like a cushingoid appearance. If the child is less than 6 years of age, she recommends a referral to nephrology for more comprehensive renovascular workup, which probably will include renal ultrasound, urinalysis, metabolic panel, and thyroid studies.

We have to be cognizant of secondary causes of hypertension, such as endocrine tumors, hyperthyroidism, aortic disease, or even medication-induced hypertension. She told us that in the majority of these cases, especially with our obese older children, primary hypertension or essential hypertension is the most likely cause.

Dr. Berk: That was my big takeaway. If they’re really young, they need a big workup, but otherwise it is likely primary hypertension. What did we learn about treatment?

Dr. Chui: Just as we tailor our assessment to the child, we also have to tailor treatment. We know that lifestyle modification is usually the first line of treatment, especially for primary hypertension, and Dr. Baker-Smith tells us that we really need to perform counseling that meets the patient where they are. So if they like dancing to the newest TikTok trends or music videos, maybe we can encourage them to move more that way. Using our motivational interviewing skills is really key here.

If you want to start medication, Dr. Baker-Smith uses things like low-dose ACE inhibitors or calcium channel blockers, but obviously it’ll be tailored to the patient and any underlying conditions.

Dr. Berk: That’s great – a lot of wonderful pearls on the diagnosis and management of pediatric hypertension. Thank you for joining us for another video recap of The Cribsiders pediatric podcast. You can download the full podcast, Off the Cuff: Managing Pediatric Hypertension in Your Primary Care Clinic, on any podcast player, or check out our website at www.theCribsiders.com.

Christopher J. Chiu, MD, is assistant professor, department of internal medicine, division of general internal medicine, Ohio State University, Columbus; lead physician, general internal medicine, OSU Outpatient Care East; department of internal medicine, division of general internal medicine, Ohio State University Wexner Medical Center. Dr. Chiu has disclosed no relevant financial relationships. Justin L. Berk, MD, MPH, MBA, is assistant professor, department of medicine; assistant professor, department of pediatrics, Brown University, Providence, R.I.

Even though men in midlife have more cardiovascular (CV) conditions and risk factors than women of the same age, women are more affected by these conditions in terms of cognitive decline, new research suggests.

Analyses of almost 1,400 participants in the population-based Mayo Clinic Study of Aging showed that diabetes, dyslipidemia, and coronary heart disease (CHD) all had stronger associations with global cognitive decline in women than in men.

“All men and women should be treated for cardiovascular risk factors and conditions, but this study really highlights the importance of very early and perhaps more aggressive treatment in women with these conditions,” co-investigator Michelle M. Mielke, PhD, professor of epidemiology and neurology, Mayo Clinic, Rochester, Minn., told this news organization.

The findings were published online Jan. 5 in Neurology.
 

Assessing sex differences

Most previous studies in this area have focused on CV risk factors in midlife in relation to late-life dementia (after age 75) or on late-life vascular risk factors and late-life dementia, Dr. Mielke noted.

However, a few recent studies have suggested vascular risk factors can affect cognition even in midlife. The current investigators sought to determine whether there are sex differences in these associations.

They assessed 1,857 nondemented participants aged 50 to 69 years from the Mayo Clinic Study on Aging. The mean education level was 14.9 years, and the mean body mass index (BMI) was 29.7.

Among the participants, 78.9% had at least one CV condition or risk factor, and the proportion was higher in men than women (83.4% vs. 74.5%; P < .0001).

Frequency of each individual CV condition or risk factor was also higher in men than women, and they had more years of education and higher BMI but took fewer medications.

Every 15 months, participants had an in-person interview and physical examination that included a neurologic assessment and short test of memory.

The neuropsychological battery included nine tests across four domains: memory, language, executive function, and visuospatial skills. Researchers calculated z-scores for these domains and for global cognition.
 

Multiple cognitive domains

Whereas this study evaluated multiple cognitive domains, most previous research has focused on global cognitive decline and/or decline in only one or two cognitive domains, the investigators note.

They collected information from medical records on CV conditions such as CHD, arrhythmias, congestive heart failure, peripheral vascular disease (PVD), and stroke; and CV risk factors such as hypertension, diabetes, dyslipidemia, smoking status, and BMI.

Because of the small number of patients with stroke and PVD, these were classified as “other cardiovascular conditions” in the statistical analysis.

Researchers adjusted for sex, age, years of education, depressive symptoms, comorbidities, medications, and apolipoprotein E (APOE) genotyping. The mean follow-up was 3 years and did not differ by sex.

As some participants didn’t have a follow-up visit, the current analysis included 1,394 individuals. Those without follow-up visits were younger, had less education and more comorbidities, and took more medications compared with those with a follow-up.

Results showed most CV conditions were more strongly associated with cognitive function among women than men. For example, CHD was associated with global decline only in women (P < .05).

CHD, diabetes, and dyslipidemia were associated with language decline in women only (all, P < .05), but congestive heart failure was significantly associated with language decline in men only.

Dr. Mielke cautioned about reading too much into the language results for women.

“It’s an intriguing finding and definitely we need to follow up on it,” she said. However, “more studies are needed to examine sex differences before we start saying it only has an effect on language.”
 

‘Treat aggressively and right away’

The researchers were somewhat surprised by the study findings. Because there is a higher prevalence of CV conditions and risk factors in men, they presumed men would be more affected by these conditions, said Dr. Mielke.

“But that’s not what we saw; we saw the reverse. It was actually the women who were affected more by these cardiovascular risk factors and conditions,” she said.

As midlife is when women enter menopause, fluctuating estrogen levels may help explain the differential impact on cognition among women. But Dr. Mielke said she wants to “move beyond” just looking at hormones.

She pointed out there are a variety of psychosocial factors that may also contribute to an imbalance in the cognitive impact of CV conditions on women.

“Midlife is when many women are still taking care of their children at home, are also taking care of their adult parents, and may be undergoing more stress while continuing to do a job,” Dr. Miekle said.

Structural brain development and genetics may also contribute to the greater effect on cognition in women, the investigators note.

Dr. Mielke stressed that the current study only identifies associations. “The next steps are to understand what some of the underlying mechanisms for this are,” she said.

In the meantime, these new results suggest middle-aged women with high blood pressure, cholesterol, or glucose measures “should be treated aggressively and right away” said Dr. Mielke.

“For example, for women who are just starting to become hypertensive, clinicians should treat them right away and not watch and wait.”

Study limitations cited include that its sample was limited to Olmsted County, Minnesota – so results may not be generalized to other populations. Also, as researchers combined PVD and stroke into one group, larger sample sizes are needed, especially for stroke. Another limitation was the study did not have information on duration of all CV conditions or risk factors.
 

Helpful for tailoring interventions?

Commenting on the study, Glen R. Finney, MD, director, Memory and Cognition Program, Geisinger Health Clinic, Wilkes-Barre, Pennsylvania, said the results are important.

“The more we understand about risk factors for the development of Alzheimer’s disease and related dementias, the better we understand how we can reduce the risks,” said Dr. Finney, who was not involved with the research.

Awareness that CV conditions are major risk factors in midlife has been “definitely rising,” said Dr. Finney. “Many studies originally were looking at late life and are now looking more at earlier in the disease process, and I think that’s important.”

Understanding how sex, ethnicity, and other demographic variables affect risks can help to “tailor interventions” for individual patients, he said.

The study was supported by the National Institutes of Health, the GHR Foundation, and the Rochester Epidemiology Project. Dr. Mielke is a consultant for Biogen and Brain Protection Company and is on the editorial boards of Neurology and Alzheimer’s and Dementia. Dr. Finney has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Even though men in midlife have more cardiovascular (CV) conditions and risk factors than women of the same age, women are more affected by these conditions in terms of cognitive decline, new research suggests.

Analyses of almost 1,400 participants in the population-based Mayo Clinic Study of Aging showed that diabetes, dyslipidemia, and coronary heart disease (CHD) all had stronger associations with global cognitive decline in women than in men.

“All men and women should be treated for cardiovascular risk factors and conditions, but this study really highlights the importance of very early and perhaps more aggressive treatment in women with these conditions,” co-investigator Michelle M. Mielke, PhD, professor of epidemiology and neurology, Mayo Clinic, Rochester, Minn., told this news organization.

The findings were published online Jan. 5 in Neurology.
 

Assessing sex differences

Most previous studies in this area have focused on CV risk factors in midlife in relation to late-life dementia (after age 75) or on late-life vascular risk factors and late-life dementia, Dr. Mielke noted.

However, a few recent studies have suggested vascular risk factors can affect cognition even in midlife. The current investigators sought to determine whether there are sex differences in these associations.

They assessed 1,857 nondemented participants aged 50 to 69 years from the Mayo Clinic Study on Aging. The mean education level was 14.9 years, and the mean body mass index (BMI) was 29.7.

Among the participants, 78.9% had at least one CV condition or risk factor, and the proportion was higher in men than women (83.4% vs. 74.5%; P < .0001).

Frequency of each individual CV condition or risk factor was also higher in men than women, and they had more years of education and higher BMI but took fewer medications.

Every 15 months, participants had an in-person interview and physical examination that included a neurologic assessment and short test of memory.

The neuropsychological battery included nine tests across four domains: memory, language, executive function, and visuospatial skills. Researchers calculated z-scores for these domains and for global cognition.
 

Multiple cognitive domains

Whereas this study evaluated multiple cognitive domains, most previous research has focused on global cognitive decline and/or decline in only one or two cognitive domains, the investigators note.

They collected information from medical records on CV conditions such as CHD, arrhythmias, congestive heart failure, peripheral vascular disease (PVD), and stroke; and CV risk factors such as hypertension, diabetes, dyslipidemia, smoking status, and BMI.

Because of the small number of patients with stroke and PVD, these were classified as “other cardiovascular conditions” in the statistical analysis.

Researchers adjusted for sex, age, years of education, depressive symptoms, comorbidities, medications, and apolipoprotein E (APOE) genotyping. The mean follow-up was 3 years and did not differ by sex.

As some participants didn’t have a follow-up visit, the current analysis included 1,394 individuals. Those without follow-up visits were younger, had less education and more comorbidities, and took more medications compared with those with a follow-up.

Results showed most CV conditions were more strongly associated with cognitive function among women than men. For example, CHD was associated with global decline only in women (P < .05).

CHD, diabetes, and dyslipidemia were associated with language decline in women only (all, P < .05), but congestive heart failure was significantly associated with language decline in men only.

Dr. Mielke cautioned about reading too much into the language results for women.

“It’s an intriguing finding and definitely we need to follow up on it,” she said. However, “more studies are needed to examine sex differences before we start saying it only has an effect on language.”
 

‘Treat aggressively and right away’

The researchers were somewhat surprised by the study findings. Because there is a higher prevalence of CV conditions and risk factors in men, they presumed men would be more affected by these conditions, said Dr. Mielke.

“But that’s not what we saw; we saw the reverse. It was actually the women who were affected more by these cardiovascular risk factors and conditions,” she said.

As midlife is when women enter menopause, fluctuating estrogen levels may help explain the differential impact on cognition among women. But Dr. Mielke said she wants to “move beyond” just looking at hormones.

She pointed out there are a variety of psychosocial factors that may also contribute to an imbalance in the cognitive impact of CV conditions on women.

“Midlife is when many women are still taking care of their children at home, are also taking care of their adult parents, and may be undergoing more stress while continuing to do a job,” Dr. Miekle said.

Structural brain development and genetics may also contribute to the greater effect on cognition in women, the investigators note.

Dr. Mielke stressed that the current study only identifies associations. “The next steps are to understand what some of the underlying mechanisms for this are,” she said.

In the meantime, these new results suggest middle-aged women with high blood pressure, cholesterol, or glucose measures “should be treated aggressively and right away” said Dr. Mielke.

“For example, for women who are just starting to become hypertensive, clinicians should treat them right away and not watch and wait.”

Study limitations cited include that its sample was limited to Olmsted County, Minnesota – so results may not be generalized to other populations. Also, as researchers combined PVD and stroke into one group, larger sample sizes are needed, especially for stroke. Another limitation was the study did not have information on duration of all CV conditions or risk factors.
 

Helpful for tailoring interventions?

Commenting on the study, Glen R. Finney, MD, director, Memory and Cognition Program, Geisinger Health Clinic, Wilkes-Barre, Pennsylvania, said the results are important.

“The more we understand about risk factors for the development of Alzheimer’s disease and related dementias, the better we understand how we can reduce the risks,” said Dr. Finney, who was not involved with the research.

Awareness that CV conditions are major risk factors in midlife has been “definitely rising,” said Dr. Finney. “Many studies originally were looking at late life and are now looking more at earlier in the disease process, and I think that’s important.”

Understanding how sex, ethnicity, and other demographic variables affect risks can help to “tailor interventions” for individual patients, he said.

The study was supported by the National Institutes of Health, the GHR Foundation, and the Rochester Epidemiology Project. Dr. Mielke is a consultant for Biogen and Brain Protection Company and is on the editorial boards of Neurology and Alzheimer’s and Dementia. Dr. Finney has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Even though men in midlife have more cardiovascular (CV) conditions and risk factors than women of the same age, women are more affected by these conditions in terms of cognitive decline, new research suggests.

Analyses of almost 1,400 participants in the population-based Mayo Clinic Study of Aging showed that diabetes, dyslipidemia, and coronary heart disease (CHD) all had stronger associations with global cognitive decline in women than in men.

“All men and women should be treated for cardiovascular risk factors and conditions, but this study really highlights the importance of very early and perhaps more aggressive treatment in women with these conditions,” co-investigator Michelle M. Mielke, PhD, professor of epidemiology and neurology, Mayo Clinic, Rochester, Minn., told this news organization.

The findings were published online Jan. 5 in Neurology.
 

Assessing sex differences

Most previous studies in this area have focused on CV risk factors in midlife in relation to late-life dementia (after age 75) or on late-life vascular risk factors and late-life dementia, Dr. Mielke noted.

However, a few recent studies have suggested vascular risk factors can affect cognition even in midlife. The current investigators sought to determine whether there are sex differences in these associations.

They assessed 1,857 nondemented participants aged 50 to 69 years from the Mayo Clinic Study on Aging. The mean education level was 14.9 years, and the mean body mass index (BMI) was 29.7.

Among the participants, 78.9% had at least one CV condition or risk factor, and the proportion was higher in men than women (83.4% vs. 74.5%; P < .0001).

Frequency of each individual CV condition or risk factor was also higher in men than women, and they had more years of education and higher BMI but took fewer medications.

Every 15 months, participants had an in-person interview and physical examination that included a neurologic assessment and short test of memory.

The neuropsychological battery included nine tests across four domains: memory, language, executive function, and visuospatial skills. Researchers calculated z-scores for these domains and for global cognition.
 

Multiple cognitive domains

Whereas this study evaluated multiple cognitive domains, most previous research has focused on global cognitive decline and/or decline in only one or two cognitive domains, the investigators note.

They collected information from medical records on CV conditions such as CHD, arrhythmias, congestive heart failure, peripheral vascular disease (PVD), and stroke; and CV risk factors such as hypertension, diabetes, dyslipidemia, smoking status, and BMI.

Because of the small number of patients with stroke and PVD, these were classified as “other cardiovascular conditions” in the statistical analysis.

Researchers adjusted for sex, age, years of education, depressive symptoms, comorbidities, medications, and apolipoprotein E (APOE) genotyping. The mean follow-up was 3 years and did not differ by sex.

As some participants didn’t have a follow-up visit, the current analysis included 1,394 individuals. Those without follow-up visits were younger, had less education and more comorbidities, and took more medications compared with those with a follow-up.

Results showed most CV conditions were more strongly associated with cognitive function among women than men. For example, CHD was associated with global decline only in women (P < .05).

CHD, diabetes, and dyslipidemia were associated with language decline in women only (all, P < .05), but congestive heart failure was significantly associated with language decline in men only.

Dr. Mielke cautioned about reading too much into the language results for women.

“It’s an intriguing finding and definitely we need to follow up on it,” she said. However, “more studies are needed to examine sex differences before we start saying it only has an effect on language.”
 

‘Treat aggressively and right away’

The researchers were somewhat surprised by the study findings. Because there is a higher prevalence of CV conditions and risk factors in men, they presumed men would be more affected by these conditions, said Dr. Mielke.

“But that’s not what we saw; we saw the reverse. It was actually the women who were affected more by these cardiovascular risk factors and conditions,” she said.

As midlife is when women enter menopause, fluctuating estrogen levels may help explain the differential impact on cognition among women. But Dr. Mielke said she wants to “move beyond” just looking at hormones.

She pointed out there are a variety of psychosocial factors that may also contribute to an imbalance in the cognitive impact of CV conditions on women.

“Midlife is when many women are still taking care of their children at home, are also taking care of their adult parents, and may be undergoing more stress while continuing to do a job,” Dr. Miekle said.

Structural brain development and genetics may also contribute to the greater effect on cognition in women, the investigators note.

Dr. Mielke stressed that the current study only identifies associations. “The next steps are to understand what some of the underlying mechanisms for this are,” she said.

In the meantime, these new results suggest middle-aged women with high blood pressure, cholesterol, or glucose measures “should be treated aggressively and right away” said Dr. Mielke.

“For example, for women who are just starting to become hypertensive, clinicians should treat them right away and not watch and wait.”

Study limitations cited include that its sample was limited to Olmsted County, Minnesota – so results may not be generalized to other populations. Also, as researchers combined PVD and stroke into one group, larger sample sizes are needed, especially for stroke. Another limitation was the study did not have information on duration of all CV conditions or risk factors.
 

Helpful for tailoring interventions?

Commenting on the study, Glen R. Finney, MD, director, Memory and Cognition Program, Geisinger Health Clinic, Wilkes-Barre, Pennsylvania, said the results are important.

“The more we understand about risk factors for the development of Alzheimer’s disease and related dementias, the better we understand how we can reduce the risks,” said Dr. Finney, who was not involved with the research.

Awareness that CV conditions are major risk factors in midlife has been “definitely rising,” said Dr. Finney. “Many studies originally were looking at late life and are now looking more at earlier in the disease process, and I think that’s important.”

Understanding how sex, ethnicity, and other demographic variables affect risks can help to “tailor interventions” for individual patients, he said.

The study was supported by the National Institutes of Health, the GHR Foundation, and the Rochester Epidemiology Project. Dr. Mielke is a consultant for Biogen and Brain Protection Company and is on the editorial boards of Neurology and Alzheimer’s and Dementia. Dr. Finney has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Pregnant women who are at risk of preeclampsia can now be identified early before symptoms develop, finds new research from Kings College London and Guy’s and St Thomas’ NHS Foundation Trust, published in Nature.

The study, supported by the National Institute for Health Research and in partnership with the Mirvie RNA platform, analyzed the genetic material from over 2,500 blood samples of pregnant women from eight independent cohorts with multiple demographics, including socioeconomic background, geographic location, ethnicity, and nationality, collected 14.5 weeks before delivery.

“Because the study drew upon samples for a diverse group of women, including participants recruited across King’s Health Partners, the molecular signature is very reliable and has potential to outperform currently available tests,” said Rachel Tribe, PhD, department of women and children’s health, King’s College London.

Researchers used plasma cell-free RNA (cfRNA) transcripts to examine the standard molecular mechanism between the fetus, maternal, and placental tissues in order to determine fetal development and healthy pregnancy progression. Deviation from the standard cfRNA expression was also observed to establish the molecular pathway for those at risk of preeclampsia before clinical presentation.

A cfRNA signal from a single blood sample showed a 32.3% positive-predictive value and 75% sensitivity, which exceeds current positive-predictive values from recent clinical state-of-the-art models.

In addition, 73% of participants with a positive-predictive value were identified “as destined to have a medically indicated preterm birth over 3 months in advance of the preeclampsia symptoms,” said the authors.

With up to 1 in 12 pregnancies affected by preeclampsia, and the diagnosis most often only being made in the third trimester, these results provide a promising outlook for pregnant women “so that they can be more closely monitored and treated by the clinicians involved,” commented Dr. Tribe.

“We are now focused on ongoing clinical research to further validate these results and improve the understanding of other pregnancy complications,” she said. “As a scientist, it was also extremely interesting to see that the molecular signature tells us something about mechanisms associated with health in pregnancy and complications including preeclampsia; such knowledge will aid development of treatment strategies in the future.”

A version of this article first appeared on Medscape.com.

Pregnant women who are at risk of preeclampsia can now be identified early before symptoms develop, finds new research from Kings College London and Guy’s and St Thomas’ NHS Foundation Trust, published in Nature.

The study, supported by the National Institute for Health Research and in partnership with the Mirvie RNA platform, analyzed the genetic material from over 2,500 blood samples of pregnant women from eight independent cohorts with multiple demographics, including socioeconomic background, geographic location, ethnicity, and nationality, collected 14.5 weeks before delivery.

“Because the study drew upon samples for a diverse group of women, including participants recruited across King’s Health Partners, the molecular signature is very reliable and has potential to outperform currently available tests,” said Rachel Tribe, PhD, department of women and children’s health, King’s College London.

Researchers used plasma cell-free RNA (cfRNA) transcripts to examine the standard molecular mechanism between the fetus, maternal, and placental tissues in order to determine fetal development and healthy pregnancy progression. Deviation from the standard cfRNA expression was also observed to establish the molecular pathway for those at risk of preeclampsia before clinical presentation.

A cfRNA signal from a single blood sample showed a 32.3% positive-predictive value and 75% sensitivity, which exceeds current positive-predictive values from recent clinical state-of-the-art models.

In addition, 73% of participants with a positive-predictive value were identified “as destined to have a medically indicated preterm birth over 3 months in advance of the preeclampsia symptoms,” said the authors.

With up to 1 in 12 pregnancies affected by preeclampsia, and the diagnosis most often only being made in the third trimester, these results provide a promising outlook for pregnant women “so that they can be more closely monitored and treated by the clinicians involved,” commented Dr. Tribe.

“We are now focused on ongoing clinical research to further validate these results and improve the understanding of other pregnancy complications,” she said. “As a scientist, it was also extremely interesting to see that the molecular signature tells us something about mechanisms associated with health in pregnancy and complications including preeclampsia; such knowledge will aid development of treatment strategies in the future.”

A version of this article first appeared on Medscape.com.

Pregnant women who are at risk of preeclampsia can now be identified early before symptoms develop, finds new research from Kings College London and Guy’s and St Thomas’ NHS Foundation Trust, published in Nature.

The study, supported by the National Institute for Health Research and in partnership with the Mirvie RNA platform, analyzed the genetic material from over 2,500 blood samples of pregnant women from eight independent cohorts with multiple demographics, including socioeconomic background, geographic location, ethnicity, and nationality, collected 14.5 weeks before delivery.

“Because the study drew upon samples for a diverse group of women, including participants recruited across King’s Health Partners, the molecular signature is very reliable and has potential to outperform currently available tests,” said Rachel Tribe, PhD, department of women and children’s health, King’s College London.

Researchers used plasma cell-free RNA (cfRNA) transcripts to examine the standard molecular mechanism between the fetus, maternal, and placental tissues in order to determine fetal development and healthy pregnancy progression. Deviation from the standard cfRNA expression was also observed to establish the molecular pathway for those at risk of preeclampsia before clinical presentation.

A cfRNA signal from a single blood sample showed a 32.3% positive-predictive value and 75% sensitivity, which exceeds current positive-predictive values from recent clinical state-of-the-art models.

In addition, 73% of participants with a positive-predictive value were identified “as destined to have a medically indicated preterm birth over 3 months in advance of the preeclampsia symptoms,” said the authors.

With up to 1 in 12 pregnancies affected by preeclampsia, and the diagnosis most often only being made in the third trimester, these results provide a promising outlook for pregnant women “so that they can be more closely monitored and treated by the clinicians involved,” commented Dr. Tribe.

“We are now focused on ongoing clinical research to further validate these results and improve the understanding of other pregnancy complications,” she said. “As a scientist, it was also extremely interesting to see that the molecular signature tells us something about mechanisms associated with health in pregnancy and complications including preeclampsia; such knowledge will aid development of treatment strategies in the future.”

A version of this article first appeared on Medscape.com.

In more than 15% of people with benign adrenal tumors, the growths produce clinically relevant levels of serum cortisol that are significantly linked with an increased prevalence of hypertension and, in 5% of those with Cushing syndrome (CS), an increased prevalence of type 2 diabetes, based on data from more than 1,300 people with benign adrenal tumors, the largest reported prospective study of the disorder.

The study results showed that mild autonomous cortisol secretion (MACS) from benign adrenal tumors “is very frequent and is an important risk condition for high blood pressure and type 2 diabetes, especially in older women,” said Alessandro Prete, MD, lead author of the study which was published online Jan. 3, 2022, in Annals of Internal Medicine.

SEBASTIAN KAULITZKI/SCIENCE PHOTO LIBRARY/Getty Images

“The impact of MACS on high blood pressure and risk for type 2 diabetes has been underestimated until now,” said Dr. Prete, an endocrinologist at the University of Birmingham (England), in a written statement. 

Results from previous studies “suggested that MACS is associated with poor health. Our study is the largest to establish conclusively the extent of the risk and severity of high blood pressure and type 2 diabetes in patients with MACS,” said Wiebke Arlt, MD, DSc, senior author and director of the Institute of Metabolism & Systems Research at the University of Birmingham.

All patients found to have a benign adrenal tumor should undergo testing for MACS and have their blood pressure and glucose levels measured regularly, Dr. Arlt advised in the statement released by the University of Birmingham.
 

MACS more common than previously thought

The new findings show that MACS “is more common and may have a more negative impact on health than previously thought, including increasing the risk for type 2 diabetes,” commented Lucy Chambers, PhD, head of research communications at Diabetes UK. “The findings suggest that screening for MACS could help identify people – particularly women, in whom the condition was found to be more common – who may benefit from support to reduce their risk of type 2 diabetes.”

The study included 1,305 people with newly diagnosed, benign adrenal tumors greater than 1 cm, a subset of patients prospectively enrolled in a study with the primary purpose of validating a novel way to diagnose adrenocortical carcinomas. Patients underwent treatment in 2011-2016 at any of 14 tertiary centers in 11 countries.

Researchers used a MACS definition of failure to suppress morning serum cortisol concentration to less than 50 nmol/L after treatment with 1 mg oral dexamethasone at 11 p.m. the previous evening in those with no clinical features of CS.

Roughly half of patients (n = 649) showed normal cortisol suppression with dexamethasone, identifying them as having nonfunctioning adrenal tumors, and about 35% showed possible MACS based on having moderate levels of excess cortisol.

Nearly 11% (n = 140) showed definitive MACS with more robust cortisol levels, and 5% (n = 65) received a diagnosis of clinically overt CS despite selection criteria meant to exclude people with clinical signs of CS.

There was a clear relationship between patient sex and severity of autonomous cortisol production. Among those with nonfunctioning adrenal tumors, 64% were women, which rose to 74% women in those with definitive MACS and 86% women among those with CS. The median age of participants was 60 years old.
 

Increasing cortisol levels linked with cardiometabolic disease

Analysis of the prevalence of hypertension and type 2 diabetes after adjustment for age, sex, and body mass index showed that, compared with people with nonfunctioning adrenal tumors, those with definitive MACS had a significant 15% higher rate of hypertension and those with overt CS had a 37% higher rate. 

Higher levels of excess cortisol were also directly linked with an increased need for treatment with three or more antihypertensive agents to control blood pressure. Those with definitive MACS had a significant 31% higher rate of being on three or more drugs, and those with overt CS had a greater than twofold higher rate.

People with overt CS also had a significant 62% higher rate of type 2 diabetes, compared with those with a nonfunctioning tumor, but in those with definitive MACS the association was not significant. However, people with definitive MACS or overt CS who had type 2 diabetes and also had significantly increased rates of requiring insulin treatment.

The findings show that “people with definitive MACS carry an increased cardiometabolic burden similar to that seen in CS even if they do not display typical features of clinically overt cortisol excess,” the authors wrote in the report.

Even among those with apparently nonfunctioning tumors, each 10 nmol/L rise in cortisol level during a dexamethasone-suppression test was associated with a higher cardiometabolic disease burden. This observation suggests that current diagnostic cutoffs for the suppression test may miss some people with clinically relevant autonomous cortisol secretion, the report said. The study findings also suggest that people with benign adrenal tumors show a progressive continuum of excess cortisol with clinical consequences that increase as levels increase.
 

Determine the consequences of cortisol secretion

“These data clearly support the European Society of Endocrinology guideline recommendations that clinicians should determine precisely the cardiometabolic consequences of mild cortisol secretion in patients with adrenal lesions,” André Lacroix, MD, wrote in an accompanying editorial.

But Dr. Lacroix included some caveats. He noted the “potential pitfalls in relying on a single total serum cortisol value after the 1-mg dexamethasone test.” He also wondered whether the analysis used optimal cortisol values to distinguish patient subgroups.

Plus, “even in patients with nonfunctioning adrenal tumors the prevalence of diabetes and hypertension is higher than in the general population, raising concerns about the cardiometabolic consequences of barely detectable cortisol excess,” wrote Dr. Lacroix, an endocrinologist at the CHUM Research Center and professor of medicine at the University of Montreal.

The study received no commercial funding. Dr. Prete, Dr. Chambers, and Dr. Lacroix have reported no relevant financial relationships. Dr. Arlt is listed as an inventor on a patent on the use of steroid profiling as a biomarker tool for the differential diagnosis of adrenal tumors.

A version of this article first appeared on Medscape.com.

In more than 15% of people with benign adrenal tumors, the growths produce clinically relevant levels of serum cortisol that are significantly linked with an increased prevalence of hypertension and, in 5% of those with Cushing syndrome (CS), an increased prevalence of type 2 diabetes, based on data from more than 1,300 people with benign adrenal tumors, the largest reported prospective study of the disorder.

The study results showed that mild autonomous cortisol secretion (MACS) from benign adrenal tumors “is very frequent and is an important risk condition for high blood pressure and type 2 diabetes, especially in older women,” said Alessandro Prete, MD, lead author of the study which was published online Jan. 3, 2022, in Annals of Internal Medicine.

SEBASTIAN KAULITZKI/SCIENCE PHOTO LIBRARY/Getty Images

“The impact of MACS on high blood pressure and risk for type 2 diabetes has been underestimated until now,” said Dr. Prete, an endocrinologist at the University of Birmingham (England), in a written statement. 

Results from previous studies “suggested that MACS is associated with poor health. Our study is the largest to establish conclusively the extent of the risk and severity of high blood pressure and type 2 diabetes in patients with MACS,” said Wiebke Arlt, MD, DSc, senior author and director of the Institute of Metabolism & Systems Research at the University of Birmingham.

All patients found to have a benign adrenal tumor should undergo testing for MACS and have their blood pressure and glucose levels measured regularly, Dr. Arlt advised in the statement released by the University of Birmingham.
 

MACS more common than previously thought

The new findings show that MACS “is more common and may have a more negative impact on health than previously thought, including increasing the risk for type 2 diabetes,” commented Lucy Chambers, PhD, head of research communications at Diabetes UK. “The findings suggest that screening for MACS could help identify people – particularly women, in whom the condition was found to be more common – who may benefit from support to reduce their risk of type 2 diabetes.”

The study included 1,305 people with newly diagnosed, benign adrenal tumors greater than 1 cm, a subset of patients prospectively enrolled in a study with the primary purpose of validating a novel way to diagnose adrenocortical carcinomas. Patients underwent treatment in 2011-2016 at any of 14 tertiary centers in 11 countries.

Researchers used a MACS definition of failure to suppress morning serum cortisol concentration to less than 50 nmol/L after treatment with 1 mg oral dexamethasone at 11 p.m. the previous evening in those with no clinical features of CS.

Roughly half of patients (n = 649) showed normal cortisol suppression with dexamethasone, identifying them as having nonfunctioning adrenal tumors, and about 35% showed possible MACS based on having moderate levels of excess cortisol.

Nearly 11% (n = 140) showed definitive MACS with more robust cortisol levels, and 5% (n = 65) received a diagnosis of clinically overt CS despite selection criteria meant to exclude people with clinical signs of CS.

There was a clear relationship between patient sex and severity of autonomous cortisol production. Among those with nonfunctioning adrenal tumors, 64% were women, which rose to 74% women in those with definitive MACS and 86% women among those with CS. The median age of participants was 60 years old.
 

Increasing cortisol levels linked with cardiometabolic disease

Analysis of the prevalence of hypertension and type 2 diabetes after adjustment for age, sex, and body mass index showed that, compared with people with nonfunctioning adrenal tumors, those with definitive MACS had a significant 15% higher rate of hypertension and those with overt CS had a 37% higher rate. 

Higher levels of excess cortisol were also directly linked with an increased need for treatment with three or more antihypertensive agents to control blood pressure. Those with definitive MACS had a significant 31% higher rate of being on three or more drugs, and those with overt CS had a greater than twofold higher rate.

People with overt CS also had a significant 62% higher rate of type 2 diabetes, compared with those with a nonfunctioning tumor, but in those with definitive MACS the association was not significant. However, people with definitive MACS or overt CS who had type 2 diabetes and also had significantly increased rates of requiring insulin treatment.

The findings show that “people with definitive MACS carry an increased cardiometabolic burden similar to that seen in CS even if they do not display typical features of clinically overt cortisol excess,” the authors wrote in the report.

Even among those with apparently nonfunctioning tumors, each 10 nmol/L rise in cortisol level during a dexamethasone-suppression test was associated with a higher cardiometabolic disease burden. This observation suggests that current diagnostic cutoffs for the suppression test may miss some people with clinically relevant autonomous cortisol secretion, the report said. The study findings also suggest that people with benign adrenal tumors show a progressive continuum of excess cortisol with clinical consequences that increase as levels increase.
 

Determine the consequences of cortisol secretion

“These data clearly support the European Society of Endocrinology guideline recommendations that clinicians should determine precisely the cardiometabolic consequences of mild cortisol secretion in patients with adrenal lesions,” André Lacroix, MD, wrote in an accompanying editorial.

But Dr. Lacroix included some caveats. He noted the “potential pitfalls in relying on a single total serum cortisol value after the 1-mg dexamethasone test.” He also wondered whether the analysis used optimal cortisol values to distinguish patient subgroups.

Plus, “even in patients with nonfunctioning adrenal tumors the prevalence of diabetes and hypertension is higher than in the general population, raising concerns about the cardiometabolic consequences of barely detectable cortisol excess,” wrote Dr. Lacroix, an endocrinologist at the CHUM Research Center and professor of medicine at the University of Montreal.

The study received no commercial funding. Dr. Prete, Dr. Chambers, and Dr. Lacroix have reported no relevant financial relationships. Dr. Arlt is listed as an inventor on a patent on the use of steroid profiling as a biomarker tool for the differential diagnosis of adrenal tumors.

A version of this article first appeared on Medscape.com.

In more than 15% of people with benign adrenal tumors, the growths produce clinically relevant levels of serum cortisol that are significantly linked with an increased prevalence of hypertension and, in 5% of those with Cushing syndrome (CS), an increased prevalence of type 2 diabetes, based on data from more than 1,300 people with benign adrenal tumors, the largest reported prospective study of the disorder.

The study results showed that mild autonomous cortisol secretion (MACS) from benign adrenal tumors “is very frequent and is an important risk condition for high blood pressure and type 2 diabetes, especially in older women,” said Alessandro Prete, MD, lead author of the study which was published online Jan. 3, 2022, in Annals of Internal Medicine.

SEBASTIAN KAULITZKI/SCIENCE PHOTO LIBRARY/Getty Images

“The impact of MACS on high blood pressure and risk for type 2 diabetes has been underestimated until now,” said Dr. Prete, an endocrinologist at the University of Birmingham (England), in a written statement. 

Results from previous studies “suggested that MACS is associated with poor health. Our study is the largest to establish conclusively the extent of the risk and severity of high blood pressure and type 2 diabetes in patients with MACS,” said Wiebke Arlt, MD, DSc, senior author and director of the Institute of Metabolism & Systems Research at the University of Birmingham.

All patients found to have a benign adrenal tumor should undergo testing for MACS and have their blood pressure and glucose levels measured regularly, Dr. Arlt advised in the statement released by the University of Birmingham.
 

MACS more common than previously thought

The new findings show that MACS “is more common and may have a more negative impact on health than previously thought, including increasing the risk for type 2 diabetes,” commented Lucy Chambers, PhD, head of research communications at Diabetes UK. “The findings suggest that screening for MACS could help identify people – particularly women, in whom the condition was found to be more common – who may benefit from support to reduce their risk of type 2 diabetes.”

The study included 1,305 people with newly diagnosed, benign adrenal tumors greater than 1 cm, a subset of patients prospectively enrolled in a study with the primary purpose of validating a novel way to diagnose adrenocortical carcinomas. Patients underwent treatment in 2011-2016 at any of 14 tertiary centers in 11 countries.

Researchers used a MACS definition of failure to suppress morning serum cortisol concentration to less than 50 nmol/L after treatment with 1 mg oral dexamethasone at 11 p.m. the previous evening in those with no clinical features of CS.

Roughly half of patients (n = 649) showed normal cortisol suppression with dexamethasone, identifying them as having nonfunctioning adrenal tumors, and about 35% showed possible MACS based on having moderate levels of excess cortisol.

Nearly 11% (n = 140) showed definitive MACS with more robust cortisol levels, and 5% (n = 65) received a diagnosis of clinically overt CS despite selection criteria meant to exclude people with clinical signs of CS.

There was a clear relationship between patient sex and severity of autonomous cortisol production. Among those with nonfunctioning adrenal tumors, 64% were women, which rose to 74% women in those with definitive MACS and 86% women among those with CS. The median age of participants was 60 years old.
 

Increasing cortisol levels linked with cardiometabolic disease

Analysis of the prevalence of hypertension and type 2 diabetes after adjustment for age, sex, and body mass index showed that, compared with people with nonfunctioning adrenal tumors, those with definitive MACS had a significant 15% higher rate of hypertension and those with overt CS had a 37% higher rate. 

Higher levels of excess cortisol were also directly linked with an increased need for treatment with three or more antihypertensive agents to control blood pressure. Those with definitive MACS had a significant 31% higher rate of being on three or more drugs, and those with overt CS had a greater than twofold higher rate.

People with overt CS also had a significant 62% higher rate of type 2 diabetes, compared with those with a nonfunctioning tumor, but in those with definitive MACS the association was not significant. However, people with definitive MACS or overt CS who had type 2 diabetes and also had significantly increased rates of requiring insulin treatment.

The findings show that “people with definitive MACS carry an increased cardiometabolic burden similar to that seen in CS even if they do not display typical features of clinically overt cortisol excess,” the authors wrote in the report.

Even among those with apparently nonfunctioning tumors, each 10 nmol/L rise in cortisol level during a dexamethasone-suppression test was associated with a higher cardiometabolic disease burden. This observation suggests that current diagnostic cutoffs for the suppression test may miss some people with clinically relevant autonomous cortisol secretion, the report said. The study findings also suggest that people with benign adrenal tumors show a progressive continuum of excess cortisol with clinical consequences that increase as levels increase.
 

Determine the consequences of cortisol secretion

“These data clearly support the European Society of Endocrinology guideline recommendations that clinicians should determine precisely the cardiometabolic consequences of mild cortisol secretion in patients with adrenal lesions,” André Lacroix, MD, wrote in an accompanying editorial.

But Dr. Lacroix included some caveats. He noted the “potential pitfalls in relying on a single total serum cortisol value after the 1-mg dexamethasone test.” He also wondered whether the analysis used optimal cortisol values to distinguish patient subgroups.

Plus, “even in patients with nonfunctioning adrenal tumors the prevalence of diabetes and hypertension is higher than in the general population, raising concerns about the cardiometabolic consequences of barely detectable cortisol excess,” wrote Dr. Lacroix, an endocrinologist at the CHUM Research Center and professor of medicine at the University of Montreal.

The study received no commercial funding. Dr. Prete, Dr. Chambers, and Dr. Lacroix have reported no relevant financial relationships. Dr. Arlt is listed as an inventor on a patent on the use of steroid profiling as a biomarker tool for the differential diagnosis of adrenal tumors.

A version of this article first appeared on Medscape.com.

Yoga added to conventional therapy for vasovagal syncope (VVS), when patients faint after a sudden drop in heart rate and blood pressure, can reduce symptoms and improve quality of life, new research suggests. 

AndiP/pixabay.com

A small, open-label trial conducted in New Delhi showed that participants practicing yoga reported an improvement in VVS symptoms after only 6 weeks, with a reduction of 1.82 events at 12 months. All those practicing yoga also showed significantly improved quality of life (QoL) scores by the end of the trial.

“Yoga as add-on therapy in VVS is superior to medical therapy in reducing syncopal and presyncopal events and in improving the QoL,” report Gautam Sharma, MD, DM, Centre for Integrative Medicine and Research, All India Institute of Medical Sciences, New Delhi, and colleagues. “It may be useful to integrate a cost-effective and safe intervention such as yoga into the management of VVS.”

Results of the LIVE-Yoga study were published online in JACC: Clinical Electrophysiology.

Vasovagal syncope is a common and non–life-threatening condition, but given the severity and frequency of recurrence it can result in significant deterioration in a patient’s quality of life, the authors note. “Existing management therapies have been largely ineffective,” they write.

Recent trials have suggested some efficacy for yoga in diseases of autonomic imbalance, suggesting a possible use in VVS. To find out, the researchers enrolled adults with VVS between the ages of 15-70 years who had a positive head-up tilt test (HUTT) and at least two syncope or presyncope events within 3 months of enrollment. They also needed to be willing and able to practice yoga. Those with structural heart disease, accelerated hypertension, and underlying neurologic disorders were not included in the study.

A total of 55 patients were randomly assigned to receive either a specialized yoga training program in addition to guideline-based therapy, or guideline-based therapy alone. Standard care included physical counterpressure maneuvers, avoidance of known triggers, increased salt and water intake, and drug therapy or pacing at the discretion of the treating physician.

The primary outcome was a composite of the number of episodes of syncope and presyncope at 12 months.    

Secondary outcomes including QoL, assessed using the World Health Organization Quality of Life Brief Field questionnaire (WHOQoL-BREF) and the Syncope Functional Status Questionnaire (SFSQ) at 12 months, a head-up tilt test, and heart rate variability at 6 weeks.

For the first 2 weeks, patients in the intervention group were enrolled in eight supervised yoga sessions conducted at the Centre for Integrative Medicine and Research at the All India Institute of Medical Sciences. For the remainder of the trial, they continued a daily yoga practice at home at least 5 days a week.

The yoga module created for participants was designed with a view to the pathophysiology of VVS and featured postures, breathing, and relaxation techniques. Yoga classes were taught by qualified therapists under the guidance of physicians.

In addition to a booklet with a pictorial of the yoga regimen, participants received twice-monthly calls from the yoga center to encourage compliance. Results show that all participants adhered to their yoga routine for more than 80% of the 12-month trial.

At 12 months, the mean number of syncopal or presyncopal events was 0.7 ± 0.7 with the yoga intervention versus 2.52 ± 1.93 among patients in the control arm (P < .05). The reduction in events started as early as 6 weeks and continued to separate out to 12 months, the researchers note.

Thirteen of 30 (43.3%) intervention patients and 4 of 25 (16%) control patients remained event-free at 12 months, a statistically significant difference (P = .02). There was a trend toward fewer positive head-up tilt tests between groups that did not reach significance, and there was no difference in heart rate variability at 6 weeks.

No adverse events as a result of the yoga practice were reported, and no patient started drug therapy or received pacing therapy during the trial, they note.

The researchers point out that yoga postures can enhance vascular and muscle tone, especially in the lower limbs.

“Yoga breathing and relaxation techniques have been shown to increase vagal tone and improve autonomic balance, which could potentially curtail the sympathetic overdrive phase and interrupt the activation of the c-mechanoreceptors, which is a critical step in the syncope cascade,” they note.

“We postulate that positive effects of yoga in this study could be related to a multidimensional effect of this intervention acting through both central and peripheral mechanisms, including physical, psychological, and autonomic pathways,” the authors conclude.
 

Comprehensive regimen

Dhanunjaya Lakkireddy, MD, medical director for the Kansas City Heart Rhythm Institute, Overland Park, Kansas, says these results are in line with previous research indicating the benefits of yoga in improving cardiovascular function.

“All of this clearly shows that when you [include] a systematic diet of yoga for a reasonable amount of time to improve the plasticity of parasympathetic inputs into the chest and thereby the cardiovascular system ... you can help patients to improve their symptoms,” he said in an interview.  

He already prescribes yoga in his own practice as part of a comprehensive therapeutic regimen, he said. “We have a handful of practitioners all around the city who work with us,” Dr. Lakkireddy said.

Both he and the study authors point the economic burden of VVS both in management and in loss of patient productivity. “A low-cost intervention in the form of yoga, which essentially requires only a mat, can reduce both direct and indirect costs significantly,” note the authors.

The trial was supported under the extramural research (EMR) scheme by the Ministry of AYUSH, Government of India. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Yoga added to conventional therapy for vasovagal syncope (VVS), when patients faint after a sudden drop in heart rate and blood pressure, can reduce symptoms and improve quality of life, new research suggests. 

AndiP/pixabay.com

A small, open-label trial conducted in New Delhi showed that participants practicing yoga reported an improvement in VVS symptoms after only 6 weeks, with a reduction of 1.82 events at 12 months. All those practicing yoga also showed significantly improved quality of life (QoL) scores by the end of the trial.

“Yoga as add-on therapy in VVS is superior to medical therapy in reducing syncopal and presyncopal events and in improving the QoL,” report Gautam Sharma, MD, DM, Centre for Integrative Medicine and Research, All India Institute of Medical Sciences, New Delhi, and colleagues. “It may be useful to integrate a cost-effective and safe intervention such as yoga into the management of VVS.”

Results of the LIVE-Yoga study were published online in JACC: Clinical Electrophysiology.

Vasovagal syncope is a common and non–life-threatening condition, but given the severity and frequency of recurrence it can result in significant deterioration in a patient’s quality of life, the authors note. “Existing management therapies have been largely ineffective,” they write.

Recent trials have suggested some efficacy for yoga in diseases of autonomic imbalance, suggesting a possible use in VVS. To find out, the researchers enrolled adults with VVS between the ages of 15-70 years who had a positive head-up tilt test (HUTT) and at least two syncope or presyncope events within 3 months of enrollment. They also needed to be willing and able to practice yoga. Those with structural heart disease, accelerated hypertension, and underlying neurologic disorders were not included in the study.

A total of 55 patients were randomly assigned to receive either a specialized yoga training program in addition to guideline-based therapy, or guideline-based therapy alone. Standard care included physical counterpressure maneuvers, avoidance of known triggers, increased salt and water intake, and drug therapy or pacing at the discretion of the treating physician.

The primary outcome was a composite of the number of episodes of syncope and presyncope at 12 months.    

Secondary outcomes including QoL, assessed using the World Health Organization Quality of Life Brief Field questionnaire (WHOQoL-BREF) and the Syncope Functional Status Questionnaire (SFSQ) at 12 months, a head-up tilt test, and heart rate variability at 6 weeks.

For the first 2 weeks, patients in the intervention group were enrolled in eight supervised yoga sessions conducted at the Centre for Integrative Medicine and Research at the All India Institute of Medical Sciences. For the remainder of the trial, they continued a daily yoga practice at home at least 5 days a week.

The yoga module created for participants was designed with a view to the pathophysiology of VVS and featured postures, breathing, and relaxation techniques. Yoga classes were taught by qualified therapists under the guidance of physicians.

In addition to a booklet with a pictorial of the yoga regimen, participants received twice-monthly calls from the yoga center to encourage compliance. Results show that all participants adhered to their yoga routine for more than 80% of the 12-month trial.

At 12 months, the mean number of syncopal or presyncopal events was 0.7 ± 0.7 with the yoga intervention versus 2.52 ± 1.93 among patients in the control arm (P < .05). The reduction in events started as early as 6 weeks and continued to separate out to 12 months, the researchers note.

Thirteen of 30 (43.3%) intervention patients and 4 of 25 (16%) control patients remained event-free at 12 months, a statistically significant difference (P = .02). There was a trend toward fewer positive head-up tilt tests between groups that did not reach significance, and there was no difference in heart rate variability at 6 weeks.

No adverse events as a result of the yoga practice were reported, and no patient started drug therapy or received pacing therapy during the trial, they note.

The researchers point out that yoga postures can enhance vascular and muscle tone, especially in the lower limbs.

“Yoga breathing and relaxation techniques have been shown to increase vagal tone and improve autonomic balance, which could potentially curtail the sympathetic overdrive phase and interrupt the activation of the c-mechanoreceptors, which is a critical step in the syncope cascade,” they note.

“We postulate that positive effects of yoga in this study could be related to a multidimensional effect of this intervention acting through both central and peripheral mechanisms, including physical, psychological, and autonomic pathways,” the authors conclude.
 

Comprehensive regimen

Dhanunjaya Lakkireddy, MD, medical director for the Kansas City Heart Rhythm Institute, Overland Park, Kansas, says these results are in line with previous research indicating the benefits of yoga in improving cardiovascular function.

“All of this clearly shows that when you [include] a systematic diet of yoga for a reasonable amount of time to improve the plasticity of parasympathetic inputs into the chest and thereby the cardiovascular system ... you can help patients to improve their symptoms,” he said in an interview.  

He already prescribes yoga in his own practice as part of a comprehensive therapeutic regimen, he said. “We have a handful of practitioners all around the city who work with us,” Dr. Lakkireddy said.

Both he and the study authors point the economic burden of VVS both in management and in loss of patient productivity. “A low-cost intervention in the form of yoga, which essentially requires only a mat, can reduce both direct and indirect costs significantly,” note the authors.

The trial was supported under the extramural research (EMR) scheme by the Ministry of AYUSH, Government of India. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Yoga added to conventional therapy for vasovagal syncope (VVS), when patients faint after a sudden drop in heart rate and blood pressure, can reduce symptoms and improve quality of life, new research suggests. 

AndiP/pixabay.com

A small, open-label trial conducted in New Delhi showed that participants practicing yoga reported an improvement in VVS symptoms after only 6 weeks, with a reduction of 1.82 events at 12 months. All those practicing yoga also showed significantly improved quality of life (QoL) scores by the end of the trial.

“Yoga as add-on therapy in VVS is superior to medical therapy in reducing syncopal and presyncopal events and in improving the QoL,” report Gautam Sharma, MD, DM, Centre for Integrative Medicine and Research, All India Institute of Medical Sciences, New Delhi, and colleagues. “It may be useful to integrate a cost-effective and safe intervention such as yoga into the management of VVS.”

Results of the LIVE-Yoga study were published online in JACC: Clinical Electrophysiology.

Vasovagal syncope is a common and non–life-threatening condition, but given the severity and frequency of recurrence it can result in significant deterioration in a patient’s quality of life, the authors note. “Existing management therapies have been largely ineffective,” they write.

Recent trials have suggested some efficacy for yoga in diseases of autonomic imbalance, suggesting a possible use in VVS. To find out, the researchers enrolled adults with VVS between the ages of 15-70 years who had a positive head-up tilt test (HUTT) and at least two syncope or presyncope events within 3 months of enrollment. They also needed to be willing and able to practice yoga. Those with structural heart disease, accelerated hypertension, and underlying neurologic disorders were not included in the study.

A total of 55 patients were randomly assigned to receive either a specialized yoga training program in addition to guideline-based therapy, or guideline-based therapy alone. Standard care included physical counterpressure maneuvers, avoidance of known triggers, increased salt and water intake, and drug therapy or pacing at the discretion of the treating physician.

The primary outcome was a composite of the number of episodes of syncope and presyncope at 12 months.    

Secondary outcomes including QoL, assessed using the World Health Organization Quality of Life Brief Field questionnaire (WHOQoL-BREF) and the Syncope Functional Status Questionnaire (SFSQ) at 12 months, a head-up tilt test, and heart rate variability at 6 weeks.

For the first 2 weeks, patients in the intervention group were enrolled in eight supervised yoga sessions conducted at the Centre for Integrative Medicine and Research at the All India Institute of Medical Sciences. For the remainder of the trial, they continued a daily yoga practice at home at least 5 days a week.

The yoga module created for participants was designed with a view to the pathophysiology of VVS and featured postures, breathing, and relaxation techniques. Yoga classes were taught by qualified therapists under the guidance of physicians.

In addition to a booklet with a pictorial of the yoga regimen, participants received twice-monthly calls from the yoga center to encourage compliance. Results show that all participants adhered to their yoga routine for more than 80% of the 12-month trial.

At 12 months, the mean number of syncopal or presyncopal events was 0.7 ± 0.7 with the yoga intervention versus 2.52 ± 1.93 among patients in the control arm (P < .05). The reduction in events started as early as 6 weeks and continued to separate out to 12 months, the researchers note.

Thirteen of 30 (43.3%) intervention patients and 4 of 25 (16%) control patients remained event-free at 12 months, a statistically significant difference (P = .02). There was a trend toward fewer positive head-up tilt tests between groups that did not reach significance, and there was no difference in heart rate variability at 6 weeks.

No adverse events as a result of the yoga practice were reported, and no patient started drug therapy or received pacing therapy during the trial, they note.

The researchers point out that yoga postures can enhance vascular and muscle tone, especially in the lower limbs.

“Yoga breathing and relaxation techniques have been shown to increase vagal tone and improve autonomic balance, which could potentially curtail the sympathetic overdrive phase and interrupt the activation of the c-mechanoreceptors, which is a critical step in the syncope cascade,” they note.

“We postulate that positive effects of yoga in this study could be related to a multidimensional effect of this intervention acting through both central and peripheral mechanisms, including physical, psychological, and autonomic pathways,” the authors conclude.
 

Comprehensive regimen

Dhanunjaya Lakkireddy, MD, medical director for the Kansas City Heart Rhythm Institute, Overland Park, Kansas, says these results are in line with previous research indicating the benefits of yoga in improving cardiovascular function.

“All of this clearly shows that when you [include] a systematic diet of yoga for a reasonable amount of time to improve the plasticity of parasympathetic inputs into the chest and thereby the cardiovascular system ... you can help patients to improve their symptoms,” he said in an interview.  

He already prescribes yoga in his own practice as part of a comprehensive therapeutic regimen, he said. “We have a handful of practitioners all around the city who work with us,” Dr. Lakkireddy said.

Both he and the study authors point the economic burden of VVS both in management and in loss of patient productivity. “A low-cost intervention in the form of yoga, which essentially requires only a mat, can reduce both direct and indirect costs significantly,” note the authors.

The trial was supported under the extramural research (EMR) scheme by the Ministry of AYUSH, Government of India. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.