Hypertension

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, the associations suggest that patients with hypertension during the first 20 weeks may benefit from additional monitoring and counseling, 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.

[email protected]

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, the associations suggest that patients with hypertension during the first 20 weeks may benefit from additional monitoring and counseling, 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.

[email protected]

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, the associations suggest that patients with hypertension during the first 20 weeks may benefit from additional monitoring and counseling, 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.

[email protected]

SOURCE: Tesfalul M et al. Am J Obstet Gynecol. 2020 Jan;222(1):S92-3, Abstract 119.

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.

Bruce Jancin/MDedge News

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 I’m a much bigger fan of home blood pressure monitoring with appropriate instruction of patients. It empowers them to take some control,” 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.

[email protected]

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.

Bruce Jancin/MDedge News

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 I’m a much bigger fan of home blood pressure monitoring with appropriate instruction of patients. It empowers them to take some control,” 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.

[email protected]

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.

Bruce Jancin/MDedge News

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 I’m a much bigger fan of home blood pressure monitoring with appropriate instruction of patients. It empowers them to take some control,” 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.

[email protected]

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.

American Heart Association

“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.

[email protected]

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.

American Heart Association

“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.

[email protected]

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.

American Heart Association

“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.

[email protected]

SOURCE: Korhonen MJ et al. J Am Heart Assoc. 2020 Feb 5. doi: 10.1161/JAHA.119.014.168.

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.

[email protected]

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.

[email protected]

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.

[email protected]

SOURCE: Simard JF et al. Arthritis Care Res. 2020 Jan 31. doi: 10.1002/acr.24160.

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.

Bruce Jancin/MDedge News

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.
 

[email protected]

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.

Bruce Jancin/MDedge News

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.
 

[email protected]

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.

Bruce Jancin/MDedge News

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.
 

[email protected]

SOURCE: Pandey A. AHA 2019 Abstract EP.AOS.521.141

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.

Bruce Jancin/MDedge News

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.

[email protected]

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.

Bruce Jancin/MDedge News

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.

[email protected]

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.

Bruce Jancin/MDedge News

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.

[email protected]

PHILADELPHIA – Intensive blood pressure control in hypertensive adults at high cardiovascular risk adds a mean 6 months to 3 years of life expectancy in age-dependent fashion, compared with the older target standard BP, according to a novel analysis of data from the landmark SPRINT trial.

Bruce Jancin/MDedge News

SPRINT randomized 9,361 hypertensive patients aged 50 years or older with at least one additional cardiovascular risk factor to intensive control with a target systolic BP of less than 120 mm Hg or to the then-standard target of less than 140 mm Hg. The trial was stopped early for ethical reasons when an interim analysis showed intensive control was associated with a 27% reduction in mortality. But that 27% reduction in mortality risk is a tough concept for many patients to interpret in practical terms, Muthiah Vaduganathan, MD, observed at the American Heart Association scientific sessions.

So he and his coinvestigators sliced and diced the mountainous SPRINT data in a novel way, using an actuarial statistical analysis.

“These actuarial data from SPRINT support the survival benefits of intensive blood pressure control, especially when initiated in middle-aged, high-risk adults. Our analysis really reaffirms the original SPRINT trial results [N Engl J Med. 2015 Nov 26;373(22):2103-16] and helps present them in an alternative format that can potentially be more easily communicated to clinicians, patients, and the public at large,” explained Dr. Vaduganathan, a cardiologist at Brigham and Women’s Hospital and Harvard Medical School, both in Boston.

The impact of intensive BP control on residual survival was magnified in patients who were younger, since they intrinsically have a longer expected survival and will apply the antihypertensive regimen over a longer period. For example, the actuarial analysis concluded that the mean survival benefit of starting intensive BP lowering, rather than settling for a target systolic BP of less than 140 mm Hg starting at age 50 years, was 3 additional years of life, as compared with 1.1 additional years in 65-year-olds and 0.5 years in patients aged 85 years or older. The same approach can be applied to patients at any individual age from 50 to 95 years at the time of enrollment.

“This is very helpful in conveying messages to individual patients. Often if you tell a patient: ‘Your risk is going to go down by 27%,’ it’s tough for them to recognize what the baseline is and if that actually applied to them. So this may personalize that decision-making conversation,” according to the cardiologist.

One audience member commented that this SPRINT analysis might actually underestimate the true survival advantage of intensive BP lowering. He noted that SPRINT, which was halted after an average of 3.3 years, didn’t show a significant benefit for intensive BP lowering in terms of stroke reduction, whereas the ACCORD trial did, but that benefit didn’t occur until after 3 years into the study (Hypertension. 2018 Aug;72[2]:323-30).

Dr. Vaduganathan conceded that’s a limitation of his analysis.

“The assumption we’ve used is that long-term cardiovascular benefits are going to be as seen in the trial, but since SPRINT was stopped early, some benefits may be exaggerated and some may not have been observed yet,” he agreed.

Another audience member observed, “I think a lot of patients will think: ‘Okay, you’re tacking on a year at the end, when I’m going to be 89 and demented.’ The National Institute on Aging is focusing a lot more now on nondisabled life expectancy or healthy life expectancy.’”

Dr. Vaduganathan offered a degree of reassurance on this score. Because of time limitations, he said, he only presented the life expectancy results. But he and his coworkers have performed the same actuarial analysis of the SPRINT data for other endpoints related to freedom from various forms of disease or disability and found a consistent effect: Intensive BP control was associated with a longer time to onset of morbidity.

SPRINT was sponsored primarily by the National Heart, Lung, and Blood Institute. Dr. Vaduganathan reported that he receives research support from/and or serves on advisory boards for Amgen, AstraZeneca, Baxter Healthcare, Bayer, Boehringer Ingelheim, and Relypsa.

[email protected]

SOURCE: Vaduganathan M et al. AHA 2019, Abstract MDP233.

PHILADELPHIA – Intensive blood pressure control in hypertensive adults at high cardiovascular risk adds a mean 6 months to 3 years of life expectancy in age-dependent fashion, compared with the older target standard BP, according to a novel analysis of data from the landmark SPRINT trial.

Bruce Jancin/MDedge News

SPRINT randomized 9,361 hypertensive patients aged 50 years or older with at least one additional cardiovascular risk factor to intensive control with a target systolic BP of less than 120 mm Hg or to the then-standard target of less than 140 mm Hg. The trial was stopped early for ethical reasons when an interim analysis showed intensive control was associated with a 27% reduction in mortality. But that 27% reduction in mortality risk is a tough concept for many patients to interpret in practical terms, Muthiah Vaduganathan, MD, observed at the American Heart Association scientific sessions.

So he and his coinvestigators sliced and diced the mountainous SPRINT data in a novel way, using an actuarial statistical analysis.

“These actuarial data from SPRINT support the survival benefits of intensive blood pressure control, especially when initiated in middle-aged, high-risk adults. Our analysis really reaffirms the original SPRINT trial results [N Engl J Med. 2015 Nov 26;373(22):2103-16] and helps present them in an alternative format that can potentially be more easily communicated to clinicians, patients, and the public at large,” explained Dr. Vaduganathan, a cardiologist at Brigham and Women’s Hospital and Harvard Medical School, both in Boston.

The impact of intensive BP control on residual survival was magnified in patients who were younger, since they intrinsically have a longer expected survival and will apply the antihypertensive regimen over a longer period. For example, the actuarial analysis concluded that the mean survival benefit of starting intensive BP lowering, rather than settling for a target systolic BP of less than 140 mm Hg starting at age 50 years, was 3 additional years of life, as compared with 1.1 additional years in 65-year-olds and 0.5 years in patients aged 85 years or older. The same approach can be applied to patients at any individual age from 50 to 95 years at the time of enrollment.

“This is very helpful in conveying messages to individual patients. Often if you tell a patient: ‘Your risk is going to go down by 27%,’ it’s tough for them to recognize what the baseline is and if that actually applied to them. So this may personalize that decision-making conversation,” according to the cardiologist.

One audience member commented that this SPRINT analysis might actually underestimate the true survival advantage of intensive BP lowering. He noted that SPRINT, which was halted after an average of 3.3 years, didn’t show a significant benefit for intensive BP lowering in terms of stroke reduction, whereas the ACCORD trial did, but that benefit didn’t occur until after 3 years into the study (Hypertension. 2018 Aug;72[2]:323-30).

Dr. Vaduganathan conceded that’s a limitation of his analysis.

“The assumption we’ve used is that long-term cardiovascular benefits are going to be as seen in the trial, but since SPRINT was stopped early, some benefits may be exaggerated and some may not have been observed yet,” he agreed.

Another audience member observed, “I think a lot of patients will think: ‘Okay, you’re tacking on a year at the end, when I’m going to be 89 and demented.’ The National Institute on Aging is focusing a lot more now on nondisabled life expectancy or healthy life expectancy.’”

Dr. Vaduganathan offered a degree of reassurance on this score. Because of time limitations, he said, he only presented the life expectancy results. But he and his coworkers have performed the same actuarial analysis of the SPRINT data for other endpoints related to freedom from various forms of disease or disability and found a consistent effect: Intensive BP control was associated with a longer time to onset of morbidity.

SPRINT was sponsored primarily by the National Heart, Lung, and Blood Institute. Dr. Vaduganathan reported that he receives research support from/and or serves on advisory boards for Amgen, AstraZeneca, Baxter Healthcare, Bayer, Boehringer Ingelheim, and Relypsa.

[email protected]

SOURCE: Vaduganathan M et al. AHA 2019, Abstract MDP233.

PHILADELPHIA – Intensive blood pressure control in hypertensive adults at high cardiovascular risk adds a mean 6 months to 3 years of life expectancy in age-dependent fashion, compared with the older target standard BP, according to a novel analysis of data from the landmark SPRINT trial.

Bruce Jancin/MDedge News

SPRINT randomized 9,361 hypertensive patients aged 50 years or older with at least one additional cardiovascular risk factor to intensive control with a target systolic BP of less than 120 mm Hg or to the then-standard target of less than 140 mm Hg. The trial was stopped early for ethical reasons when an interim analysis showed intensive control was associated with a 27% reduction in mortality. But that 27% reduction in mortality risk is a tough concept for many patients to interpret in practical terms, Muthiah Vaduganathan, MD, observed at the American Heart Association scientific sessions.

So he and his coinvestigators sliced and diced the mountainous SPRINT data in a novel way, using an actuarial statistical analysis.

“These actuarial data from SPRINT support the survival benefits of intensive blood pressure control, especially when initiated in middle-aged, high-risk adults. Our analysis really reaffirms the original SPRINT trial results [N Engl J Med. 2015 Nov 26;373(22):2103-16] and helps present them in an alternative format that can potentially be more easily communicated to clinicians, patients, and the public at large,” explained Dr. Vaduganathan, a cardiologist at Brigham and Women’s Hospital and Harvard Medical School, both in Boston.

The impact of intensive BP control on residual survival was magnified in patients who were younger, since they intrinsically have a longer expected survival and will apply the antihypertensive regimen over a longer period. For example, the actuarial analysis concluded that the mean survival benefit of starting intensive BP lowering, rather than settling for a target systolic BP of less than 140 mm Hg starting at age 50 years, was 3 additional years of life, as compared with 1.1 additional years in 65-year-olds and 0.5 years in patients aged 85 years or older. The same approach can be applied to patients at any individual age from 50 to 95 years at the time of enrollment.

“This is very helpful in conveying messages to individual patients. Often if you tell a patient: ‘Your risk is going to go down by 27%,’ it’s tough for them to recognize what the baseline is and if that actually applied to them. So this may personalize that decision-making conversation,” according to the cardiologist.

One audience member commented that this SPRINT analysis might actually underestimate the true survival advantage of intensive BP lowering. He noted that SPRINT, which was halted after an average of 3.3 years, didn’t show a significant benefit for intensive BP lowering in terms of stroke reduction, whereas the ACCORD trial did, but that benefit didn’t occur until after 3 years into the study (Hypertension. 2018 Aug;72[2]:323-30).

Dr. Vaduganathan conceded that’s a limitation of his analysis.

“The assumption we’ve used is that long-term cardiovascular benefits are going to be as seen in the trial, but since SPRINT was stopped early, some benefits may be exaggerated and some may not have been observed yet,” he agreed.

Another audience member observed, “I think a lot of patients will think: ‘Okay, you’re tacking on a year at the end, when I’m going to be 89 and demented.’ The National Institute on Aging is focusing a lot more now on nondisabled life expectancy or healthy life expectancy.’”

Dr. Vaduganathan offered a degree of reassurance on this score. Because of time limitations, he said, he only presented the life expectancy results. But he and his coworkers have performed the same actuarial analysis of the SPRINT data for other endpoints related to freedom from various forms of disease or disability and found a consistent effect: Intensive BP control was associated with a longer time to onset of morbidity.

SPRINT was sponsored primarily by the National Heart, Lung, and Blood Institute. Dr. Vaduganathan reported that he receives research support from/and or serves on advisory boards for Amgen, AstraZeneca, Baxter Healthcare, Bayer, Boehringer Ingelheim, and Relypsa.

[email protected]

SOURCE: Vaduganathan M et al. AHA 2019, Abstract MDP233.

PHILADELPHIA – A home blood pressure telemonitoring program featuring pharmacist management of patients with uncontrolled hypertension reduced cardiovascular events by half and was cost saving over the course of 5 years, even though the intervention ended after year 1, Karen L. Margolis, MD, reported at the American Heart Association scientific sessions.

Bruce Jancin/MDedge News

“The return on investment was 126%. That means that for every dollar spent on the intervention, that dollar was recouped by $1.00 plus another $1.26,” explained Dr. Margolis, a general internist who serves as executive director for research at the HealthPartners Institute in Bloomington, Minn., and professor of medicine at the University of Minnesota, Minneapolis.

She presented 5-year follow-up data from the Hyperlink (Home Blood Pressure Telemonitoring and Case Management to Control Hypertension) study, a cluster randomized controlled trial involving 16 primary care clinics. Half of the clinics were randomized to the intervention, which entailed home blood pressure telemonitoring and pharmacist-led case management in collaboration with the primary care team. The other eight clinics provided usual care. The intervention portion of the trial, which lasted for 12 months, included 450 adults with uncontrolled hypertension as defined by repeated on-treatment blood pressure readings of 140/90 mm Hg or more. Participants’ baseline mean blood pressure was 148/85 mm Hg while on an average of one and a half antihypertensive drug classes. On average, pharmacists ended up adding one additional drug from a different antihypertensive drug class to achieve improved blood pressure control.

The details of the intervention and the short-term blood pressure results have previously been reported (JAMA. 2013 Jul 3;310[1]:46-56). Briefly, 6 months into the study, patients in the intervention arm averaged 11/6 mm Hg lower blood pressure than did the usual care controls. At 12 months – when the intervention ended – the between-group difference was similar at 10/5 mm Hg. At 18 months, the difference, while attenuated, remained significant at 7/3 mm Hg in favor of the intervention group. However, at 54 months, the intervention group’s advantage – a 3–mm Hg lower SBP and a 1–mm Hg lower DBP than in controls – was no longer significant.

The exciting new findings Dr. Margolis presented at the AHA scientific sessions focused on 5-year outcomes. Since HealthPartners is an integrated health care system, follow-up was essentially complete.

“None of the other telemetry studies I’m aware of have published anything on cardiovascular events. And we were somewhat surprised when we looked at our data to see fairly substantial differences in our primary outcome,” she noted.

That outcome was a composite of MI, stroke, heart failure, or cardiovascular death occurring over 5 years. The rate was 4.4% in the intervention group and nearly double at 8.6% in controls. That translated to a 51% relative risk reduction. The biggest difference was in stroke: 4 cases in the intervention arm, 12 in usual care controls.

The 5-year coronary revascularization rate was 5.3% in the intervention arm and 10.4% in controls, for a 52% relative risk reduction.

A major caveat regarding the Hyperlink trial was that, even at 450 patients and 5 years of follow-up, the study was underpowered to show significant differences in event rates, with P =.09 for the primary endpoint.

That being said, the financial results were striking. The intervention cost $1,511 per patient in 2017 U.S. dollars. The cost of treatment for major adverse cardiovascular events totaled $758,000 in the intervention group and $1,538,000 in usual care controls. That works out to $3,420 less per patient in the intervention arm. Offset by the cost of the intervention, that spells a net savings of $1,908 per patient achieved by implementing the year-long intervention. It’s a rare instance in health care of an intervention that actually makes money.

These results were unusual enough that Dr. Margolis and her coinvestigators decided to feed their wealth of SBP readings into a microsimulation model, which they ran 1,000 times. The model predicted – in light of the fact that patients in the intervention group were on average 2 years older than the controls were – that the expected reduction in the primary endpoint was 12% rather than the observed 51% relative risk reduction.

How to explain the discrepancy? The Hyperlink results could have been due to chance. Or it could be, Dr. Margolis surmised, that the pharmacists helped accomplish improvements in other cardiovascular risk factors, such as hyperlipidemia, smoking, or sedentary behavior. That’s unknown, since the investigators focused on changes in blood pressure only. Future studies of home telemonitoring and pharmacist case management of uncontrolled hypertension should be powered to detect significant differences in cardiovascular events and should track additional risk factors, she concluded.

She reported having no financial conflicts regarding the study.

[email protected]

SOURCE: Margolis KL. AHA 2019. Abstract MDP232.

PHILADELPHIA – A home blood pressure telemonitoring program featuring pharmacist management of patients with uncontrolled hypertension reduced cardiovascular events by half and was cost saving over the course of 5 years, even though the intervention ended after year 1, Karen L. Margolis, MD, reported at the American Heart Association scientific sessions.

Bruce Jancin/MDedge News

“The return on investment was 126%. That means that for every dollar spent on the intervention, that dollar was recouped by $1.00 plus another $1.26,” explained Dr. Margolis, a general internist who serves as executive director for research at the HealthPartners Institute in Bloomington, Minn., and professor of medicine at the University of Minnesota, Minneapolis.

She presented 5-year follow-up data from the Hyperlink (Home Blood Pressure Telemonitoring and Case Management to Control Hypertension) study, a cluster randomized controlled trial involving 16 primary care clinics. Half of the clinics were randomized to the intervention, which entailed home blood pressure telemonitoring and pharmacist-led case management in collaboration with the primary care team. The other eight clinics provided usual care. The intervention portion of the trial, which lasted for 12 months, included 450 adults with uncontrolled hypertension as defined by repeated on-treatment blood pressure readings of 140/90 mm Hg or more. Participants’ baseline mean blood pressure was 148/85 mm Hg while on an average of one and a half antihypertensive drug classes. On average, pharmacists ended up adding one additional drug from a different antihypertensive drug class to achieve improved blood pressure control.

The details of the intervention and the short-term blood pressure results have previously been reported (JAMA. 2013 Jul 3;310[1]:46-56). Briefly, 6 months into the study, patients in the intervention arm averaged 11/6 mm Hg lower blood pressure than did the usual care controls. At 12 months – when the intervention ended – the between-group difference was similar at 10/5 mm Hg. At 18 months, the difference, while attenuated, remained significant at 7/3 mm Hg in favor of the intervention group. However, at 54 months, the intervention group’s advantage – a 3–mm Hg lower SBP and a 1–mm Hg lower DBP than in controls – was no longer significant.

The exciting new findings Dr. Margolis presented at the AHA scientific sessions focused on 5-year outcomes. Since HealthPartners is an integrated health care system, follow-up was essentially complete.

“None of the other telemetry studies I’m aware of have published anything on cardiovascular events. And we were somewhat surprised when we looked at our data to see fairly substantial differences in our primary outcome,” she noted.

That outcome was a composite of MI, stroke, heart failure, or cardiovascular death occurring over 5 years. The rate was 4.4% in the intervention group and nearly double at 8.6% in controls. That translated to a 51% relative risk reduction. The biggest difference was in stroke: 4 cases in the intervention arm, 12 in usual care controls.

The 5-year coronary revascularization rate was 5.3% in the intervention arm and 10.4% in controls, for a 52% relative risk reduction.

A major caveat regarding the Hyperlink trial was that, even at 450 patients and 5 years of follow-up, the study was underpowered to show significant differences in event rates, with P =.09 for the primary endpoint.

That being said, the financial results were striking. The intervention cost $1,511 per patient in 2017 U.S. dollars. The cost of treatment for major adverse cardiovascular events totaled $758,000 in the intervention group and $1,538,000 in usual care controls. That works out to $3,420 less per patient in the intervention arm. Offset by the cost of the intervention, that spells a net savings of $1,908 per patient achieved by implementing the year-long intervention. It’s a rare instance in health care of an intervention that actually makes money.

These results were unusual enough that Dr. Margolis and her coinvestigators decided to feed their wealth of SBP readings into a microsimulation model, which they ran 1,000 times. The model predicted – in light of the fact that patients in the intervention group were on average 2 years older than the controls were – that the expected reduction in the primary endpoint was 12% rather than the observed 51% relative risk reduction.

How to explain the discrepancy? The Hyperlink results could have been due to chance. Or it could be, Dr. Margolis surmised, that the pharmacists helped accomplish improvements in other cardiovascular risk factors, such as hyperlipidemia, smoking, or sedentary behavior. That’s unknown, since the investigators focused on changes in blood pressure only. Future studies of home telemonitoring and pharmacist case management of uncontrolled hypertension should be powered to detect significant differences in cardiovascular events and should track additional risk factors, she concluded.

She reported having no financial conflicts regarding the study.

[email protected]

SOURCE: Margolis KL. AHA 2019. Abstract MDP232.

PHILADELPHIA – A home blood pressure telemonitoring program featuring pharmacist management of patients with uncontrolled hypertension reduced cardiovascular events by half and was cost saving over the course of 5 years, even though the intervention ended after year 1, Karen L. Margolis, MD, reported at the American Heart Association scientific sessions.

Bruce Jancin/MDedge News

“The return on investment was 126%. That means that for every dollar spent on the intervention, that dollar was recouped by $1.00 plus another $1.26,” explained Dr. Margolis, a general internist who serves as executive director for research at the HealthPartners Institute in Bloomington, Minn., and professor of medicine at the University of Minnesota, Minneapolis.

She presented 5-year follow-up data from the Hyperlink (Home Blood Pressure Telemonitoring and Case Management to Control Hypertension) study, a cluster randomized controlled trial involving 16 primary care clinics. Half of the clinics were randomized to the intervention, which entailed home blood pressure telemonitoring and pharmacist-led case management in collaboration with the primary care team. The other eight clinics provided usual care. The intervention portion of the trial, which lasted for 12 months, included 450 adults with uncontrolled hypertension as defined by repeated on-treatment blood pressure readings of 140/90 mm Hg or more. Participants’ baseline mean blood pressure was 148/85 mm Hg while on an average of one and a half antihypertensive drug classes. On average, pharmacists ended up adding one additional drug from a different antihypertensive drug class to achieve improved blood pressure control.

The details of the intervention and the short-term blood pressure results have previously been reported (JAMA. 2013 Jul 3;310[1]:46-56). Briefly, 6 months into the study, patients in the intervention arm averaged 11/6 mm Hg lower blood pressure than did the usual care controls. At 12 months – when the intervention ended – the between-group difference was similar at 10/5 mm Hg. At 18 months, the difference, while attenuated, remained significant at 7/3 mm Hg in favor of the intervention group. However, at 54 months, the intervention group’s advantage – a 3–mm Hg lower SBP and a 1–mm Hg lower DBP than in controls – was no longer significant.

The exciting new findings Dr. Margolis presented at the AHA scientific sessions focused on 5-year outcomes. Since HealthPartners is an integrated health care system, follow-up was essentially complete.

“None of the other telemetry studies I’m aware of have published anything on cardiovascular events. And we were somewhat surprised when we looked at our data to see fairly substantial differences in our primary outcome,” she noted.

That outcome was a composite of MI, stroke, heart failure, or cardiovascular death occurring over 5 years. The rate was 4.4% in the intervention group and nearly double at 8.6% in controls. That translated to a 51% relative risk reduction. The biggest difference was in stroke: 4 cases in the intervention arm, 12 in usual care controls.

The 5-year coronary revascularization rate was 5.3% in the intervention arm and 10.4% in controls, for a 52% relative risk reduction.

A major caveat regarding the Hyperlink trial was that, even at 450 patients and 5 years of follow-up, the study was underpowered to show significant differences in event rates, with P =.09 for the primary endpoint.

That being said, the financial results were striking. The intervention cost $1,511 per patient in 2017 U.S. dollars. The cost of treatment for major adverse cardiovascular events totaled $758,000 in the intervention group and $1,538,000 in usual care controls. That works out to $3,420 less per patient in the intervention arm. Offset by the cost of the intervention, that spells a net savings of $1,908 per patient achieved by implementing the year-long intervention. It’s a rare instance in health care of an intervention that actually makes money.

These results were unusual enough that Dr. Margolis and her coinvestigators decided to feed their wealth of SBP readings into a microsimulation model, which they ran 1,000 times. The model predicted – in light of the fact that patients in the intervention group were on average 2 years older than the controls were – that the expected reduction in the primary endpoint was 12% rather than the observed 51% relative risk reduction.

How to explain the discrepancy? The Hyperlink results could have been due to chance. Or it could be, Dr. Margolis surmised, that the pharmacists helped accomplish improvements in other cardiovascular risk factors, such as hyperlipidemia, smoking, or sedentary behavior. That’s unknown, since the investigators focused on changes in blood pressure only. Future studies of home telemonitoring and pharmacist case management of uncontrolled hypertension should be powered to detect significant differences in cardiovascular events and should track additional risk factors, she concluded.

She reported having no financial conflicts regarding the study.

[email protected]

SOURCE: Margolis KL. AHA 2019. Abstract MDP232.

WASHINGTON – Research on pravastatin for the prevention of preeclampsia is moving along after “reassuring” data from pilot studies, with a large National Institutes of Health–funded trial currently recruiting women with a prior history of the disorder with preterm delivery at less than 34 weeks, Maged Costantine, MD, said at the biennial Diabetes in Pregnancy Study Group of North America meeting.

Creatas Images

More should be learned about low-dose aspirin, in the meantime, once the outcomes of a global study involving first-trimester initiation are published, said another speaker, Cynthia Gyamfi-Bannerman, MD, MS. Low-dose aspirin currently is recommended for preeclampsia prevention starting between 12 and 28 weeks, optimally before 16 weeks.

The biological plausibility of using pravastatin for preeclampsia prevention stems from the overlapping pathophysiology of preeclampsia with atherosclerotic cardiovascular disease – endothelial dysfunction and inflammation are common key mechanisms – as well as common risk factors, including diabetes and obesity, said Dr. Costantine, director of the division of maternal-fetal medicine at Ohio State University, Columbus, who is chairing the study.

In animal models of preeclampsia, pravastatin has been shown to upregulate placental growth factor, reduce antiangiogenic factors such as soluble fms-like tyrosine kinase 1 (sFlt1), and upregulate endothelial nitric oxide synthase. Mice have shown improved vascular reactivity, decreased proteinuria, decreased oxidative stress, and other positive effects, without any detrimental outcomes.

A pilot randomized controlled trial conducted with the Obstetric-Fetal Pharmacology Research Units Network and published in the American Journal of Obstetrics and Gynecology in 2016 assigned 10 women to 10 mg daily pravastatin and 10 women to placebo. The drug reduced maternal cholesterol concentrations but there were no differences in birth weight or umbilical cord cholesterol concentrations between the two groups.

Women in the pravastatin group were less likely to develop preeclampsia (none, compared with four in the placebo group), less likely to have an indicated preterm delivery (one, compared with five in the placebo group), and less likely to have their neonates admitted to the neonatal ICU.

There were no differences in side effects, congenital anomalies, or other adverse events. Dr. Costantine, principal investigator of the pilot study, and his colleagues wrote in the paper that the “favorable risk-benefit analysis justifies continued research with a dose escalation” (Am J Obstet Gynecol. 2016 Jun;214[6]:720.e1-17).

The new multicenter randomized controlled trial is randomizing 1,550 women to either 20 mg pravastatin or placebo starting between 12 weeks 0 days and 16 weeks 6 days. The primary outcome is a composite of preeclampsia, maternal death, or fetal loss. Secondary outcomes include a composite of severe maternal morbidity and various measures representing preeclampsia severity and complications, as well as preterm delivery less than 37 weeks and less than 34 weeks and various fetal/neonatal outcomes.

“In addition, we’ll look at development,” Dr. Costantine said, with offspring assessed at 2 and 5 years of age. The trial is sponsored by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Heart, Lung, and Blood Institute.

In the meantime, he said, the use of pravastatin to ameliorate early-onset preeclampsia is being tested in a small European proof-of-concept trial that has randomized women with early-onset preeclampsia (between 24 and 31 6/7 weeks) to 40 mg pravastatin or placebo. The primary outcome is reduction of antiangiogenic markers. Results are expected in another year or 2, he said.

The aspirin trial referred to by Dr. Gyamfi-Bannerman has been looking at the 81-mg dose of aspirin initiated between 6 0/7 and 13 6/7 weeks in nulliparous women who had no more than two previous pregnancy losses. The key question of the Aspirin Supplementation for Pregnancy Indicated Risk Reduction in Nulliparas (ASPIRIN) trial – conducted in the NICHD Global Network for Women’s and Children’s Health – is whether low-dose aspirin can reduce the rate of preterm birth. Preeclampsia is a secondary outcome (https://clinicaltrials.gov/ct2/show/NCT02409680).

“It may eventually be that the use of baby aspirin is further expanded to reduce the risk of preterm birth,” she said.

Overall, “we need more data on first-trimester use [of low-dose aspirin] and long-term outcomes,” Dr. Gyamfi-Bannerman said. And with respect to preeclampsia prevention specifically, more research is needed looking at risk reduction levels within specific groups of patients.

Since 2014, the U.S. Preventive Services Task Force (USPSTF) has called for low-dose aspirin at 81 mg/day in women who have one or more high-risk factors for preeclampsia (including type 1 or type 2 diabetes mellitus), and consideration of such treatment in patients with several moderate-risk factors. The American College of Obstetricians and Gynecologists’ recommendation varies slightly in that it advises treatment in patients with more than one (versus several) moderate-level risk factors (Obstet Gynecol. 2018;132[1]:e44-52).

Moderate-level risk factors include nulliparity, obesity, family history of preeclampsia, a baseline demographic risk (African-American or low socioeconomic status), and prior poor history (intrauterine growth restriction/small-for-gestational-age, previous poor outcome). “This is just about everyone I see,” Dr. Gyamfi-Bannerman said.

Dr. Gyamfi-Bannerman said she’d “love to see more data on higher doses” of low-dose aspirin – data that compares 81 mg/day with 150 mg/day, for instance.

A study published in 2017 in the New England Journal of Medicine randomized 1,776 women at high risk for preeclampsia to 150 mg/day or placebo and found a significant reduction in preterm preeclampsia (4.3% vs. 1.6%) in the aspirin group. Women in this European trial were deemed to be at high risk, however, based on a first-trimester screening algorithm that incorporated serum markers (maternal serum pregnancy-associated plasma protein A and placental growth factor) and uterine artery Doppler measures (N Engl J Med. 2017 Aug 17;377[7]:613-22).

“So it was a very interesting study, very provocative, but it’s hard to know how it would translate to the U.S. population [given that such screening practices] are not the way most of us are practicing here,” said Dr. Gyamfi-Bannerman, codirector of the Preterm Birth Prevention Center at Columbia University, New York, and professor of obstetrics and gynecology at the university.

The USPSTF based its recommendations on a systematic review that pooled data from 15 high-quality randomized controlled trials, including 13 that reported preeclampsia incidence among women at highest risk of disease. They found a 24% reduction in preeclampsia, but the actual risk reduction depends on the baseline population risk and may be closer to 10%, she said.

In a presentation on gaps in knowledge, Leslie Myatt, PhD, of the department of obstetrics and gynecology at Oregon Health and Science University, Portland, emphasized that preeclampsia is a syndrome with a heterogeneity of presentation and pathophysiology. “We don’t completely understand the pathophysiology,” he said.

Research needs to be “directed at the existence of multiple pathways [and subtypes],” he said, such that future therapies can be targeted and personalized.

Dr. Costantine did not report any disclosures. Dr. Gyamfi-Bannerman reported a Society of Maternal Fetal Medicine/AMAG Pharmaceuticals unrestricted grant and Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Heart, Lung and Blood Institute funding. Dr. Myatt reported that he has no financial or other ties that pose a conflict of interest.

WASHINGTON – Research on pravastatin for the prevention of preeclampsia is moving along after “reassuring” data from pilot studies, with a large National Institutes of Health–funded trial currently recruiting women with a prior history of the disorder with preterm delivery at less than 34 weeks, Maged Costantine, MD, said at the biennial Diabetes in Pregnancy Study Group of North America meeting.

Creatas Images

More should be learned about low-dose aspirin, in the meantime, once the outcomes of a global study involving first-trimester initiation are published, said another speaker, Cynthia Gyamfi-Bannerman, MD, MS. Low-dose aspirin currently is recommended for preeclampsia prevention starting between 12 and 28 weeks, optimally before 16 weeks.

The biological plausibility of using pravastatin for preeclampsia prevention stems from the overlapping pathophysiology of preeclampsia with atherosclerotic cardiovascular disease – endothelial dysfunction and inflammation are common key mechanisms – as well as common risk factors, including diabetes and obesity, said Dr. Costantine, director of the division of maternal-fetal medicine at Ohio State University, Columbus, who is chairing the study.

In animal models of preeclampsia, pravastatin has been shown to upregulate placental growth factor, reduce antiangiogenic factors such as soluble fms-like tyrosine kinase 1 (sFlt1), and upregulate endothelial nitric oxide synthase. Mice have shown improved vascular reactivity, decreased proteinuria, decreased oxidative stress, and other positive effects, without any detrimental outcomes.

A pilot randomized controlled trial conducted with the Obstetric-Fetal Pharmacology Research Units Network and published in the American Journal of Obstetrics and Gynecology in 2016 assigned 10 women to 10 mg daily pravastatin and 10 women to placebo. The drug reduced maternal cholesterol concentrations but there were no differences in birth weight or umbilical cord cholesterol concentrations between the two groups.

Women in the pravastatin group were less likely to develop preeclampsia (none, compared with four in the placebo group), less likely to have an indicated preterm delivery (one, compared with five in the placebo group), and less likely to have their neonates admitted to the neonatal ICU.

There were no differences in side effects, congenital anomalies, or other adverse events. Dr. Costantine, principal investigator of the pilot study, and his colleagues wrote in the paper that the “favorable risk-benefit analysis justifies continued research with a dose escalation” (Am J Obstet Gynecol. 2016 Jun;214[6]:720.e1-17).

The new multicenter randomized controlled trial is randomizing 1,550 women to either 20 mg pravastatin or placebo starting between 12 weeks 0 days and 16 weeks 6 days. The primary outcome is a composite of preeclampsia, maternal death, or fetal loss. Secondary outcomes include a composite of severe maternal morbidity and various measures representing preeclampsia severity and complications, as well as preterm delivery less than 37 weeks and less than 34 weeks and various fetal/neonatal outcomes.

“In addition, we’ll look at development,” Dr. Costantine said, with offspring assessed at 2 and 5 years of age. The trial is sponsored by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Heart, Lung, and Blood Institute.

In the meantime, he said, the use of pravastatin to ameliorate early-onset preeclampsia is being tested in a small European proof-of-concept trial that has randomized women with early-onset preeclampsia (between 24 and 31 6/7 weeks) to 40 mg pravastatin or placebo. The primary outcome is reduction of antiangiogenic markers. Results are expected in another year or 2, he said.

The aspirin trial referred to by Dr. Gyamfi-Bannerman has been looking at the 81-mg dose of aspirin initiated between 6 0/7 and 13 6/7 weeks in nulliparous women who had no more than two previous pregnancy losses. The key question of the Aspirin Supplementation for Pregnancy Indicated Risk Reduction in Nulliparas (ASPIRIN) trial – conducted in the NICHD Global Network for Women’s and Children’s Health – is whether low-dose aspirin can reduce the rate of preterm birth. Preeclampsia is a secondary outcome (https://clinicaltrials.gov/ct2/show/NCT02409680).

“It may eventually be that the use of baby aspirin is further expanded to reduce the risk of preterm birth,” she said.

Overall, “we need more data on first-trimester use [of low-dose aspirin] and long-term outcomes,” Dr. Gyamfi-Bannerman said. And with respect to preeclampsia prevention specifically, more research is needed looking at risk reduction levels within specific groups of patients.

Since 2014, the U.S. Preventive Services Task Force (USPSTF) has called for low-dose aspirin at 81 mg/day in women who have one or more high-risk factors for preeclampsia (including type 1 or type 2 diabetes mellitus), and consideration of such treatment in patients with several moderate-risk factors. The American College of Obstetricians and Gynecologists’ recommendation varies slightly in that it advises treatment in patients with more than one (versus several) moderate-level risk factors (Obstet Gynecol. 2018;132[1]:e44-52).

Moderate-level risk factors include nulliparity, obesity, family history of preeclampsia, a baseline demographic risk (African-American or low socioeconomic status), and prior poor history (intrauterine growth restriction/small-for-gestational-age, previous poor outcome). “This is just about everyone I see,” Dr. Gyamfi-Bannerman said.

Dr. Gyamfi-Bannerman said she’d “love to see more data on higher doses” of low-dose aspirin – data that compares 81 mg/day with 150 mg/day, for instance.

A study published in 2017 in the New England Journal of Medicine randomized 1,776 women at high risk for preeclampsia to 150 mg/day or placebo and found a significant reduction in preterm preeclampsia (4.3% vs. 1.6%) in the aspirin group. Women in this European trial were deemed to be at high risk, however, based on a first-trimester screening algorithm that incorporated serum markers (maternal serum pregnancy-associated plasma protein A and placental growth factor) and uterine artery Doppler measures (N Engl J Med. 2017 Aug 17;377[7]:613-22).

“So it was a very interesting study, very provocative, but it’s hard to know how it would translate to the U.S. population [given that such screening practices] are not the way most of us are practicing here,” said Dr. Gyamfi-Bannerman, codirector of the Preterm Birth Prevention Center at Columbia University, New York, and professor of obstetrics and gynecology at the university.

The USPSTF based its recommendations on a systematic review that pooled data from 15 high-quality randomized controlled trials, including 13 that reported preeclampsia incidence among women at highest risk of disease. They found a 24% reduction in preeclampsia, but the actual risk reduction depends on the baseline population risk and may be closer to 10%, she said.

In a presentation on gaps in knowledge, Leslie Myatt, PhD, of the department of obstetrics and gynecology at Oregon Health and Science University, Portland, emphasized that preeclampsia is a syndrome with a heterogeneity of presentation and pathophysiology. “We don’t completely understand the pathophysiology,” he said.

Research needs to be “directed at the existence of multiple pathways [and subtypes],” he said, such that future therapies can be targeted and personalized.

Dr. Costantine did not report any disclosures. Dr. Gyamfi-Bannerman reported a Society of Maternal Fetal Medicine/AMAG Pharmaceuticals unrestricted grant and Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Heart, Lung and Blood Institute funding. Dr. Myatt reported that he has no financial or other ties that pose a conflict of interest.

WASHINGTON – Research on pravastatin for the prevention of preeclampsia is moving along after “reassuring” data from pilot studies, with a large National Institutes of Health–funded trial currently recruiting women with a prior history of the disorder with preterm delivery at less than 34 weeks, Maged Costantine, MD, said at the biennial Diabetes in Pregnancy Study Group of North America meeting.

Creatas Images

More should be learned about low-dose aspirin, in the meantime, once the outcomes of a global study involving first-trimester initiation are published, said another speaker, Cynthia Gyamfi-Bannerman, MD, MS. Low-dose aspirin currently is recommended for preeclampsia prevention starting between 12 and 28 weeks, optimally before 16 weeks.

The biological plausibility of using pravastatin for preeclampsia prevention stems from the overlapping pathophysiology of preeclampsia with atherosclerotic cardiovascular disease – endothelial dysfunction and inflammation are common key mechanisms – as well as common risk factors, including diabetes and obesity, said Dr. Costantine, director of the division of maternal-fetal medicine at Ohio State University, Columbus, who is chairing the study.

In animal models of preeclampsia, pravastatin has been shown to upregulate placental growth factor, reduce antiangiogenic factors such as soluble fms-like tyrosine kinase 1 (sFlt1), and upregulate endothelial nitric oxide synthase. Mice have shown improved vascular reactivity, decreased proteinuria, decreased oxidative stress, and other positive effects, without any detrimental outcomes.

A pilot randomized controlled trial conducted with the Obstetric-Fetal Pharmacology Research Units Network and published in the American Journal of Obstetrics and Gynecology in 2016 assigned 10 women to 10 mg daily pravastatin and 10 women to placebo. The drug reduced maternal cholesterol concentrations but there were no differences in birth weight or umbilical cord cholesterol concentrations between the two groups.

Women in the pravastatin group were less likely to develop preeclampsia (none, compared with four in the placebo group), less likely to have an indicated preterm delivery (one, compared with five in the placebo group), and less likely to have their neonates admitted to the neonatal ICU.

There were no differences in side effects, congenital anomalies, or other adverse events. Dr. Costantine, principal investigator of the pilot study, and his colleagues wrote in the paper that the “favorable risk-benefit analysis justifies continued research with a dose escalation” (Am J Obstet Gynecol. 2016 Jun;214[6]:720.e1-17).

The new multicenter randomized controlled trial is randomizing 1,550 women to either 20 mg pravastatin or placebo starting between 12 weeks 0 days and 16 weeks 6 days. The primary outcome is a composite of preeclampsia, maternal death, or fetal loss. Secondary outcomes include a composite of severe maternal morbidity and various measures representing preeclampsia severity and complications, as well as preterm delivery less than 37 weeks and less than 34 weeks and various fetal/neonatal outcomes.

“In addition, we’ll look at development,” Dr. Costantine said, with offspring assessed at 2 and 5 years of age. The trial is sponsored by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Heart, Lung, and Blood Institute.

In the meantime, he said, the use of pravastatin to ameliorate early-onset preeclampsia is being tested in a small European proof-of-concept trial that has randomized women with early-onset preeclampsia (between 24 and 31 6/7 weeks) to 40 mg pravastatin or placebo. The primary outcome is reduction of antiangiogenic markers. Results are expected in another year or 2, he said.

The aspirin trial referred to by Dr. Gyamfi-Bannerman has been looking at the 81-mg dose of aspirin initiated between 6 0/7 and 13 6/7 weeks in nulliparous women who had no more than two previous pregnancy losses. The key question of the Aspirin Supplementation for Pregnancy Indicated Risk Reduction in Nulliparas (ASPIRIN) trial – conducted in the NICHD Global Network for Women’s and Children’s Health – is whether low-dose aspirin can reduce the rate of preterm birth. Preeclampsia is a secondary outcome (https://clinicaltrials.gov/ct2/show/NCT02409680).

“It may eventually be that the use of baby aspirin is further expanded to reduce the risk of preterm birth,” she said.

Overall, “we need more data on first-trimester use [of low-dose aspirin] and long-term outcomes,” Dr. Gyamfi-Bannerman said. And with respect to preeclampsia prevention specifically, more research is needed looking at risk reduction levels within specific groups of patients.

Since 2014, the U.S. Preventive Services Task Force (USPSTF) has called for low-dose aspirin at 81 mg/day in women who have one or more high-risk factors for preeclampsia (including type 1 or type 2 diabetes mellitus), and consideration of such treatment in patients with several moderate-risk factors. The American College of Obstetricians and Gynecologists’ recommendation varies slightly in that it advises treatment in patients with more than one (versus several) moderate-level risk factors (Obstet Gynecol. 2018;132[1]:e44-52).

Moderate-level risk factors include nulliparity, obesity, family history of preeclampsia, a baseline demographic risk (African-American or low socioeconomic status), and prior poor history (intrauterine growth restriction/small-for-gestational-age, previous poor outcome). “This is just about everyone I see,” Dr. Gyamfi-Bannerman said.

Dr. Gyamfi-Bannerman said she’d “love to see more data on higher doses” of low-dose aspirin – data that compares 81 mg/day with 150 mg/day, for instance.

A study published in 2017 in the New England Journal of Medicine randomized 1,776 women at high risk for preeclampsia to 150 mg/day or placebo and found a significant reduction in preterm preeclampsia (4.3% vs. 1.6%) in the aspirin group. Women in this European trial were deemed to be at high risk, however, based on a first-trimester screening algorithm that incorporated serum markers (maternal serum pregnancy-associated plasma protein A and placental growth factor) and uterine artery Doppler measures (N Engl J Med. 2017 Aug 17;377[7]:613-22).

“So it was a very interesting study, very provocative, but it’s hard to know how it would translate to the U.S. population [given that such screening practices] are not the way most of us are practicing here,” said Dr. Gyamfi-Bannerman, codirector of the Preterm Birth Prevention Center at Columbia University, New York, and professor of obstetrics and gynecology at the university.

The USPSTF based its recommendations on a systematic review that pooled data from 15 high-quality randomized controlled trials, including 13 that reported preeclampsia incidence among women at highest risk of disease. They found a 24% reduction in preeclampsia, but the actual risk reduction depends on the baseline population risk and may be closer to 10%, she said.

In a presentation on gaps in knowledge, Leslie Myatt, PhD, of the department of obstetrics and gynecology at Oregon Health and Science University, Portland, emphasized that preeclampsia is a syndrome with a heterogeneity of presentation and pathophysiology. “We don’t completely understand the pathophysiology,” he said.

Research needs to be “directed at the existence of multiple pathways [and subtypes],” he said, such that future therapies can be targeted and personalized.

Dr. Costantine did not report any disclosures. Dr. Gyamfi-Bannerman reported a Society of Maternal Fetal Medicine/AMAG Pharmaceuticals unrestricted grant and Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Heart, Lung and Blood Institute funding. Dr. Myatt reported that he has no financial or other ties that pose a conflict of interest.

Persons who trained for a marathon showed improvement in age-related aortic stiffness and reduction in blood pressure in a study of 138 first-time completers of the London Marathon.

Pavel1964/Getty Images

Compared with pretraining values, the descending aortas of marathon completers were 9% more distensible at the level of the bifurcation of the pulmonary artery and 16% more distensible at the level of the diaphragm (P = .0009 and .002, respectively). There was no change in distensibility of the ascending aorta.

Additionally, central systolic BP dropped by 4 mm Hg and diastolic BP by 3 mm Hg by the time marathon training was completed.

“Training and completion of a first-time marathon result in beneficial reductions in BP and intrinsic aortic stiffening in healthy participants,” concluded Anish Bhuva, MBBS, and coinvestigators. “These changes are equivalent to approximately a 4-year reduction in vascular age.”

The study points to a role for exercise in the reduction of arterial stiffness, a known aging-related contributor to cardiovascular disease for which there currently is no good pharmacologic option, said Julio Chirinos, MD, Phd, in an accompanying editorial (J Am Coll Cardiol. 2020 Jan 6. doi: 10.1016/j.jacc.2019.11.007). The challenge lies in implementing exercise interventions on a large scale in societies where “there remains an immense paradoxical gap” between the known benefits of physical activity and increasingly sedentary populations, he added, calling for increased implementation research.

Using cardiovascular magnetic resonance to assess aortic distensibility, Dr. Bhuva, of the Institute of Cardiovascular Science, University College London, and colleagues assessed aortic BP and aortic stiffness at two points via the noninvasive imaging method. The first assessment was conducted before the study participants began marathon training; the second was obtained between 1 and 3 weeks after marathon completion, after any acute effects of the marathon had abated.

Anthropometric data, peripheral BP, and aerobic capacity (peak VO₂) were also assessed at both study points.

Although the study wasn’t designed to track individual training regimens, first-time London Marathon participants were given a 17-week “Beginner’s Training Plan” by event organizers, and asked to follow the plan while participating in the study. The goal of the beginner’s plan was marathon completion, with a schedule of about three runs weekly increasing in duration and intensity over the training period.

Participants had to be first-time marathon participants and running less than 2 hours per week at enrollment. Only those who completed the marathon were included in the data analysis, though baseline characteristics didn’t differ between completers and those who dropped out.

For 2016, the first study year, only participants aged 18-39 years were included, while in 2017, all ages were included in the study. The final age range was 21-69 years, with a mean age of 37; 51% of participants were female. Those with a history of hypertension or taking antihypertensive medication and those who had other significant medical conditions were excluded.

The differential increase in distensibility along the length of the aorta reflects known differences in tissue composition, agreed the authors and Dr. Chirinos, a cardiologist at the University of Pennsylvania, Philadelphia. In addition to the magnetic resonance–obtained distensibility measurements, the investigators conducted further calculations to adjust for baseline mean central arterial pressure, since arterial stiffness is a function both of intrinsic tissue characteristics and loading conditions.

In youth, aortic distensibility buffers the effect of pulse pressure on both the left ventricle and the peripheral vascular system. As the aorta and other large arteries stiffen predictably with age, isolated systolic hypertension can result. The stiffening “also favors adverse patterns of pulsatile left ventricular overload,” which can lead to left ventricular remodeling and, eventually, heart failure, noted Dr. Chirinos. Reduced aortic pliancy also allows pulse pressure variation to be transmitted downstream “into the microvasculature of target organs (such as the kidney and brain) that require high blood flow and thus operate at low arteriolar resistance,” he added.

The assessment that marathon training reversed aortic age by a median 3.9 years was derived from the baseline cross-sectional data regarding participants’ age and aortic stiffness. The effect size was largest in those older than 37 years and in those with higher baseline systolic BP, and men saw greater benefit by a median 1.4 years. Those with slower running times also saw greater benefit.

Study participants had small but significant reductions in heart rate, body fat percentage, and weight by the postmarathon assessment, but these differences were not associated with changes in aortic stiffness. Aerobic exercise capacity as measured by peak VO₂ didn’t change significantly from pre- to post training, but the fact that participants were semirecumbent during exercise testing (to allow concurrent echocardiography) may have affected results.

The real-world design of this study had the strengths of assessing free-living, healthy individuals who participated in a self-directed training plan. Dr. Bhuva and coauthors acknowledged that marathon training may include changes in diet, sleep, and other potentially confounding lifestyle factors, as well as improvement in lipid and glucose metabolism. Further, noted Dr. Chirinos, there was no control group. Also, results from individuals training for an endurance event may have limited generalizability to the general population.

Still, said Dr. Chirinos, the innovative study design took advantage of a large-scale athletic event to see how a realistic training regimen affected healthy individuals. “Perhaps the contemporary marathon can teach us some lessons about exploiting the confluence of interests of the general public, media, industry, scientific community, and government to accomplish worthy goals at the individual and societal levels.”

The study was funded by the British Heart Foundation, Cardiac Risk in the Young, and the Barts Cardiovascular Biomedical Research Centre. Exercise testing equipment and technical support were provided by COSMED. Dr. Bhuva reported receiving funding from the British Heart Foundation. Dr. Chirinos reported having been a consultant or receiving research funding from multiple pharmaceutical companies and Microsoft; he is also an inventor of University of Pennsylvania–held patents for cardiovascular pharmaceutical agents.

[email protected]

SOURCE: Bhuva A et al. J Am Coll Cardiol. 2020 Jan;75(1):60-71.

Persons who trained for a marathon showed improvement in age-related aortic stiffness and reduction in blood pressure in a study of 138 first-time completers of the London Marathon.

Pavel1964/Getty Images

Compared with pretraining values, the descending aortas of marathon completers were 9% more distensible at the level of the bifurcation of the pulmonary artery and 16% more distensible at the level of the diaphragm (P = .0009 and .002, respectively). There was no change in distensibility of the ascending aorta.

Additionally, central systolic BP dropped by 4 mm Hg and diastolic BP by 3 mm Hg by the time marathon training was completed.

“Training and completion of a first-time marathon result in beneficial reductions in BP and intrinsic aortic stiffening in healthy participants,” concluded Anish Bhuva, MBBS, and coinvestigators. “These changes are equivalent to approximately a 4-year reduction in vascular age.”

The study points to a role for exercise in the reduction of arterial stiffness, a known aging-related contributor to cardiovascular disease for which there currently is no good pharmacologic option, said Julio Chirinos, MD, Phd, in an accompanying editorial (J Am Coll Cardiol. 2020 Jan 6. doi: 10.1016/j.jacc.2019.11.007). The challenge lies in implementing exercise interventions on a large scale in societies where “there remains an immense paradoxical gap” between the known benefits of physical activity and increasingly sedentary populations, he added, calling for increased implementation research.

Using cardiovascular magnetic resonance to assess aortic distensibility, Dr. Bhuva, of the Institute of Cardiovascular Science, University College London, and colleagues assessed aortic BP and aortic stiffness at two points via the noninvasive imaging method. The first assessment was conducted before the study participants began marathon training; the second was obtained between 1 and 3 weeks after marathon completion, after any acute effects of the marathon had abated.

Anthropometric data, peripheral BP, and aerobic capacity (peak VO₂) were also assessed at both study points.

Although the study wasn’t designed to track individual training regimens, first-time London Marathon participants were given a 17-week “Beginner’s Training Plan” by event organizers, and asked to follow the plan while participating in the study. The goal of the beginner’s plan was marathon completion, with a schedule of about three runs weekly increasing in duration and intensity over the training period.

Participants had to be first-time marathon participants and running less than 2 hours per week at enrollment. Only those who completed the marathon were included in the data analysis, though baseline characteristics didn’t differ between completers and those who dropped out.

For 2016, the first study year, only participants aged 18-39 years were included, while in 2017, all ages were included in the study. The final age range was 21-69 years, with a mean age of 37; 51% of participants were female. Those with a history of hypertension or taking antihypertensive medication and those who had other significant medical conditions were excluded.

The differential increase in distensibility along the length of the aorta reflects known differences in tissue composition, agreed the authors and Dr. Chirinos, a cardiologist at the University of Pennsylvania, Philadelphia. In addition to the magnetic resonance–obtained distensibility measurements, the investigators conducted further calculations to adjust for baseline mean central arterial pressure, since arterial stiffness is a function both of intrinsic tissue characteristics and loading conditions.

In youth, aortic distensibility buffers the effect of pulse pressure on both the left ventricle and the peripheral vascular system. As the aorta and other large arteries stiffen predictably with age, isolated systolic hypertension can result. The stiffening “also favors adverse patterns of pulsatile left ventricular overload,” which can lead to left ventricular remodeling and, eventually, heart failure, noted Dr. Chirinos. Reduced aortic pliancy also allows pulse pressure variation to be transmitted downstream “into the microvasculature of target organs (such as the kidney and brain) that require high blood flow and thus operate at low arteriolar resistance,” he added.

The assessment that marathon training reversed aortic age by a median 3.9 years was derived from the baseline cross-sectional data regarding participants’ age and aortic stiffness. The effect size was largest in those older than 37 years and in those with higher baseline systolic BP, and men saw greater benefit by a median 1.4 years. Those with slower running times also saw greater benefit.

Study participants had small but significant reductions in heart rate, body fat percentage, and weight by the postmarathon assessment, but these differences were not associated with changes in aortic stiffness. Aerobic exercise capacity as measured by peak VO₂ didn’t change significantly from pre- to post training, but the fact that participants were semirecumbent during exercise testing (to allow concurrent echocardiography) may have affected results.

The real-world design of this study had the strengths of assessing free-living, healthy individuals who participated in a self-directed training plan. Dr. Bhuva and coauthors acknowledged that marathon training may include changes in diet, sleep, and other potentially confounding lifestyle factors, as well as improvement in lipid and glucose metabolism. Further, noted Dr. Chirinos, there was no control group. Also, results from individuals training for an endurance event may have limited generalizability to the general population.

Still, said Dr. Chirinos, the innovative study design took advantage of a large-scale athletic event to see how a realistic training regimen affected healthy individuals. “Perhaps the contemporary marathon can teach us some lessons about exploiting the confluence of interests of the general public, media, industry, scientific community, and government to accomplish worthy goals at the individual and societal levels.”

The study was funded by the British Heart Foundation, Cardiac Risk in the Young, and the Barts Cardiovascular Biomedical Research Centre. Exercise testing equipment and technical support were provided by COSMED. Dr. Bhuva reported receiving funding from the British Heart Foundation. Dr. Chirinos reported having been a consultant or receiving research funding from multiple pharmaceutical companies and Microsoft; he is also an inventor of University of Pennsylvania–held patents for cardiovascular pharmaceutical agents.

[email protected]

SOURCE: Bhuva A et al. J Am Coll Cardiol. 2020 Jan;75(1):60-71.

Persons who trained for a marathon showed improvement in age-related aortic stiffness and reduction in blood pressure in a study of 138 first-time completers of the London Marathon.

Pavel1964/Getty Images

Compared with pretraining values, the descending aortas of marathon completers were 9% more distensible at the level of the bifurcation of the pulmonary artery and 16% more distensible at the level of the diaphragm (P = .0009 and .002, respectively). There was no change in distensibility of the ascending aorta.

Additionally, central systolic BP dropped by 4 mm Hg and diastolic BP by 3 mm Hg by the time marathon training was completed.

“Training and completion of a first-time marathon result in beneficial reductions in BP and intrinsic aortic stiffening in healthy participants,” concluded Anish Bhuva, MBBS, and coinvestigators. “These changes are equivalent to approximately a 4-year reduction in vascular age.”

The study points to a role for exercise in the reduction of arterial stiffness, a known aging-related contributor to cardiovascular disease for which there currently is no good pharmacologic option, said Julio Chirinos, MD, Phd, in an accompanying editorial (J Am Coll Cardiol. 2020 Jan 6. doi: 10.1016/j.jacc.2019.11.007). The challenge lies in implementing exercise interventions on a large scale in societies where “there remains an immense paradoxical gap” between the known benefits of physical activity and increasingly sedentary populations, he added, calling for increased implementation research.

Using cardiovascular magnetic resonance to assess aortic distensibility, Dr. Bhuva, of the Institute of Cardiovascular Science, University College London, and colleagues assessed aortic BP and aortic stiffness at two points via the noninvasive imaging method. The first assessment was conducted before the study participants began marathon training; the second was obtained between 1 and 3 weeks after marathon completion, after any acute effects of the marathon had abated.

Anthropometric data, peripheral BP, and aerobic capacity (peak VO₂) were also assessed at both study points.

Although the study wasn’t designed to track individual training regimens, first-time London Marathon participants were given a 17-week “Beginner’s Training Plan” by event organizers, and asked to follow the plan while participating in the study. The goal of the beginner’s plan was marathon completion, with a schedule of about three runs weekly increasing in duration and intensity over the training period.

Participants had to be first-time marathon participants and running less than 2 hours per week at enrollment. Only those who completed the marathon were included in the data analysis, though baseline characteristics didn’t differ between completers and those who dropped out.

For 2016, the first study year, only participants aged 18-39 years were included, while in 2017, all ages were included in the study. The final age range was 21-69 years, with a mean age of 37; 51% of participants were female. Those with a history of hypertension or taking antihypertensive medication and those who had other significant medical conditions were excluded.

The differential increase in distensibility along the length of the aorta reflects known differences in tissue composition, agreed the authors and Dr. Chirinos, a cardiologist at the University of Pennsylvania, Philadelphia. In addition to the magnetic resonance–obtained distensibility measurements, the investigators conducted further calculations to adjust for baseline mean central arterial pressure, since arterial stiffness is a function both of intrinsic tissue characteristics and loading conditions.

In youth, aortic distensibility buffers the effect of pulse pressure on both the left ventricle and the peripheral vascular system. As the aorta and other large arteries stiffen predictably with age, isolated systolic hypertension can result. The stiffening “also favors adverse patterns of pulsatile left ventricular overload,” which can lead to left ventricular remodeling and, eventually, heart failure, noted Dr. Chirinos. Reduced aortic pliancy also allows pulse pressure variation to be transmitted downstream “into the microvasculature of target organs (such as the kidney and brain) that require high blood flow and thus operate at low arteriolar resistance,” he added.

The assessment that marathon training reversed aortic age by a median 3.9 years was derived from the baseline cross-sectional data regarding participants’ age and aortic stiffness. The effect size was largest in those older than 37 years and in those with higher baseline systolic BP, and men saw greater benefit by a median 1.4 years. Those with slower running times also saw greater benefit.

Study participants had small but significant reductions in heart rate, body fat percentage, and weight by the postmarathon assessment, but these differences were not associated with changes in aortic stiffness. Aerobic exercise capacity as measured by peak VO₂ didn’t change significantly from pre- to post training, but the fact that participants were semirecumbent during exercise testing (to allow concurrent echocardiography) may have affected results.

The real-world design of this study had the strengths of assessing free-living, healthy individuals who participated in a self-directed training plan. Dr. Bhuva and coauthors acknowledged that marathon training may include changes in diet, sleep, and other potentially confounding lifestyle factors, as well as improvement in lipid and glucose metabolism. Further, noted Dr. Chirinos, there was no control group. Also, results from individuals training for an endurance event may have limited generalizability to the general population.

Still, said Dr. Chirinos, the innovative study design took advantage of a large-scale athletic event to see how a realistic training regimen affected healthy individuals. “Perhaps the contemporary marathon can teach us some lessons about exploiting the confluence of interests of the general public, media, industry, scientific community, and government to accomplish worthy goals at the individual and societal levels.”

The study was funded by the British Heart Foundation, Cardiac Risk in the Young, and the Barts Cardiovascular Biomedical Research Centre. Exercise testing equipment and technical support were provided by COSMED. Dr. Bhuva reported receiving funding from the British Heart Foundation. Dr. Chirinos reported having been a consultant or receiving research funding from multiple pharmaceutical companies and Microsoft; he is also an inventor of University of Pennsylvania–held patents for cardiovascular pharmaceutical agents.

[email protected]

SOURCE: Bhuva A et al. J Am Coll Cardiol. 2020 Jan;75(1):60-71.