User login
Key to denervation response for hypertension may be in carotid body
NATIONAL HARBOR, MD. – Of characteristics that might predict which patients with resistant hypertension will respond to carotid body ablation, the relative activity of the carotid body organ itself might be critical for moving this technology forward, an investigator on a first-in-man study suggests.
The study, first presented in 2018 at the European Society of Cardiology congress, showed carotid body ablation resulted in significant but modest reductions in blood pressure in patients with resistant hypertension.
For many reasons, the carotid body is an attractive target for sustained or indefinite control of resistant hypertension, but median systolic blood pressure reductions following ultrasound ablation were highly variable in the first-in-man study, according to Felix Mahfoud, MD, of Saarland University Hospital in Homburg, Germany, a coinvestigator on the study who discussed the findings at CRT 2020 sponsored by MedStar Heart & Vascular Institute.
Of several strategies being pursued to separate those most likely to gain a major benefit, simply measuring carotid body activity is now emerging as particularly promising.
“Patients with a high degree of carotid body activity had a significantly larger fall in blood pressure versus all other methods of grouping patients,” Dr. Mahfoud reported.
The carotid body is a “grain-size” organ of about 2 mm in size that sits on the carotid bifurcation. It communicates directly with the brain to alter sympathetic activity in response to changing levels of such physiologic variable as oxygen, carbon dioxide, and pH, according to Dr. Mahfoud.
In a 2016 proof-of-principle study conducted in resistant hypertension patients, surgical resection of the carotid body was associated with a median 18–mm Hg reduction in systolic blood pressure (SBP) on 24-hour ambulatory monitoring that was sustained through 24 months (Narkiewicz K et al. JACC Basic Transl Sci. 2016;29:313-24).
Subsequently, ultrasound ablation of the carotid body was by way of a transcatheter approach. Dr. Mahfoud’s unpublished first-in-man study, conducted in 2018 enrolled 38 patients with resistant hypertension. The median reductions from baseline of 7-8 mm Hg at 1, 3, and 6 months were significant (P less than .01), but the benefit was disappointingly modest.
However, the variability was large. Some patients achieved SBP reductions of up to 20 mm Hg at 6 months, prompting additional analyses to understand if the best responders could be identified. When compared to the mean reduction of 7 mm Hg at 6 months, this represented a 13–mm Hg additional reduction. There are now several potential approaches being considered.
In addition to carotid body activity, which is readily measured and has substantial potential to serve as a routine selection criterion, isolated systolic hypertension (ISH) was also found to be a discriminator for response. For those with ISH, which Dr. Mahfoud noted is also characterized as “stiff arteries,” SBP reductions at 6 months were negligible, but in those without ISH, the median reduction from baseline was 11 mm Hg.
Further investigations are now planned to evaluate potential predictors of response, according to Dr. Mahfoud. He believes carotid body ablation might have advantages over alternatives, including other experimental therapies, in at least some patients.
To deliver ultrasound ablation in the first-in-man study, a propriety catheter (Cibiem transvenous system) was advanced through the jugular vein guided with intravascular ultrasound. When the carotid body was reached, two to three ultrasound ablations of 8-12 seconds each were applied. The procedure time was 20-30 minutes.
Initially, an arterial approach to the carotid body was used. However, after a transient ischemic attack early in the series, the approach was switched to the jugular vein. There have been no serious subsequent procedural-related complications since.
Although the median SBP reductions were modest, they were not insignificant in a population selected for severe resistant hypertension. The median SBP at entry was 180 mm Hg in patients taking a median of 4.5 antihypertensive drugs, according to Dr. Mahfoud.
In other words, this approach still retains promise for selected patients if larger studies demonstrate that response can be predicted, and the data continue to support tolerability.
A venous approach to the carotid body with intravascular ultrasound guidance and therapeutic ultrasound appears “to offer a safe and effective treatment option in resistant hypertension,” according to Dr. Mahfoud. “A companion diagnostic test is being developed to determine whether patients are likely to respond to this therapy.”
Dr. Mahfoud reports financial relationships with Medtronic, St. Jude, and ReCor.
This article was updated to clarify the study details and correct misspellings of the presenter's name.
SOURCE: CRT 2020.
NATIONAL HARBOR, MD. – Of characteristics that might predict which patients with resistant hypertension will respond to carotid body ablation, the relative activity of the carotid body organ itself might be critical for moving this technology forward, an investigator on a first-in-man study suggests.
The study, first presented in 2018 at the European Society of Cardiology congress, showed carotid body ablation resulted in significant but modest reductions in blood pressure in patients with resistant hypertension.
For many reasons, the carotid body is an attractive target for sustained or indefinite control of resistant hypertension, but median systolic blood pressure reductions following ultrasound ablation were highly variable in the first-in-man study, according to Felix Mahfoud, MD, of Saarland University Hospital in Homburg, Germany, a coinvestigator on the study who discussed the findings at CRT 2020 sponsored by MedStar Heart & Vascular Institute.
Of several strategies being pursued to separate those most likely to gain a major benefit, simply measuring carotid body activity is now emerging as particularly promising.
“Patients with a high degree of carotid body activity had a significantly larger fall in blood pressure versus all other methods of grouping patients,” Dr. Mahfoud reported.
The carotid body is a “grain-size” organ of about 2 mm in size that sits on the carotid bifurcation. It communicates directly with the brain to alter sympathetic activity in response to changing levels of such physiologic variable as oxygen, carbon dioxide, and pH, according to Dr. Mahfoud.
In a 2016 proof-of-principle study conducted in resistant hypertension patients, surgical resection of the carotid body was associated with a median 18–mm Hg reduction in systolic blood pressure (SBP) on 24-hour ambulatory monitoring that was sustained through 24 months (Narkiewicz K et al. JACC Basic Transl Sci. 2016;29:313-24).
Subsequently, ultrasound ablation of the carotid body was by way of a transcatheter approach. Dr. Mahfoud’s unpublished first-in-man study, conducted in 2018 enrolled 38 patients with resistant hypertension. The median reductions from baseline of 7-8 mm Hg at 1, 3, and 6 months were significant (P less than .01), but the benefit was disappointingly modest.
However, the variability was large. Some patients achieved SBP reductions of up to 20 mm Hg at 6 months, prompting additional analyses to understand if the best responders could be identified. When compared to the mean reduction of 7 mm Hg at 6 months, this represented a 13–mm Hg additional reduction. There are now several potential approaches being considered.
In addition to carotid body activity, which is readily measured and has substantial potential to serve as a routine selection criterion, isolated systolic hypertension (ISH) was also found to be a discriminator for response. For those with ISH, which Dr. Mahfoud noted is also characterized as “stiff arteries,” SBP reductions at 6 months were negligible, but in those without ISH, the median reduction from baseline was 11 mm Hg.
Further investigations are now planned to evaluate potential predictors of response, according to Dr. Mahfoud. He believes carotid body ablation might have advantages over alternatives, including other experimental therapies, in at least some patients.
To deliver ultrasound ablation in the first-in-man study, a propriety catheter (Cibiem transvenous system) was advanced through the jugular vein guided with intravascular ultrasound. When the carotid body was reached, two to three ultrasound ablations of 8-12 seconds each were applied. The procedure time was 20-30 minutes.
Initially, an arterial approach to the carotid body was used. However, after a transient ischemic attack early in the series, the approach was switched to the jugular vein. There have been no serious subsequent procedural-related complications since.
Although the median SBP reductions were modest, they were not insignificant in a population selected for severe resistant hypertension. The median SBP at entry was 180 mm Hg in patients taking a median of 4.5 antihypertensive drugs, according to Dr. Mahfoud.
In other words, this approach still retains promise for selected patients if larger studies demonstrate that response can be predicted, and the data continue to support tolerability.
A venous approach to the carotid body with intravascular ultrasound guidance and therapeutic ultrasound appears “to offer a safe and effective treatment option in resistant hypertension,” according to Dr. Mahfoud. “A companion diagnostic test is being developed to determine whether patients are likely to respond to this therapy.”
Dr. Mahfoud reports financial relationships with Medtronic, St. Jude, and ReCor.
This article was updated to clarify the study details and correct misspellings of the presenter's name.
SOURCE: CRT 2020.
NATIONAL HARBOR, MD. – Of characteristics that might predict which patients with resistant hypertension will respond to carotid body ablation, the relative activity of the carotid body organ itself might be critical for moving this technology forward, an investigator on a first-in-man study suggests.
The study, first presented in 2018 at the European Society of Cardiology congress, showed carotid body ablation resulted in significant but modest reductions in blood pressure in patients with resistant hypertension.
For many reasons, the carotid body is an attractive target for sustained or indefinite control of resistant hypertension, but median systolic blood pressure reductions following ultrasound ablation were highly variable in the first-in-man study, according to Felix Mahfoud, MD, of Saarland University Hospital in Homburg, Germany, a coinvestigator on the study who discussed the findings at CRT 2020 sponsored by MedStar Heart & Vascular Institute.
Of several strategies being pursued to separate those most likely to gain a major benefit, simply measuring carotid body activity is now emerging as particularly promising.
“Patients with a high degree of carotid body activity had a significantly larger fall in blood pressure versus all other methods of grouping patients,” Dr. Mahfoud reported.
The carotid body is a “grain-size” organ of about 2 mm in size that sits on the carotid bifurcation. It communicates directly with the brain to alter sympathetic activity in response to changing levels of such physiologic variable as oxygen, carbon dioxide, and pH, according to Dr. Mahfoud.
In a 2016 proof-of-principle study conducted in resistant hypertension patients, surgical resection of the carotid body was associated with a median 18–mm Hg reduction in systolic blood pressure (SBP) on 24-hour ambulatory monitoring that was sustained through 24 months (Narkiewicz K et al. JACC Basic Transl Sci. 2016;29:313-24).
Subsequently, ultrasound ablation of the carotid body was by way of a transcatheter approach. Dr. Mahfoud’s unpublished first-in-man study, conducted in 2018 enrolled 38 patients with resistant hypertension. The median reductions from baseline of 7-8 mm Hg at 1, 3, and 6 months were significant (P less than .01), but the benefit was disappointingly modest.
However, the variability was large. Some patients achieved SBP reductions of up to 20 mm Hg at 6 months, prompting additional analyses to understand if the best responders could be identified. When compared to the mean reduction of 7 mm Hg at 6 months, this represented a 13–mm Hg additional reduction. There are now several potential approaches being considered.
In addition to carotid body activity, which is readily measured and has substantial potential to serve as a routine selection criterion, isolated systolic hypertension (ISH) was also found to be a discriminator for response. For those with ISH, which Dr. Mahfoud noted is also characterized as “stiff arteries,” SBP reductions at 6 months were negligible, but in those without ISH, the median reduction from baseline was 11 mm Hg.
Further investigations are now planned to evaluate potential predictors of response, according to Dr. Mahfoud. He believes carotid body ablation might have advantages over alternatives, including other experimental therapies, in at least some patients.
To deliver ultrasound ablation in the first-in-man study, a propriety catheter (Cibiem transvenous system) was advanced through the jugular vein guided with intravascular ultrasound. When the carotid body was reached, two to three ultrasound ablations of 8-12 seconds each were applied. The procedure time was 20-30 minutes.
Initially, an arterial approach to the carotid body was used. However, after a transient ischemic attack early in the series, the approach was switched to the jugular vein. There have been no serious subsequent procedural-related complications since.
Although the median SBP reductions were modest, they were not insignificant in a population selected for severe resistant hypertension. The median SBP at entry was 180 mm Hg in patients taking a median of 4.5 antihypertensive drugs, according to Dr. Mahfoud.
In other words, this approach still retains promise for selected patients if larger studies demonstrate that response can be predicted, and the data continue to support tolerability.
A venous approach to the carotid body with intravascular ultrasound guidance and therapeutic ultrasound appears “to offer a safe and effective treatment option in resistant hypertension,” according to Dr. Mahfoud. “A companion diagnostic test is being developed to determine whether patients are likely to respond to this therapy.”
Dr. Mahfoud reports financial relationships with Medtronic, St. Jude, and ReCor.
This article was updated to clarify the study details and correct misspellings of the presenter's name.
SOURCE: CRT 2020.
REPORTING FROM CRT 2020
Study implicates gut bacteria in PAH
Model finds microbiota highly predictive
A unique collection of bacteria in the gut may have a strong association with pulmonary arterial hypertension and could be highly predictive of the disease in undiagnosed patients, according to a study published in the journal Hypertension.
This is the first study to show that people with PAH have a common specific gut microbiota profile, wrote lead study author Mohan Raizada, PhD, distinguished professor in the department of physiology and functional genomics at the University of Florida, Gainesville.
The findings have the potential to change how cardiologists diagnose and treat PAH, he added. “While current PAH treatments focus on the lungs, looking at the lung/gut axis could open the door to new therapies centered in the digestive system,” Dr. Raizada said.
The researchers developed a model that found the specific microbiota profile was 83% accurate in predicting the presence or absence of PAH. If a larger study can validate the findings, the researchers wrote, this could lead to a new test for diagnosing PAH that’s less invasive than cardiac catheterization. It could also lead to new treatments that target the gut microbiome.
Study investigators collected stool samples from 18 PAH patients and 12 people without a history of cardiopulmonary disease. The microbiota DNA from the stool samples were isolated and sequenced. The analysis revealed that PAH patients had reduced richness and evenness of the gut bacteria, known as alpha diversity. They had increased levels of bacteria associated with atherosclerosis, and healthy patients had increased levels of bacteria that produced short-chain fatty acids.
Although recent studies have begun to show potential associations between the gut microbiome and cardiovascular diseases, this research is in its infancy, Mariell Jessup, MD, commented. “Even though the study by Dr. Raizada and colleagues predicted pulmonary arterial hypertension based on an individual’s microbiome with some accuracy, it is an observational study, so it does not prove cause and effect. Many other factors, especially diet, affect the gut microbiome,” added Dr. Jessup, Chief Science and Medical Officer for the American Heart Association.
She stressed that, “In addition, even if studies confirm an association between the gut microbiome and cardiovascular diseases such as PAH, more research is needed to determine if improving gut microbiota could directly impact PAH or other cardiovascular diseases. The findings of this study will not impact clinical practice.”
Dr. Raizada and his coinvestigators offered two possible mechanisms through which the gut microbiome influences pulmonary physiology. One is that lower levels of bacteria that produce the short-chain fatty acid butyrate, such as Coprococcus, Butyrivibrio, Lachnospiraceae, and Eubacterium, along with Clostridia in the gut of PAH patients, may increase gut permeability. Reduced butyrate weakens gut barrier function and can induce inflammation and leakage. This can allow microbial metabolites to enter the circulatory system, disrupting metabolism and immunity and affecting pulmonary vessels.
The second potential mechanism is that increased Collinsella in the PAH cohort may be the culprit that increases gut permeability, resulting in the ensuing gut barrier dysfunction and inflammation. The study noted Collinsella contributed most of the increased genes for the biosynthesis on the amino acid proline in these patients, and that a previous study implicated Collinsella and its parent, Cariobacteriales, in trimethylamine/trimethylamine N-oxide production (TMA/TMAO) in atherosclerosis (Cell. 2015;163[7]:1585-95). The non-PAH patients had higher levels of bacteria that had a low correlation with TMA/TMAO.
“We were very surprised to see such an association within a small group of study subjects,” wrote Dr. Raizada and associates. “It usually requires hundreds of patients to achieve such significance.”
More research is needed to determine if the specific microbiota associated with PAH causes the disease or is a result of it, they concluded.
The study was funded by grants from the National Institutes of Health, the NIH National Center for Research Resources, and the U.S. Department of Defense. Dr. Raizada and coauthors reported no relevant financial relationships.
SOURCE: Raizada MK et al. Hypertension. 2020. doi: 10.1161/HYPERTENSIONAHA.119.14294.
Model finds microbiota highly predictive
Model finds microbiota highly predictive
A unique collection of bacteria in the gut may have a strong association with pulmonary arterial hypertension and could be highly predictive of the disease in undiagnosed patients, according to a study published in the journal Hypertension.
This is the first study to show that people with PAH have a common specific gut microbiota profile, wrote lead study author Mohan Raizada, PhD, distinguished professor in the department of physiology and functional genomics at the University of Florida, Gainesville.
The findings have the potential to change how cardiologists diagnose and treat PAH, he added. “While current PAH treatments focus on the lungs, looking at the lung/gut axis could open the door to new therapies centered in the digestive system,” Dr. Raizada said.
The researchers developed a model that found the specific microbiota profile was 83% accurate in predicting the presence or absence of PAH. If a larger study can validate the findings, the researchers wrote, this could lead to a new test for diagnosing PAH that’s less invasive than cardiac catheterization. It could also lead to new treatments that target the gut microbiome.
Study investigators collected stool samples from 18 PAH patients and 12 people without a history of cardiopulmonary disease. The microbiota DNA from the stool samples were isolated and sequenced. The analysis revealed that PAH patients had reduced richness and evenness of the gut bacteria, known as alpha diversity. They had increased levels of bacteria associated with atherosclerosis, and healthy patients had increased levels of bacteria that produced short-chain fatty acids.
Although recent studies have begun to show potential associations between the gut microbiome and cardiovascular diseases, this research is in its infancy, Mariell Jessup, MD, commented. “Even though the study by Dr. Raizada and colleagues predicted pulmonary arterial hypertension based on an individual’s microbiome with some accuracy, it is an observational study, so it does not prove cause and effect. Many other factors, especially diet, affect the gut microbiome,” added Dr. Jessup, Chief Science and Medical Officer for the American Heart Association.
She stressed that, “In addition, even if studies confirm an association between the gut microbiome and cardiovascular diseases such as PAH, more research is needed to determine if improving gut microbiota could directly impact PAH or other cardiovascular diseases. The findings of this study will not impact clinical practice.”
Dr. Raizada and his coinvestigators offered two possible mechanisms through which the gut microbiome influences pulmonary physiology. One is that lower levels of bacteria that produce the short-chain fatty acid butyrate, such as Coprococcus, Butyrivibrio, Lachnospiraceae, and Eubacterium, along with Clostridia in the gut of PAH patients, may increase gut permeability. Reduced butyrate weakens gut barrier function and can induce inflammation and leakage. This can allow microbial metabolites to enter the circulatory system, disrupting metabolism and immunity and affecting pulmonary vessels.
The second potential mechanism is that increased Collinsella in the PAH cohort may be the culprit that increases gut permeability, resulting in the ensuing gut barrier dysfunction and inflammation. The study noted Collinsella contributed most of the increased genes for the biosynthesis on the amino acid proline in these patients, and that a previous study implicated Collinsella and its parent, Cariobacteriales, in trimethylamine/trimethylamine N-oxide production (TMA/TMAO) in atherosclerosis (Cell. 2015;163[7]:1585-95). The non-PAH patients had higher levels of bacteria that had a low correlation with TMA/TMAO.
“We were very surprised to see such an association within a small group of study subjects,” wrote Dr. Raizada and associates. “It usually requires hundreds of patients to achieve such significance.”
More research is needed to determine if the specific microbiota associated with PAH causes the disease or is a result of it, they concluded.
The study was funded by grants from the National Institutes of Health, the NIH National Center for Research Resources, and the U.S. Department of Defense. Dr. Raizada and coauthors reported no relevant financial relationships.
SOURCE: Raizada MK et al. Hypertension. 2020. doi: 10.1161/HYPERTENSIONAHA.119.14294.
A unique collection of bacteria in the gut may have a strong association with pulmonary arterial hypertension and could be highly predictive of the disease in undiagnosed patients, according to a study published in the journal Hypertension.
This is the first study to show that people with PAH have a common specific gut microbiota profile, wrote lead study author Mohan Raizada, PhD, distinguished professor in the department of physiology and functional genomics at the University of Florida, Gainesville.
The findings have the potential to change how cardiologists diagnose and treat PAH, he added. “While current PAH treatments focus on the lungs, looking at the lung/gut axis could open the door to new therapies centered in the digestive system,” Dr. Raizada said.
The researchers developed a model that found the specific microbiota profile was 83% accurate in predicting the presence or absence of PAH. If a larger study can validate the findings, the researchers wrote, this could lead to a new test for diagnosing PAH that’s less invasive than cardiac catheterization. It could also lead to new treatments that target the gut microbiome.
Study investigators collected stool samples from 18 PAH patients and 12 people without a history of cardiopulmonary disease. The microbiota DNA from the stool samples were isolated and sequenced. The analysis revealed that PAH patients had reduced richness and evenness of the gut bacteria, known as alpha diversity. They had increased levels of bacteria associated with atherosclerosis, and healthy patients had increased levels of bacteria that produced short-chain fatty acids.
Although recent studies have begun to show potential associations between the gut microbiome and cardiovascular diseases, this research is in its infancy, Mariell Jessup, MD, commented. “Even though the study by Dr. Raizada and colleagues predicted pulmonary arterial hypertension based on an individual’s microbiome with some accuracy, it is an observational study, so it does not prove cause and effect. Many other factors, especially diet, affect the gut microbiome,” added Dr. Jessup, Chief Science and Medical Officer for the American Heart Association.
She stressed that, “In addition, even if studies confirm an association between the gut microbiome and cardiovascular diseases such as PAH, more research is needed to determine if improving gut microbiota could directly impact PAH or other cardiovascular diseases. The findings of this study will not impact clinical practice.”
Dr. Raizada and his coinvestigators offered two possible mechanisms through which the gut microbiome influences pulmonary physiology. One is that lower levels of bacteria that produce the short-chain fatty acid butyrate, such as Coprococcus, Butyrivibrio, Lachnospiraceae, and Eubacterium, along with Clostridia in the gut of PAH patients, may increase gut permeability. Reduced butyrate weakens gut barrier function and can induce inflammation and leakage. This can allow microbial metabolites to enter the circulatory system, disrupting metabolism and immunity and affecting pulmonary vessels.
The second potential mechanism is that increased Collinsella in the PAH cohort may be the culprit that increases gut permeability, resulting in the ensuing gut barrier dysfunction and inflammation. The study noted Collinsella contributed most of the increased genes for the biosynthesis on the amino acid proline in these patients, and that a previous study implicated Collinsella and its parent, Cariobacteriales, in trimethylamine/trimethylamine N-oxide production (TMA/TMAO) in atherosclerosis (Cell. 2015;163[7]:1585-95). The non-PAH patients had higher levels of bacteria that had a low correlation with TMA/TMAO.
“We were very surprised to see such an association within a small group of study subjects,” wrote Dr. Raizada and associates. “It usually requires hundreds of patients to achieve such significance.”
More research is needed to determine if the specific microbiota associated with PAH causes the disease or is a result of it, they concluded.
The study was funded by grants from the National Institutes of Health, the NIH National Center for Research Resources, and the U.S. Department of Defense. Dr. Raizada and coauthors reported no relevant financial relationships.
SOURCE: Raizada MK et al. Hypertension. 2020. doi: 10.1161/HYPERTENSIONAHA.119.14294.
FROM HYPERTENSION
Exercise PH poised for comeback as new definition takes hold
Patients with a pulmonary artery pressure/cardiac output slope greater than 3 mm Hg/L/min on cardiopulmonary exercise tests have more than double the risk of cardiovascular hospitalization and all-cause mortality, according to a prospective study of 714 subjects with exertional dyspnea but preserved ejection fractions.
The findings “suggest that across a wide range of individuals with chronic dyspnea, exercise can unmask abnormal pulmonary vascular responses that in turn bear significant clinical implications. These findings, coupled with a growing body of work ... suggest that reintroduction of an exercise based definition of [pulmonary hypertension (PH)] in PH guidelines” – using the pulmonary artery pressure/cardiac output slope – “merits consideration,” wrote Jennifer Ho, MD, a heart failure and transplantation cardiologist at Massachusetts General Hospital, Boston, and colleagues (J Am Coll Cardiol. 2020 Jan 7;75[1]:17-26. doi: 10.1016/j.jacc.2019.10.048).
A new definition takes hold
The slope captures the steepness of pulmonary artery pressure increase as cardiac output goes up, giving a measure of overall pulmonary resistance. A value above 3 mm Hg/L/min means that pulmonary artery pressure (PAP) is too high for a given cardiac output (CO). The slope “is preferable to using a single absolute cut point value for exercise PAP” to define exercise pulmonary hypertension.“ Indeed, we confirm that in the absence of elevated PAP/CO, an absolute exercise PAP [above] 30 mm Hg” – the definition of exercise-induced pulmonary hypertension in years past – “does not portend worse outcomes,” Dr. Ho and her team noted.
In an accompanying editorial titled, “Exercise Pulmonary Hypertension Is Back,” Marius Hoeper, MD, a senior physician in the department of respiratory medicine at Hannover (Germany) Medical School, explained that the findings likely signal the revival of exercise pulmonary hypertension as a useful clinical concept (J Am Coll Cardiol. 2020 Jan 7;75[1]:27-8. doi: 10.1016/j.jacc.2019.11.010).
The standalone 30 mm Hg cut point was largely abandoned about a decade ago when it was realized that pressures above that mark were “not necessarily abnormal in certain subjects, for instance in athletes or elderly individuals,” he said.
But it’s become clear in recent years, and now confirmed by Dr. Ho and her team, that what matters is not the stand-alone measurement, but it’s relationship to cardiac output. “There is now sufficient evidence to define exercise PH by an abnormal [mean]PAP/CO slope [above] 3 mm Hg/L/min,” Dr. Hoeper said.
Abnormal slopes in over 40%
Each subject in the Massachusetts General study had an average of 10 paired PAP and CO measurements taken by invasive hemodynamic monitoring, including pulmonary artery catheterization via the internal jugular vein, while they road a stationary bicycle. The measurements were used to calculate the PAP/CO slope. A slope greater than 3 mm Hg/L/min was defined as abnormal based on previous research.
Results of the one-time assessment were correlated with the study’s primary outcome – cardiovascular hospitalization or all-cause death – over a mean follow up of 3.7 years. Subjects were 57 years old, on average, and 59% were women; just 2% had a previous diagnosis of pulmonary hypertension. Overall, 41% of the subjects had abnormal PAP/CO slopes, 26% had abnormal slopes without resting pulmonary hypertension, and 208 subjects (29%) met the primary outcome.
After adjustments for age, sex, and cardiopulmonary comorbidities, abnormal slopes more than doubled the risk of the primary outcome (hazard ratio [HR] 2.03; 95% confidence interval [CI]: 1.48-2.78; P less than .001). The risk remained elevated even in the absence of resting pulmonary hypertension (HR 1.75, 95% CI 1.21-2.54, P = .003), and in people with only mildly elevated resting PAPs of 21-29 mm Hg.
Older people were more likely to have abnormally elevated slopes, as well as were those with cardiopulmonary comorbidities, lower exercise tolerance, lower peak oxygen uptake, and more severely impaired right ventricular function. Diabetes, prior heart failure, chronic obstructive pulmonary disease, and interstitial lung disease were more prevalent in the elevated slope group, and their median N-terminal pro–B type natriuretic peptide level was 154 pg/mL, versus 52 pg/mL among people with normal slopes.
A simpler test is needed
In his editorial, Dr. Hoeper noted that diagnosing exercise PH by elevated slope “will occasionally help physicians and patients to better understand exertional dyspnea and to detect early pulmonary vascular disease in patients at risk,” but for the most part, the new definition “will have little immediate [effect] on clinical practice, as evidence-based treatments for this condition are not yet available.”
Even so, “having a globally accepted gold standard” for exercise PH based on the PAP/CO slope might well spur development of “simpler, noninvasive” ways to measure it so it can be used outside of specialty settings.
Dr. Ho and her team agreed. “These findings should prompt additional work using less invasive measurement modalities such as exercise echocardiography to evaluate” exercise PAP/CO slopes, they said.
The work was funded by the National Institutes of Health, Gilead Sciences, the American Heart Association, and the Massachusetts General Hospital Heart Failure Research Innovation Fund. The investigators had no relevant disclosures. Dr. Hoeper reported lecture and consultation fees from Actelion, Bayer, Merck Sharp and Dohme, and Pfizer.
SOURCE: Ho JE et al., J Am Coll Cardiol. 2020 Jan 7;75(1):17-26. doi: 10.1016/j.jacc.2019.10.048.
Patients with a pulmonary artery pressure/cardiac output slope greater than 3 mm Hg/L/min on cardiopulmonary exercise tests have more than double the risk of cardiovascular hospitalization and all-cause mortality, according to a prospective study of 714 subjects with exertional dyspnea but preserved ejection fractions.
The findings “suggest that across a wide range of individuals with chronic dyspnea, exercise can unmask abnormal pulmonary vascular responses that in turn bear significant clinical implications. These findings, coupled with a growing body of work ... suggest that reintroduction of an exercise based definition of [pulmonary hypertension (PH)] in PH guidelines” – using the pulmonary artery pressure/cardiac output slope – “merits consideration,” wrote Jennifer Ho, MD, a heart failure and transplantation cardiologist at Massachusetts General Hospital, Boston, and colleagues (J Am Coll Cardiol. 2020 Jan 7;75[1]:17-26. doi: 10.1016/j.jacc.2019.10.048).
A new definition takes hold
The slope captures the steepness of pulmonary artery pressure increase as cardiac output goes up, giving a measure of overall pulmonary resistance. A value above 3 mm Hg/L/min means that pulmonary artery pressure (PAP) is too high for a given cardiac output (CO). The slope “is preferable to using a single absolute cut point value for exercise PAP” to define exercise pulmonary hypertension.“ Indeed, we confirm that in the absence of elevated PAP/CO, an absolute exercise PAP [above] 30 mm Hg” – the definition of exercise-induced pulmonary hypertension in years past – “does not portend worse outcomes,” Dr. Ho and her team noted.
In an accompanying editorial titled, “Exercise Pulmonary Hypertension Is Back,” Marius Hoeper, MD, a senior physician in the department of respiratory medicine at Hannover (Germany) Medical School, explained that the findings likely signal the revival of exercise pulmonary hypertension as a useful clinical concept (J Am Coll Cardiol. 2020 Jan 7;75[1]:27-8. doi: 10.1016/j.jacc.2019.11.010).
The standalone 30 mm Hg cut point was largely abandoned about a decade ago when it was realized that pressures above that mark were “not necessarily abnormal in certain subjects, for instance in athletes or elderly individuals,” he said.
But it’s become clear in recent years, and now confirmed by Dr. Ho and her team, that what matters is not the stand-alone measurement, but it’s relationship to cardiac output. “There is now sufficient evidence to define exercise PH by an abnormal [mean]PAP/CO slope [above] 3 mm Hg/L/min,” Dr. Hoeper said.
Abnormal slopes in over 40%
Each subject in the Massachusetts General study had an average of 10 paired PAP and CO measurements taken by invasive hemodynamic monitoring, including pulmonary artery catheterization via the internal jugular vein, while they road a stationary bicycle. The measurements were used to calculate the PAP/CO slope. A slope greater than 3 mm Hg/L/min was defined as abnormal based on previous research.
Results of the one-time assessment were correlated with the study’s primary outcome – cardiovascular hospitalization or all-cause death – over a mean follow up of 3.7 years. Subjects were 57 years old, on average, and 59% were women; just 2% had a previous diagnosis of pulmonary hypertension. Overall, 41% of the subjects had abnormal PAP/CO slopes, 26% had abnormal slopes without resting pulmonary hypertension, and 208 subjects (29%) met the primary outcome.
After adjustments for age, sex, and cardiopulmonary comorbidities, abnormal slopes more than doubled the risk of the primary outcome (hazard ratio [HR] 2.03; 95% confidence interval [CI]: 1.48-2.78; P less than .001). The risk remained elevated even in the absence of resting pulmonary hypertension (HR 1.75, 95% CI 1.21-2.54, P = .003), and in people with only mildly elevated resting PAPs of 21-29 mm Hg.
Older people were more likely to have abnormally elevated slopes, as well as were those with cardiopulmonary comorbidities, lower exercise tolerance, lower peak oxygen uptake, and more severely impaired right ventricular function. Diabetes, prior heart failure, chronic obstructive pulmonary disease, and interstitial lung disease were more prevalent in the elevated slope group, and their median N-terminal pro–B type natriuretic peptide level was 154 pg/mL, versus 52 pg/mL among people with normal slopes.
A simpler test is needed
In his editorial, Dr. Hoeper noted that diagnosing exercise PH by elevated slope “will occasionally help physicians and patients to better understand exertional dyspnea and to detect early pulmonary vascular disease in patients at risk,” but for the most part, the new definition “will have little immediate [effect] on clinical practice, as evidence-based treatments for this condition are not yet available.”
Even so, “having a globally accepted gold standard” for exercise PH based on the PAP/CO slope might well spur development of “simpler, noninvasive” ways to measure it so it can be used outside of specialty settings.
Dr. Ho and her team agreed. “These findings should prompt additional work using less invasive measurement modalities such as exercise echocardiography to evaluate” exercise PAP/CO slopes, they said.
The work was funded by the National Institutes of Health, Gilead Sciences, the American Heart Association, and the Massachusetts General Hospital Heart Failure Research Innovation Fund. The investigators had no relevant disclosures. Dr. Hoeper reported lecture and consultation fees from Actelion, Bayer, Merck Sharp and Dohme, and Pfizer.
SOURCE: Ho JE et al., J Am Coll Cardiol. 2020 Jan 7;75(1):17-26. doi: 10.1016/j.jacc.2019.10.048.
Patients with a pulmonary artery pressure/cardiac output slope greater than 3 mm Hg/L/min on cardiopulmonary exercise tests have more than double the risk of cardiovascular hospitalization and all-cause mortality, according to a prospective study of 714 subjects with exertional dyspnea but preserved ejection fractions.
The findings “suggest that across a wide range of individuals with chronic dyspnea, exercise can unmask abnormal pulmonary vascular responses that in turn bear significant clinical implications. These findings, coupled with a growing body of work ... suggest that reintroduction of an exercise based definition of [pulmonary hypertension (PH)] in PH guidelines” – using the pulmonary artery pressure/cardiac output slope – “merits consideration,” wrote Jennifer Ho, MD, a heart failure and transplantation cardiologist at Massachusetts General Hospital, Boston, and colleagues (J Am Coll Cardiol. 2020 Jan 7;75[1]:17-26. doi: 10.1016/j.jacc.2019.10.048).
A new definition takes hold
The slope captures the steepness of pulmonary artery pressure increase as cardiac output goes up, giving a measure of overall pulmonary resistance. A value above 3 mm Hg/L/min means that pulmonary artery pressure (PAP) is too high for a given cardiac output (CO). The slope “is preferable to using a single absolute cut point value for exercise PAP” to define exercise pulmonary hypertension.“ Indeed, we confirm that in the absence of elevated PAP/CO, an absolute exercise PAP [above] 30 mm Hg” – the definition of exercise-induced pulmonary hypertension in years past – “does not portend worse outcomes,” Dr. Ho and her team noted.
In an accompanying editorial titled, “Exercise Pulmonary Hypertension Is Back,” Marius Hoeper, MD, a senior physician in the department of respiratory medicine at Hannover (Germany) Medical School, explained that the findings likely signal the revival of exercise pulmonary hypertension as a useful clinical concept (J Am Coll Cardiol. 2020 Jan 7;75[1]:27-8. doi: 10.1016/j.jacc.2019.11.010).
The standalone 30 mm Hg cut point was largely abandoned about a decade ago when it was realized that pressures above that mark were “not necessarily abnormal in certain subjects, for instance in athletes or elderly individuals,” he said.
But it’s become clear in recent years, and now confirmed by Dr. Ho and her team, that what matters is not the stand-alone measurement, but it’s relationship to cardiac output. “There is now sufficient evidence to define exercise PH by an abnormal [mean]PAP/CO slope [above] 3 mm Hg/L/min,” Dr. Hoeper said.
Abnormal slopes in over 40%
Each subject in the Massachusetts General study had an average of 10 paired PAP and CO measurements taken by invasive hemodynamic monitoring, including pulmonary artery catheterization via the internal jugular vein, while they road a stationary bicycle. The measurements were used to calculate the PAP/CO slope. A slope greater than 3 mm Hg/L/min was defined as abnormal based on previous research.
Results of the one-time assessment were correlated with the study’s primary outcome – cardiovascular hospitalization or all-cause death – over a mean follow up of 3.7 years. Subjects were 57 years old, on average, and 59% were women; just 2% had a previous diagnosis of pulmonary hypertension. Overall, 41% of the subjects had abnormal PAP/CO slopes, 26% had abnormal slopes without resting pulmonary hypertension, and 208 subjects (29%) met the primary outcome.
After adjustments for age, sex, and cardiopulmonary comorbidities, abnormal slopes more than doubled the risk of the primary outcome (hazard ratio [HR] 2.03; 95% confidence interval [CI]: 1.48-2.78; P less than .001). The risk remained elevated even in the absence of resting pulmonary hypertension (HR 1.75, 95% CI 1.21-2.54, P = .003), and in people with only mildly elevated resting PAPs of 21-29 mm Hg.
Older people were more likely to have abnormally elevated slopes, as well as were those with cardiopulmonary comorbidities, lower exercise tolerance, lower peak oxygen uptake, and more severely impaired right ventricular function. Diabetes, prior heart failure, chronic obstructive pulmonary disease, and interstitial lung disease were more prevalent in the elevated slope group, and their median N-terminal pro–B type natriuretic peptide level was 154 pg/mL, versus 52 pg/mL among people with normal slopes.
A simpler test is needed
In his editorial, Dr. Hoeper noted that diagnosing exercise PH by elevated slope “will occasionally help physicians and patients to better understand exertional dyspnea and to detect early pulmonary vascular disease in patients at risk,” but for the most part, the new definition “will have little immediate [effect] on clinical practice, as evidence-based treatments for this condition are not yet available.”
Even so, “having a globally accepted gold standard” for exercise PH based on the PAP/CO slope might well spur development of “simpler, noninvasive” ways to measure it so it can be used outside of specialty settings.
Dr. Ho and her team agreed. “These findings should prompt additional work using less invasive measurement modalities such as exercise echocardiography to evaluate” exercise PAP/CO slopes, they said.
The work was funded by the National Institutes of Health, Gilead Sciences, the American Heart Association, and the Massachusetts General Hospital Heart Failure Research Innovation Fund. The investigators had no relevant disclosures. Dr. Hoeper reported lecture and consultation fees from Actelion, Bayer, Merck Sharp and Dohme, and Pfizer.
SOURCE: Ho JE et al., J Am Coll Cardiol. 2020 Jan 7;75(1):17-26. doi: 10.1016/j.jacc.2019.10.048.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Tools for preventing heart failure
SNOWMASS, COLO. – If ever there was a major chronic disease that’s teed up and ready to be stamped into submission through diligent application of preventive medicine, it’s the epidemic of heart failure.
“The best way to treat heart failure is to prevent it in the first place. There will be more than 1 million new cases of heart failure this year, and the vast majority of them could have been prevented,” Gregg C. Fonarow, MD, asserted at the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
Using firmly evidence-based, guideline-directed therapies, it’s often possible to prevent patients at high risk for developing heart failure (HF) from actually doing so. Or, in the terminology of the ACC/American Heart Association heart failure guidelines coauthored by Dr. Fonarow, the goal is to keep patients who are stage A – that is, pre-HF but at high risk because of hypertension, coronary artery disease, diabetes, family history of cardiomyopathy, or other reasons – from progressing to stage B, marked by asymptomatic left ventricular dysfunction, a prior MI, or asymptomatic valvular disease; and blocking those who are stage B from then moving on to stage C, the classic symptomatic form of HF; and thence to end-stage stage D disease.
Heart failure is an enormous public health problem, and one of the most expensive of all diseases. The prognostic impact of newly diagnosed HF is profound, with 10-15 years of life lost, compared with the general population. Even today, roughly one in five newly diagnosed patients won’t survive for a year, and the 5-year mortality is about 50%, said Dr. Fonarow, who is professor of cardiovascular medicine and chief of the division of cardiology at the University of California, Los Angeles, and director of the Ahmanson-UCLA Cardiomyopathy Center, also in Los Angeles.
Symptomatic stage C is “the tip of the iceberg,” the cardiologist stressed. Vastly more patients are in stages A and B. In order to keep them from progressing to stage C, it’s first necessary to identify them. That’s why the 2013 guidelines give a class IC recommendation for periodic evaluation for signs and symptoms of HF in patients who are at high risk, and for a noninvasive assessment of left ventricular ejection fraction in those with a strong family history of cardiomyopathy or who are on cardiotoxic drugs (J Am Coll Cardiol. 2013 Oct 15;62[16]:e147-239).
The two biggest risk factors for the development of symptomatic stage C HF are hypertension and atherosclerotic cardiovascular disease. Close to 80% of patients presenting with heart failure have prevalent hypertension, and a history of ischemic heart disease is nearly as common.
Other major modifiable risk factors are diabetes, overweight and obesity, metabolic syndrome, dyslipidemia, smoking, valvular heart disease, and chronic kidney disease.
Hypertension
Most patients with high blood pressure believe they’re on antihypertensive medication to prevent MI and stroke, but in reality the largest benefit is what Dr. Fonarow termed the “phenomenal” reduction in the risk of developing HF, which amounted to a 52% relative risk reduction in one meta-analysis of older randomized trials. In the contemporary era, the landmark SPRINT trial of close to 10,000 randomized hypertensive patients showed that more-intensive blood pressure lowering to a target systolic BP of less than 120 mm Hg resulted in a 38% reduction in the risk of new-onset HF, compared with standard treatment to a target of less than 140 mm Hg. That’s why the 2017 focused update of the HF guidelines gives a strong class IB recommendation for a target blood pressure of less than 130/80 mm Hg in hypertensive patients with stage A HF (J Am Coll Cardiol. 2017 Aug 8;70[6]:776-803).
Atherosclerotic cardiovascular disease
Within 6 years after diagnosis of an MI, 22% of men and 46% of women will develop symptomatic heart failure. Intensive statin therapy gets a strong recommendation post MI in the guidelines, not only because in a meta-analysis of four major randomized trials it resulted in a further 64% reduction in the risk of coronary death or recurrent MI, compared with moderate statin therapy, but also because of the 27% relative risk reduction in new-onset HF. ACE inhibitors get a class IA recommendation for prevention of symptomatic HF in patients who are stage A with a history of atherosclerotic disease, diabetes, or hypertension. Angiotensin receptor blockers get a class IC recommendation.
Diabetes
Diabetes markedly increases the risk of developing HF: by two to four times overall and by four to eight times in younger diabetes patients. The two chronic diseases are highly comorbid, with roughly 45% of patients with HF also having diabetes. Moreover, diabetes in HF patients is associated with a substantially worse prognosis, even when standard HF therapies are applied.
Choices regarding glycemic management can markedly affect HF risk and outcomes. Randomized trials show that the peroxisome proliferator-activated receptor agonists double the risk of HF. The glucagonlike peptide–1 receptor agonists are absolutely neutral with regard to HF outcomes. Similarly, the dipeptidyl peptidase–4 inhibitors have no impact on the risks of major adverse cardiovascular events or HF. Intensive glycemic control has no impact on the risk of new-onset HF. Insulin therapy, too, is neutral on this score.
“Depressingly, even lifestyle modification with weight loss, once you have type 2 diabetes, does not lower the risk,” Dr. Fonarow continued.
In contrast, the sodium-glucose transporter 2 (SGLT2) inhibitors have impressive cardiovascular and renal protective benefits in patients with type 2 diabetes, as demonstrated in a meta-analysis of more than 34,000 participants in the randomized trials of empagliflozin (Jardiance) in EMPA-REG OUTCOME, canagliflozin (Invokana) in CANVAS/CANVAS-R, and dapagliflozin (Farxiga) in DECLARE-TIMI 58. The SGLT2 inhibitors collectively reduced the risk of HF hospitalization by 21% in participants with no baseline history of the disease and by 29% in those with a history of HF. Moreover, the risk of progression of renal disease was reduced by 45% (Lancet. 2019 Jan 5;393[10166]:31-9).
More recently, the landmark DAPA-HF trial established SGLT2 inhibitor therapy as part of standard-of-care, guideline-directed medical therapy for patients with HF with reduced ejection fraction regardless of whether they have comorbid type 2 diabetes (N Engl J Med. 2019 Nov 21;381[21]:1995-2008).
These are remarkable medications, generally very well tolerated, and it’s critical that cardiologists get on board in prescribing them, Dr. Fonarow emphasized. He alerted his colleagues to what he called an “incredibly helpful” review article that provides practical guidance for cardiologists in how to start using the SGLT2 inhibitors (JACC Heart Fail. 2019 Feb;7[2]:169-72).
“It’s pretty straightforward,” according to Dr. Fonarow. “If you’re comfortable enough in using ACE inhibitors, angiotensin receptor blockers, and beta-blockers, I think you’ll find these medications fit similarly when you actually get experience in utilizing them.”
He reported serving as a consultant to 10 pharmaceutical or medical device companies.
SNOWMASS, COLO. – If ever there was a major chronic disease that’s teed up and ready to be stamped into submission through diligent application of preventive medicine, it’s the epidemic of heart failure.
“The best way to treat heart failure is to prevent it in the first place. There will be more than 1 million new cases of heart failure this year, and the vast majority of them could have been prevented,” Gregg C. Fonarow, MD, asserted at the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
Using firmly evidence-based, guideline-directed therapies, it’s often possible to prevent patients at high risk for developing heart failure (HF) from actually doing so. Or, in the terminology of the ACC/American Heart Association heart failure guidelines coauthored by Dr. Fonarow, the goal is to keep patients who are stage A – that is, pre-HF but at high risk because of hypertension, coronary artery disease, diabetes, family history of cardiomyopathy, or other reasons – from progressing to stage B, marked by asymptomatic left ventricular dysfunction, a prior MI, or asymptomatic valvular disease; and blocking those who are stage B from then moving on to stage C, the classic symptomatic form of HF; and thence to end-stage stage D disease.
Heart failure is an enormous public health problem, and one of the most expensive of all diseases. The prognostic impact of newly diagnosed HF is profound, with 10-15 years of life lost, compared with the general population. Even today, roughly one in five newly diagnosed patients won’t survive for a year, and the 5-year mortality is about 50%, said Dr. Fonarow, who is professor of cardiovascular medicine and chief of the division of cardiology at the University of California, Los Angeles, and director of the Ahmanson-UCLA Cardiomyopathy Center, also in Los Angeles.
Symptomatic stage C is “the tip of the iceberg,” the cardiologist stressed. Vastly more patients are in stages A and B. In order to keep them from progressing to stage C, it’s first necessary to identify them. That’s why the 2013 guidelines give a class IC recommendation for periodic evaluation for signs and symptoms of HF in patients who are at high risk, and for a noninvasive assessment of left ventricular ejection fraction in those with a strong family history of cardiomyopathy or who are on cardiotoxic drugs (J Am Coll Cardiol. 2013 Oct 15;62[16]:e147-239).
The two biggest risk factors for the development of symptomatic stage C HF are hypertension and atherosclerotic cardiovascular disease. Close to 80% of patients presenting with heart failure have prevalent hypertension, and a history of ischemic heart disease is nearly as common.
Other major modifiable risk factors are diabetes, overweight and obesity, metabolic syndrome, dyslipidemia, smoking, valvular heart disease, and chronic kidney disease.
Hypertension
Most patients with high blood pressure believe they’re on antihypertensive medication to prevent MI and stroke, but in reality the largest benefit is what Dr. Fonarow termed the “phenomenal” reduction in the risk of developing HF, which amounted to a 52% relative risk reduction in one meta-analysis of older randomized trials. In the contemporary era, the landmark SPRINT trial of close to 10,000 randomized hypertensive patients showed that more-intensive blood pressure lowering to a target systolic BP of less than 120 mm Hg resulted in a 38% reduction in the risk of new-onset HF, compared with standard treatment to a target of less than 140 mm Hg. That’s why the 2017 focused update of the HF guidelines gives a strong class IB recommendation for a target blood pressure of less than 130/80 mm Hg in hypertensive patients with stage A HF (J Am Coll Cardiol. 2017 Aug 8;70[6]:776-803).
Atherosclerotic cardiovascular disease
Within 6 years after diagnosis of an MI, 22% of men and 46% of women will develop symptomatic heart failure. Intensive statin therapy gets a strong recommendation post MI in the guidelines, not only because in a meta-analysis of four major randomized trials it resulted in a further 64% reduction in the risk of coronary death or recurrent MI, compared with moderate statin therapy, but also because of the 27% relative risk reduction in new-onset HF. ACE inhibitors get a class IA recommendation for prevention of symptomatic HF in patients who are stage A with a history of atherosclerotic disease, diabetes, or hypertension. Angiotensin receptor blockers get a class IC recommendation.
Diabetes
Diabetes markedly increases the risk of developing HF: by two to four times overall and by four to eight times in younger diabetes patients. The two chronic diseases are highly comorbid, with roughly 45% of patients with HF also having diabetes. Moreover, diabetes in HF patients is associated with a substantially worse prognosis, even when standard HF therapies are applied.
Choices regarding glycemic management can markedly affect HF risk and outcomes. Randomized trials show that the peroxisome proliferator-activated receptor agonists double the risk of HF. The glucagonlike peptide–1 receptor agonists are absolutely neutral with regard to HF outcomes. Similarly, the dipeptidyl peptidase–4 inhibitors have no impact on the risks of major adverse cardiovascular events or HF. Intensive glycemic control has no impact on the risk of new-onset HF. Insulin therapy, too, is neutral on this score.
“Depressingly, even lifestyle modification with weight loss, once you have type 2 diabetes, does not lower the risk,” Dr. Fonarow continued.
In contrast, the sodium-glucose transporter 2 (SGLT2) inhibitors have impressive cardiovascular and renal protective benefits in patients with type 2 diabetes, as demonstrated in a meta-analysis of more than 34,000 participants in the randomized trials of empagliflozin (Jardiance) in EMPA-REG OUTCOME, canagliflozin (Invokana) in CANVAS/CANVAS-R, and dapagliflozin (Farxiga) in DECLARE-TIMI 58. The SGLT2 inhibitors collectively reduced the risk of HF hospitalization by 21% in participants with no baseline history of the disease and by 29% in those with a history of HF. Moreover, the risk of progression of renal disease was reduced by 45% (Lancet. 2019 Jan 5;393[10166]:31-9).
More recently, the landmark DAPA-HF trial established SGLT2 inhibitor therapy as part of standard-of-care, guideline-directed medical therapy for patients with HF with reduced ejection fraction regardless of whether they have comorbid type 2 diabetes (N Engl J Med. 2019 Nov 21;381[21]:1995-2008).
These are remarkable medications, generally very well tolerated, and it’s critical that cardiologists get on board in prescribing them, Dr. Fonarow emphasized. He alerted his colleagues to what he called an “incredibly helpful” review article that provides practical guidance for cardiologists in how to start using the SGLT2 inhibitors (JACC Heart Fail. 2019 Feb;7[2]:169-72).
“It’s pretty straightforward,” according to Dr. Fonarow. “If you’re comfortable enough in using ACE inhibitors, angiotensin receptor blockers, and beta-blockers, I think you’ll find these medications fit similarly when you actually get experience in utilizing them.”
He reported serving as a consultant to 10 pharmaceutical or medical device companies.
SNOWMASS, COLO. – If ever there was a major chronic disease that’s teed up and ready to be stamped into submission through diligent application of preventive medicine, it’s the epidemic of heart failure.
“The best way to treat heart failure is to prevent it in the first place. There will be more than 1 million new cases of heart failure this year, and the vast majority of them could have been prevented,” Gregg C. Fonarow, MD, asserted at the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
Using firmly evidence-based, guideline-directed therapies, it’s often possible to prevent patients at high risk for developing heart failure (HF) from actually doing so. Or, in the terminology of the ACC/American Heart Association heart failure guidelines coauthored by Dr. Fonarow, the goal is to keep patients who are stage A – that is, pre-HF but at high risk because of hypertension, coronary artery disease, diabetes, family history of cardiomyopathy, or other reasons – from progressing to stage B, marked by asymptomatic left ventricular dysfunction, a prior MI, or asymptomatic valvular disease; and blocking those who are stage B from then moving on to stage C, the classic symptomatic form of HF; and thence to end-stage stage D disease.
Heart failure is an enormous public health problem, and one of the most expensive of all diseases. The prognostic impact of newly diagnosed HF is profound, with 10-15 years of life lost, compared with the general population. Even today, roughly one in five newly diagnosed patients won’t survive for a year, and the 5-year mortality is about 50%, said Dr. Fonarow, who is professor of cardiovascular medicine and chief of the division of cardiology at the University of California, Los Angeles, and director of the Ahmanson-UCLA Cardiomyopathy Center, also in Los Angeles.
Symptomatic stage C is “the tip of the iceberg,” the cardiologist stressed. Vastly more patients are in stages A and B. In order to keep them from progressing to stage C, it’s first necessary to identify them. That’s why the 2013 guidelines give a class IC recommendation for periodic evaluation for signs and symptoms of HF in patients who are at high risk, and for a noninvasive assessment of left ventricular ejection fraction in those with a strong family history of cardiomyopathy or who are on cardiotoxic drugs (J Am Coll Cardiol. 2013 Oct 15;62[16]:e147-239).
The two biggest risk factors for the development of symptomatic stage C HF are hypertension and atherosclerotic cardiovascular disease. Close to 80% of patients presenting with heart failure have prevalent hypertension, and a history of ischemic heart disease is nearly as common.
Other major modifiable risk factors are diabetes, overweight and obesity, metabolic syndrome, dyslipidemia, smoking, valvular heart disease, and chronic kidney disease.
Hypertension
Most patients with high blood pressure believe they’re on antihypertensive medication to prevent MI and stroke, but in reality the largest benefit is what Dr. Fonarow termed the “phenomenal” reduction in the risk of developing HF, which amounted to a 52% relative risk reduction in one meta-analysis of older randomized trials. In the contemporary era, the landmark SPRINT trial of close to 10,000 randomized hypertensive patients showed that more-intensive blood pressure lowering to a target systolic BP of less than 120 mm Hg resulted in a 38% reduction in the risk of new-onset HF, compared with standard treatment to a target of less than 140 mm Hg. That’s why the 2017 focused update of the HF guidelines gives a strong class IB recommendation for a target blood pressure of less than 130/80 mm Hg in hypertensive patients with stage A HF (J Am Coll Cardiol. 2017 Aug 8;70[6]:776-803).
Atherosclerotic cardiovascular disease
Within 6 years after diagnosis of an MI, 22% of men and 46% of women will develop symptomatic heart failure. Intensive statin therapy gets a strong recommendation post MI in the guidelines, not only because in a meta-analysis of four major randomized trials it resulted in a further 64% reduction in the risk of coronary death or recurrent MI, compared with moderate statin therapy, but also because of the 27% relative risk reduction in new-onset HF. ACE inhibitors get a class IA recommendation for prevention of symptomatic HF in patients who are stage A with a history of atherosclerotic disease, diabetes, or hypertension. Angiotensin receptor blockers get a class IC recommendation.
Diabetes
Diabetes markedly increases the risk of developing HF: by two to four times overall and by four to eight times in younger diabetes patients. The two chronic diseases are highly comorbid, with roughly 45% of patients with HF also having diabetes. Moreover, diabetes in HF patients is associated with a substantially worse prognosis, even when standard HF therapies are applied.
Choices regarding glycemic management can markedly affect HF risk and outcomes. Randomized trials show that the peroxisome proliferator-activated receptor agonists double the risk of HF. The glucagonlike peptide–1 receptor agonists are absolutely neutral with regard to HF outcomes. Similarly, the dipeptidyl peptidase–4 inhibitors have no impact on the risks of major adverse cardiovascular events or HF. Intensive glycemic control has no impact on the risk of new-onset HF. Insulin therapy, too, is neutral on this score.
“Depressingly, even lifestyle modification with weight loss, once you have type 2 diabetes, does not lower the risk,” Dr. Fonarow continued.
In contrast, the sodium-glucose transporter 2 (SGLT2) inhibitors have impressive cardiovascular and renal protective benefits in patients with type 2 diabetes, as demonstrated in a meta-analysis of more than 34,000 participants in the randomized trials of empagliflozin (Jardiance) in EMPA-REG OUTCOME, canagliflozin (Invokana) in CANVAS/CANVAS-R, and dapagliflozin (Farxiga) in DECLARE-TIMI 58. The SGLT2 inhibitors collectively reduced the risk of HF hospitalization by 21% in participants with no baseline history of the disease and by 29% in those with a history of HF. Moreover, the risk of progression of renal disease was reduced by 45% (Lancet. 2019 Jan 5;393[10166]:31-9).
More recently, the landmark DAPA-HF trial established SGLT2 inhibitor therapy as part of standard-of-care, guideline-directed medical therapy for patients with HF with reduced ejection fraction regardless of whether they have comorbid type 2 diabetes (N Engl J Med. 2019 Nov 21;381[21]:1995-2008).
These are remarkable medications, generally very well tolerated, and it’s critical that cardiologists get on board in prescribing them, Dr. Fonarow emphasized. He alerted his colleagues to what he called an “incredibly helpful” review article that provides practical guidance for cardiologists in how to start using the SGLT2 inhibitors (JACC Heart Fail. 2019 Feb;7[2]:169-72).
“It’s pretty straightforward,” according to Dr. Fonarow. “If you’re comfortable enough in using ACE inhibitors, angiotensin receptor blockers, and beta-blockers, I think you’ll find these medications fit similarly when you actually get experience in utilizing them.”
He reported serving as a consultant to 10 pharmaceutical or medical device companies.
EXPERT ANALYSIS FROM ACC SNOWMASS 2020
Blood pressure categories may signal maternal, perinatal risks
GRAPEVINE, TEX. – Blood pressure categories created by the American College of Cardiology (ACC) and American Heart Association (AHA) in 2017 identify patients with increased risk of preeclampsia, preterm birth, and perinatal death when applied to the first 20 weeks of pregnancy, according to a retrospective study presented at the meeting sponsored by the Society for Maternal-Fetal Medicine.
The absolute risk increases are small, and it is unknown whether treating these patients differently would be beneficial, said study author Martha Tesfalul, MD, maternal-fetal medicine clinical fellow at University of California, San Francisco. Nevertheless, , Dr. Tesfalul said.
Cutoffs with unclear implications
The ACC/AHA in November 2017 reclassified blood pressure in nonpregnant adults, but “implications of these categories in pregnancy are still unclear,” Dr. Tesfalul and colleagues said. Under the guidelines, normal blood pressure is systolic blood pressure less than 120 mm Hg and diastolic blood pressure less than 80 mm Hg. Elevated blood pressure is defined as systolic blood pressure between 120 and 129 mm Hg and diastolic blood pressure less than 80 mm Hg. Stage 1 hypertension is systolic blood pressure between 130 and 139 mm Hg or diastolic blood pressure between 80 and 89 mm Hg. And stage 2 hypertension is systolic blood pressure of at least 140 mm Hg or diastolic blood pressure of at least 90 mm Hg.
For the present analysis, the researchers retrospectively compared obstetric and perinatal outcomes for approximately 6,000 pregnancies at an academic center for which they had at least one blood pressure measurement prior to 20 weeks. The highest measurement was used to identify women with normal blood pressure, elevated blood pressure, or stage 1 hypertension according to the 2017 thresholds.
The researchers included singleton pregnancies with delivery between January 2014 and October 2017. They excluded patients with a prior diagnosis of chronic hypertension, autoimmune or chronic renal disease, or fetal anomalies. They examined rates of gestational hypertension, preeclampsia, preterm birth, neonatal intensive care admission, and perinatal death.
Adjusted relative risks
Dr. Tesfalul and colleagues identified about 3,500 pregnancies with normal blood pressure, more than 1,300 pregnancies with elevated blood pressure, and nearly 1,100 pregnancies with stage 1 hypertension.
After adjusting for relevant covariates – maternal age, nulliparity, race, body mass index, in vitro fertilization, tobacco use, pregestational diabetes, and aspirin use – elevated blood pressure and stage 1 hypertension were associated with a higher risk of preeclampsia and severe preeclampsia, relative to normal blood pressure. The proportion of patients with preeclampsia was 5.7% in the normal blood pressure group, 11.7% in the elevated blood pressure group (adjusted relative risk, 1.8), and 15% in the stage 1 hypertension group (adjusted RR, 2.1). The proportion with preeclampsia with severe features was 3.1% in the normal blood pressure group, 5.7% in the elevated blood pressure group (adjusted RR, 1.6), and 6.8% in the stage 1 hypertension group (adjusted RR, 1.8).
In addition, stage 1 hypertension, compared with normal blood pressure, was associated with increased odds of preterm birth at less than 37 weeks (7.9% vs. 5.1%; adjusted RR, 1.4) and perinatal death (0.7% vs. 0.4%; adjusted RR, 2.8).
“Patients with elevated blood pressure and stage 1 hypertension prior to 20 weeks are at increased risk of adverse outcomes,” the authors concluded. “Further research [is] needed to determine optimal care of patients with elevated blood pressure and stage 1 hypertension in pregnancy.”
Dr. Tesfalul receives support from the Foundation for SMFM.
SOURCE: Tesfalul M et al. Am J Obstet Gynecol. 2020 Jan;222(1):S92-3, Abstract 119.
GRAPEVINE, TEX. – Blood pressure categories created by the American College of Cardiology (ACC) and American Heart Association (AHA) in 2017 identify patients with increased risk of preeclampsia, preterm birth, and perinatal death when applied to the first 20 weeks of pregnancy, according to a retrospective study presented at the meeting sponsored by the Society for Maternal-Fetal Medicine.
The absolute risk increases are small, and it is unknown whether treating these patients differently would be beneficial, said study author Martha Tesfalul, MD, maternal-fetal medicine clinical fellow at University of California, San Francisco. Nevertheless, , Dr. Tesfalul said.
Cutoffs with unclear implications
The ACC/AHA in November 2017 reclassified blood pressure in nonpregnant adults, but “implications of these categories in pregnancy are still unclear,” Dr. Tesfalul and colleagues said. Under the guidelines, normal blood pressure is systolic blood pressure less than 120 mm Hg and diastolic blood pressure less than 80 mm Hg. Elevated blood pressure is defined as systolic blood pressure between 120 and 129 mm Hg and diastolic blood pressure less than 80 mm Hg. Stage 1 hypertension is systolic blood pressure between 130 and 139 mm Hg or diastolic blood pressure between 80 and 89 mm Hg. And stage 2 hypertension is systolic blood pressure of at least 140 mm Hg or diastolic blood pressure of at least 90 mm Hg.
For the present analysis, the researchers retrospectively compared obstetric and perinatal outcomes for approximately 6,000 pregnancies at an academic center for which they had at least one blood pressure measurement prior to 20 weeks. The highest measurement was used to identify women with normal blood pressure, elevated blood pressure, or stage 1 hypertension according to the 2017 thresholds.
The researchers included singleton pregnancies with delivery between January 2014 and October 2017. They excluded patients with a prior diagnosis of chronic hypertension, autoimmune or chronic renal disease, or fetal anomalies. They examined rates of gestational hypertension, preeclampsia, preterm birth, neonatal intensive care admission, and perinatal death.
Adjusted relative risks
Dr. Tesfalul and colleagues identified about 3,500 pregnancies with normal blood pressure, more than 1,300 pregnancies with elevated blood pressure, and nearly 1,100 pregnancies with stage 1 hypertension.
After adjusting for relevant covariates – maternal age, nulliparity, race, body mass index, in vitro fertilization, tobacco use, pregestational diabetes, and aspirin use – elevated blood pressure and stage 1 hypertension were associated with a higher risk of preeclampsia and severe preeclampsia, relative to normal blood pressure. The proportion of patients with preeclampsia was 5.7% in the normal blood pressure group, 11.7% in the elevated blood pressure group (adjusted relative risk, 1.8), and 15% in the stage 1 hypertension group (adjusted RR, 2.1). The proportion with preeclampsia with severe features was 3.1% in the normal blood pressure group, 5.7% in the elevated blood pressure group (adjusted RR, 1.6), and 6.8% in the stage 1 hypertension group (adjusted RR, 1.8).
In addition, stage 1 hypertension, compared with normal blood pressure, was associated with increased odds of preterm birth at less than 37 weeks (7.9% vs. 5.1%; adjusted RR, 1.4) and perinatal death (0.7% vs. 0.4%; adjusted RR, 2.8).
“Patients with elevated blood pressure and stage 1 hypertension prior to 20 weeks are at increased risk of adverse outcomes,” the authors concluded. “Further research [is] needed to determine optimal care of patients with elevated blood pressure and stage 1 hypertension in pregnancy.”
Dr. Tesfalul receives support from the Foundation for SMFM.
SOURCE: Tesfalul M et al. Am J Obstet Gynecol. 2020 Jan;222(1):S92-3, Abstract 119.
GRAPEVINE, TEX. – Blood pressure categories created by the American College of Cardiology (ACC) and American Heart Association (AHA) in 2017 identify patients with increased risk of preeclampsia, preterm birth, and perinatal death when applied to the first 20 weeks of pregnancy, according to a retrospective study presented at the meeting sponsored by the Society for Maternal-Fetal Medicine.
The absolute risk increases are small, and it is unknown whether treating these patients differently would be beneficial, said study author Martha Tesfalul, MD, maternal-fetal medicine clinical fellow at University of California, San Francisco. Nevertheless, , Dr. Tesfalul said.
Cutoffs with unclear implications
The ACC/AHA in November 2017 reclassified blood pressure in nonpregnant adults, but “implications of these categories in pregnancy are still unclear,” Dr. Tesfalul and colleagues said. Under the guidelines, normal blood pressure is systolic blood pressure less than 120 mm Hg and diastolic blood pressure less than 80 mm Hg. Elevated blood pressure is defined as systolic blood pressure between 120 and 129 mm Hg and diastolic blood pressure less than 80 mm Hg. Stage 1 hypertension is systolic blood pressure between 130 and 139 mm Hg or diastolic blood pressure between 80 and 89 mm Hg. And stage 2 hypertension is systolic blood pressure of at least 140 mm Hg or diastolic blood pressure of at least 90 mm Hg.
For the present analysis, the researchers retrospectively compared obstetric and perinatal outcomes for approximately 6,000 pregnancies at an academic center for which they had at least one blood pressure measurement prior to 20 weeks. The highest measurement was used to identify women with normal blood pressure, elevated blood pressure, or stage 1 hypertension according to the 2017 thresholds.
The researchers included singleton pregnancies with delivery between January 2014 and October 2017. They excluded patients with a prior diagnosis of chronic hypertension, autoimmune or chronic renal disease, or fetal anomalies. They examined rates of gestational hypertension, preeclampsia, preterm birth, neonatal intensive care admission, and perinatal death.
Adjusted relative risks
Dr. Tesfalul and colleagues identified about 3,500 pregnancies with normal blood pressure, more than 1,300 pregnancies with elevated blood pressure, and nearly 1,100 pregnancies with stage 1 hypertension.
After adjusting for relevant covariates – maternal age, nulliparity, race, body mass index, in vitro fertilization, tobacco use, pregestational diabetes, and aspirin use – elevated blood pressure and stage 1 hypertension were associated with a higher risk of preeclampsia and severe preeclampsia, relative to normal blood pressure. The proportion of patients with preeclampsia was 5.7% in the normal blood pressure group, 11.7% in the elevated blood pressure group (adjusted relative risk, 1.8), and 15% in the stage 1 hypertension group (adjusted RR, 2.1). The proportion with preeclampsia with severe features was 3.1% in the normal blood pressure group, 5.7% in the elevated blood pressure group (adjusted RR, 1.6), and 6.8% in the stage 1 hypertension group (adjusted RR, 1.8).
In addition, stage 1 hypertension, compared with normal blood pressure, was associated with increased odds of preterm birth at less than 37 weeks (7.9% vs. 5.1%; adjusted RR, 1.4) and perinatal death (0.7% vs. 0.4%; adjusted RR, 2.8).
“Patients with elevated blood pressure and stage 1 hypertension prior to 20 weeks are at increased risk of adverse outcomes,” the authors concluded. “Further research [is] needed to determine optimal care of patients with elevated blood pressure and stage 1 hypertension in pregnancy.”
Dr. Tesfalul receives support from the Foundation for SMFM.
SOURCE: Tesfalul M et al. Am J Obstet Gynecol. 2020 Jan;222(1):S92-3, Abstract 119.
REPORTING FROM THE PREGNANCY MEETING
Home BP now a class Ia recommendation, with good reason
SNOWMASS, COLO. – The redefinition of hypertension as 130/80 mm Hg or higher introduced in the current American College of Cardiology/American Heart Association hypertension management guidelines has generated considerable controversy. Often overlooked, however, has been another major innovation included in the 2017 guidelines: the rise in the status of out-of-office 24-hour ambulatory blood pressure monitoring and home blood pressure self-measurement to a class I, level of evidence A recommendation, Andrew M. Kates, MD, observed at the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
It’s a guideline he strongly endorses.
“We do a lot of this. It can be a challenge to get 24-hour ambulatory blood pressure monitoring covered by payers, so said Dr. Kates, professor of medicine and director of the cardiology fellowship program at Washington University, St. Louis.
He explained that one of the four key questions the guideline committee was tasked with answering at the outset of deliberations was this: What’s the evidence base for self-directed out-of-office blood pressure monitoring? Based on the panel’s systematic review of the literature, this practice wound up receiving the strongest possible class Ia recommendation, specifically for confirming the diagnosis of hypertension and for titration of antihypertensive medications. Moreover, the guidelines also endorsed home blood pressure monitoring for the detection of white-coat hypertension, this time as a Class IIa recommendation, as well as for identification of patients with masked hypertension, with class IIb status (Circulation. 2018 Oct 23;138[17]:e484-594).
The 2017 ACC/AHA guidelines include a detailed checklist for obtaining accurate measurements of office blood pressure. The suggestions include having the patient sit relaxed in a chair with both feet on the floor for at least 5 minutes before taking the measurement, no coffee or exercise for 30 minutes beforehand, empty the bladder, no talking, no clothing over the arm, and other recommendations. Many busy clinicians roll their eyes at the impracticality of doing all this on a routine basis.
“I don’t want to take an audience survey, but I’ll say that even in our office we are not successful in doing this. Patients run up the stairs to the office after dealing with traffic and the parking garage, they’re late for their appointment, in winter they’re wearing a sweater and don’t want to take it off. These are things we don’t do well, and they’re low-hanging fruit where we could do better,” Dr. Kates commented.
The challenges inherent in performing by-the-book office blood pressure measurement reinforce the importance of home self-monitoring of blood pressure in what is hopefully a more stress-free environment.
“We can give patients specific guidance about checking their blood pressure an hour after taking their medications, sitting for 5 minutes, and checking the pressures on a bare arm and not with the sleeve rolled up,” he noted.
The guidelines recommend using home blood pressure monitoring or ambulatory monitoring to detect white-coat hypertension in patients with an office blood pressure of 130/80 mm Hg or more, but less than 160/100 mm Hg, after a 3-month trial of lifestyle modification. If the home blood pressure is less than 130/80 mm Hg, that’s evidence of white-coat hypertension, for which the recommended treatment consists of continued lifestyle modification plus periodic monitoring of out-of-office blood pressures in order to promptly detect progression to hypertension. If, however, the out-of-office blood pressure is not less than 130/80 mm Hg, that’s hypertension, and the guidelines recommend starting dual-agent antihypertensive drug therapy while continuing lifestyle modification.
A confusing array of definitions of hypertension are now in use by various medical societies. While the 2017 ACC/AHA hypertension guidelines define hypertension as office blood pressure of 130/80 mm Hg or more, the 2018 European Society of Cardiology/European Society of Hypertension guidelines use a threshold of 140/90 mm Hg or more. Joint American Academy of Family Physicians/American College of Physicians guidelines recommend a treatment target of less than 150 mm Hg in hypertensive patients aged 60 years or older. And at the other end of the spectrum, the SPRINT trial showed a significant cardiovascular benefit for intensive treatment of hypertension to a target systolic blood pressure below 120 mm Hg, rather than less than 140 mm Hg (N Engl J Med. 2015 Nov 26;373[22]:2103-16).
Dr. Kates believes the debate over the “right” treatment target misses the central point, which is that hypertension is staggeringly undertreated. Indeed, the Centers for Disease Control and Prevention estimates only one in four adults with hypertension have their disease under control. That’s a disconcerting statistic given that hypertension accounts for more cardiovascular deaths than any other modifiable cardiovascular risk factor.
“There’s been some concern raised that maybe too much weight has been put on the SPRINT trial in making the ACC/AHA recommendations, but I think it’s helpful to understand that we vastly undertreat patients with hypertension. So I think that, rather than being so concerned that we’re going to be treating people to too low a target or we’re being overly aggressive, it should give us some pause to think about the fact that we’re ordinarily not being aggressive enough with many of our patients as it is,” the cardiologist said.
Dr. Kates reported having no financial conflicts regarding his presentation.
SNOWMASS, COLO. – The redefinition of hypertension as 130/80 mm Hg or higher introduced in the current American College of Cardiology/American Heart Association hypertension management guidelines has generated considerable controversy. Often overlooked, however, has been another major innovation included in the 2017 guidelines: the rise in the status of out-of-office 24-hour ambulatory blood pressure monitoring and home blood pressure self-measurement to a class I, level of evidence A recommendation, Andrew M. Kates, MD, observed at the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
It’s a guideline he strongly endorses.
“We do a lot of this. It can be a challenge to get 24-hour ambulatory blood pressure monitoring covered by payers, so said Dr. Kates, professor of medicine and director of the cardiology fellowship program at Washington University, St. Louis.
He explained that one of the four key questions the guideline committee was tasked with answering at the outset of deliberations was this: What’s the evidence base for self-directed out-of-office blood pressure monitoring? Based on the panel’s systematic review of the literature, this practice wound up receiving the strongest possible class Ia recommendation, specifically for confirming the diagnosis of hypertension and for titration of antihypertensive medications. Moreover, the guidelines also endorsed home blood pressure monitoring for the detection of white-coat hypertension, this time as a Class IIa recommendation, as well as for identification of patients with masked hypertension, with class IIb status (Circulation. 2018 Oct 23;138[17]:e484-594).
The 2017 ACC/AHA guidelines include a detailed checklist for obtaining accurate measurements of office blood pressure. The suggestions include having the patient sit relaxed in a chair with both feet on the floor for at least 5 minutes before taking the measurement, no coffee or exercise for 30 minutes beforehand, empty the bladder, no talking, no clothing over the arm, and other recommendations. Many busy clinicians roll their eyes at the impracticality of doing all this on a routine basis.
“I don’t want to take an audience survey, but I’ll say that even in our office we are not successful in doing this. Patients run up the stairs to the office after dealing with traffic and the parking garage, they’re late for their appointment, in winter they’re wearing a sweater and don’t want to take it off. These are things we don’t do well, and they’re low-hanging fruit where we could do better,” Dr. Kates commented.
The challenges inherent in performing by-the-book office blood pressure measurement reinforce the importance of home self-monitoring of blood pressure in what is hopefully a more stress-free environment.
“We can give patients specific guidance about checking their blood pressure an hour after taking their medications, sitting for 5 minutes, and checking the pressures on a bare arm and not with the sleeve rolled up,” he noted.
The guidelines recommend using home blood pressure monitoring or ambulatory monitoring to detect white-coat hypertension in patients with an office blood pressure of 130/80 mm Hg or more, but less than 160/100 mm Hg, after a 3-month trial of lifestyle modification. If the home blood pressure is less than 130/80 mm Hg, that’s evidence of white-coat hypertension, for which the recommended treatment consists of continued lifestyle modification plus periodic monitoring of out-of-office blood pressures in order to promptly detect progression to hypertension. If, however, the out-of-office blood pressure is not less than 130/80 mm Hg, that’s hypertension, and the guidelines recommend starting dual-agent antihypertensive drug therapy while continuing lifestyle modification.
A confusing array of definitions of hypertension are now in use by various medical societies. While the 2017 ACC/AHA hypertension guidelines define hypertension as office blood pressure of 130/80 mm Hg or more, the 2018 European Society of Cardiology/European Society of Hypertension guidelines use a threshold of 140/90 mm Hg or more. Joint American Academy of Family Physicians/American College of Physicians guidelines recommend a treatment target of less than 150 mm Hg in hypertensive patients aged 60 years or older. And at the other end of the spectrum, the SPRINT trial showed a significant cardiovascular benefit for intensive treatment of hypertension to a target systolic blood pressure below 120 mm Hg, rather than less than 140 mm Hg (N Engl J Med. 2015 Nov 26;373[22]:2103-16).
Dr. Kates believes the debate over the “right” treatment target misses the central point, which is that hypertension is staggeringly undertreated. Indeed, the Centers for Disease Control and Prevention estimates only one in four adults with hypertension have their disease under control. That’s a disconcerting statistic given that hypertension accounts for more cardiovascular deaths than any other modifiable cardiovascular risk factor.
“There’s been some concern raised that maybe too much weight has been put on the SPRINT trial in making the ACC/AHA recommendations, but I think it’s helpful to understand that we vastly undertreat patients with hypertension. So I think that, rather than being so concerned that we’re going to be treating people to too low a target or we’re being overly aggressive, it should give us some pause to think about the fact that we’re ordinarily not being aggressive enough with many of our patients as it is,” the cardiologist said.
Dr. Kates reported having no financial conflicts regarding his presentation.
SNOWMASS, COLO. – The redefinition of hypertension as 130/80 mm Hg or higher introduced in the current American College of Cardiology/American Heart Association hypertension management guidelines has generated considerable controversy. Often overlooked, however, has been another major innovation included in the 2017 guidelines: the rise in the status of out-of-office 24-hour ambulatory blood pressure monitoring and home blood pressure self-measurement to a class I, level of evidence A recommendation, Andrew M. Kates, MD, observed at the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
It’s a guideline he strongly endorses.
“We do a lot of this. It can be a challenge to get 24-hour ambulatory blood pressure monitoring covered by payers, so said Dr. Kates, professor of medicine and director of the cardiology fellowship program at Washington University, St. Louis.
He explained that one of the four key questions the guideline committee was tasked with answering at the outset of deliberations was this: What’s the evidence base for self-directed out-of-office blood pressure monitoring? Based on the panel’s systematic review of the literature, this practice wound up receiving the strongest possible class Ia recommendation, specifically for confirming the diagnosis of hypertension and for titration of antihypertensive medications. Moreover, the guidelines also endorsed home blood pressure monitoring for the detection of white-coat hypertension, this time as a Class IIa recommendation, as well as for identification of patients with masked hypertension, with class IIb status (Circulation. 2018 Oct 23;138[17]:e484-594).
The 2017 ACC/AHA guidelines include a detailed checklist for obtaining accurate measurements of office blood pressure. The suggestions include having the patient sit relaxed in a chair with both feet on the floor for at least 5 minutes before taking the measurement, no coffee or exercise for 30 minutes beforehand, empty the bladder, no talking, no clothing over the arm, and other recommendations. Many busy clinicians roll their eyes at the impracticality of doing all this on a routine basis.
“I don’t want to take an audience survey, but I’ll say that even in our office we are not successful in doing this. Patients run up the stairs to the office after dealing with traffic and the parking garage, they’re late for their appointment, in winter they’re wearing a sweater and don’t want to take it off. These are things we don’t do well, and they’re low-hanging fruit where we could do better,” Dr. Kates commented.
The challenges inherent in performing by-the-book office blood pressure measurement reinforce the importance of home self-monitoring of blood pressure in what is hopefully a more stress-free environment.
“We can give patients specific guidance about checking their blood pressure an hour after taking their medications, sitting for 5 minutes, and checking the pressures on a bare arm and not with the sleeve rolled up,” he noted.
The guidelines recommend using home blood pressure monitoring or ambulatory monitoring to detect white-coat hypertension in patients with an office blood pressure of 130/80 mm Hg or more, but less than 160/100 mm Hg, after a 3-month trial of lifestyle modification. If the home blood pressure is less than 130/80 mm Hg, that’s evidence of white-coat hypertension, for which the recommended treatment consists of continued lifestyle modification plus periodic monitoring of out-of-office blood pressures in order to promptly detect progression to hypertension. If, however, the out-of-office blood pressure is not less than 130/80 mm Hg, that’s hypertension, and the guidelines recommend starting dual-agent antihypertensive drug therapy while continuing lifestyle modification.
A confusing array of definitions of hypertension are now in use by various medical societies. While the 2017 ACC/AHA hypertension guidelines define hypertension as office blood pressure of 130/80 mm Hg or more, the 2018 European Society of Cardiology/European Society of Hypertension guidelines use a threshold of 140/90 mm Hg or more. Joint American Academy of Family Physicians/American College of Physicians guidelines recommend a treatment target of less than 150 mm Hg in hypertensive patients aged 60 years or older. And at the other end of the spectrum, the SPRINT trial showed a significant cardiovascular benefit for intensive treatment of hypertension to a target systolic blood pressure below 120 mm Hg, rather than less than 140 mm Hg (N Engl J Med. 2015 Nov 26;373[22]:2103-16).
Dr. Kates believes the debate over the “right” treatment target misses the central point, which is that hypertension is staggeringly undertreated. Indeed, the Centers for Disease Control and Prevention estimates only one in four adults with hypertension have their disease under control. That’s a disconcerting statistic given that hypertension accounts for more cardiovascular deaths than any other modifiable cardiovascular risk factor.
“There’s been some concern raised that maybe too much weight has been put on the SPRINT trial in making the ACC/AHA recommendations, but I think it’s helpful to understand that we vastly undertreat patients with hypertension. So I think that, rather than being so concerned that we’re going to be treating people to too low a target or we’re being overly aggressive, it should give us some pause to think about the fact that we’re ordinarily not being aggressive enough with many of our patients as it is,” the cardiologist said.
Dr. Kates reported having no financial conflicts regarding his presentation.
EXPERT ANALYSIS FROM ACC SNOWMASS 2020
Statin, antihypertensive treatment don’t guarantee healthier lifestyles
When people learn they have enough cardiovascular disease risk to start treatment with a statin or antihypertensive drug, the impact on their healthy-lifestyle choices seems to often be a wash, based on findings from more than 40,000 Finland residents followed for at least 4 years after starting their primary-prevention regimen.
“Patients’ awareness of their risk factors alone seems not to be effective in improving health behaviors,” wrote Maarit J. Korhonen, PhD, and associates in a report published in the Journal of the American Heart Association.
“Initiation of antihypertensive or statin therapy appears to be associated with lifestyle changes, some positive and others negative,” wrote Dr. Korhonen, a pharmacoepidemiologist at the University of Turku (Finland), and associates. This was the first reported study to assess a large-scale and prospectively followed cohort to look for associations between the use of medicines that prevent cardiovascular disease (CVD) and lifestyle changes. Most previous studies of these associations “have been cross sectional and provide no information on potential lifestyle changes during the time window around the initiation of medication use,” they added.
The new study specifically found that, on average, people who began treatment with at least one CVD-prevention medication for the first time were more likely to gain weight and more likely to become less active during the years following their treatment onset. But at the same time, these patients were also more likely to either quit or cut down on their smoking and alcohol consumption, the researchers found.
Their analysis used data from 41,225 people enrolled in the Finnish Public Sector Study, which prospectively began collecting data on a large number of Finland residents in the 1990s. They specifically focused on 81,772 completed questionnaires – collected at 4-year intervals – from people who completed at least two consecutive rounds of the survey during 2000-2013, and who were also at least 40 years old and free of prevalent CVD at the time of their first survey. The participants averaged nearly 53 years of age at their first survey, and 84% were women.
The researchers subdivided the survey responses into 8,837 (11%) people who began a statin, antihypertensive drug, or both during their participation; 26,914 (33%) already on a statin or antihypertensive drug when they completed their first questionnaire; and 46,021 response sets (56%) from people who never began treatment with either drug class. People who initiated a relevant drug began a median of 1.7 years following completion of their first survey, and a median of 2.4 years before their next survey. During follow-up, about 2% of all participants became newly diagnosed with some form of CVD.
The results showed that, after full adjustment for possible confounders, the mean increase in body mass index was larger among those who initiated a CVD-prevention drug, compared with those who did not. Among participants who were obese at entry, those who started a CVD drug had a statistically significant 37% increased rate of remaining obese, compared with those not starting these drugs. Among those who were not obese at baseline, those who began a CVD prevention drug had a statistically significant 82%% higher rate of becoming obese, compared with those not on a CVD-prevention drug. In addition, average daily energy expenditure, a measure of physical activity, showed a statistically significant decline among those who started a CVD drug, compared with those who did not. In contrast, CVD drug initiators had an average 1.85 gram/week decline in alcohol intake, compared with noninitiators, and those who were current smokers at the first survey and then started a CVD drug had a 26% relative drop in their smoking prevalence, compared with those who did not start a CVD drug, both statistically significant differences.
The findings suggest that “patients’ awareness of their risk factors alone seems not to be effective in improving health behaviors,” the authors concluded. “This means that expansion of pharmacologic interventions toward populations at low CVD risk may not necessarily lead to expected benefits at the population level.”
The study received no commercial funding. Dr. Korhonen had no disclosures.
SOURCE: Korhonen MJ et al. J Am Heart Assoc. 2020 Feb 5. doi: 10.1161/JAHA.119.014.168.
When people learn they have enough cardiovascular disease risk to start treatment with a statin or antihypertensive drug, the impact on their healthy-lifestyle choices seems to often be a wash, based on findings from more than 40,000 Finland residents followed for at least 4 years after starting their primary-prevention regimen.
“Patients’ awareness of their risk factors alone seems not to be effective in improving health behaviors,” wrote Maarit J. Korhonen, PhD, and associates in a report published in the Journal of the American Heart Association.
“Initiation of antihypertensive or statin therapy appears to be associated with lifestyle changes, some positive and others negative,” wrote Dr. Korhonen, a pharmacoepidemiologist at the University of Turku (Finland), and associates. This was the first reported study to assess a large-scale and prospectively followed cohort to look for associations between the use of medicines that prevent cardiovascular disease (CVD) and lifestyle changes. Most previous studies of these associations “have been cross sectional and provide no information on potential lifestyle changes during the time window around the initiation of medication use,” they added.
The new study specifically found that, on average, people who began treatment with at least one CVD-prevention medication for the first time were more likely to gain weight and more likely to become less active during the years following their treatment onset. But at the same time, these patients were also more likely to either quit or cut down on their smoking and alcohol consumption, the researchers found.
Their analysis used data from 41,225 people enrolled in the Finnish Public Sector Study, which prospectively began collecting data on a large number of Finland residents in the 1990s. They specifically focused on 81,772 completed questionnaires – collected at 4-year intervals – from people who completed at least two consecutive rounds of the survey during 2000-2013, and who were also at least 40 years old and free of prevalent CVD at the time of their first survey. The participants averaged nearly 53 years of age at their first survey, and 84% were women.
The researchers subdivided the survey responses into 8,837 (11%) people who began a statin, antihypertensive drug, or both during their participation; 26,914 (33%) already on a statin or antihypertensive drug when they completed their first questionnaire; and 46,021 response sets (56%) from people who never began treatment with either drug class. People who initiated a relevant drug began a median of 1.7 years following completion of their first survey, and a median of 2.4 years before their next survey. During follow-up, about 2% of all participants became newly diagnosed with some form of CVD.
The results showed that, after full adjustment for possible confounders, the mean increase in body mass index was larger among those who initiated a CVD-prevention drug, compared with those who did not. Among participants who were obese at entry, those who started a CVD drug had a statistically significant 37% increased rate of remaining obese, compared with those not starting these drugs. Among those who were not obese at baseline, those who began a CVD prevention drug had a statistically significant 82%% higher rate of becoming obese, compared with those not on a CVD-prevention drug. In addition, average daily energy expenditure, a measure of physical activity, showed a statistically significant decline among those who started a CVD drug, compared with those who did not. In contrast, CVD drug initiators had an average 1.85 gram/week decline in alcohol intake, compared with noninitiators, and those who were current smokers at the first survey and then started a CVD drug had a 26% relative drop in their smoking prevalence, compared with those who did not start a CVD drug, both statistically significant differences.
The findings suggest that “patients’ awareness of their risk factors alone seems not to be effective in improving health behaviors,” the authors concluded. “This means that expansion of pharmacologic interventions toward populations at low CVD risk may not necessarily lead to expected benefits at the population level.”
The study received no commercial funding. Dr. Korhonen had no disclosures.
SOURCE: Korhonen MJ et al. J Am Heart Assoc. 2020 Feb 5. doi: 10.1161/JAHA.119.014.168.
When people learn they have enough cardiovascular disease risk to start treatment with a statin or antihypertensive drug, the impact on their healthy-lifestyle choices seems to often be a wash, based on findings from more than 40,000 Finland residents followed for at least 4 years after starting their primary-prevention regimen.
“Patients’ awareness of their risk factors alone seems not to be effective in improving health behaviors,” wrote Maarit J. Korhonen, PhD, and associates in a report published in the Journal of the American Heart Association.
“Initiation of antihypertensive or statin therapy appears to be associated with lifestyle changes, some positive and others negative,” wrote Dr. Korhonen, a pharmacoepidemiologist at the University of Turku (Finland), and associates. This was the first reported study to assess a large-scale and prospectively followed cohort to look for associations between the use of medicines that prevent cardiovascular disease (CVD) and lifestyle changes. Most previous studies of these associations “have been cross sectional and provide no information on potential lifestyle changes during the time window around the initiation of medication use,” they added.
The new study specifically found that, on average, people who began treatment with at least one CVD-prevention medication for the first time were more likely to gain weight and more likely to become less active during the years following their treatment onset. But at the same time, these patients were also more likely to either quit or cut down on their smoking and alcohol consumption, the researchers found.
Their analysis used data from 41,225 people enrolled in the Finnish Public Sector Study, which prospectively began collecting data on a large number of Finland residents in the 1990s. They specifically focused on 81,772 completed questionnaires – collected at 4-year intervals – from people who completed at least two consecutive rounds of the survey during 2000-2013, and who were also at least 40 years old and free of prevalent CVD at the time of their first survey. The participants averaged nearly 53 years of age at their first survey, and 84% were women.
The researchers subdivided the survey responses into 8,837 (11%) people who began a statin, antihypertensive drug, or both during their participation; 26,914 (33%) already on a statin or antihypertensive drug when they completed their first questionnaire; and 46,021 response sets (56%) from people who never began treatment with either drug class. People who initiated a relevant drug began a median of 1.7 years following completion of their first survey, and a median of 2.4 years before their next survey. During follow-up, about 2% of all participants became newly diagnosed with some form of CVD.
The results showed that, after full adjustment for possible confounders, the mean increase in body mass index was larger among those who initiated a CVD-prevention drug, compared with those who did not. Among participants who were obese at entry, those who started a CVD drug had a statistically significant 37% increased rate of remaining obese, compared with those not starting these drugs. Among those who were not obese at baseline, those who began a CVD prevention drug had a statistically significant 82%% higher rate of becoming obese, compared with those not on a CVD-prevention drug. In addition, average daily energy expenditure, a measure of physical activity, showed a statistically significant decline among those who started a CVD drug, compared with those who did not. In contrast, CVD drug initiators had an average 1.85 gram/week decline in alcohol intake, compared with noninitiators, and those who were current smokers at the first survey and then started a CVD drug had a 26% relative drop in their smoking prevalence, compared with those who did not start a CVD drug, both statistically significant differences.
The findings suggest that “patients’ awareness of their risk factors alone seems not to be effective in improving health behaviors,” the authors concluded. “This means that expansion of pharmacologic interventions toward populations at low CVD risk may not necessarily lead to expected benefits at the population level.”
The study received no commercial funding. Dr. Korhonen had no disclosures.
SOURCE: Korhonen MJ et al. J Am Heart Assoc. 2020 Feb 5. doi: 10.1161/JAHA.119.014.168.
FROM THE JOURNAL OF THE AMERICAN HEART ASSOCIATION
Hypertensive disorders of pregnancy in SLE contribute to later CV outcomes
Women with systemic lupus erythematosus (SLE) who experience hypertensive disorders of pregnancy may have a higher rate of cardiovascular outcomes after pregnancy, as well as a higher rate of hypertension later in life, than do those without maternal hypertension, according to findings from a Swedish population-based, longitudinal cohort study.
“Premature CVD [cardiovascular disease] is a well-documented complication in women with SLE, which is likely, at least in part, due to renal disease, prothrombotic [antiphospholipid antibodies], and systemic inflammation. Our data confirm that women who experience a hypertensive disorder in pregnancy [HDP] are at greater risk of developing hypertension after pregnancy, and that this association is also evident for women with SLE. Women with SLE and HDP were also at increased risk of CVD, particularly stroke, at young ages and should be monitored closely and consider treatment to attenuate risk,” wrote first author Julia F. Simard, ScD, of Stanford (Calif.) University and colleagues in Arthritis Care & Research.
To reach those conclusions, the researchers identified 3,340 women in the Swedish Medical Birth Register with their first singleton delivery during 1987-2012. They matched each of the 450 women with prevalent SLE from the Medical Birth Register to 5 women without SLE in the National Patient Register based on sex, birth year, calendar time, and county of residence.
During a median follow-up period of nearly 11 years, women with SLE had an unadjusted incidence rate of incident cardiovascular outcomes of 50 cases per 10,000 person-years versus 7.2 for women without SLE. Cardiovascular outcomes included fatal and nonfatal acute MI, fatal and nonfatal stroke, transient ischemic attacks, unstable angina, and heart failure. A history of HDP in women with SLE, including preeclampsia, was linked with about a twofold higher rate of cardiovascular outcomes regardless of multiple sensitivity analyses, both before and after adjusting for maternal age at delivery, county of birth, education, body mass index, and first-trimester smoking.
The researchers found that the hazard ratio for cardiovascular outcomes in women with SLE and HDP was about eight times higher than the hazard ratio for women without SLE but with HDP, but the relative rarity of cardiovascular events seen during the follow-up period, particularly among women without SLE, made it so that they “could not confirm established associations between HDP and CVD, possibly due to the relatively short follow-up time given that premenopausal CVD is rare among women free of SLE.”
HDP was associated with a threefold higher risk for incident hypertension later in life regardless of SLE status, even though the unadjusted incidence rate was 524 cases per 10,000 person-years among women with both SLE and HDP, compared with 177 per 10,000 person-years among women with HDP in the general population, which sensitivity analyses suggested “was not due to misclassification of antihypertensive use for renal disease in women with SLE nor antihypertensive use for possible HDP in subsequent pregnancies,” the researchers wrote.
Several authors reported research grants from the National Institutes of Health, the Karolinska Institute, the Swedish Research Council, Swedish Heart-Lung Foundation, Stockholm County Council, the King Gustaf V 80th Birthday Fund, the Swedish Rheumatism Association, and Ingegerd Johansson’s Foundation that helped to fund the study. All authors reported having no competing interests.
SOURCE: Simard JF et al. Arthritis Care Res. 2020 Jan 31. doi: 10.1002/acr.24160.
Women with systemic lupus erythematosus (SLE) who experience hypertensive disorders of pregnancy may have a higher rate of cardiovascular outcomes after pregnancy, as well as a higher rate of hypertension later in life, than do those without maternal hypertension, according to findings from a Swedish population-based, longitudinal cohort study.
“Premature CVD [cardiovascular disease] is a well-documented complication in women with SLE, which is likely, at least in part, due to renal disease, prothrombotic [antiphospholipid antibodies], and systemic inflammation. Our data confirm that women who experience a hypertensive disorder in pregnancy [HDP] are at greater risk of developing hypertension after pregnancy, and that this association is also evident for women with SLE. Women with SLE and HDP were also at increased risk of CVD, particularly stroke, at young ages and should be monitored closely and consider treatment to attenuate risk,” wrote first author Julia F. Simard, ScD, of Stanford (Calif.) University and colleagues in Arthritis Care & Research.
To reach those conclusions, the researchers identified 3,340 women in the Swedish Medical Birth Register with their first singleton delivery during 1987-2012. They matched each of the 450 women with prevalent SLE from the Medical Birth Register to 5 women without SLE in the National Patient Register based on sex, birth year, calendar time, and county of residence.
During a median follow-up period of nearly 11 years, women with SLE had an unadjusted incidence rate of incident cardiovascular outcomes of 50 cases per 10,000 person-years versus 7.2 for women without SLE. Cardiovascular outcomes included fatal and nonfatal acute MI, fatal and nonfatal stroke, transient ischemic attacks, unstable angina, and heart failure. A history of HDP in women with SLE, including preeclampsia, was linked with about a twofold higher rate of cardiovascular outcomes regardless of multiple sensitivity analyses, both before and after adjusting for maternal age at delivery, county of birth, education, body mass index, and first-trimester smoking.
The researchers found that the hazard ratio for cardiovascular outcomes in women with SLE and HDP was about eight times higher than the hazard ratio for women without SLE but with HDP, but the relative rarity of cardiovascular events seen during the follow-up period, particularly among women without SLE, made it so that they “could not confirm established associations between HDP and CVD, possibly due to the relatively short follow-up time given that premenopausal CVD is rare among women free of SLE.”
HDP was associated with a threefold higher risk for incident hypertension later in life regardless of SLE status, even though the unadjusted incidence rate was 524 cases per 10,000 person-years among women with both SLE and HDP, compared with 177 per 10,000 person-years among women with HDP in the general population, which sensitivity analyses suggested “was not due to misclassification of antihypertensive use for renal disease in women with SLE nor antihypertensive use for possible HDP in subsequent pregnancies,” the researchers wrote.
Several authors reported research grants from the National Institutes of Health, the Karolinska Institute, the Swedish Research Council, Swedish Heart-Lung Foundation, Stockholm County Council, the King Gustaf V 80th Birthday Fund, the Swedish Rheumatism Association, and Ingegerd Johansson’s Foundation that helped to fund the study. All authors reported having no competing interests.
SOURCE: Simard JF et al. Arthritis Care Res. 2020 Jan 31. doi: 10.1002/acr.24160.
Women with systemic lupus erythematosus (SLE) who experience hypertensive disorders of pregnancy may have a higher rate of cardiovascular outcomes after pregnancy, as well as a higher rate of hypertension later in life, than do those without maternal hypertension, according to findings from a Swedish population-based, longitudinal cohort study.
“Premature CVD [cardiovascular disease] is a well-documented complication in women with SLE, which is likely, at least in part, due to renal disease, prothrombotic [antiphospholipid antibodies], and systemic inflammation. Our data confirm that women who experience a hypertensive disorder in pregnancy [HDP] are at greater risk of developing hypertension after pregnancy, and that this association is also evident for women with SLE. Women with SLE and HDP were also at increased risk of CVD, particularly stroke, at young ages and should be monitored closely and consider treatment to attenuate risk,” wrote first author Julia F. Simard, ScD, of Stanford (Calif.) University and colleagues in Arthritis Care & Research.
To reach those conclusions, the researchers identified 3,340 women in the Swedish Medical Birth Register with their first singleton delivery during 1987-2012. They matched each of the 450 women with prevalent SLE from the Medical Birth Register to 5 women without SLE in the National Patient Register based on sex, birth year, calendar time, and county of residence.
During a median follow-up period of nearly 11 years, women with SLE had an unadjusted incidence rate of incident cardiovascular outcomes of 50 cases per 10,000 person-years versus 7.2 for women without SLE. Cardiovascular outcomes included fatal and nonfatal acute MI, fatal and nonfatal stroke, transient ischemic attacks, unstable angina, and heart failure. A history of HDP in women with SLE, including preeclampsia, was linked with about a twofold higher rate of cardiovascular outcomes regardless of multiple sensitivity analyses, both before and after adjusting for maternal age at delivery, county of birth, education, body mass index, and first-trimester smoking.
The researchers found that the hazard ratio for cardiovascular outcomes in women with SLE and HDP was about eight times higher than the hazard ratio for women without SLE but with HDP, but the relative rarity of cardiovascular events seen during the follow-up period, particularly among women without SLE, made it so that they “could not confirm established associations between HDP and CVD, possibly due to the relatively short follow-up time given that premenopausal CVD is rare among women free of SLE.”
HDP was associated with a threefold higher risk for incident hypertension later in life regardless of SLE status, even though the unadjusted incidence rate was 524 cases per 10,000 person-years among women with both SLE and HDP, compared with 177 per 10,000 person-years among women with HDP in the general population, which sensitivity analyses suggested “was not due to misclassification of antihypertensive use for renal disease in women with SLE nor antihypertensive use for possible HDP in subsequent pregnancies,” the researchers wrote.
Several authors reported research grants from the National Institutes of Health, the Karolinska Institute, the Swedish Research Council, Swedish Heart-Lung Foundation, Stockholm County Council, the King Gustaf V 80th Birthday Fund, the Swedish Rheumatism Association, and Ingegerd Johansson’s Foundation that helped to fund the study. All authors reported having no competing interests.
SOURCE: Simard JF et al. Arthritis Care Res. 2020 Jan 31. doi: 10.1002/acr.24160.
FROM ARTHRITIS CARE & RESEARCH
Cardiac biomarkers refine antihypertensive drug initiation decisions
PHILADELPHIA – Incorporation of cardiac biomarkers into current guideline-based decision-making regarding initiation of antihypertensive medication in patients with previously untreated mild or moderate high blood pressure leads to more appropriate and selective matching of intensive blood pressure control with true patient risk, Ambarish Pandey, MD, reported at the American Heart Association scientific sessions.
That’s because the 2017 American College of Cardiology/AHA blood pressure guidelines recommend incorporating the ACC/AHA 10-Year Atherosclerotic Cardiovascular Disease (ASCVD) Risk Calculator into decision making as to whether to start antihypertensive drug therapy in patients with stage 1 hypertension (130-139/80-89 mm Hg), but the risk calculator doesn’t account for the risk of heart failure.
Yet by far the greatest benefit of intensive BP lowering is in reducing the risk of developing heart failure, as demonstrated in the landmark SPRINT trial, which showed that intensive BP lowering achieved much greater risk reduction in new-onset heart failure than in atherosclerotic cardiovascular events.
Thus, there’s a need for better strategies to guide antihypertensive therapy. And therein lies the rationale for incorporating into the risk assessment an individual’s values for N-terminal pro–brain natriuretic peptide (NT-proBNP), which reflects chronic myocardial stress, and high-sensitivity cardiac troponin T (hs-cTnT), which when elevated signals myocardial injury.
“Cardiac biomarkers are intermediate phenotypes from hypertension to future cardiovascular events. They can identify individuals at increased risk for atherosclerotic events, and at even higher risk for heart failure events,” explained Dr. Pandey, a cardiologist at the University of Texas Southwestern Medical Center, Dallas.
He presented a study of 12,987 participants in three major U.S. cohort studies: the Atherosclerosis Risk In Communities (ARIC) study, the Multi-Ethnic Study of Atherosclerosis (MESA), and the Dallas Heart Study. At baseline, none of the participants were on antihypertensive therapy or had known cardiovascular disease. During 10 years of prospective follow-up, 825 of them experienced a first cardiovascular disease event: 251 developed heart failure and 574 had an MI, stroke, or cardiovascular death. Dr. Pandey and his coworkers calculated the cardiovascular event incidence rate and number-needed-to-treat with intensive antihypertensive drug therapy to prevent a first cardiovascular disease event on the basis of whether patients in the various BP categories were positive or negative for one or more biomarkers.
The results
Fifty-four percent of subjects had normal BP, defined in the guidelines as less than 120/80 mm Hg. Another 3% had BP in excess of 160/100 mm Hg. No controversy exists regarding pharmacotherapy in either of these groups: It’s not warranted in the former, essential in the latter.
Another 3,000 individuals had what the ACC/AHA guidelines define as elevated BP, meaning 120-129/<80 mm Hg, or low-risk stage 1 hypertension of 130-139/80-89 mm Hg and a 10-year ASCVD risk score of less than 10%. Initiation of antihypertensive medication in these groups is not recommended in the guidelines. Yet 36% of these individuals had at least one positive cardiac biomarker. And here’s the eye-opening finding: Notably, the 10-year cardiovascular event incidence rate in this biomarker group not currently recommended for antihypertensive pharmacotherapy was 11%, more than double the 4.6% rate in the biomarker-negative group, which in turn was comparable to the 3.8% in the normal BP participants.
Antihypertensive therapy was recommended according to the guidelines in 20% of the total study population, comprising patients with stage 1 hypertension who had an ASCVD risk score of 10% or more as well as those with stage 2 hypertension, defined as BP greater than 140/90 mm Hg but less than 160/100 mm Hg. Forty-eight percent of these subjects were positive for at least one biomarker. Their cardiovascular incidence rate was 15.1%, compared to the 7.9% rate in biomarker-negative individuals.
The estimated number-needed-to-treat (NNT) with intensive blood pressure–lowering therapy to a target systolic BP of less than 120 mm Hg, as in SPRINT, to prevent one cardiovascular event in individuals not currently guideline-recommended for antihypertensive medications was 86 in those who were biomarker-negative. The NNT dropped to 36 in the biomarker-positive subgroup, a far more attractive figure that suggests a reasonable likelihood of benefit from intensive blood pressure control, in Dr. Pandey’s view.
Similarly, among individuals currently recommended for pharmacotherapy initiation, the NNTs were 49 if biomarker-negative, improving to 26 in those positive for one or both biomarkers, which was comparable to the NNT of 22 in the group with blood pressures greater than 160/100 mm Hg. The NNT of 49 in the biomarker-negative subgroup is in a borderline gray zone warranting individualized shared decision-making regarding pharmacotherapy, Dr. Pandey said.
In this study, an elevated hs-cTnT was defined as 6 ng/L or more, while an elevated NT-proBNP was considered to be at least 100 pg/mL.
“It’s noteworthy that the degree of elevation in hs-cTnT and NT-proBNP which were observed in our study were pretty subtle and much below the threshold used for diagnosis of ischemic events or heart failure. Thus, these elevations were largely representative of subtle chronic injury and not acute events,” according to the cardiologist.
One audience member asked if the elevated biomarkers could simply be a surrogate for longer duration of exposure of the heart to high BP. Sure, Dr. Pandey replied, pointing to the 6-year greater average age of the biomarker-positive participants.
“It is likely that biomarker-positive status is capturing the culmination of longstanding exposure. But the thing about hypertension is there are no symptoms that can signal to the patient or the doctor that they have this disease, so testing for the biomarkers can actually capture the high-risk group that may have had hypertension for a long duration but now needs to be treated in order to prevent the advance of downstream adverse events,” he said.
Dr. Pandey reported having no financial conflicts of interest regarding his study, conducted free of commercial support.
SOURCE: Pandey A. AHA 2019 Abstract EP.AOS.521.141
PHILADELPHIA – Incorporation of cardiac biomarkers into current guideline-based decision-making regarding initiation of antihypertensive medication in patients with previously untreated mild or moderate high blood pressure leads to more appropriate and selective matching of intensive blood pressure control with true patient risk, Ambarish Pandey, MD, reported at the American Heart Association scientific sessions.
That’s because the 2017 American College of Cardiology/AHA blood pressure guidelines recommend incorporating the ACC/AHA 10-Year Atherosclerotic Cardiovascular Disease (ASCVD) Risk Calculator into decision making as to whether to start antihypertensive drug therapy in patients with stage 1 hypertension (130-139/80-89 mm Hg), but the risk calculator doesn’t account for the risk of heart failure.
Yet by far the greatest benefit of intensive BP lowering is in reducing the risk of developing heart failure, as demonstrated in the landmark SPRINT trial, which showed that intensive BP lowering achieved much greater risk reduction in new-onset heart failure than in atherosclerotic cardiovascular events.
Thus, there’s a need for better strategies to guide antihypertensive therapy. And therein lies the rationale for incorporating into the risk assessment an individual’s values for N-terminal pro–brain natriuretic peptide (NT-proBNP), which reflects chronic myocardial stress, and high-sensitivity cardiac troponin T (hs-cTnT), which when elevated signals myocardial injury.
“Cardiac biomarkers are intermediate phenotypes from hypertension to future cardiovascular events. They can identify individuals at increased risk for atherosclerotic events, and at even higher risk for heart failure events,” explained Dr. Pandey, a cardiologist at the University of Texas Southwestern Medical Center, Dallas.
He presented a study of 12,987 participants in three major U.S. cohort studies: the Atherosclerosis Risk In Communities (ARIC) study, the Multi-Ethnic Study of Atherosclerosis (MESA), and the Dallas Heart Study. At baseline, none of the participants were on antihypertensive therapy or had known cardiovascular disease. During 10 years of prospective follow-up, 825 of them experienced a first cardiovascular disease event: 251 developed heart failure and 574 had an MI, stroke, or cardiovascular death. Dr. Pandey and his coworkers calculated the cardiovascular event incidence rate and number-needed-to-treat with intensive antihypertensive drug therapy to prevent a first cardiovascular disease event on the basis of whether patients in the various BP categories were positive or negative for one or more biomarkers.
The results
Fifty-four percent of subjects had normal BP, defined in the guidelines as less than 120/80 mm Hg. Another 3% had BP in excess of 160/100 mm Hg. No controversy exists regarding pharmacotherapy in either of these groups: It’s not warranted in the former, essential in the latter.
Another 3,000 individuals had what the ACC/AHA guidelines define as elevated BP, meaning 120-129/<80 mm Hg, or low-risk stage 1 hypertension of 130-139/80-89 mm Hg and a 10-year ASCVD risk score of less than 10%. Initiation of antihypertensive medication in these groups is not recommended in the guidelines. Yet 36% of these individuals had at least one positive cardiac biomarker. And here’s the eye-opening finding: Notably, the 10-year cardiovascular event incidence rate in this biomarker group not currently recommended for antihypertensive pharmacotherapy was 11%, more than double the 4.6% rate in the biomarker-negative group, which in turn was comparable to the 3.8% in the normal BP participants.
Antihypertensive therapy was recommended according to the guidelines in 20% of the total study population, comprising patients with stage 1 hypertension who had an ASCVD risk score of 10% or more as well as those with stage 2 hypertension, defined as BP greater than 140/90 mm Hg but less than 160/100 mm Hg. Forty-eight percent of these subjects were positive for at least one biomarker. Their cardiovascular incidence rate was 15.1%, compared to the 7.9% rate in biomarker-negative individuals.
The estimated number-needed-to-treat (NNT) with intensive blood pressure–lowering therapy to a target systolic BP of less than 120 mm Hg, as in SPRINT, to prevent one cardiovascular event in individuals not currently guideline-recommended for antihypertensive medications was 86 in those who were biomarker-negative. The NNT dropped to 36 in the biomarker-positive subgroup, a far more attractive figure that suggests a reasonable likelihood of benefit from intensive blood pressure control, in Dr. Pandey’s view.
Similarly, among individuals currently recommended for pharmacotherapy initiation, the NNTs were 49 if biomarker-negative, improving to 26 in those positive for one or both biomarkers, which was comparable to the NNT of 22 in the group with blood pressures greater than 160/100 mm Hg. The NNT of 49 in the biomarker-negative subgroup is in a borderline gray zone warranting individualized shared decision-making regarding pharmacotherapy, Dr. Pandey said.
In this study, an elevated hs-cTnT was defined as 6 ng/L or more, while an elevated NT-proBNP was considered to be at least 100 pg/mL.
“It’s noteworthy that the degree of elevation in hs-cTnT and NT-proBNP which were observed in our study were pretty subtle and much below the threshold used for diagnosis of ischemic events or heart failure. Thus, these elevations were largely representative of subtle chronic injury and not acute events,” according to the cardiologist.
One audience member asked if the elevated biomarkers could simply be a surrogate for longer duration of exposure of the heart to high BP. Sure, Dr. Pandey replied, pointing to the 6-year greater average age of the biomarker-positive participants.
“It is likely that biomarker-positive status is capturing the culmination of longstanding exposure. But the thing about hypertension is there are no symptoms that can signal to the patient or the doctor that they have this disease, so testing for the biomarkers can actually capture the high-risk group that may have had hypertension for a long duration but now needs to be treated in order to prevent the advance of downstream adverse events,” he said.
Dr. Pandey reported having no financial conflicts of interest regarding his study, conducted free of commercial support.
SOURCE: Pandey A. AHA 2019 Abstract EP.AOS.521.141
PHILADELPHIA – Incorporation of cardiac biomarkers into current guideline-based decision-making regarding initiation of antihypertensive medication in patients with previously untreated mild or moderate high blood pressure leads to more appropriate and selective matching of intensive blood pressure control with true patient risk, Ambarish Pandey, MD, reported at the American Heart Association scientific sessions.
That’s because the 2017 American College of Cardiology/AHA blood pressure guidelines recommend incorporating the ACC/AHA 10-Year Atherosclerotic Cardiovascular Disease (ASCVD) Risk Calculator into decision making as to whether to start antihypertensive drug therapy in patients with stage 1 hypertension (130-139/80-89 mm Hg), but the risk calculator doesn’t account for the risk of heart failure.
Yet by far the greatest benefit of intensive BP lowering is in reducing the risk of developing heart failure, as demonstrated in the landmark SPRINT trial, which showed that intensive BP lowering achieved much greater risk reduction in new-onset heart failure than in atherosclerotic cardiovascular events.
Thus, there’s a need for better strategies to guide antihypertensive therapy. And therein lies the rationale for incorporating into the risk assessment an individual’s values for N-terminal pro–brain natriuretic peptide (NT-proBNP), which reflects chronic myocardial stress, and high-sensitivity cardiac troponin T (hs-cTnT), which when elevated signals myocardial injury.
“Cardiac biomarkers are intermediate phenotypes from hypertension to future cardiovascular events. They can identify individuals at increased risk for atherosclerotic events, and at even higher risk for heart failure events,” explained Dr. Pandey, a cardiologist at the University of Texas Southwestern Medical Center, Dallas.
He presented a study of 12,987 participants in three major U.S. cohort studies: the Atherosclerosis Risk In Communities (ARIC) study, the Multi-Ethnic Study of Atherosclerosis (MESA), and the Dallas Heart Study. At baseline, none of the participants were on antihypertensive therapy or had known cardiovascular disease. During 10 years of prospective follow-up, 825 of them experienced a first cardiovascular disease event: 251 developed heart failure and 574 had an MI, stroke, or cardiovascular death. Dr. Pandey and his coworkers calculated the cardiovascular event incidence rate and number-needed-to-treat with intensive antihypertensive drug therapy to prevent a first cardiovascular disease event on the basis of whether patients in the various BP categories were positive or negative for one or more biomarkers.
The results
Fifty-four percent of subjects had normal BP, defined in the guidelines as less than 120/80 mm Hg. Another 3% had BP in excess of 160/100 mm Hg. No controversy exists regarding pharmacotherapy in either of these groups: It’s not warranted in the former, essential in the latter.
Another 3,000 individuals had what the ACC/AHA guidelines define as elevated BP, meaning 120-129/<80 mm Hg, or low-risk stage 1 hypertension of 130-139/80-89 mm Hg and a 10-year ASCVD risk score of less than 10%. Initiation of antihypertensive medication in these groups is not recommended in the guidelines. Yet 36% of these individuals had at least one positive cardiac biomarker. And here’s the eye-opening finding: Notably, the 10-year cardiovascular event incidence rate in this biomarker group not currently recommended for antihypertensive pharmacotherapy was 11%, more than double the 4.6% rate in the biomarker-negative group, which in turn was comparable to the 3.8% in the normal BP participants.
Antihypertensive therapy was recommended according to the guidelines in 20% of the total study population, comprising patients with stage 1 hypertension who had an ASCVD risk score of 10% or more as well as those with stage 2 hypertension, defined as BP greater than 140/90 mm Hg but less than 160/100 mm Hg. Forty-eight percent of these subjects were positive for at least one biomarker. Their cardiovascular incidence rate was 15.1%, compared to the 7.9% rate in biomarker-negative individuals.
The estimated number-needed-to-treat (NNT) with intensive blood pressure–lowering therapy to a target systolic BP of less than 120 mm Hg, as in SPRINT, to prevent one cardiovascular event in individuals not currently guideline-recommended for antihypertensive medications was 86 in those who were biomarker-negative. The NNT dropped to 36 in the biomarker-positive subgroup, a far more attractive figure that suggests a reasonable likelihood of benefit from intensive blood pressure control, in Dr. Pandey’s view.
Similarly, among individuals currently recommended for pharmacotherapy initiation, the NNTs were 49 if biomarker-negative, improving to 26 in those positive for one or both biomarkers, which was comparable to the NNT of 22 in the group with blood pressures greater than 160/100 mm Hg. The NNT of 49 in the biomarker-negative subgroup is in a borderline gray zone warranting individualized shared decision-making regarding pharmacotherapy, Dr. Pandey said.
In this study, an elevated hs-cTnT was defined as 6 ng/L or more, while an elevated NT-proBNP was considered to be at least 100 pg/mL.
“It’s noteworthy that the degree of elevation in hs-cTnT and NT-proBNP which were observed in our study were pretty subtle and much below the threshold used for diagnosis of ischemic events or heart failure. Thus, these elevations were largely representative of subtle chronic injury and not acute events,” according to the cardiologist.
One audience member asked if the elevated biomarkers could simply be a surrogate for longer duration of exposure of the heart to high BP. Sure, Dr. Pandey replied, pointing to the 6-year greater average age of the biomarker-positive participants.
“It is likely that biomarker-positive status is capturing the culmination of longstanding exposure. But the thing about hypertension is there are no symptoms that can signal to the patient or the doctor that they have this disease, so testing for the biomarkers can actually capture the high-risk group that may have had hypertension for a long duration but now needs to be treated in order to prevent the advance of downstream adverse events,” he said.
Dr. Pandey reported having no financial conflicts of interest regarding his study, conducted free of commercial support.
SOURCE: Pandey A. AHA 2019 Abstract EP.AOS.521.141
REPORTING FROM AHA 2019
Renal denervation rebounds
PHILADELPHIA – Enthusiasm for catheter-based renal denervation as a potential nondrug treatment for hypertension is once again on the rise, Michael Bohm, MD, observed at the American Heart Association scientific sessions.
The field experienced “a big depression” in 2014 with the publication of the unexpectedly negative results of the Symplicity HTN-3 trial (N Engl J Med. 2014;370:1393-401), he said. But post hoc analysis of the trial revealed significant shortcomings in design and execution.
“All of the flaws of this trial have been eliminated and now there is a very tightly controlled program to show whether renal denervation will work or not,” according to Dr. Bohm, director of the department of internal medicine and professor of cardiology at Saarland University in Homburg, Germany.
Indeed, three randomized, double-blind, sham-controlled, proof-of-concept clinical trials – all with strongly positive results – were published in Lancet in 2017 and 2018: SPYRAL HTN-OFF (2017 Nov 11;390:2160-70), RADIANCE SOLO (2018 Jun 9;391:2335-45), and SPYRAL HTN-ON (2018 May 23;391:2346-55). Based on the encouraging findings, four large pivotal trials of renal denervation (RDN) for hypertension are ongoing: RADIANCE HTN, REQUIRE, RADIANCE II, and SPYRAL HTN-ON MED. In addition, the SPYRAL HTN-OFF MED pivotal trial has been completed and will be presented soon, Dr. Bohm said.
Defining who’s most likely to benefit
Treatment response has been quite variable within the various RDN trials. A reliable predictor of response would be an important advance because it would enable physicians to select the best candidates for treatment while sparing others from an invasive procedure – albeit a relatively safe one – that they may not benefit from. On this front, Dr. Bohm and colleagues have recently reported that a baseline 24-hour heart rate above the median value of 73.5 bpm in the SPYRAL HTN-OFF MED trial – a marker for sympathetic overdrive – was associated with a 10.7/7.5 mm Hg greater reduction in average ambulatory blood pressures post-RDN than with a sham procedure. In contrast, blood pressure changes in RDN recipients with a below-median baseline 24-hour heart rate weren’t significant (Eur Heart J. 2019 Mar 1;40:743-51).
“Although this is a little bit rough, there is no other really true and reliable marker,” the cardiologist observed.
A pressing need exists for a reliable intraprocedural indicator of success. Dr. Bohm noted that Australian investigators are pursuing a promising approach in animal studies: intraprocedural transvascular high-frequency pacing of the aorticorenal ganglia. Abolition of the pacing-induced increase in blood pressure may be an indicator of complete RDN (JACC Cardiovasc Interv. 2019 Jun 24;12:1109-20).
Applications other than hypertension
Renal denervation is under early-stage investigation for a range of other cardiovascular diseases in which sympathetic overdrive figures prominently.
“The truly interesting things in renal denervation are what happens beyond hypertension. There are a lot of potential applications,” according to Dr. Bohm.
For example, when RDN was performed alongside pulmonary vein isolation for treatment of paroxysmal atrial fibrillation in hypertensive patients, the arrhythmia recurrence rate was significantly reduced during 1 year of follow-up, compared with AF ablation alone, in the randomized, multicenter, 302-patient ERADICATE-AF trial, presented at the most recent meeting of the Heart Rhythm Society.
Also, a small, uncontrolled registry study of RDN in patients with cardiomyopathy and electrical storm suggests the procedure may have an immediate anti–ventricular arrhythmia effect.
Meanwhile, Dr. Bohm is pressing the German government to sponsor an independent randomized controlled trial of RDN for heart failure. He and others have shown in small pilot studies a promising signal that the treatment may improve myocardial function and the signs and symptoms of heart failure in both patients with reduced and preserved left ventricular ejection fraction – and without reducing their blood pressure, which is often already low.
Dr. Bohm and others have also been exploring the impact of RDN in patients with metabolic syndrome. The treatment has a sound pathophysiologic rationale because insulin resistance is dependent upon sympathetic nervous system activation. Preliminary reports show improved insulin sensitivity in response to RDN. Patients also report better quality of life, presumably because of the reduction in sympathetic overactivity.
A couple of small Chinese studies suggest denervating the pulmonary vein in patients with pulmonary hypertension leads to a salutary reduction in pulmonary blood pressures.
“We haven’t done that yet. There is no properly designed catheter. They’ve used a Spyra unipolar catheter. It could work, but it hasn’t been rigorously investigated,” the cardiologist said.
Dr. Bohm reported serving as a scientific adviser to Abbott, AstraZeneca, BMS, Boehringer Ingelheim, and Servier.
PHILADELPHIA – Enthusiasm for catheter-based renal denervation as a potential nondrug treatment for hypertension is once again on the rise, Michael Bohm, MD, observed at the American Heart Association scientific sessions.
The field experienced “a big depression” in 2014 with the publication of the unexpectedly negative results of the Symplicity HTN-3 trial (N Engl J Med. 2014;370:1393-401), he said. But post hoc analysis of the trial revealed significant shortcomings in design and execution.
“All of the flaws of this trial have been eliminated and now there is a very tightly controlled program to show whether renal denervation will work or not,” according to Dr. Bohm, director of the department of internal medicine and professor of cardiology at Saarland University in Homburg, Germany.
Indeed, three randomized, double-blind, sham-controlled, proof-of-concept clinical trials – all with strongly positive results – were published in Lancet in 2017 and 2018: SPYRAL HTN-OFF (2017 Nov 11;390:2160-70), RADIANCE SOLO (2018 Jun 9;391:2335-45), and SPYRAL HTN-ON (2018 May 23;391:2346-55). Based on the encouraging findings, four large pivotal trials of renal denervation (RDN) for hypertension are ongoing: RADIANCE HTN, REQUIRE, RADIANCE II, and SPYRAL HTN-ON MED. In addition, the SPYRAL HTN-OFF MED pivotal trial has been completed and will be presented soon, Dr. Bohm said.
Defining who’s most likely to benefit
Treatment response has been quite variable within the various RDN trials. A reliable predictor of response would be an important advance because it would enable physicians to select the best candidates for treatment while sparing others from an invasive procedure – albeit a relatively safe one – that they may not benefit from. On this front, Dr. Bohm and colleagues have recently reported that a baseline 24-hour heart rate above the median value of 73.5 bpm in the SPYRAL HTN-OFF MED trial – a marker for sympathetic overdrive – was associated with a 10.7/7.5 mm Hg greater reduction in average ambulatory blood pressures post-RDN than with a sham procedure. In contrast, blood pressure changes in RDN recipients with a below-median baseline 24-hour heart rate weren’t significant (Eur Heart J. 2019 Mar 1;40:743-51).
“Although this is a little bit rough, there is no other really true and reliable marker,” the cardiologist observed.
A pressing need exists for a reliable intraprocedural indicator of success. Dr. Bohm noted that Australian investigators are pursuing a promising approach in animal studies: intraprocedural transvascular high-frequency pacing of the aorticorenal ganglia. Abolition of the pacing-induced increase in blood pressure may be an indicator of complete RDN (JACC Cardiovasc Interv. 2019 Jun 24;12:1109-20).
Applications other than hypertension
Renal denervation is under early-stage investigation for a range of other cardiovascular diseases in which sympathetic overdrive figures prominently.
“The truly interesting things in renal denervation are what happens beyond hypertension. There are a lot of potential applications,” according to Dr. Bohm.
For example, when RDN was performed alongside pulmonary vein isolation for treatment of paroxysmal atrial fibrillation in hypertensive patients, the arrhythmia recurrence rate was significantly reduced during 1 year of follow-up, compared with AF ablation alone, in the randomized, multicenter, 302-patient ERADICATE-AF trial, presented at the most recent meeting of the Heart Rhythm Society.
Also, a small, uncontrolled registry study of RDN in patients with cardiomyopathy and electrical storm suggests the procedure may have an immediate anti–ventricular arrhythmia effect.
Meanwhile, Dr. Bohm is pressing the German government to sponsor an independent randomized controlled trial of RDN for heart failure. He and others have shown in small pilot studies a promising signal that the treatment may improve myocardial function and the signs and symptoms of heart failure in both patients with reduced and preserved left ventricular ejection fraction – and without reducing their blood pressure, which is often already low.
Dr. Bohm and others have also been exploring the impact of RDN in patients with metabolic syndrome. The treatment has a sound pathophysiologic rationale because insulin resistance is dependent upon sympathetic nervous system activation. Preliminary reports show improved insulin sensitivity in response to RDN. Patients also report better quality of life, presumably because of the reduction in sympathetic overactivity.
A couple of small Chinese studies suggest denervating the pulmonary vein in patients with pulmonary hypertension leads to a salutary reduction in pulmonary blood pressures.
“We haven’t done that yet. There is no properly designed catheter. They’ve used a Spyra unipolar catheter. It could work, but it hasn’t been rigorously investigated,” the cardiologist said.
Dr. Bohm reported serving as a scientific adviser to Abbott, AstraZeneca, BMS, Boehringer Ingelheim, and Servier.
PHILADELPHIA – Enthusiasm for catheter-based renal denervation as a potential nondrug treatment for hypertension is once again on the rise, Michael Bohm, MD, observed at the American Heart Association scientific sessions.
The field experienced “a big depression” in 2014 with the publication of the unexpectedly negative results of the Symplicity HTN-3 trial (N Engl J Med. 2014;370:1393-401), he said. But post hoc analysis of the trial revealed significant shortcomings in design and execution.
“All of the flaws of this trial have been eliminated and now there is a very tightly controlled program to show whether renal denervation will work or not,” according to Dr. Bohm, director of the department of internal medicine and professor of cardiology at Saarland University in Homburg, Germany.
Indeed, three randomized, double-blind, sham-controlled, proof-of-concept clinical trials – all with strongly positive results – were published in Lancet in 2017 and 2018: SPYRAL HTN-OFF (2017 Nov 11;390:2160-70), RADIANCE SOLO (2018 Jun 9;391:2335-45), and SPYRAL HTN-ON (2018 May 23;391:2346-55). Based on the encouraging findings, four large pivotal trials of renal denervation (RDN) for hypertension are ongoing: RADIANCE HTN, REQUIRE, RADIANCE II, and SPYRAL HTN-ON MED. In addition, the SPYRAL HTN-OFF MED pivotal trial has been completed and will be presented soon, Dr. Bohm said.
Defining who’s most likely to benefit
Treatment response has been quite variable within the various RDN trials. A reliable predictor of response would be an important advance because it would enable physicians to select the best candidates for treatment while sparing others from an invasive procedure – albeit a relatively safe one – that they may not benefit from. On this front, Dr. Bohm and colleagues have recently reported that a baseline 24-hour heart rate above the median value of 73.5 bpm in the SPYRAL HTN-OFF MED trial – a marker for sympathetic overdrive – was associated with a 10.7/7.5 mm Hg greater reduction in average ambulatory blood pressures post-RDN than with a sham procedure. In contrast, blood pressure changes in RDN recipients with a below-median baseline 24-hour heart rate weren’t significant (Eur Heart J. 2019 Mar 1;40:743-51).
“Although this is a little bit rough, there is no other really true and reliable marker,” the cardiologist observed.
A pressing need exists for a reliable intraprocedural indicator of success. Dr. Bohm noted that Australian investigators are pursuing a promising approach in animal studies: intraprocedural transvascular high-frequency pacing of the aorticorenal ganglia. Abolition of the pacing-induced increase in blood pressure may be an indicator of complete RDN (JACC Cardiovasc Interv. 2019 Jun 24;12:1109-20).
Applications other than hypertension
Renal denervation is under early-stage investigation for a range of other cardiovascular diseases in which sympathetic overdrive figures prominently.
“The truly interesting things in renal denervation are what happens beyond hypertension. There are a lot of potential applications,” according to Dr. Bohm.
For example, when RDN was performed alongside pulmonary vein isolation for treatment of paroxysmal atrial fibrillation in hypertensive patients, the arrhythmia recurrence rate was significantly reduced during 1 year of follow-up, compared with AF ablation alone, in the randomized, multicenter, 302-patient ERADICATE-AF trial, presented at the most recent meeting of the Heart Rhythm Society.
Also, a small, uncontrolled registry study of RDN in patients with cardiomyopathy and electrical storm suggests the procedure may have an immediate anti–ventricular arrhythmia effect.
Meanwhile, Dr. Bohm is pressing the German government to sponsor an independent randomized controlled trial of RDN for heart failure. He and others have shown in small pilot studies a promising signal that the treatment may improve myocardial function and the signs and symptoms of heart failure in both patients with reduced and preserved left ventricular ejection fraction – and without reducing their blood pressure, which is often already low.
Dr. Bohm and others have also been exploring the impact of RDN in patients with metabolic syndrome. The treatment has a sound pathophysiologic rationale because insulin resistance is dependent upon sympathetic nervous system activation. Preliminary reports show improved insulin sensitivity in response to RDN. Patients also report better quality of life, presumably because of the reduction in sympathetic overactivity.
A couple of small Chinese studies suggest denervating the pulmonary vein in patients with pulmonary hypertension leads to a salutary reduction in pulmonary blood pressures.
“We haven’t done that yet. There is no properly designed catheter. They’ve used a Spyra unipolar catheter. It could work, but it hasn’t been rigorously investigated,” the cardiologist said.
Dr. Bohm reported serving as a scientific adviser to Abbott, AstraZeneca, BMS, Boehringer Ingelheim, and Servier.
EXPERT ANALYSIS FROM AHA 2019