Hypertension

Up to 10 different menopausal symptoms were linked to an increased risk of cardiovascular disease when they were moderate to severe in women who initially had no evidence of cardiovascular disease, according to research presented at the North American Menopause Society annual meeting in Atlanta.

“The take-home message is that severe menopausal symptoms may increase the risk of cardiovascular disease,” Matthew Nudy, MD, an assistant professor of medicine at the Heart and Vascular Institute at Penn State University, Hershey, said in an interview about his findings. “Physicians and patients should be aware of this association. Women with severe symptoms may be more likely to see their physician, and this would be an ideal time to have their cardiovascular risk assessed.”

Margaret Nachtigall, MD, a clinical associate professor of obstetrics and gynecology at New York University and at NYU Langone Health, noted that these findings lined up with other studies showing an increased risk of cardiovascular disease in patients who have more symptoms, especially hot flashes.

“Other recent studies showed that an increase in severity of hot flush is associated with worse blood vessel function, leading to heart disease,” Dr. Nachtigall, who was not involved with the study, said in an interview. “The next step that makes sense is to try to eliminate these symptoms and hope that, in turn, would lower cardiovascular disease and improve survival.”

The researchers compared menopausal symptoms with cardiovascular outcomes and all-cause mortality in an observational cohort of 80,278 postmenopausal women for a median 8.2 years of follow-up. None of the women, all enrolled in the Women’s Health Initiative, had known cardiovascular disease at baseline. They had an average age of 63 years and average body mass index (BMI) of 25.9 at baseline. Most participants were White (86.7%), with 7% being Black and 4.1% Hispanic. Cardiovascular disease was a composite outcome that included hospitalized myocardial infarction, definite silent myocardial infarction, coronary death, stroke, congestive heart failure, angina, peripheral vascular disease, carotid artery disease, and coronary revascularization.

The researchers used a four-item Likert scale (0-3) to assess the severity of 15 symptoms experienced within the past 4 weeks at baseline: “night sweats, hot flashes, waking up several times at night, joint pain or stiffness, headaches or migraines, vaginal or genital dryness, heart racing or skipping beats, breast tenderness, dizziness, tremors (shakes), feeling tired, forgetfulness, mood swings, [feeling] restless or fidgety, and difficulty concentrating.”

The associations were adjusted for the following covariates: race/ethnicity, blood pressure, education, smoking status, bilateral oophorectomy, menopausal hormone therapy use (never/past/current), sleep duration, statin use, history of high cholesterol, aspirin use, use of antihypertensives, treated diabetes, and family history of heart attack. Continuous variables included age, age at menopause, BMI, blood pressure, and physical activity levels. Because of the high number of multiple comparisons, the researchers also used a Bonferroni correction to reduce the risk of spurious statistical significance.

The researchers found some clustering of symptoms. Among women who had at least two moderate or severe menopausal symptoms, more than half frequently woke up at night, had joint pain, or felt tired, the researchers reported. Those symptoms were also the most commonly reported ones overall. Younger women, between ages 50 and 59, were more likely than older women (60-79 years old) to experience vasomotor symptoms and all cognitive affective symptoms except forgetfulness.

The researchers identified 10 symptoms whose severity was significantly associated with cardiovascular disease. Compared to having no symptoms at all, the following moderate or severe symptoms were associated with an increased risk of a cardiovascular event after adjustment for covariates and corrected for multiple comparisons: night sweats – a 19% increased risk (P = .03), waking up several times at night – 11% increased risk (P = .05), joint pain or stiffness – 27% increased risk (P < .001), heart racing or skipping beats – 55% increased risk (P < .001), dizziness – 34% increased risk (P < .001), feeling tired – 35% increased risk (P < .001), forgetfulness – 25% increased risk (P < .001), mood swings – 21% increased risk (P = .02), feeling restless or fidgety – 29% increased risk (P < .001), and difficulty concentrating – 31% increased risk (P < .001)

In addition, all-cause mortality was associated with these symptoms when they were moderate or severe: heart racing or skipping beats (32% increased risk of all-cause mortality; hazard ratio, 1.32; P =.006), dizziness (HR, 1.58; P < .001), tremors (HR, 1.44; P < .001), feeling tired (HR, 1.26; P < .001), forgetfulness (HR, 1.29; P = .01), mood swings (HR, 1.35; P = .02), feeling restless or fidgety (HR, 1.35; P < .001), and difficulty concentrating (HR, 1.47; P < .001).

The symptom with the greatest association with all-cause mortality was dizziness, which was associated with an increased risk of 58% when rated moderate or severe. Any dizziness at all was linked to a 12% increased risk of cardiovascular disease, compared with no dizziness. Machine learning with the LASSO method determined that the symptoms most predictive of cardiovascular disease were dizziness, heart racing, feeling tired, and joint pain. The symptoms most associated with all-cause mortality, based on the machine learning algorithm, were dizziness, tremors, and feeling tired.

Dr. Nudy said that their study did not look at mitigation strategies. “Women should discuss with their physician the best methods for cardiovascular risk reduction,” he said. He also cautioned that severe menopausal symptoms can also indicate other health conditions that may require investigation.

“It is certainly possible some symptoms may represent other medical conditions we were unable to control for and may not be directly related to menopause,” such as autoimmune diseases, endocrine abnormalities, or subclinical cardiovascular disease, he said. Additional limitations of the study included an older cohort and retrospective assessment of menopausal symptoms only at baseline. In addition, ”we did not assess the cardiovascular risk among women whose symptoms persisted versus resolved during the study period,” Dr. Nudy said.

Dr. Nachtigall said a key message is that people who are experiencing these symptoms should try to get treatment for them and attempt to alleviate them, hopefully reducing the risk of heart disease and death.

”Estrogen treatment is one excellent option for some individuals and should be considered in the appropriate person,” Dr. Nachtigall said. “If estrogen treatment is to be considered, it should be given closer to menopause, within the first 10 years after menopause and in younger individuals (under 59) at start.”

Dr. Nachtigall referred to the NAMS 2022 position statement concluding that, for healthy women within 10 years of menopause who have bothersome menopause symptoms, “the benefits of hormone therapy outweigh its risks, with fewer cardiovascular events in younger versus older women.”

”Menopause and having menopausal symptoms is an opportunity for clinicians and patients to have a conversation about appropriate individualized management options,” Dr. Nachtigall said.

Women may also be able to mitigate their cardiovascular risk with regular exercise, eating a healthy diet, not smoking, and getting adequate sleep, Dr. Nachtigall said. But these healthy behaviors may not adequately treat moderate or severe menopausal symptoms.

“Some health care providers have said that because menopause happens naturally, individuals should just accept the symptoms and try to wait it out and not get treatment, but this study, as well as others, makes it clear that it actually may be beneficial to treat the symptoms,” Dr. Nachtigall said.

The research used no external funding. Dr. Nudy and Dr. Nachtigall had no disclosures.

Up to 10 different menopausal symptoms were linked to an increased risk of cardiovascular disease when they were moderate to severe in women who initially had no evidence of cardiovascular disease, according to research presented at the North American Menopause Society annual meeting in Atlanta.

“The take-home message is that severe menopausal symptoms may increase the risk of cardiovascular disease,” Matthew Nudy, MD, an assistant professor of medicine at the Heart and Vascular Institute at Penn State University, Hershey, said in an interview about his findings. “Physicians and patients should be aware of this association. Women with severe symptoms may be more likely to see their physician, and this would be an ideal time to have their cardiovascular risk assessed.”

Margaret Nachtigall, MD, a clinical associate professor of obstetrics and gynecology at New York University and at NYU Langone Health, noted that these findings lined up with other studies showing an increased risk of cardiovascular disease in patients who have more symptoms, especially hot flashes.

“Other recent studies showed that an increase in severity of hot flush is associated with worse blood vessel function, leading to heart disease,” Dr. Nachtigall, who was not involved with the study, said in an interview. “The next step that makes sense is to try to eliminate these symptoms and hope that, in turn, would lower cardiovascular disease and improve survival.”

The researchers compared menopausal symptoms with cardiovascular outcomes and all-cause mortality in an observational cohort of 80,278 postmenopausal women for a median 8.2 years of follow-up. None of the women, all enrolled in the Women’s Health Initiative, had known cardiovascular disease at baseline. They had an average age of 63 years and average body mass index (BMI) of 25.9 at baseline. Most participants were White (86.7%), with 7% being Black and 4.1% Hispanic. Cardiovascular disease was a composite outcome that included hospitalized myocardial infarction, definite silent myocardial infarction, coronary death, stroke, congestive heart failure, angina, peripheral vascular disease, carotid artery disease, and coronary revascularization.

The researchers used a four-item Likert scale (0-3) to assess the severity of 15 symptoms experienced within the past 4 weeks at baseline: “night sweats, hot flashes, waking up several times at night, joint pain or stiffness, headaches or migraines, vaginal or genital dryness, heart racing or skipping beats, breast tenderness, dizziness, tremors (shakes), feeling tired, forgetfulness, mood swings, [feeling] restless or fidgety, and difficulty concentrating.”

The associations were adjusted for the following covariates: race/ethnicity, blood pressure, education, smoking status, bilateral oophorectomy, menopausal hormone therapy use (never/past/current), sleep duration, statin use, history of high cholesterol, aspirin use, use of antihypertensives, treated diabetes, and family history of heart attack. Continuous variables included age, age at menopause, BMI, blood pressure, and physical activity levels. Because of the high number of multiple comparisons, the researchers also used a Bonferroni correction to reduce the risk of spurious statistical significance.

The researchers found some clustering of symptoms. Among women who had at least two moderate or severe menopausal symptoms, more than half frequently woke up at night, had joint pain, or felt tired, the researchers reported. Those symptoms were also the most commonly reported ones overall. Younger women, between ages 50 and 59, were more likely than older women (60-79 years old) to experience vasomotor symptoms and all cognitive affective symptoms except forgetfulness.

The researchers identified 10 symptoms whose severity was significantly associated with cardiovascular disease. Compared to having no symptoms at all, the following moderate or severe symptoms were associated with an increased risk of a cardiovascular event after adjustment for covariates and corrected for multiple comparisons: night sweats – a 19% increased risk (P = .03), waking up several times at night – 11% increased risk (P = .05), joint pain or stiffness – 27% increased risk (P < .001), heart racing or skipping beats – 55% increased risk (P < .001), dizziness – 34% increased risk (P < .001), feeling tired – 35% increased risk (P < .001), forgetfulness – 25% increased risk (P < .001), mood swings – 21% increased risk (P = .02), feeling restless or fidgety – 29% increased risk (P < .001), and difficulty concentrating – 31% increased risk (P < .001)

In addition, all-cause mortality was associated with these symptoms when they were moderate or severe: heart racing or skipping beats (32% increased risk of all-cause mortality; hazard ratio, 1.32; P =.006), dizziness (HR, 1.58; P < .001), tremors (HR, 1.44; P < .001), feeling tired (HR, 1.26; P < .001), forgetfulness (HR, 1.29; P = .01), mood swings (HR, 1.35; P = .02), feeling restless or fidgety (HR, 1.35; P < .001), and difficulty concentrating (HR, 1.47; P < .001).

The symptom with the greatest association with all-cause mortality was dizziness, which was associated with an increased risk of 58% when rated moderate or severe. Any dizziness at all was linked to a 12% increased risk of cardiovascular disease, compared with no dizziness. Machine learning with the LASSO method determined that the symptoms most predictive of cardiovascular disease were dizziness, heart racing, feeling tired, and joint pain. The symptoms most associated with all-cause mortality, based on the machine learning algorithm, were dizziness, tremors, and feeling tired.

Dr. Nudy said that their study did not look at mitigation strategies. “Women should discuss with their physician the best methods for cardiovascular risk reduction,” he said. He also cautioned that severe menopausal symptoms can also indicate other health conditions that may require investigation.

“It is certainly possible some symptoms may represent other medical conditions we were unable to control for and may not be directly related to menopause,” such as autoimmune diseases, endocrine abnormalities, or subclinical cardiovascular disease, he said. Additional limitations of the study included an older cohort and retrospective assessment of menopausal symptoms only at baseline. In addition, ”we did not assess the cardiovascular risk among women whose symptoms persisted versus resolved during the study period,” Dr. Nudy said.

Dr. Nachtigall said a key message is that people who are experiencing these symptoms should try to get treatment for them and attempt to alleviate them, hopefully reducing the risk of heart disease and death.

”Estrogen treatment is one excellent option for some individuals and should be considered in the appropriate person,” Dr. Nachtigall said. “If estrogen treatment is to be considered, it should be given closer to menopause, within the first 10 years after menopause and in younger individuals (under 59) at start.”

Dr. Nachtigall referred to the NAMS 2022 position statement concluding that, for healthy women within 10 years of menopause who have bothersome menopause symptoms, “the benefits of hormone therapy outweigh its risks, with fewer cardiovascular events in younger versus older women.”

”Menopause and having menopausal symptoms is an opportunity for clinicians and patients to have a conversation about appropriate individualized management options,” Dr. Nachtigall said.

Women may also be able to mitigate their cardiovascular risk with regular exercise, eating a healthy diet, not smoking, and getting adequate sleep, Dr. Nachtigall said. But these healthy behaviors may not adequately treat moderate or severe menopausal symptoms.

“Some health care providers have said that because menopause happens naturally, individuals should just accept the symptoms and try to wait it out and not get treatment, but this study, as well as others, makes it clear that it actually may be beneficial to treat the symptoms,” Dr. Nachtigall said.

The research used no external funding. Dr. Nudy and Dr. Nachtigall had no disclosures.

Up to 10 different menopausal symptoms were linked to an increased risk of cardiovascular disease when they were moderate to severe in women who initially had no evidence of cardiovascular disease, according to research presented at the North American Menopause Society annual meeting in Atlanta.

“The take-home message is that severe menopausal symptoms may increase the risk of cardiovascular disease,” Matthew Nudy, MD, an assistant professor of medicine at the Heart and Vascular Institute at Penn State University, Hershey, said in an interview about his findings. “Physicians and patients should be aware of this association. Women with severe symptoms may be more likely to see their physician, and this would be an ideal time to have their cardiovascular risk assessed.”

Margaret Nachtigall, MD, a clinical associate professor of obstetrics and gynecology at New York University and at NYU Langone Health, noted that these findings lined up with other studies showing an increased risk of cardiovascular disease in patients who have more symptoms, especially hot flashes.

“Other recent studies showed that an increase in severity of hot flush is associated with worse blood vessel function, leading to heart disease,” Dr. Nachtigall, who was not involved with the study, said in an interview. “The next step that makes sense is to try to eliminate these symptoms and hope that, in turn, would lower cardiovascular disease and improve survival.”

The researchers compared menopausal symptoms with cardiovascular outcomes and all-cause mortality in an observational cohort of 80,278 postmenopausal women for a median 8.2 years of follow-up. None of the women, all enrolled in the Women’s Health Initiative, had known cardiovascular disease at baseline. They had an average age of 63 years and average body mass index (BMI) of 25.9 at baseline. Most participants were White (86.7%), with 7% being Black and 4.1% Hispanic. Cardiovascular disease was a composite outcome that included hospitalized myocardial infarction, definite silent myocardial infarction, coronary death, stroke, congestive heart failure, angina, peripheral vascular disease, carotid artery disease, and coronary revascularization.

The researchers used a four-item Likert scale (0-3) to assess the severity of 15 symptoms experienced within the past 4 weeks at baseline: “night sweats, hot flashes, waking up several times at night, joint pain or stiffness, headaches or migraines, vaginal or genital dryness, heart racing or skipping beats, breast tenderness, dizziness, tremors (shakes), feeling tired, forgetfulness, mood swings, [feeling] restless or fidgety, and difficulty concentrating.”

The associations were adjusted for the following covariates: race/ethnicity, blood pressure, education, smoking status, bilateral oophorectomy, menopausal hormone therapy use (never/past/current), sleep duration, statin use, history of high cholesterol, aspirin use, use of antihypertensives, treated diabetes, and family history of heart attack. Continuous variables included age, age at menopause, BMI, blood pressure, and physical activity levels. Because of the high number of multiple comparisons, the researchers also used a Bonferroni correction to reduce the risk of spurious statistical significance.

The researchers found some clustering of symptoms. Among women who had at least two moderate or severe menopausal symptoms, more than half frequently woke up at night, had joint pain, or felt tired, the researchers reported. Those symptoms were also the most commonly reported ones overall. Younger women, between ages 50 and 59, were more likely than older women (60-79 years old) to experience vasomotor symptoms and all cognitive affective symptoms except forgetfulness.

The researchers identified 10 symptoms whose severity was significantly associated with cardiovascular disease. Compared to having no symptoms at all, the following moderate or severe symptoms were associated with an increased risk of a cardiovascular event after adjustment for covariates and corrected for multiple comparisons: night sweats – a 19% increased risk (P = .03), waking up several times at night – 11% increased risk (P = .05), joint pain or stiffness – 27% increased risk (P < .001), heart racing or skipping beats – 55% increased risk (P < .001), dizziness – 34% increased risk (P < .001), feeling tired – 35% increased risk (P < .001), forgetfulness – 25% increased risk (P < .001), mood swings – 21% increased risk (P = .02), feeling restless or fidgety – 29% increased risk (P < .001), and difficulty concentrating – 31% increased risk (P < .001)

In addition, all-cause mortality was associated with these symptoms when they were moderate or severe: heart racing or skipping beats (32% increased risk of all-cause mortality; hazard ratio, 1.32; P =.006), dizziness (HR, 1.58; P < .001), tremors (HR, 1.44; P < .001), feeling tired (HR, 1.26; P < .001), forgetfulness (HR, 1.29; P = .01), mood swings (HR, 1.35; P = .02), feeling restless or fidgety (HR, 1.35; P < .001), and difficulty concentrating (HR, 1.47; P < .001).

The symptom with the greatest association with all-cause mortality was dizziness, which was associated with an increased risk of 58% when rated moderate or severe. Any dizziness at all was linked to a 12% increased risk of cardiovascular disease, compared with no dizziness. Machine learning with the LASSO method determined that the symptoms most predictive of cardiovascular disease were dizziness, heart racing, feeling tired, and joint pain. The symptoms most associated with all-cause mortality, based on the machine learning algorithm, were dizziness, tremors, and feeling tired.

Dr. Nudy said that their study did not look at mitigation strategies. “Women should discuss with their physician the best methods for cardiovascular risk reduction,” he said. He also cautioned that severe menopausal symptoms can also indicate other health conditions that may require investigation.

“It is certainly possible some symptoms may represent other medical conditions we were unable to control for and may not be directly related to menopause,” such as autoimmune diseases, endocrine abnormalities, or subclinical cardiovascular disease, he said. Additional limitations of the study included an older cohort and retrospective assessment of menopausal symptoms only at baseline. In addition, ”we did not assess the cardiovascular risk among women whose symptoms persisted versus resolved during the study period,” Dr. Nudy said.

Dr. Nachtigall said a key message is that people who are experiencing these symptoms should try to get treatment for them and attempt to alleviate them, hopefully reducing the risk of heart disease and death.

”Estrogen treatment is one excellent option for some individuals and should be considered in the appropriate person,” Dr. Nachtigall said. “If estrogen treatment is to be considered, it should be given closer to menopause, within the first 10 years after menopause and in younger individuals (under 59) at start.”

Dr. Nachtigall referred to the NAMS 2022 position statement concluding that, for healthy women within 10 years of menopause who have bothersome menopause symptoms, “the benefits of hormone therapy outweigh its risks, with fewer cardiovascular events in younger versus older women.”

”Menopause and having menopausal symptoms is an opportunity for clinicians and patients to have a conversation about appropriate individualized management options,” Dr. Nachtigall said.

Women may also be able to mitigate their cardiovascular risk with regular exercise, eating a healthy diet, not smoking, and getting adequate sleep, Dr. Nachtigall said. But these healthy behaviors may not adequately treat moderate or severe menopausal symptoms.

“Some health care providers have said that because menopause happens naturally, individuals should just accept the symptoms and try to wait it out and not get treatment, but this study, as well as others, makes it clear that it actually may be beneficial to treat the symptoms,” Dr. Nachtigall said.

The research used no external funding. Dr. Nudy and Dr. Nachtigall had no disclosures.

Patients with the systemic sclerosis subtype of pulmonary arterial hypertension showed a distinctive bioactive metabolic profile associated with more severe disease than other subgroups, based on data from approximately 1,500 individuals.

The overall prognosis and therapeutic response for patients with pulmonary arterial hypertension associated with systemic sclerosis (SSc-PAH) tends to be worse than for patients with other types of PAH, such as idiopathic pulmonary arterial hypertension (IPAH), but the impact of different metabolite profiles among subtypes of disease has not been explored, wrote Mona Alotaibi, MD, of the University of California, San Diego, and colleagues.

“Recently, metabolic dysregulation has been proposed as a key mechanism by which IPAH and SSc-PAH differ and could control such disparities,” they noted. Clarifying the molecular mechanisms of SSc-PAH could inform management and treatment, they added.

In a study published in the journal Chest, the researchers sought to identify a bioactive lipid signature unique to SSc-PAH. They identified 400 patients with SSc-PAH and 1,082 with IPAH. An additional 100 patients with scleroderma but no PH and 44 patients with scleroderma who had PH were included for external validation. The mean ages of the patients with IPAH and SSc-PAH in the discovery and validation cohorts ranged from approximately 51 to 65 years; more than 75% of patients across the groups were women.

The researchers tested more than 700 bioactive lipid metabolites using liquid chromatography/mass spectrometry. They found five metabolites that distinguished SSc-PAH and IPAH that were significantly associated with markers of disease severity: 17-beta estradiol, novel Eic, nervonic acid, fatty acid esters of hydroxy fatty acids, and prostaglandin F2 alpha (PGF 2 alpha).

The biomarkers were increased in SSc-PAH patients compared to patients with SSC alone, which suggests that the biomarkers are related to PAH and not to scleroderma alone, the researchers noted.

In particular, nervonic acid was associated with worse functional capacity, in SSc-PAH patients, as were higher levels of 17-beta estradiol and prostaglandin F2 alpha. Also, 17-beta estradiol was associated with lower cardiac impairment (CI) and stroke volume index (SVI) in SSc-PAH patients, but higher SVI in IPAH patients. PGF 2 alpha was associated with lower CI and SVI and higher pulmonary vascular resistance in SSc-PAH and IPAH combined.

The study findings were limited by several factors including the inability to adjust for all potential confounders between IPAH and SSc-PAH, and the fact that a clear causal relationship could not be determined, the researchers noted. Inadequate statistical power to analyze SSc-PAH data was another limitation, and studies with detailed scleroderma phenotypes are needed to validate the results, they said.

However, the current study provides insight on the metabolic differences in SSc-PAH and the potential impact on disease pathology that may inform diagnosis, prognosis, and treatment strategies for SSc-PAH patients, they concluded.

The study was supported by the National Institutes of Health. Several individual investigators received support from organizations including the American Heart Association and the Chest Foundation, and from companies including Livanova, Equillium, Corvus, Bayer, and Actelion, but the authors had no relevant financial conflicts to disclose.

Patients with the systemic sclerosis subtype of pulmonary arterial hypertension showed a distinctive bioactive metabolic profile associated with more severe disease than other subgroups, based on data from approximately 1,500 individuals.

The overall prognosis and therapeutic response for patients with pulmonary arterial hypertension associated with systemic sclerosis (SSc-PAH) tends to be worse than for patients with other types of PAH, such as idiopathic pulmonary arterial hypertension (IPAH), but the impact of different metabolite profiles among subtypes of disease has not been explored, wrote Mona Alotaibi, MD, of the University of California, San Diego, and colleagues.

“Recently, metabolic dysregulation has been proposed as a key mechanism by which IPAH and SSc-PAH differ and could control such disparities,” they noted. Clarifying the molecular mechanisms of SSc-PAH could inform management and treatment, they added.

In a study published in the journal Chest, the researchers sought to identify a bioactive lipid signature unique to SSc-PAH. They identified 400 patients with SSc-PAH and 1,082 with IPAH. An additional 100 patients with scleroderma but no PH and 44 patients with scleroderma who had PH were included for external validation. The mean ages of the patients with IPAH and SSc-PAH in the discovery and validation cohorts ranged from approximately 51 to 65 years; more than 75% of patients across the groups were women.

The researchers tested more than 700 bioactive lipid metabolites using liquid chromatography/mass spectrometry. They found five metabolites that distinguished SSc-PAH and IPAH that were significantly associated with markers of disease severity: 17-beta estradiol, novel Eic, nervonic acid, fatty acid esters of hydroxy fatty acids, and prostaglandin F2 alpha (PGF 2 alpha).

The biomarkers were increased in SSc-PAH patients compared to patients with SSC alone, which suggests that the biomarkers are related to PAH and not to scleroderma alone, the researchers noted.

In particular, nervonic acid was associated with worse functional capacity, in SSc-PAH patients, as were higher levels of 17-beta estradiol and prostaglandin F2 alpha. Also, 17-beta estradiol was associated with lower cardiac impairment (CI) and stroke volume index (SVI) in SSc-PAH patients, but higher SVI in IPAH patients. PGF 2 alpha was associated with lower CI and SVI and higher pulmonary vascular resistance in SSc-PAH and IPAH combined.

The study findings were limited by several factors including the inability to adjust for all potential confounders between IPAH and SSc-PAH, and the fact that a clear causal relationship could not be determined, the researchers noted. Inadequate statistical power to analyze SSc-PAH data was another limitation, and studies with detailed scleroderma phenotypes are needed to validate the results, they said.

However, the current study provides insight on the metabolic differences in SSc-PAH and the potential impact on disease pathology that may inform diagnosis, prognosis, and treatment strategies for SSc-PAH patients, they concluded.

The study was supported by the National Institutes of Health. Several individual investigators received support from organizations including the American Heart Association and the Chest Foundation, and from companies including Livanova, Equillium, Corvus, Bayer, and Actelion, but the authors had no relevant financial conflicts to disclose.

Patients with the systemic sclerosis subtype of pulmonary arterial hypertension showed a distinctive bioactive metabolic profile associated with more severe disease than other subgroups, based on data from approximately 1,500 individuals.

The overall prognosis and therapeutic response for patients with pulmonary arterial hypertension associated with systemic sclerosis (SSc-PAH) tends to be worse than for patients with other types of PAH, such as idiopathic pulmonary arterial hypertension (IPAH), but the impact of different metabolite profiles among subtypes of disease has not been explored, wrote Mona Alotaibi, MD, of the University of California, San Diego, and colleagues.

“Recently, metabolic dysregulation has been proposed as a key mechanism by which IPAH and SSc-PAH differ and could control such disparities,” they noted. Clarifying the molecular mechanisms of SSc-PAH could inform management and treatment, they added.

In a study published in the journal Chest, the researchers sought to identify a bioactive lipid signature unique to SSc-PAH. They identified 400 patients with SSc-PAH and 1,082 with IPAH. An additional 100 patients with scleroderma but no PH and 44 patients with scleroderma who had PH were included for external validation. The mean ages of the patients with IPAH and SSc-PAH in the discovery and validation cohorts ranged from approximately 51 to 65 years; more than 75% of patients across the groups were women.

The researchers tested more than 700 bioactive lipid metabolites using liquid chromatography/mass spectrometry. They found five metabolites that distinguished SSc-PAH and IPAH that were significantly associated with markers of disease severity: 17-beta estradiol, novel Eic, nervonic acid, fatty acid esters of hydroxy fatty acids, and prostaglandin F2 alpha (PGF 2 alpha).

The biomarkers were increased in SSc-PAH patients compared to patients with SSC alone, which suggests that the biomarkers are related to PAH and not to scleroderma alone, the researchers noted.

In particular, nervonic acid was associated with worse functional capacity, in SSc-PAH patients, as were higher levels of 17-beta estradiol and prostaglandin F2 alpha. Also, 17-beta estradiol was associated with lower cardiac impairment (CI) and stroke volume index (SVI) in SSc-PAH patients, but higher SVI in IPAH patients. PGF 2 alpha was associated with lower CI and SVI and higher pulmonary vascular resistance in SSc-PAH and IPAH combined.

The study findings were limited by several factors including the inability to adjust for all potential confounders between IPAH and SSc-PAH, and the fact that a clear causal relationship could not be determined, the researchers noted. Inadequate statistical power to analyze SSc-PAH data was another limitation, and studies with detailed scleroderma phenotypes are needed to validate the results, they said.

However, the current study provides insight on the metabolic differences in SSc-PAH and the potential impact on disease pathology that may inform diagnosis, prognosis, and treatment strategies for SSc-PAH patients, they concluded.

The study was supported by the National Institutes of Health. Several individual investigators received support from organizations including the American Heart Association and the Chest Foundation, and from companies including Livanova, Equillium, Corvus, Bayer, and Actelion, but the authors had no relevant financial conflicts to disclose.

Rates of subarachnoid hemorrhage (SAH) are increasing, particularly in Black people, new research suggests.

Results of a new study based on hospital discharge data show Black people have disproportionately high rates of SAH versus other racial groups. Compared with White and Hispanic people, who had an average of 10 cases per 100,000, or Asian people, with 8 per 100,000 people, Black people had an average of 15 cases per 100,000 population.

Whereas case rates held steady for other racial groups in the study over a 10-year period, Black people were the only racial group for whom SAH incidence increased over time, at a rate of 1.8% per year.

“Root causes of the higher SAH incidence in Black [people] are complex and likely extend beyond simple differences in risk factor characteristics to other socioeconomic factors including level of education, poverty level, lack of insurance, access to quality care, and structural racism,” study investigator Fadar Oliver Otite, MD, assistant professor of neurology at SUNY Upstate Medical University, Syracuse, said in an interview.

“Addressing this racial disparity will require multidisciplinary factors targeted not just at subarachnoid hemorrhage risk factors but also at socioeconomic equity,” he added.

The study was published online in Neurology.
 

Uncontrolled hypertension

The average incidence of SAH for all participants was 11 cases per 100,000 people. Men had an average rate of 10 cases and women an average rate of 13 cases per 100,000.

As expected, incidence increased with age: For middle-aged men, the average was four cases per 100,000 people whereas for men 65 and older, the average was 22 cases.

Dr. Otite and his team combined U.S. Census data with two state hospitalization databases in New York and Florida and found that there were nearly 40,000 people hospitalized for SAH between 2007 and 2017. To find annual incidences of SAH per 100,000 population, they calculated the number of SAH cases and the total adult population for the year.

“Smoking and hypertension are two of the strongest risk factors for subarachnoid hemorrhage,” Dr. Otite said. “Hypertension is more prevalent in Black people in the United States, and Black patients with hypertension are more likely to have it uncontrolled.”
 

Racism, toxic stress

Anjail Sharieff, MD, associate professor of neurology at UT Health, Houston, said aside from a high rate of common SAH risk factors such as hypertension, Black Americans also face a barrage of inequities to health education and quality health care that contributes to higher SAH rates.

“The impact of toxic stress related to racism and discrimination experiences, and chronic stress related to poverty, can contribute to hypertension in Black people,” Dr. Sharieff said, adding that these factors contribute to stroke risk and are not usually accounted for in studies.

Dr. Sharieff said many of her first-time patients end up in her office due to a heart attack or stroke because they were previously uninsured and did not have access to primary care. “We need to begin leveraging trust with people in communities – meeting people where they are,” to educate them about hypertension and other health issues, she said.

A shining example of community engagement to reduce hypertension in Black communities was the Cedars-Sinai Barbershop Study, where 52 barbershops in Los Angeles implemented blood pressure checks and interventions among customers. A year later, the project was still working.

“Once we can identify the health problems in Black communities,” said Dr. Sharieff, “we can treat them.”

Dr. Otite and Dr. Sharieff report no relevant financial relationships.

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

Rates of subarachnoid hemorrhage (SAH) are increasing, particularly in Black people, new research suggests.

Results of a new study based on hospital discharge data show Black people have disproportionately high rates of SAH versus other racial groups. Compared with White and Hispanic people, who had an average of 10 cases per 100,000, or Asian people, with 8 per 100,000 people, Black people had an average of 15 cases per 100,000 population.

Whereas case rates held steady for other racial groups in the study over a 10-year period, Black people were the only racial group for whom SAH incidence increased over time, at a rate of 1.8% per year.

“Root causes of the higher SAH incidence in Black [people] are complex and likely extend beyond simple differences in risk factor characteristics to other socioeconomic factors including level of education, poverty level, lack of insurance, access to quality care, and structural racism,” study investigator Fadar Oliver Otite, MD, assistant professor of neurology at SUNY Upstate Medical University, Syracuse, said in an interview.

“Addressing this racial disparity will require multidisciplinary factors targeted not just at subarachnoid hemorrhage risk factors but also at socioeconomic equity,” he added.

The study was published online in Neurology.
 

Uncontrolled hypertension

The average incidence of SAH for all participants was 11 cases per 100,000 people. Men had an average rate of 10 cases and women an average rate of 13 cases per 100,000.

As expected, incidence increased with age: For middle-aged men, the average was four cases per 100,000 people whereas for men 65 and older, the average was 22 cases.

Dr. Otite and his team combined U.S. Census data with two state hospitalization databases in New York and Florida and found that there were nearly 40,000 people hospitalized for SAH between 2007 and 2017. To find annual incidences of SAH per 100,000 population, they calculated the number of SAH cases and the total adult population for the year.

“Smoking and hypertension are two of the strongest risk factors for subarachnoid hemorrhage,” Dr. Otite said. “Hypertension is more prevalent in Black people in the United States, and Black patients with hypertension are more likely to have it uncontrolled.”
 

Racism, toxic stress

Anjail Sharieff, MD, associate professor of neurology at UT Health, Houston, said aside from a high rate of common SAH risk factors such as hypertension, Black Americans also face a barrage of inequities to health education and quality health care that contributes to higher SAH rates.

“The impact of toxic stress related to racism and discrimination experiences, and chronic stress related to poverty, can contribute to hypertension in Black people,” Dr. Sharieff said, adding that these factors contribute to stroke risk and are not usually accounted for in studies.

Dr. Sharieff said many of her first-time patients end up in her office due to a heart attack or stroke because they were previously uninsured and did not have access to primary care. “We need to begin leveraging trust with people in communities – meeting people where they are,” to educate them about hypertension and other health issues, she said.

A shining example of community engagement to reduce hypertension in Black communities was the Cedars-Sinai Barbershop Study, where 52 barbershops in Los Angeles implemented blood pressure checks and interventions among customers. A year later, the project was still working.

“Once we can identify the health problems in Black communities,” said Dr. Sharieff, “we can treat them.”

Dr. Otite and Dr. Sharieff report no relevant financial relationships.

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

Rates of subarachnoid hemorrhage (SAH) are increasing, particularly in Black people, new research suggests.

Results of a new study based on hospital discharge data show Black people have disproportionately high rates of SAH versus other racial groups. Compared with White and Hispanic people, who had an average of 10 cases per 100,000, or Asian people, with 8 per 100,000 people, Black people had an average of 15 cases per 100,000 population.

Whereas case rates held steady for other racial groups in the study over a 10-year period, Black people were the only racial group for whom SAH incidence increased over time, at a rate of 1.8% per year.

“Root causes of the higher SAH incidence in Black [people] are complex and likely extend beyond simple differences in risk factor characteristics to other socioeconomic factors including level of education, poverty level, lack of insurance, access to quality care, and structural racism,” study investigator Fadar Oliver Otite, MD, assistant professor of neurology at SUNY Upstate Medical University, Syracuse, said in an interview.

“Addressing this racial disparity will require multidisciplinary factors targeted not just at subarachnoid hemorrhage risk factors but also at socioeconomic equity,” he added.

The study was published online in Neurology.
 

Uncontrolled hypertension

The average incidence of SAH for all participants was 11 cases per 100,000 people. Men had an average rate of 10 cases and women an average rate of 13 cases per 100,000.

As expected, incidence increased with age: For middle-aged men, the average was four cases per 100,000 people whereas for men 65 and older, the average was 22 cases.

Dr. Otite and his team combined U.S. Census data with two state hospitalization databases in New York and Florida and found that there were nearly 40,000 people hospitalized for SAH between 2007 and 2017. To find annual incidences of SAH per 100,000 population, they calculated the number of SAH cases and the total adult population for the year.

“Smoking and hypertension are two of the strongest risk factors for subarachnoid hemorrhage,” Dr. Otite said. “Hypertension is more prevalent in Black people in the United States, and Black patients with hypertension are more likely to have it uncontrolled.”
 

Racism, toxic stress

Anjail Sharieff, MD, associate professor of neurology at UT Health, Houston, said aside from a high rate of common SAH risk factors such as hypertension, Black Americans also face a barrage of inequities to health education and quality health care that contributes to higher SAH rates.

“The impact of toxic stress related to racism and discrimination experiences, and chronic stress related to poverty, can contribute to hypertension in Black people,” Dr. Sharieff said, adding that these factors contribute to stroke risk and are not usually accounted for in studies.

Dr. Sharieff said many of her first-time patients end up in her office due to a heart attack or stroke because they were previously uninsured and did not have access to primary care. “We need to begin leveraging trust with people in communities – meeting people where they are,” to educate them about hypertension and other health issues, she said.

A shining example of community engagement to reduce hypertension in Black communities was the Cedars-Sinai Barbershop Study, where 52 barbershops in Los Angeles implemented blood pressure checks and interventions among customers. A year later, the project was still working.

“Once we can identify the health problems in Black communities,” said Dr. Sharieff, “we can treat them.”

Dr. Otite and Dr. Sharieff report no relevant financial relationships.

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

Diabetes persists as a risk factor for cardiovascular events, but where it once meant the same risk of heart attack or stroke as cardiovascular disease itself, a large Canadian population study reports that’s no longer the case. Thanks to advances in diabetes management over the past quarter century, diabetes is no longer considered equivalent to CVD as a risk factor for cardiovascular events, researchers from the University of Toronto reported.

The retrospective, population-based study used administrative data from Ontario’s provincial universal health care system. The researchers created five population-based cohorts of adults at 5-year intervals from 1994 to 2014, consisting of 1.87 million adults in the first cohort and 1.5 million in the last. In that 20-year span, the prevalence of diabetes in this population tripled, from 3.1% to 9%.

“In the last 25 years we’ve seen wholesale changes in the way people approach diabetes,” lead study author Calvin Ke, MD, PhD, an endocrinologist and assistant professor at the University of Toronto, said in an interview. “Part of the findings show that diabetes and cardiovascular disease were equivalent for risk of cardiovascular events in 1994, but by 2014 that was not the case.”

However, Dr. Ke added, “Diabetes is still a very strong cardiovascular risk factor.”

The investigators for the study, reported as a research letter in JAMA, analyzed the risk of cardiovascular events in four subgroups: those who had both diabetes and CVD, CVD only, diabetes only, and no CVD or diabetes.

Between 1994 and 2014, the cardiovascular event rates declined significantly among people with diabetes alone, compared with people with no disease: from 28.4 to 12.7 per 1,000 person-years, or an absolute risk increase (ARI) of 4.4% and a relative risk (RR) more than double (2.06), in 1994 to 14 vs. 8 per 1,000 person-years, and an ARI of 2% and RR less than double (1.58) 20 years later.

Among people with CVD only, those values shifted from 36.1 per 1,000 person-years, ARI of 5.1% and RR of 2.16 in 1994 to 23.9, ARI of 3.7% and RR still more than double (2.06) in 2014.

People with both CVD and diabetes had the highest CVD event rates across all 5-year cohorts: 74 per 1,000 person-years, ARI of 12% and RR almost four times greater (3.81) in 1994 than people with no disease. By 2014, the ARI in this group was 7.6% and the RR 3.10.

The investigators calculated that event rates from 1994 to 2014 declined across all four subgroups, with rate ratios of 0.49 for diabetes only, 0.66 for CVD only, 0.60 for both diabetes and CVD, and 0.63 for neither disease.

Shift in practice

The study noted that the shift in diabetes as a risk factor for heart attack and stroke is “a change that likely reflects the use of modern, multifactorial approaches to diabetes.”

“A number of changes have occurred in practice that really focus on this idea of a multifactorial approach to diabetes: more aggressive management of blood sugar, blood pressure, and lipids,” Dr. Ke said. “We know from the statin trials that statins can reduce the risk of heart disease significantly, and the use of statins increased from 28.4% in 1999 to 56.3% in 2018 in the United States,” Dr. Ke said. He added that statin use in Canada in adults ages 40 and older went from 1.2% in 1994 to 58.4% in 2010-2015. Use of ACE inhibitors and angiotensin receptor blockers for hypertension followed similar trends, contributing further to reducing risks for heart attack and stroke, Dr. Ke said.

Dr. Ke also noted that the evolution of guidelines and advances in treatments for both CVD and diabetes since 1994 have contributed to improving risks for people with diabetes. SGLT2 inhibitors have been linked to a 2%-6% reduction in hemoglobin A1c, he said. “All of these factors combined have had a major effect on the reduced risk of cardiovascular events.”

Prakash Deedwania, MD, professor at the University of California, San Francisco, Fresno, said that this study confirms a trend that others have reported regarding the risk of CVD in diabetes. The large database covering millions of adults is a study strength, he said.

And the findings, Dr. Deedwania added, underscore what’s been published in clinical guidelines, notably the American Heart Association scientific statement for managing CVD risk in patients with diabetes. “This means that, from observations made 20-plus years ago, when most people were not being treated for diabetes or heart disease, the pendulum has swung,” he said.

However, he added, “The authors state clearly that it does not mean that diabetes is not associated with a higher risk of cardiovascular events; it just means it is no longer equivalent to CVD.”

Managing diabetes continues to be “particularly important,” Dr. Deedwania said, because the prevalence of diabetes continues to rise. “This is a phenomenal risk, and it emphasizes that, to really conquer or control diabetes, we should make every effort to prevent diabetes,” he said.

Dr. Ke and Dr. Deedwania have no relevant financial relationships to disclose.

Diabetes persists as a risk factor for cardiovascular events, but where it once meant the same risk of heart attack or stroke as cardiovascular disease itself, a large Canadian population study reports that’s no longer the case. Thanks to advances in diabetes management over the past quarter century, diabetes is no longer considered equivalent to CVD as a risk factor for cardiovascular events, researchers from the University of Toronto reported.

The retrospective, population-based study used administrative data from Ontario’s provincial universal health care system. The researchers created five population-based cohorts of adults at 5-year intervals from 1994 to 2014, consisting of 1.87 million adults in the first cohort and 1.5 million in the last. In that 20-year span, the prevalence of diabetes in this population tripled, from 3.1% to 9%.

“In the last 25 years we’ve seen wholesale changes in the way people approach diabetes,” lead study author Calvin Ke, MD, PhD, an endocrinologist and assistant professor at the University of Toronto, said in an interview. “Part of the findings show that diabetes and cardiovascular disease were equivalent for risk of cardiovascular events in 1994, but by 2014 that was not the case.”

However, Dr. Ke added, “Diabetes is still a very strong cardiovascular risk factor.”

The investigators for the study, reported as a research letter in JAMA, analyzed the risk of cardiovascular events in four subgroups: those who had both diabetes and CVD, CVD only, diabetes only, and no CVD or diabetes.

Between 1994 and 2014, the cardiovascular event rates declined significantly among people with diabetes alone, compared with people with no disease: from 28.4 to 12.7 per 1,000 person-years, or an absolute risk increase (ARI) of 4.4% and a relative risk (RR) more than double (2.06), in 1994 to 14 vs. 8 per 1,000 person-years, and an ARI of 2% and RR less than double (1.58) 20 years later.

Among people with CVD only, those values shifted from 36.1 per 1,000 person-years, ARI of 5.1% and RR of 2.16 in 1994 to 23.9, ARI of 3.7% and RR still more than double (2.06) in 2014.

People with both CVD and diabetes had the highest CVD event rates across all 5-year cohorts: 74 per 1,000 person-years, ARI of 12% and RR almost four times greater (3.81) in 1994 than people with no disease. By 2014, the ARI in this group was 7.6% and the RR 3.10.

The investigators calculated that event rates from 1994 to 2014 declined across all four subgroups, with rate ratios of 0.49 for diabetes only, 0.66 for CVD only, 0.60 for both diabetes and CVD, and 0.63 for neither disease.

Shift in practice

The study noted that the shift in diabetes as a risk factor for heart attack and stroke is “a change that likely reflects the use of modern, multifactorial approaches to diabetes.”

“A number of changes have occurred in practice that really focus on this idea of a multifactorial approach to diabetes: more aggressive management of blood sugar, blood pressure, and lipids,” Dr. Ke said. “We know from the statin trials that statins can reduce the risk of heart disease significantly, and the use of statins increased from 28.4% in 1999 to 56.3% in 2018 in the United States,” Dr. Ke said. He added that statin use in Canada in adults ages 40 and older went from 1.2% in 1994 to 58.4% in 2010-2015. Use of ACE inhibitors and angiotensin receptor blockers for hypertension followed similar trends, contributing further to reducing risks for heart attack and stroke, Dr. Ke said.

Dr. Ke also noted that the evolution of guidelines and advances in treatments for both CVD and diabetes since 1994 have contributed to improving risks for people with diabetes. SGLT2 inhibitors have been linked to a 2%-6% reduction in hemoglobin A1c, he said. “All of these factors combined have had a major effect on the reduced risk of cardiovascular events.”

Prakash Deedwania, MD, professor at the University of California, San Francisco, Fresno, said that this study confirms a trend that others have reported regarding the risk of CVD in diabetes. The large database covering millions of adults is a study strength, he said.

And the findings, Dr. Deedwania added, underscore what’s been published in clinical guidelines, notably the American Heart Association scientific statement for managing CVD risk in patients with diabetes. “This means that, from observations made 20-plus years ago, when most people were not being treated for diabetes or heart disease, the pendulum has swung,” he said.

However, he added, “The authors state clearly that it does not mean that diabetes is not associated with a higher risk of cardiovascular events; it just means it is no longer equivalent to CVD.”

Managing diabetes continues to be “particularly important,” Dr. Deedwania said, because the prevalence of diabetes continues to rise. “This is a phenomenal risk, and it emphasizes that, to really conquer or control diabetes, we should make every effort to prevent diabetes,” he said.

Dr. Ke and Dr. Deedwania have no relevant financial relationships to disclose.

Diabetes persists as a risk factor for cardiovascular events, but where it once meant the same risk of heart attack or stroke as cardiovascular disease itself, a large Canadian population study reports that’s no longer the case. Thanks to advances in diabetes management over the past quarter century, diabetes is no longer considered equivalent to CVD as a risk factor for cardiovascular events, researchers from the University of Toronto reported.

The retrospective, population-based study used administrative data from Ontario’s provincial universal health care system. The researchers created five population-based cohorts of adults at 5-year intervals from 1994 to 2014, consisting of 1.87 million adults in the first cohort and 1.5 million in the last. In that 20-year span, the prevalence of diabetes in this population tripled, from 3.1% to 9%.

“In the last 25 years we’ve seen wholesale changes in the way people approach diabetes,” lead study author Calvin Ke, MD, PhD, an endocrinologist and assistant professor at the University of Toronto, said in an interview. “Part of the findings show that diabetes and cardiovascular disease were equivalent for risk of cardiovascular events in 1994, but by 2014 that was not the case.”

However, Dr. Ke added, “Diabetes is still a very strong cardiovascular risk factor.”

The investigators for the study, reported as a research letter in JAMA, analyzed the risk of cardiovascular events in four subgroups: those who had both diabetes and CVD, CVD only, diabetes only, and no CVD or diabetes.

Between 1994 and 2014, the cardiovascular event rates declined significantly among people with diabetes alone, compared with people with no disease: from 28.4 to 12.7 per 1,000 person-years, or an absolute risk increase (ARI) of 4.4% and a relative risk (RR) more than double (2.06), in 1994 to 14 vs. 8 per 1,000 person-years, and an ARI of 2% and RR less than double (1.58) 20 years later.

Among people with CVD only, those values shifted from 36.1 per 1,000 person-years, ARI of 5.1% and RR of 2.16 in 1994 to 23.9, ARI of 3.7% and RR still more than double (2.06) in 2014.

People with both CVD and diabetes had the highest CVD event rates across all 5-year cohorts: 74 per 1,000 person-years, ARI of 12% and RR almost four times greater (3.81) in 1994 than people with no disease. By 2014, the ARI in this group was 7.6% and the RR 3.10.

The investigators calculated that event rates from 1994 to 2014 declined across all four subgroups, with rate ratios of 0.49 for diabetes only, 0.66 for CVD only, 0.60 for both diabetes and CVD, and 0.63 for neither disease.

Shift in practice

The study noted that the shift in diabetes as a risk factor for heart attack and stroke is “a change that likely reflects the use of modern, multifactorial approaches to diabetes.”

“A number of changes have occurred in practice that really focus on this idea of a multifactorial approach to diabetes: more aggressive management of blood sugar, blood pressure, and lipids,” Dr. Ke said. “We know from the statin trials that statins can reduce the risk of heart disease significantly, and the use of statins increased from 28.4% in 1999 to 56.3% in 2018 in the United States,” Dr. Ke said. He added that statin use in Canada in adults ages 40 and older went from 1.2% in 1994 to 58.4% in 2010-2015. Use of ACE inhibitors and angiotensin receptor blockers for hypertension followed similar trends, contributing further to reducing risks for heart attack and stroke, Dr. Ke said.

Dr. Ke also noted that the evolution of guidelines and advances in treatments for both CVD and diabetes since 1994 have contributed to improving risks for people with diabetes. SGLT2 inhibitors have been linked to a 2%-6% reduction in hemoglobin A1c, he said. “All of these factors combined have had a major effect on the reduced risk of cardiovascular events.”

Prakash Deedwania, MD, professor at the University of California, San Francisco, Fresno, said that this study confirms a trend that others have reported regarding the risk of CVD in diabetes. The large database covering millions of adults is a study strength, he said.

And the findings, Dr. Deedwania added, underscore what’s been published in clinical guidelines, notably the American Heart Association scientific statement for managing CVD risk in patients with diabetes. “This means that, from observations made 20-plus years ago, when most people were not being treated for diabetes or heart disease, the pendulum has swung,” he said.

However, he added, “The authors state clearly that it does not mean that diabetes is not associated with a higher risk of cardiovascular events; it just means it is no longer equivalent to CVD.”

Managing diabetes continues to be “particularly important,” Dr. Deedwania said, because the prevalence of diabetes continues to rise. “This is a phenomenal risk, and it emphasizes that, to really conquer or control diabetes, we should make every effort to prevent diabetes,” he said.

Dr. Ke and Dr. Deedwania have no relevant financial relationships to disclose.

Treatment with finerenone produced roughly similar reductions in heart failure–related outcomes in people with type 2 diabetes and chronic kidney disease (CKD) across the spectrum of kidney function, compared with placebo, including those who had albuminuria but a preserved estimated glomerular filtration rate (eGFR), in a post hoc analysis of pooled data from more than 13,000 people.

The findings, from the two pivotal trials for the agent, “reinforce the importance of routine eGFR and UACR [urinary albumin-to-creatinine ratio] screening” in people with type 2 diabetes to identify new candidates for treatment with finerenone (Kerendia), Gerasimos Filippatos, MD, and coauthors said in a report published online in JACC: Heart Failure.

Mitchel L. Zoler/MDedge news

Among the 13,026 patients in the two combined trials, 40% had a preserved eGFR of greater than 60 mL/min per 1.73 m^{2 despite also having albuminuria with a UACR of at least 30 mg/g}, showing how often this combination occurs. But many clinicians “do not follow the guidelines” and fail to measure the UACR in these patients in routine practice, noted Dr. Filippatos at the annual congress of the European Society of Cardiology in August.

“We now have something to do for these patients,” treat them with finerenone, said Dr. Filippatos, professor and director of heart failure at the Attikon University Hospital, Athens.

The availability of finerenone following its U.S. approval in 2021 means clinicians “must get used to measuring UACR” in people with type 2 diabetes even when their eGFR is normal, especially people with type 2 diabetes plus high cardiovascular disease risk, he said.

The Food and Drug Administration approved finerenone, a nonsteroidal mineralocorticoid receptor antagonist, for treating people with type 2 diabetes and CKD in July 2021, but its uptake has been slow, experts say. In a talk in September 2022 during the annual meeting of the European Association for the Study of Diabetes, Jennifer B. Green, MD, estimated that U.S. uptake of finerenone for appropriate people with type 2 diabetes had not advanced beyond 10%.

Mitchel L. Zoler/MDedge News

A recent review also noted that uptake of screening for elevated UACR in U.S. patients with type 2 diabetes was in the range of 10%-40% during 2017-2019, a “shockingly low rate,” said Dr. Green, a professor and diabetes specialist at Duke University, Durham, N.C.
 

A new reason to screen for albuminuria

“It’s an extremely important message,” Johann Bauersachs, MD, commented in an interview. Results from “many studies have shown that albuminuria is an excellent additional marker for cardiovascular disease risk. But measurement of albuminuria is not widely done, despite guidelines that recommend annual albuminuria testing in people with type 2 diabetes,” said Dr. Bauersachs, professor and head of the department of cardiology at Hannover (Germany) Medical School.

Mitchel L. Zoler/MDedge News

“Even before there was finerenone, there were reasons to measure UACR, but I hope adding finerenone will help, and more clinicians will incorporate UACR into their routine practice,” said Dr. Bauersachs, who was not involved with the finerenone studies.

The analyses reported by Dr. Filippatos and coauthors used data from two related trials of finerenone, FIDELIO-DKD and FIGARO-DKD, combined by prespecified design into a single dataset, FIDELITY, with a total of 13,026 participants eligible for analysis and followed for a median of 3 years. All had type 2 diabetes and CKD based on having a UACR of at least 30 mg/g. Their eGFR levels could run as high as 74 mL/min per 1.73 m² in FIDELIO-DKD, and as high as 90 mL/min/1.73m² in FIGARO-DKD. The two trials excluded people with heart failure with reduced ejection fraction, and those with a serum potassium greater than 4.8 mmol/L.

In the FIDELITY dataset treatment with finerenone led to a significant 17% reduction in the combined incidence of cardiovascular death or first hospitalization for heart failure relative to those who received placebo. This relative risk reduction was not affected by either eGFR or UACR values at baseline, the new analysis showed.

The analysis also demonstrated a nonsignificant trend toward greater reductions in heart failure–related outcomes among study participants who began with an eGFR in the normal range of at least 60 mL/min per 1.73 m². The researchers also found a nonsignificant trend to a greater reduction in heart failure–related events among those with a UACR of less than 300 mg/g.
 

Finerenone favors patients with less advanced CKD

In short “the magnitude of the treatment benefit tended to favor patients with less advanced CKD,” concluded the researchers, suggesting that “earlier intervention [with finerenone] in the CKD course is likely to provide the greatest long-term benefit on heart failure–related outcomes.” This led them to further infer “the importance of not only routine assessing eGFR, but also perhaps more importantly, routinely screening for UACR to facilitate early diagnosis and early intervention in patients with type 2 diabetes.”

Findings from FIDELIO-DKD and FIGARO-DKD led to recent guideline additions for finerenone by several medical groups. In August 2022, the American Association of Clinical Endocrinologists released an update to its guideline for managing people with diabetes that recommended treating people with type 2 diabetes with finerenone when they have a UACR of at least 30 mg/g if they are already treated with a maximum-tolerated dose of a renin-angiotensin system inhibitor, have a normal serum potassium level, and have an eGFR of at least 25 mL/min per 1.73 m2. The identical recommendation also appeared in a Consensus Report from the American Diabetes Association and KDIGO, an international organization promoting evidence-based management of patients with CKD.

Mitchel L. Zoler/MDedge news

“Finerenone provides a very important contribution because it improves prognosis even in very well managed patients” with type 2 diabetes, commented Lars Rydén, MD, professor of cardiology at the Karolinska Institute in Stockholm, as designated discussant for the report by Dr. Filippatos at the ESC congress.

The findings from the FIDELITY analysis are “trustworthy, and clinically important,” Dr. Rydén said. When left untreated, diabetic kidney disease “reduces life expectancy by an average of 16 years.”

The finerenone trials were sponsored by Bayer, which markets finerenone (Kerendia). Dr. Filippatos has received lecture fees from Bayer as well as from Amgen, Medtronic, Novartis, Servier, and Vifor. Dr. Green has financial ties to Bayer as well as to Anji, AstraZeneca, Boehringer Ingelheim/Lilly, Hawthorne Effect/Omada, Merck, Novo Nordisk, Pfizer, Roche, Sanofi/Lexicon, and Valo. Dr. Bauersachs has been a consultant to Bayer as well as to Amgen, AstraZeneca, Boehringer Ingelheim, Cardior, Cervia, CVRx, Novartis, Pfizer, and Vifor, and he has received research funding from Abiomed. Dr. Rydén has financial ties to Bayer, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk.

Treatment with finerenone produced roughly similar reductions in heart failure–related outcomes in people with type 2 diabetes and chronic kidney disease (CKD) across the spectrum of kidney function, compared with placebo, including those who had albuminuria but a preserved estimated glomerular filtration rate (eGFR), in a post hoc analysis of pooled data from more than 13,000 people.

The findings, from the two pivotal trials for the agent, “reinforce the importance of routine eGFR and UACR [urinary albumin-to-creatinine ratio] screening” in people with type 2 diabetes to identify new candidates for treatment with finerenone (Kerendia), Gerasimos Filippatos, MD, and coauthors said in a report published online in JACC: Heart Failure.

Mitchel L. Zoler/MDedge news

Among the 13,026 patients in the two combined trials, 40% had a preserved eGFR of greater than 60 mL/min per 1.73 m^{2 despite also having albuminuria with a UACR of at least 30 mg/g}, showing how often this combination occurs. But many clinicians “do not follow the guidelines” and fail to measure the UACR in these patients in routine practice, noted Dr. Filippatos at the annual congress of the European Society of Cardiology in August.

“We now have something to do for these patients,” treat them with finerenone, said Dr. Filippatos, professor and director of heart failure at the Attikon University Hospital, Athens.

The availability of finerenone following its U.S. approval in 2021 means clinicians “must get used to measuring UACR” in people with type 2 diabetes even when their eGFR is normal, especially people with type 2 diabetes plus high cardiovascular disease risk, he said.

The Food and Drug Administration approved finerenone, a nonsteroidal mineralocorticoid receptor antagonist, for treating people with type 2 diabetes and CKD in July 2021, but its uptake has been slow, experts say. In a talk in September 2022 during the annual meeting of the European Association for the Study of Diabetes, Jennifer B. Green, MD, estimated that U.S. uptake of finerenone for appropriate people with type 2 diabetes had not advanced beyond 10%.

Mitchel L. Zoler/MDedge News

A recent review also noted that uptake of screening for elevated UACR in U.S. patients with type 2 diabetes was in the range of 10%-40% during 2017-2019, a “shockingly low rate,” said Dr. Green, a professor and diabetes specialist at Duke University, Durham, N.C.
 

A new reason to screen for albuminuria

“It’s an extremely important message,” Johann Bauersachs, MD, commented in an interview. Results from “many studies have shown that albuminuria is an excellent additional marker for cardiovascular disease risk. But measurement of albuminuria is not widely done, despite guidelines that recommend annual albuminuria testing in people with type 2 diabetes,” said Dr. Bauersachs, professor and head of the department of cardiology at Hannover (Germany) Medical School.

Mitchel L. Zoler/MDedge News

“Even before there was finerenone, there were reasons to measure UACR, but I hope adding finerenone will help, and more clinicians will incorporate UACR into their routine practice,” said Dr. Bauersachs, who was not involved with the finerenone studies.

The analyses reported by Dr. Filippatos and coauthors used data from two related trials of finerenone, FIDELIO-DKD and FIGARO-DKD, combined by prespecified design into a single dataset, FIDELITY, with a total of 13,026 participants eligible for analysis and followed for a median of 3 years. All had type 2 diabetes and CKD based on having a UACR of at least 30 mg/g. Their eGFR levels could run as high as 74 mL/min per 1.73 m² in FIDELIO-DKD, and as high as 90 mL/min/1.73m² in FIGARO-DKD. The two trials excluded people with heart failure with reduced ejection fraction, and those with a serum potassium greater than 4.8 mmol/L.

In the FIDELITY dataset treatment with finerenone led to a significant 17% reduction in the combined incidence of cardiovascular death or first hospitalization for heart failure relative to those who received placebo. This relative risk reduction was not affected by either eGFR or UACR values at baseline, the new analysis showed.

The analysis also demonstrated a nonsignificant trend toward greater reductions in heart failure–related outcomes among study participants who began with an eGFR in the normal range of at least 60 mL/min per 1.73 m². The researchers also found a nonsignificant trend to a greater reduction in heart failure–related events among those with a UACR of less than 300 mg/g.
 

Finerenone favors patients with less advanced CKD

In short “the magnitude of the treatment benefit tended to favor patients with less advanced CKD,” concluded the researchers, suggesting that “earlier intervention [with finerenone] in the CKD course is likely to provide the greatest long-term benefit on heart failure–related outcomes.” This led them to further infer “the importance of not only routine assessing eGFR, but also perhaps more importantly, routinely screening for UACR to facilitate early diagnosis and early intervention in patients with type 2 diabetes.”

Findings from FIDELIO-DKD and FIGARO-DKD led to recent guideline additions for finerenone by several medical groups. In August 2022, the American Association of Clinical Endocrinologists released an update to its guideline for managing people with diabetes that recommended treating people with type 2 diabetes with finerenone when they have a UACR of at least 30 mg/g if they are already treated with a maximum-tolerated dose of a renin-angiotensin system inhibitor, have a normal serum potassium level, and have an eGFR of at least 25 mL/min per 1.73 m2. The identical recommendation also appeared in a Consensus Report from the American Diabetes Association and KDIGO, an international organization promoting evidence-based management of patients with CKD.

Mitchel L. Zoler/MDedge news

“Finerenone provides a very important contribution because it improves prognosis even in very well managed patients” with type 2 diabetes, commented Lars Rydén, MD, professor of cardiology at the Karolinska Institute in Stockholm, as designated discussant for the report by Dr. Filippatos at the ESC congress.

The findings from the FIDELITY analysis are “trustworthy, and clinically important,” Dr. Rydén said. When left untreated, diabetic kidney disease “reduces life expectancy by an average of 16 years.”

The finerenone trials were sponsored by Bayer, which markets finerenone (Kerendia). Dr. Filippatos has received lecture fees from Bayer as well as from Amgen, Medtronic, Novartis, Servier, and Vifor. Dr. Green has financial ties to Bayer as well as to Anji, AstraZeneca, Boehringer Ingelheim/Lilly, Hawthorne Effect/Omada, Merck, Novo Nordisk, Pfizer, Roche, Sanofi/Lexicon, and Valo. Dr. Bauersachs has been a consultant to Bayer as well as to Amgen, AstraZeneca, Boehringer Ingelheim, Cardior, Cervia, CVRx, Novartis, Pfizer, and Vifor, and he has received research funding from Abiomed. Dr. Rydén has financial ties to Bayer, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk.

Treatment with finerenone produced roughly similar reductions in heart failure–related outcomes in people with type 2 diabetes and chronic kidney disease (CKD) across the spectrum of kidney function, compared with placebo, including those who had albuminuria but a preserved estimated glomerular filtration rate (eGFR), in a post hoc analysis of pooled data from more than 13,000 people.

The findings, from the two pivotal trials for the agent, “reinforce the importance of routine eGFR and UACR [urinary albumin-to-creatinine ratio] screening” in people with type 2 diabetes to identify new candidates for treatment with finerenone (Kerendia), Gerasimos Filippatos, MD, and coauthors said in a report published online in JACC: Heart Failure.

Mitchel L. Zoler/MDedge news

Among the 13,026 patients in the two combined trials, 40% had a preserved eGFR of greater than 60 mL/min per 1.73 m^{2 despite also having albuminuria with a UACR of at least 30 mg/g}, showing how often this combination occurs. But many clinicians “do not follow the guidelines” and fail to measure the UACR in these patients in routine practice, noted Dr. Filippatos at the annual congress of the European Society of Cardiology in August.

“We now have something to do for these patients,” treat them with finerenone, said Dr. Filippatos, professor and director of heart failure at the Attikon University Hospital, Athens.

The availability of finerenone following its U.S. approval in 2021 means clinicians “must get used to measuring UACR” in people with type 2 diabetes even when their eGFR is normal, especially people with type 2 diabetes plus high cardiovascular disease risk, he said.

The Food and Drug Administration approved finerenone, a nonsteroidal mineralocorticoid receptor antagonist, for treating people with type 2 diabetes and CKD in July 2021, but its uptake has been slow, experts say. In a talk in September 2022 during the annual meeting of the European Association for the Study of Diabetes, Jennifer B. Green, MD, estimated that U.S. uptake of finerenone for appropriate people with type 2 diabetes had not advanced beyond 10%.

Mitchel L. Zoler/MDedge News

A recent review also noted that uptake of screening for elevated UACR in U.S. patients with type 2 diabetes was in the range of 10%-40% during 2017-2019, a “shockingly low rate,” said Dr. Green, a professor and diabetes specialist at Duke University, Durham, N.C.
 

A new reason to screen for albuminuria

“It’s an extremely important message,” Johann Bauersachs, MD, commented in an interview. Results from “many studies have shown that albuminuria is an excellent additional marker for cardiovascular disease risk. But measurement of albuminuria is not widely done, despite guidelines that recommend annual albuminuria testing in people with type 2 diabetes,” said Dr. Bauersachs, professor and head of the department of cardiology at Hannover (Germany) Medical School.

Mitchel L. Zoler/MDedge News

“Even before there was finerenone, there were reasons to measure UACR, but I hope adding finerenone will help, and more clinicians will incorporate UACR into their routine practice,” said Dr. Bauersachs, who was not involved with the finerenone studies.

The analyses reported by Dr. Filippatos and coauthors used data from two related trials of finerenone, FIDELIO-DKD and FIGARO-DKD, combined by prespecified design into a single dataset, FIDELITY, with a total of 13,026 participants eligible for analysis and followed for a median of 3 years. All had type 2 diabetes and CKD based on having a UACR of at least 30 mg/g. Their eGFR levels could run as high as 74 mL/min per 1.73 m² in FIDELIO-DKD, and as high as 90 mL/min/1.73m² in FIGARO-DKD. The two trials excluded people with heart failure with reduced ejection fraction, and those with a serum potassium greater than 4.8 mmol/L.

In the FIDELITY dataset treatment with finerenone led to a significant 17% reduction in the combined incidence of cardiovascular death or first hospitalization for heart failure relative to those who received placebo. This relative risk reduction was not affected by either eGFR or UACR values at baseline, the new analysis showed.

The analysis also demonstrated a nonsignificant trend toward greater reductions in heart failure–related outcomes among study participants who began with an eGFR in the normal range of at least 60 mL/min per 1.73 m². The researchers also found a nonsignificant trend to a greater reduction in heart failure–related events among those with a UACR of less than 300 mg/g.
 

Finerenone favors patients with less advanced CKD

In short “the magnitude of the treatment benefit tended to favor patients with less advanced CKD,” concluded the researchers, suggesting that “earlier intervention [with finerenone] in the CKD course is likely to provide the greatest long-term benefit on heart failure–related outcomes.” This led them to further infer “the importance of not only routine assessing eGFR, but also perhaps more importantly, routinely screening for UACR to facilitate early diagnosis and early intervention in patients with type 2 diabetes.”

Findings from FIDELIO-DKD and FIGARO-DKD led to recent guideline additions for finerenone by several medical groups. In August 2022, the American Association of Clinical Endocrinologists released an update to its guideline for managing people with diabetes that recommended treating people with type 2 diabetes with finerenone when they have a UACR of at least 30 mg/g if they are already treated with a maximum-tolerated dose of a renin-angiotensin system inhibitor, have a normal serum potassium level, and have an eGFR of at least 25 mL/min per 1.73 m2. The identical recommendation also appeared in a Consensus Report from the American Diabetes Association and KDIGO, an international organization promoting evidence-based management of patients with CKD.

Mitchel L. Zoler/MDedge news

“Finerenone provides a very important contribution because it improves prognosis even in very well managed patients” with type 2 diabetes, commented Lars Rydén, MD, professor of cardiology at the Karolinska Institute in Stockholm, as designated discussant for the report by Dr. Filippatos at the ESC congress.

The findings from the FIDELITY analysis are “trustworthy, and clinically important,” Dr. Rydén said. When left untreated, diabetic kidney disease “reduces life expectancy by an average of 16 years.”

The finerenone trials were sponsored by Bayer, which markets finerenone (Kerendia). Dr. Filippatos has received lecture fees from Bayer as well as from Amgen, Medtronic, Novartis, Servier, and Vifor. Dr. Green has financial ties to Bayer as well as to Anji, AstraZeneca, Boehringer Ingelheim/Lilly, Hawthorne Effect/Omada, Merck, Novo Nordisk, Pfizer, Roche, Sanofi/Lexicon, and Valo. Dr. Bauersachs has been a consultant to Bayer as well as to Amgen, AstraZeneca, Boehringer Ingelheim, Cardior, Cervia, CVRx, Novartis, Pfizer, and Vifor, and he has received research funding from Abiomed. Dr. Rydén has financial ties to Bayer, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk.

Nirmatrelvir/ritonavir (Paxlovid) has been a game changer for high-risk patients with early COVID-19 symptoms but has significant interactions with commonly used cardiovascular medications, a new paper cautions.

COVID-19 patients with cardiovascular disease (CVD) or risk factors such as diabetes, hypertension, and chronic kidney disease are at high risk of severe disease and account for the lion’s share of those receiving Paxlovid. Data from the initial EPIC-HR trial and recent real-world data also suggest they’re among the most likely to benefit from the oral antiviral, regardless of their COVID-19 vaccination status.

ClaudioVentrella/Thinkstock

“But at the same time, it unfortunately interacts with many very commonly prescribed cardiovascular medications and with many of them in a very clinically meaningful way, which may lead to serious adverse consequences,” senior author Sarju Ganatra, MD, said in an interview. “So, while it’s being prescribed with a good intention to help these people, we may actually end up doing more harm than good.

“We don’t want to deter people from getting their necessary COVID-19 treatment, which is excellent for the most part these days as an outpatient,” he added. “So, we felt the need to make a comprehensive list of cardiac medications and level of interactions with Paxlovid and also to help the clinicians and prescribers at the point of care to make the clinical decision of what modifications they may need to do.”

The paper, published online in the Journal of the American College of Cardiology, details drug-drug interactions with some 80 CV medications including statins, antihypertensive agents, heart failure therapies, and antiplatelet/anticoagulants.

It also includes a color-coded figure denoting whether a drug is safe to coadminister with Paxlovid, may potentially interact and require a dose adjustment or temporary discontinuation, or is contraindicated.

Among the commonly used blood thinners, for example, the paper notes that Paxlovid significantly increases drug levels of the direct oral anticoagulants (DOACs) apixaban, rivaroxaban, edoxaban, and dabigatran and, thus, increases the risk of bleeding.

“It can still be administered, if it’s necessary, but the dose of the DOAC either needs to be reduced or held depending on what they are getting it for, whether they’re getting it for pulmonary embolism or atrial fibrillation, and we adjust for all those things in the table in the paper,” said Dr. Ganatra, from Lahey Hospital and Medical Center, Burlington, Mass.

When the DOAC can’t be interrupted or dose adjusted, however, Paxlovid should not be given, the experts said. The antiviral is safe to use with enoxaparin, a low-molecular-weight heparin, but can increase or decrease levels of warfarin and should be used with close international normalized ratio monitoring.

For patients on antiplatelet agents, clinicians are advised to avoid prescribing nirmatrelvir/ritonavir to those on ticagrelor or clopidogrel unless the agents can be replaced by prasugrel.

Ritonavir – an inhibitor of cytochrome P 450 enzymes, particularly CYP3A4 – poses an increased risk of bleeding when given with ticagrelor, a CYP3A4 substrate, and decreases the active metabolite of clopidogrel, cutting its platelet inhibition by 20%. Although there’s a twofold decrease in the maximum concentration of prasugrel in patients on ritonavir, this does not affect its antiplatelet activity, the paper explains.

Among the lipid-lowering agents, experts suggested temporarily withholding atorvastatin, rosuvastatin, simvastatin, and lovastatin because of an increased risk for myopathy and liver toxicity but say that other statins, fibrates, ezetimibe, and the proprotein convertase subtilisin/kexin type 9 inhibitors evolocumab and alirocumab are safe to coadminister with Paxlovid.

While statins typically leave the body within hours, most of the antiarrhythmic drugs, except for sotalol, are not safe to give with Paxlovid, Dr. Ganatra said. It’s technically not feasible to hold these drugs because most have long half-lives, reaching about 100 days, for example, for amiodarone.

“It’s going to hang around in your system for a long time, so you don’t want to be falsely reassured that you’re holding the drug and it’s going to be fine to go back slowly,” he said. “You need to look for alternative therapies in those scenarios for COVID-19 treatment, which could be other antivirals, or a monoclonal antibody individualized to the patient’s risk.”

Although there’s limited clinical information regarding interaction-related adverse events with Paxlovid, the team used pharmacokinetics and pharmacodynamics data to provide the guidance. Serious adverse events are also well documented for ritonavir, which has been prescribed for years to treat HIV, Dr. Ganatra noted.

The Infectious Disease Society of America also published guidance on the management of potential drug interactions with Paxlovid in May and, earlier in October, the Food and Drug Administration updated its Paxlovid patient eligibility screening checklist.

Still, most prescribers are actually primary care physicians and even pharmacists, who may not be completely attuned, said Dr. Ganatra, who noted that some centers have started programs to help connect primary care physicians with their cardiology colleagues to check on CV drugs in their COVID-19 patients.

“We need to be thinking more broadly and at a system level where the hospital or health care system leverages the electronic health record systems,” he said. “Most of them are sophisticated enough to incorporate simple drug-drug interaction information, so if you try to prescribe someone Paxlovid and it’s a heart transplant patient who is on immunosuppressive therapy or a patient on a blood thinner, then it should give you a warning ... or at least give them a link to our paper or other valuable resources.

“If someone is on a blood thinner and the blood thinner level goes up by ninefold, we can only imagine what we would be dealing with,” Dr. Ganatra said. “So, these interactions should be taken very seriously and I think it’s worth the time and investment.”

The authors reported no relevant financial relationships.

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

Nirmatrelvir/ritonavir (Paxlovid) has been a game changer for high-risk patients with early COVID-19 symptoms but has significant interactions with commonly used cardiovascular medications, a new paper cautions.

COVID-19 patients with cardiovascular disease (CVD) or risk factors such as diabetes, hypertension, and chronic kidney disease are at high risk of severe disease and account for the lion’s share of those receiving Paxlovid. Data from the initial EPIC-HR trial and recent real-world data also suggest they’re among the most likely to benefit from the oral antiviral, regardless of their COVID-19 vaccination status.

ClaudioVentrella/Thinkstock

“But at the same time, it unfortunately interacts with many very commonly prescribed cardiovascular medications and with many of them in a very clinically meaningful way, which may lead to serious adverse consequences,” senior author Sarju Ganatra, MD, said in an interview. “So, while it’s being prescribed with a good intention to help these people, we may actually end up doing more harm than good.

“We don’t want to deter people from getting their necessary COVID-19 treatment, which is excellent for the most part these days as an outpatient,” he added. “So, we felt the need to make a comprehensive list of cardiac medications and level of interactions with Paxlovid and also to help the clinicians and prescribers at the point of care to make the clinical decision of what modifications they may need to do.”

The paper, published online in the Journal of the American College of Cardiology, details drug-drug interactions with some 80 CV medications including statins, antihypertensive agents, heart failure therapies, and antiplatelet/anticoagulants.

It also includes a color-coded figure denoting whether a drug is safe to coadminister with Paxlovid, may potentially interact and require a dose adjustment or temporary discontinuation, or is contraindicated.

Among the commonly used blood thinners, for example, the paper notes that Paxlovid significantly increases drug levels of the direct oral anticoagulants (DOACs) apixaban, rivaroxaban, edoxaban, and dabigatran and, thus, increases the risk of bleeding.

“It can still be administered, if it’s necessary, but the dose of the DOAC either needs to be reduced or held depending on what they are getting it for, whether they’re getting it for pulmonary embolism or atrial fibrillation, and we adjust for all those things in the table in the paper,” said Dr. Ganatra, from Lahey Hospital and Medical Center, Burlington, Mass.

When the DOAC can’t be interrupted or dose adjusted, however, Paxlovid should not be given, the experts said. The antiviral is safe to use with enoxaparin, a low-molecular-weight heparin, but can increase or decrease levels of warfarin and should be used with close international normalized ratio monitoring.

For patients on antiplatelet agents, clinicians are advised to avoid prescribing nirmatrelvir/ritonavir to those on ticagrelor or clopidogrel unless the agents can be replaced by prasugrel.

Ritonavir – an inhibitor of cytochrome P 450 enzymes, particularly CYP3A4 – poses an increased risk of bleeding when given with ticagrelor, a CYP3A4 substrate, and decreases the active metabolite of clopidogrel, cutting its platelet inhibition by 20%. Although there’s a twofold decrease in the maximum concentration of prasugrel in patients on ritonavir, this does not affect its antiplatelet activity, the paper explains.

Among the lipid-lowering agents, experts suggested temporarily withholding atorvastatin, rosuvastatin, simvastatin, and lovastatin because of an increased risk for myopathy and liver toxicity but say that other statins, fibrates, ezetimibe, and the proprotein convertase subtilisin/kexin type 9 inhibitors evolocumab and alirocumab are safe to coadminister with Paxlovid.

While statins typically leave the body within hours, most of the antiarrhythmic drugs, except for sotalol, are not safe to give with Paxlovid, Dr. Ganatra said. It’s technically not feasible to hold these drugs because most have long half-lives, reaching about 100 days, for example, for amiodarone.

“It’s going to hang around in your system for a long time, so you don’t want to be falsely reassured that you’re holding the drug and it’s going to be fine to go back slowly,” he said. “You need to look for alternative therapies in those scenarios for COVID-19 treatment, which could be other antivirals, or a monoclonal antibody individualized to the patient’s risk.”

Although there’s limited clinical information regarding interaction-related adverse events with Paxlovid, the team used pharmacokinetics and pharmacodynamics data to provide the guidance. Serious adverse events are also well documented for ritonavir, which has been prescribed for years to treat HIV, Dr. Ganatra noted.

The Infectious Disease Society of America also published guidance on the management of potential drug interactions with Paxlovid in May and, earlier in October, the Food and Drug Administration updated its Paxlovid patient eligibility screening checklist.

Still, most prescribers are actually primary care physicians and even pharmacists, who may not be completely attuned, said Dr. Ganatra, who noted that some centers have started programs to help connect primary care physicians with their cardiology colleagues to check on CV drugs in their COVID-19 patients.

“We need to be thinking more broadly and at a system level where the hospital or health care system leverages the electronic health record systems,” he said. “Most of them are sophisticated enough to incorporate simple drug-drug interaction information, so if you try to prescribe someone Paxlovid and it’s a heart transplant patient who is on immunosuppressive therapy or a patient on a blood thinner, then it should give you a warning ... or at least give them a link to our paper or other valuable resources.

“If someone is on a blood thinner and the blood thinner level goes up by ninefold, we can only imagine what we would be dealing with,” Dr. Ganatra said. “So, these interactions should be taken very seriously and I think it’s worth the time and investment.”

The authors reported no relevant financial relationships.

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

Nirmatrelvir/ritonavir (Paxlovid) has been a game changer for high-risk patients with early COVID-19 symptoms but has significant interactions with commonly used cardiovascular medications, a new paper cautions.

COVID-19 patients with cardiovascular disease (CVD) or risk factors such as diabetes, hypertension, and chronic kidney disease are at high risk of severe disease and account for the lion’s share of those receiving Paxlovid. Data from the initial EPIC-HR trial and recent real-world data also suggest they’re among the most likely to benefit from the oral antiviral, regardless of their COVID-19 vaccination status.

ClaudioVentrella/Thinkstock

“But at the same time, it unfortunately interacts with many very commonly prescribed cardiovascular medications and with many of them in a very clinically meaningful way, which may lead to serious adverse consequences,” senior author Sarju Ganatra, MD, said in an interview. “So, while it’s being prescribed with a good intention to help these people, we may actually end up doing more harm than good.

“We don’t want to deter people from getting their necessary COVID-19 treatment, which is excellent for the most part these days as an outpatient,” he added. “So, we felt the need to make a comprehensive list of cardiac medications and level of interactions with Paxlovid and also to help the clinicians and prescribers at the point of care to make the clinical decision of what modifications they may need to do.”

The paper, published online in the Journal of the American College of Cardiology, details drug-drug interactions with some 80 CV medications including statins, antihypertensive agents, heart failure therapies, and antiplatelet/anticoagulants.

It also includes a color-coded figure denoting whether a drug is safe to coadminister with Paxlovid, may potentially interact and require a dose adjustment or temporary discontinuation, or is contraindicated.

Among the commonly used blood thinners, for example, the paper notes that Paxlovid significantly increases drug levels of the direct oral anticoagulants (DOACs) apixaban, rivaroxaban, edoxaban, and dabigatran and, thus, increases the risk of bleeding.

“It can still be administered, if it’s necessary, but the dose of the DOAC either needs to be reduced or held depending on what they are getting it for, whether they’re getting it for pulmonary embolism or atrial fibrillation, and we adjust for all those things in the table in the paper,” said Dr. Ganatra, from Lahey Hospital and Medical Center, Burlington, Mass.

When the DOAC can’t be interrupted or dose adjusted, however, Paxlovid should not be given, the experts said. The antiviral is safe to use with enoxaparin, a low-molecular-weight heparin, but can increase or decrease levels of warfarin and should be used with close international normalized ratio monitoring.

For patients on antiplatelet agents, clinicians are advised to avoid prescribing nirmatrelvir/ritonavir to those on ticagrelor or clopidogrel unless the agents can be replaced by prasugrel.

Ritonavir – an inhibitor of cytochrome P 450 enzymes, particularly CYP3A4 – poses an increased risk of bleeding when given with ticagrelor, a CYP3A4 substrate, and decreases the active metabolite of clopidogrel, cutting its platelet inhibition by 20%. Although there’s a twofold decrease in the maximum concentration of prasugrel in patients on ritonavir, this does not affect its antiplatelet activity, the paper explains.

Among the lipid-lowering agents, experts suggested temporarily withholding atorvastatin, rosuvastatin, simvastatin, and lovastatin because of an increased risk for myopathy and liver toxicity but say that other statins, fibrates, ezetimibe, and the proprotein convertase subtilisin/kexin type 9 inhibitors evolocumab and alirocumab are safe to coadminister with Paxlovid.

While statins typically leave the body within hours, most of the antiarrhythmic drugs, except for sotalol, are not safe to give with Paxlovid, Dr. Ganatra said. It’s technically not feasible to hold these drugs because most have long half-lives, reaching about 100 days, for example, for amiodarone.

“It’s going to hang around in your system for a long time, so you don’t want to be falsely reassured that you’re holding the drug and it’s going to be fine to go back slowly,” he said. “You need to look for alternative therapies in those scenarios for COVID-19 treatment, which could be other antivirals, or a monoclonal antibody individualized to the patient’s risk.”

Although there’s limited clinical information regarding interaction-related adverse events with Paxlovid, the team used pharmacokinetics and pharmacodynamics data to provide the guidance. Serious adverse events are also well documented for ritonavir, which has been prescribed for years to treat HIV, Dr. Ganatra noted.

The Infectious Disease Society of America also published guidance on the management of potential drug interactions with Paxlovid in May and, earlier in October, the Food and Drug Administration updated its Paxlovid patient eligibility screening checklist.

Still, most prescribers are actually primary care physicians and even pharmacists, who may not be completely attuned, said Dr. Ganatra, who noted that some centers have started programs to help connect primary care physicians with their cardiology colleagues to check on CV drugs in their COVID-19 patients.

“We need to be thinking more broadly and at a system level where the hospital or health care system leverages the electronic health record systems,” he said. “Most of them are sophisticated enough to incorporate simple drug-drug interaction information, so if you try to prescribe someone Paxlovid and it’s a heart transplant patient who is on immunosuppressive therapy or a patient on a blood thinner, then it should give you a warning ... or at least give them a link to our paper or other valuable resources.

“If someone is on a blood thinner and the blood thinner level goes up by ninefold, we can only imagine what we would be dealing with,” Dr. Ganatra said. “So, these interactions should be taken very seriously and I think it’s worth the time and investment.”

The authors reported no relevant financial relationships.

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

Cardiac biomarkers vary according to sex hormones in healthy transgender adults, just as in cisgender individuals, a new cross-sectional study suggests.

Previous research in the general population has shown that females have a lower 99th percentile upper reference limit for high-sensitivity cardiac troponin (hs-cTn) than males, whereas N-terminal prohormone brain natriuretic peptide (NT-proBNP) concentrations are higher in females than males across all ages after puberty.

“That trend is similar for people that have been on gender-affirming hormones, saying that sex hormones are playing a role in how cardiac turnover happens in a healthy state,” study author Dina M. Greene, PhD, University of Washington, Seattle, said in an interview.

Although the number of transgender people seeking gender-affirming care is increasing, studies are limited and largely retrospective cohorts, she noted. The scientific literature evaluating and defining cardiac biomarker concentrations is “currently absent.”

The American Heart Association’s recent scientific statement on the cardiovascular health of transgender and gender diverse (TGD) people says mounting evidence points to worse CV health in TGD people and that part of this excess risk is driven by significant psychosocial stressors across the lifespan. “In addition, the use of gender-affirming hormone therapy may be associated with cardiometabolic changes, but health research in this area remains limited and, at times, contradictory.”

For the present study, Dr. Greene and colleagues reached out to LGBTQ-oriented primary care and internal medicine clinics in Seattle and Iowa City to recruit 79 transgender men prescribed testosterone (mean age, 28.8 years) and 93 transgender women (mean age, 35.1 years) prescribed estradiol for at least 12 months. The mean duration of hormone therapy was 4.8 and 3.5 years, respectively.

The median estradiol concentration was 51 pg/mL in transgender men and 207 pg/mL in transgender women. Median testosterone concentrations were 4.6 ng/mL and 0.4 ng/mL, respectively.

The cardiac biomarkers were measured with the ARCHITECT STAT (Abbott Diagnostics) and ACCESS (Beckman Coulter) high-sensitivity troponin I assays, the Elecsys Troponin T Gen 5 STAT assay (Roche Diagnostics), and the Elecsys ProBNP II immunoassay (Roche Diagnostics).

As reported in JAMA Cardiology, the median hs-cTnI level on the ARCHITECT STAT assay was 0.9 ng/L (range, 0.6-1.7) in transgender men and 0.6 ng/L (range, 0.3-1.0) in transgender women. The pattern was consistent across the two other assays.

In contrast, the median NT-proBNP level was 17 ng/L (range, 13-27) in transgender men and 49 ng/L (range, 32-86) in transgender women.

“It seems that sex hormone concentration is a stronger driver of baseline cardiac troponin and NT-proBNP concentrations relative to sex assigned at birth,” Dr. Greene said.

The observed differences in hs-cTn concentrations “are likely physiological and not pathological,” given that concentrations between healthy cisgender people are also apparent and not thought to portend adverse events, the authors noted.

Teasing out the clinical implications of sex-specific hs-cTn upper reference limits for ruling in acute myocardial infarction (MI), however, is complicated by biological and social factors that contribute to poorer outcomes in women, despite lower baseline levels, they added. “Ultimately, the psychosocial benefits of gender-affirming hormones are substantial, and informed consent is likely the ideal method to balance the undetermined risks.”

Dr. Greene pointed out that the study wasn’t powered to accurately calculate gender-specific hs-cTn 99th percentiles or reference intervals for NT-proBNP and assessed the biomarkers at a single time point.

For the transgender person presenting with chest pain, she said, the clinical implications are not yet known, but the data suggest that when sex-specific 99th percentiles for hs-cTn are used, the numeric value associated with the affirmed gender, rather than the sex assigned at birth, may be the appropriate URL.

“It really depends on what the triage pathway is and if that pathway has differences for people of different sexes and how often people get serial measurements,” Dr. Greene said. “Within this population, it’s very important to look at those serial measurements because for people that are not cismen, those 99th percentiles when they’re non–sex specific, are going to favor in detection of a heart attack. So, you need to look at the second value to make sure there hasn’t been a change over time.”

The observed differences in the distribution of NT-proBNP concentrations is similar to that in the cisgender population, Dr. Greene noted. But these differences do not lead to sex-specific diagnostic thresholds because of the significant elevations present in overt heart failure and cardiovascular disease. “For NT-proBNP, it’s not as important. People don’t usually have a little bit of heart failure, they have heart failure, where people have small MIs.”

Dr. Greene said she would like to see larger trials looking at biomarker measurements and cardiac imaging before hormone therapy but that the biggest issue is the need for inclusion of transgender people in all cardiovascular trials.

“The sample sizes are never going to be as big as we get for cisgender people for a number of reasons but ensuring that it’s something that’s being asked on intake and monitored over time so we can understand how transgender people fit into the general population for cardiac disease,” Dr. Greene said. “And so, we can normalize that they exist. I keep driving this point home, but this is the biggest thing right now when it’s such a political issue.”

The study was supported in part by the department of laboratory medicine at the University of Washington, the department of pathology at the University of Iowa, and a grant from Abbott Diagnostics for in-kind high-sensitivity cardiac troponin I reagent. One coauthor reported financial relationships with Siemens Healthineers, Roche Diagnostics, Beckman Coulter, Becton, Dickinson, Abbott Diagnostics, Quidel Diagnostics, Sphingotech, and PixCell Medical. No other disclosures were reported.

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

Cardiac biomarkers vary according to sex hormones in healthy transgender adults, just as in cisgender individuals, a new cross-sectional study suggests.

Previous research in the general population has shown that females have a lower 99th percentile upper reference limit for high-sensitivity cardiac troponin (hs-cTn) than males, whereas N-terminal prohormone brain natriuretic peptide (NT-proBNP) concentrations are higher in females than males across all ages after puberty.

“That trend is similar for people that have been on gender-affirming hormones, saying that sex hormones are playing a role in how cardiac turnover happens in a healthy state,” study author Dina M. Greene, PhD, University of Washington, Seattle, said in an interview.

Although the number of transgender people seeking gender-affirming care is increasing, studies are limited and largely retrospective cohorts, she noted. The scientific literature evaluating and defining cardiac biomarker concentrations is “currently absent.”

The American Heart Association’s recent scientific statement on the cardiovascular health of transgender and gender diverse (TGD) people says mounting evidence points to worse CV health in TGD people and that part of this excess risk is driven by significant psychosocial stressors across the lifespan. “In addition, the use of gender-affirming hormone therapy may be associated with cardiometabolic changes, but health research in this area remains limited and, at times, contradictory.”

For the present study, Dr. Greene and colleagues reached out to LGBTQ-oriented primary care and internal medicine clinics in Seattle and Iowa City to recruit 79 transgender men prescribed testosterone (mean age, 28.8 years) and 93 transgender women (mean age, 35.1 years) prescribed estradiol for at least 12 months. The mean duration of hormone therapy was 4.8 and 3.5 years, respectively.

The median estradiol concentration was 51 pg/mL in transgender men and 207 pg/mL in transgender women. Median testosterone concentrations were 4.6 ng/mL and 0.4 ng/mL, respectively.

The cardiac biomarkers were measured with the ARCHITECT STAT (Abbott Diagnostics) and ACCESS (Beckman Coulter) high-sensitivity troponin I assays, the Elecsys Troponin T Gen 5 STAT assay (Roche Diagnostics), and the Elecsys ProBNP II immunoassay (Roche Diagnostics).

As reported in JAMA Cardiology, the median hs-cTnI level on the ARCHITECT STAT assay was 0.9 ng/L (range, 0.6-1.7) in transgender men and 0.6 ng/L (range, 0.3-1.0) in transgender women. The pattern was consistent across the two other assays.

In contrast, the median NT-proBNP level was 17 ng/L (range, 13-27) in transgender men and 49 ng/L (range, 32-86) in transgender women.

“It seems that sex hormone concentration is a stronger driver of baseline cardiac troponin and NT-proBNP concentrations relative to sex assigned at birth,” Dr. Greene said.

The observed differences in hs-cTn concentrations “are likely physiological and not pathological,” given that concentrations between healthy cisgender people are also apparent and not thought to portend adverse events, the authors noted.

Teasing out the clinical implications of sex-specific hs-cTn upper reference limits for ruling in acute myocardial infarction (MI), however, is complicated by biological and social factors that contribute to poorer outcomes in women, despite lower baseline levels, they added. “Ultimately, the psychosocial benefits of gender-affirming hormones are substantial, and informed consent is likely the ideal method to balance the undetermined risks.”

Dr. Greene pointed out that the study wasn’t powered to accurately calculate gender-specific hs-cTn 99th percentiles or reference intervals for NT-proBNP and assessed the biomarkers at a single time point.

For the transgender person presenting with chest pain, she said, the clinical implications are not yet known, but the data suggest that when sex-specific 99th percentiles for hs-cTn are used, the numeric value associated with the affirmed gender, rather than the sex assigned at birth, may be the appropriate URL.

“It really depends on what the triage pathway is and if that pathway has differences for people of different sexes and how often people get serial measurements,” Dr. Greene said. “Within this population, it’s very important to look at those serial measurements because for people that are not cismen, those 99th percentiles when they’re non–sex specific, are going to favor in detection of a heart attack. So, you need to look at the second value to make sure there hasn’t been a change over time.”

The observed differences in the distribution of NT-proBNP concentrations is similar to that in the cisgender population, Dr. Greene noted. But these differences do not lead to sex-specific diagnostic thresholds because of the significant elevations present in overt heart failure and cardiovascular disease. “For NT-proBNP, it’s not as important. People don’t usually have a little bit of heart failure, they have heart failure, where people have small MIs.”

Dr. Greene said she would like to see larger trials looking at biomarker measurements and cardiac imaging before hormone therapy but that the biggest issue is the need for inclusion of transgender people in all cardiovascular trials.

“The sample sizes are never going to be as big as we get for cisgender people for a number of reasons but ensuring that it’s something that’s being asked on intake and monitored over time so we can understand how transgender people fit into the general population for cardiac disease,” Dr. Greene said. “And so, we can normalize that they exist. I keep driving this point home, but this is the biggest thing right now when it’s such a political issue.”

The study was supported in part by the department of laboratory medicine at the University of Washington, the department of pathology at the University of Iowa, and a grant from Abbott Diagnostics for in-kind high-sensitivity cardiac troponin I reagent. One coauthor reported financial relationships with Siemens Healthineers, Roche Diagnostics, Beckman Coulter, Becton, Dickinson, Abbott Diagnostics, Quidel Diagnostics, Sphingotech, and PixCell Medical. No other disclosures were reported.

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

Cardiac biomarkers vary according to sex hormones in healthy transgender adults, just as in cisgender individuals, a new cross-sectional study suggests.

Previous research in the general population has shown that females have a lower 99th percentile upper reference limit for high-sensitivity cardiac troponin (hs-cTn) than males, whereas N-terminal prohormone brain natriuretic peptide (NT-proBNP) concentrations are higher in females than males across all ages after puberty.

“That trend is similar for people that have been on gender-affirming hormones, saying that sex hormones are playing a role in how cardiac turnover happens in a healthy state,” study author Dina M. Greene, PhD, University of Washington, Seattle, said in an interview.

Although the number of transgender people seeking gender-affirming care is increasing, studies are limited and largely retrospective cohorts, she noted. The scientific literature evaluating and defining cardiac biomarker concentrations is “currently absent.”

The American Heart Association’s recent scientific statement on the cardiovascular health of transgender and gender diverse (TGD) people says mounting evidence points to worse CV health in TGD people and that part of this excess risk is driven by significant psychosocial stressors across the lifespan. “In addition, the use of gender-affirming hormone therapy may be associated with cardiometabolic changes, but health research in this area remains limited and, at times, contradictory.”

For the present study, Dr. Greene and colleagues reached out to LGBTQ-oriented primary care and internal medicine clinics in Seattle and Iowa City to recruit 79 transgender men prescribed testosterone (mean age, 28.8 years) and 93 transgender women (mean age, 35.1 years) prescribed estradiol for at least 12 months. The mean duration of hormone therapy was 4.8 and 3.5 years, respectively.

The median estradiol concentration was 51 pg/mL in transgender men and 207 pg/mL in transgender women. Median testosterone concentrations were 4.6 ng/mL and 0.4 ng/mL, respectively.

The cardiac biomarkers were measured with the ARCHITECT STAT (Abbott Diagnostics) and ACCESS (Beckman Coulter) high-sensitivity troponin I assays, the Elecsys Troponin T Gen 5 STAT assay (Roche Diagnostics), and the Elecsys ProBNP II immunoassay (Roche Diagnostics).

As reported in JAMA Cardiology, the median hs-cTnI level on the ARCHITECT STAT assay was 0.9 ng/L (range, 0.6-1.7) in transgender men and 0.6 ng/L (range, 0.3-1.0) in transgender women. The pattern was consistent across the two other assays.

In contrast, the median NT-proBNP level was 17 ng/L (range, 13-27) in transgender men and 49 ng/L (range, 32-86) in transgender women.

“It seems that sex hormone concentration is a stronger driver of baseline cardiac troponin and NT-proBNP concentrations relative to sex assigned at birth,” Dr. Greene said.

The observed differences in hs-cTn concentrations “are likely physiological and not pathological,” given that concentrations between healthy cisgender people are also apparent and not thought to portend adverse events, the authors noted.

Teasing out the clinical implications of sex-specific hs-cTn upper reference limits for ruling in acute myocardial infarction (MI), however, is complicated by biological and social factors that contribute to poorer outcomes in women, despite lower baseline levels, they added. “Ultimately, the psychosocial benefits of gender-affirming hormones are substantial, and informed consent is likely the ideal method to balance the undetermined risks.”

Dr. Greene pointed out that the study wasn’t powered to accurately calculate gender-specific hs-cTn 99th percentiles or reference intervals for NT-proBNP and assessed the biomarkers at a single time point.

For the transgender person presenting with chest pain, she said, the clinical implications are not yet known, but the data suggest that when sex-specific 99th percentiles for hs-cTn are used, the numeric value associated with the affirmed gender, rather than the sex assigned at birth, may be the appropriate URL.

“It really depends on what the triage pathway is and if that pathway has differences for people of different sexes and how often people get serial measurements,” Dr. Greene said. “Within this population, it’s very important to look at those serial measurements because for people that are not cismen, those 99th percentiles when they’re non–sex specific, are going to favor in detection of a heart attack. So, you need to look at the second value to make sure there hasn’t been a change over time.”

The observed differences in the distribution of NT-proBNP concentrations is similar to that in the cisgender population, Dr. Greene noted. But these differences do not lead to sex-specific diagnostic thresholds because of the significant elevations present in overt heart failure and cardiovascular disease. “For NT-proBNP, it’s not as important. People don’t usually have a little bit of heart failure, they have heart failure, where people have small MIs.”

Dr. Greene said she would like to see larger trials looking at biomarker measurements and cardiac imaging before hormone therapy but that the biggest issue is the need for inclusion of transgender people in all cardiovascular trials.

“The sample sizes are never going to be as big as we get for cisgender people for a number of reasons but ensuring that it’s something that’s being asked on intake and monitored over time so we can understand how transgender people fit into the general population for cardiac disease,” Dr. Greene said. “And so, we can normalize that they exist. I keep driving this point home, but this is the biggest thing right now when it’s such a political issue.”

The study was supported in part by the department of laboratory medicine at the University of Washington, the department of pathology at the University of Iowa, and a grant from Abbott Diagnostics for in-kind high-sensitivity cardiac troponin I reagent. One coauthor reported financial relationships with Siemens Healthineers, Roche Diagnostics, Beckman Coulter, Becton, Dickinson, Abbott Diagnostics, Quidel Diagnostics, Sphingotech, and PixCell Medical. No other disclosures were reported.

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

A new statement from the American College of Cardiology is calling for a greater degree of career flexibility in the specialty to promote cardiologists’ personal and professional well-being and preserve excellence in patient care.

The statement recommends that cardiologists, from trainees to those contemplating retirement, be granted more leeway in their careers to allow them to take time for common life events, such as child-rearing, taking care of aged parents, or reducing their workload in case of poor health or physical disabilities, without jeopardizing their careers.

The “2022 ACC Health Policy Statement on Career Flexibility in Cardiology: A Report of the American College of Cardiology Solution Set Oversight Committee” was published online in the Journal of the American College of Cardiology.
 

‘Hard-driving profession’

The well-being of the cardiovascular workforce is critical to the achievement of the mission of the ACC, which is to transform cardiovascular care and improve heart health, the Health Policy writing committee stated. Career flexibility is an important component of ensuring that well-being, the authors wrote.

“The ACC has critically looked at the factors that contribute to the lack of diversity and inclusion in cardiovascular practice, and one of the issues is the lack of flexibility in our profession,” writing committee chair, Mary Norine Walsh, MD, medical director of the heart failure and cardiac transplantation programs, Ascension St. Vincent Heart Center, Indianapolis, Ind., told this news organization.

The notion of work-life balance has become increasingly important but cardiology as a profession has traditionally not been open to the idea of its value, Dr. Walsh said.

“We have a very hard-driving profession. It takes many years to train to do the work we do. The need for on-call services is very significant, and we go along because we have always done it this way, but if you don’t reexamine the way that you are structuring your work, you’ll never change it,” she said.

“For example, the ‘full time, full call, come to work after you’ve been up all night’ work ethic, which is no longer allowed for trainees, is still in effect once you get into university practice or clinical practice. We have interventional cardiologists up all night doing STEMI care for patients and then having a full clinic the next day,” Dr. Walsh said. “The changes that came about for trainees have not trickled up to the faculty or clinical practice level. It’s really a patient safety issue.”

She emphasized that the new policy statement is not focused solely on women. “The need for time away or flexible time around family planning, childbirth, and parental leave is increasingly important to our younger colleagues, both men and women.”

Dr. Walsh pointed out that the writing committee was carefully composed to include representation from all stakeholders.

“We have representation from very young cardiologists, one of whom was in training at the time we began our work. We have two systems CEOs who are cardiologists, we have a chair of medicine, we have two very senior cardiologists, and someone who works in industry,” she said.

The ACC also believes that cardiologists with physically demanding roles should have pathways to transition into other opportunities in patient care, research, or education.

“Right now, there are many cardiology practices that have traditional policies, where you are either all in, or you are all out. They do not allow for what we term a ‘step down’ policy, where you perhaps stop going into the cath lab, but you still do clinic and see patients,” Dr. Walsh noted.

“One of the goals of this policy statement is to allow for such practices to look at their compensation and structure, and to realize that their most senior cardiologists may be willing to stay on for several more years and be contributing members to the practice, but they may no longer wish to stay in the cath lab or be in the night call pool,” she said.

Transparency around compensation is also very important because cardiologists contemplating a reduced work schedule need to know how this will affect the amount of money they will be earning, she added.

“Transparency about policies around compensation are crucial because if an individual cardiologist wishes to pursue a flexible scheduling at any time in their career, it’s clear that they won’t have the same compensation as someone who is a full-time employee. All of this has to be very transparent and clear on both sides, so that the person deciding toward some flexibility understands what the implications are from a financial and compensation standpoint,” Dr. Walsh said.

As an example, a senior career cardiologist who no longer wants to take night calls should know what this may cost financially.

“The practice should set a valuation of night calls, so that the individual who makes the choice to step out of the call pool understands what the impact on their compensation will be. That type of transparency is necessary for all to ensure that individuals who seek flexibility will not be blindsided by the resulting decrease in financial compensation,” she said.
 

A growing need

“In its new health policy statement, the American College of Cardiology addresses the growing need for career flexibility as an important component of ensuring the well-being of the cardiovascular care workforce,” Harlan M. Krumholz, MD, SM, Harold H. Hines Jr. Professor of Medicine and professor in the Institute for Social and Policy Studies at Yale University, New Haven, Conn., told this news organization.

Courtesy Yale University

“The writing committee reviews opportunities for offering flexibility at all career levels to combat burnout and increase retention in the field, as well as proposes system, policy, and practice solutions to allow both men and women to emphasize and embrace work-life balance,” Dr. Krumholz said.

“The document provides pathways for cardiologists looking to pursue other interests or career transitions while maintaining excellence in clinical care,” he added. “Chief among these recommendations are flexible/part-time hours, leave and reentry policies, changes in job descriptions to support overarching cultural change, and equitable compensation and opportunities. The document is intended to be used as a guide for innovation in the cardiology workforce.”
 

‘Thoughtful and long overdue’

“This policy statement is thoughtful and long overdue,” Steven E. Nissen, MD, Lewis and Patricia Dickey Chair in Cardiovascular Medicine and professor of medicine at Cleveland Clinic, told this news organization.

“Career flexibility will allow cardiologists to fulfill family responsibilities while continuing to advance their careers. Successfully contributing to patient care and research does not require physicians to isolate themselves from all their other responsibilities,” Dr. Nissen added.

“I am pleased that the ACC has articulated the value of a balanced approach to career and family.”

Dr. Walsh, Dr. Krumholz, and Dr. Nissen report no relevant financial relationships.

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

A new statement from the American College of Cardiology is calling for a greater degree of career flexibility in the specialty to promote cardiologists’ personal and professional well-being and preserve excellence in patient care.

The statement recommends that cardiologists, from trainees to those contemplating retirement, be granted more leeway in their careers to allow them to take time for common life events, such as child-rearing, taking care of aged parents, or reducing their workload in case of poor health or physical disabilities, without jeopardizing their careers.

The “2022 ACC Health Policy Statement on Career Flexibility in Cardiology: A Report of the American College of Cardiology Solution Set Oversight Committee” was published online in the Journal of the American College of Cardiology.
 

‘Hard-driving profession’

The well-being of the cardiovascular workforce is critical to the achievement of the mission of the ACC, which is to transform cardiovascular care and improve heart health, the Health Policy writing committee stated. Career flexibility is an important component of ensuring that well-being, the authors wrote.

“The ACC has critically looked at the factors that contribute to the lack of diversity and inclusion in cardiovascular practice, and one of the issues is the lack of flexibility in our profession,” writing committee chair, Mary Norine Walsh, MD, medical director of the heart failure and cardiac transplantation programs, Ascension St. Vincent Heart Center, Indianapolis, Ind., told this news organization.

The notion of work-life balance has become increasingly important but cardiology as a profession has traditionally not been open to the idea of its value, Dr. Walsh said.

“We have a very hard-driving profession. It takes many years to train to do the work we do. The need for on-call services is very significant, and we go along because we have always done it this way, but if you don’t reexamine the way that you are structuring your work, you’ll never change it,” she said.

“For example, the ‘full time, full call, come to work after you’ve been up all night’ work ethic, which is no longer allowed for trainees, is still in effect once you get into university practice or clinical practice. We have interventional cardiologists up all night doing STEMI care for patients and then having a full clinic the next day,” Dr. Walsh said. “The changes that came about for trainees have not trickled up to the faculty or clinical practice level. It’s really a patient safety issue.”

She emphasized that the new policy statement is not focused solely on women. “The need for time away or flexible time around family planning, childbirth, and parental leave is increasingly important to our younger colleagues, both men and women.”

Dr. Walsh pointed out that the writing committee was carefully composed to include representation from all stakeholders.

“We have representation from very young cardiologists, one of whom was in training at the time we began our work. We have two systems CEOs who are cardiologists, we have a chair of medicine, we have two very senior cardiologists, and someone who works in industry,” she said.

The ACC also believes that cardiologists with physically demanding roles should have pathways to transition into other opportunities in patient care, research, or education.

“Right now, there are many cardiology practices that have traditional policies, where you are either all in, or you are all out. They do not allow for what we term a ‘step down’ policy, where you perhaps stop going into the cath lab, but you still do clinic and see patients,” Dr. Walsh noted.

“One of the goals of this policy statement is to allow for such practices to look at their compensation and structure, and to realize that their most senior cardiologists may be willing to stay on for several more years and be contributing members to the practice, but they may no longer wish to stay in the cath lab or be in the night call pool,” she said.

Transparency around compensation is also very important because cardiologists contemplating a reduced work schedule need to know how this will affect the amount of money they will be earning, she added.

“Transparency about policies around compensation are crucial because if an individual cardiologist wishes to pursue a flexible scheduling at any time in their career, it’s clear that they won’t have the same compensation as someone who is a full-time employee. All of this has to be very transparent and clear on both sides, so that the person deciding toward some flexibility understands what the implications are from a financial and compensation standpoint,” Dr. Walsh said.

As an example, a senior career cardiologist who no longer wants to take night calls should know what this may cost financially.

“The practice should set a valuation of night calls, so that the individual who makes the choice to step out of the call pool understands what the impact on their compensation will be. That type of transparency is necessary for all to ensure that individuals who seek flexibility will not be blindsided by the resulting decrease in financial compensation,” she said.
 

A growing need

“In its new health policy statement, the American College of Cardiology addresses the growing need for career flexibility as an important component of ensuring the well-being of the cardiovascular care workforce,” Harlan M. Krumholz, MD, SM, Harold H. Hines Jr. Professor of Medicine and professor in the Institute for Social and Policy Studies at Yale University, New Haven, Conn., told this news organization.

Courtesy Yale University

“The writing committee reviews opportunities for offering flexibility at all career levels to combat burnout and increase retention in the field, as well as proposes system, policy, and practice solutions to allow both men and women to emphasize and embrace work-life balance,” Dr. Krumholz said.

“The document provides pathways for cardiologists looking to pursue other interests or career transitions while maintaining excellence in clinical care,” he added. “Chief among these recommendations are flexible/part-time hours, leave and reentry policies, changes in job descriptions to support overarching cultural change, and equitable compensation and opportunities. The document is intended to be used as a guide for innovation in the cardiology workforce.”
 

‘Thoughtful and long overdue’

“This policy statement is thoughtful and long overdue,” Steven E. Nissen, MD, Lewis and Patricia Dickey Chair in Cardiovascular Medicine and professor of medicine at Cleveland Clinic, told this news organization.

“Career flexibility will allow cardiologists to fulfill family responsibilities while continuing to advance their careers. Successfully contributing to patient care and research does not require physicians to isolate themselves from all their other responsibilities,” Dr. Nissen added.

“I am pleased that the ACC has articulated the value of a balanced approach to career and family.”

Dr. Walsh, Dr. Krumholz, and Dr. Nissen report no relevant financial relationships.

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

A new statement from the American College of Cardiology is calling for a greater degree of career flexibility in the specialty to promote cardiologists’ personal and professional well-being and preserve excellence in patient care.

The statement recommends that cardiologists, from trainees to those contemplating retirement, be granted more leeway in their careers to allow them to take time for common life events, such as child-rearing, taking care of aged parents, or reducing their workload in case of poor health or physical disabilities, without jeopardizing their careers.

The “2022 ACC Health Policy Statement on Career Flexibility in Cardiology: A Report of the American College of Cardiology Solution Set Oversight Committee” was published online in the Journal of the American College of Cardiology.
 

‘Hard-driving profession’

The well-being of the cardiovascular workforce is critical to the achievement of the mission of the ACC, which is to transform cardiovascular care and improve heart health, the Health Policy writing committee stated. Career flexibility is an important component of ensuring that well-being, the authors wrote.

“The ACC has critically looked at the factors that contribute to the lack of diversity and inclusion in cardiovascular practice, and one of the issues is the lack of flexibility in our profession,” writing committee chair, Mary Norine Walsh, MD, medical director of the heart failure and cardiac transplantation programs, Ascension St. Vincent Heart Center, Indianapolis, Ind., told this news organization.

The notion of work-life balance has become increasingly important but cardiology as a profession has traditionally not been open to the idea of its value, Dr. Walsh said.

“We have a very hard-driving profession. It takes many years to train to do the work we do. The need for on-call services is very significant, and we go along because we have always done it this way, but if you don’t reexamine the way that you are structuring your work, you’ll never change it,” she said.

“For example, the ‘full time, full call, come to work after you’ve been up all night’ work ethic, which is no longer allowed for trainees, is still in effect once you get into university practice or clinical practice. We have interventional cardiologists up all night doing STEMI care for patients and then having a full clinic the next day,” Dr. Walsh said. “The changes that came about for trainees have not trickled up to the faculty or clinical practice level. It’s really a patient safety issue.”

She emphasized that the new policy statement is not focused solely on women. “The need for time away or flexible time around family planning, childbirth, and parental leave is increasingly important to our younger colleagues, both men and women.”

Dr. Walsh pointed out that the writing committee was carefully composed to include representation from all stakeholders.

“We have representation from very young cardiologists, one of whom was in training at the time we began our work. We have two systems CEOs who are cardiologists, we have a chair of medicine, we have two very senior cardiologists, and someone who works in industry,” she said.

The ACC also believes that cardiologists with physically demanding roles should have pathways to transition into other opportunities in patient care, research, or education.

“Right now, there are many cardiology practices that have traditional policies, where you are either all in, or you are all out. They do not allow for what we term a ‘step down’ policy, where you perhaps stop going into the cath lab, but you still do clinic and see patients,” Dr. Walsh noted.

“One of the goals of this policy statement is to allow for such practices to look at their compensation and structure, and to realize that their most senior cardiologists may be willing to stay on for several more years and be contributing members to the practice, but they may no longer wish to stay in the cath lab or be in the night call pool,” she said.

Transparency around compensation is also very important because cardiologists contemplating a reduced work schedule need to know how this will affect the amount of money they will be earning, she added.

“Transparency about policies around compensation are crucial because if an individual cardiologist wishes to pursue a flexible scheduling at any time in their career, it’s clear that they won’t have the same compensation as someone who is a full-time employee. All of this has to be very transparent and clear on both sides, so that the person deciding toward some flexibility understands what the implications are from a financial and compensation standpoint,” Dr. Walsh said.

As an example, a senior career cardiologist who no longer wants to take night calls should know what this may cost financially.

“The practice should set a valuation of night calls, so that the individual who makes the choice to step out of the call pool understands what the impact on their compensation will be. That type of transparency is necessary for all to ensure that individuals who seek flexibility will not be blindsided by the resulting decrease in financial compensation,” she said.
 

A growing need

“In its new health policy statement, the American College of Cardiology addresses the growing need for career flexibility as an important component of ensuring the well-being of the cardiovascular care workforce,” Harlan M. Krumholz, MD, SM, Harold H. Hines Jr. Professor of Medicine and professor in the Institute for Social and Policy Studies at Yale University, New Haven, Conn., told this news organization.

Courtesy Yale University

“The writing committee reviews opportunities for offering flexibility at all career levels to combat burnout and increase retention in the field, as well as proposes system, policy, and practice solutions to allow both men and women to emphasize and embrace work-life balance,” Dr. Krumholz said.

“The document provides pathways for cardiologists looking to pursue other interests or career transitions while maintaining excellence in clinical care,” he added. “Chief among these recommendations are flexible/part-time hours, leave and reentry policies, changes in job descriptions to support overarching cultural change, and equitable compensation and opportunities. The document is intended to be used as a guide for innovation in the cardiology workforce.”
 

‘Thoughtful and long overdue’

“This policy statement is thoughtful and long overdue,” Steven E. Nissen, MD, Lewis and Patricia Dickey Chair in Cardiovascular Medicine and professor of medicine at Cleveland Clinic, told this news organization.

“Career flexibility will allow cardiologists to fulfill family responsibilities while continuing to advance their careers. Successfully contributing to patient care and research does not require physicians to isolate themselves from all their other responsibilities,” Dr. Nissen added.

“I am pleased that the ACC has articulated the value of a balanced approach to career and family.”

Dr. Walsh, Dr. Krumholz, and Dr. Nissen report no relevant financial relationships.

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

The substantial reductions in cardiovascular disease (CVD) and all-cause mortality achieved with intensive blood pressure lowering in the landmark SPRINT trial were not sustained in a newly released long-term follow-up.

The loss of the mortality benefits corresponded with a steady climb in the average systolic blood pressures (SBP) in the intensive treatment group after the trial ended. The long-term benefit serves as a call to develop better strategies for sustained SBP control.

“We were disappointed but not surprised that the blood pressure levels in the intensive goal group were not sustained,” acknowledged William C. Cushman, MD, Medical Director, department of preventive medicine, University of Tennessee Health Science Center, Memphis. “There are many trials showing no residual or legacy effect once the intervention is stopped.”
 

Long-term results do not weaken SPRINT

One of the coinvestigators of this most recent analysis published in JAMA Cardiology and a member of the SPRINT writing committee at the time of its 2015 publication in the New England Journal of Medicine, Dr. Cushman pointed out that the long-term results do not weaken the main trial result. Long-term adherence was not part of the trial design.

“After the trial, we were no longer treating these participants, so it was up to them and their primary care providers to decide on blood pressure goals,” he noted in an interview. Based on the trajectory of benefit when the study was stopped, “it is possible longer intensive treatment may lead to more benefit and some long-term residual benefits.”

The senior author of this most recent analysis, Nicholas M. Pajewski, PhD, associate professor of biostatistics and data science, Wake Forest University, Winston-Salem, N.C., generally agreed. However, he pointed out that the most recent data do not rule out meaningful benefit after the study ended.

For one reason, the loss of the SBP advantage was gradual so that median SBP levels of the two groups did not meet for nearly 3 years. This likely explains why there was still an attenuation of CVD mortality for several years after the all-cause mortality benefit was lost, according to Dr. Pajewski.

“It is important to mention that we were not able to assess nonfatal cardiovascular events, so while the two groups do eventually come together, if one thinks about the distinction of healthspan versus lifespan, there was probably residual benefit in terms of delaying CVD morbidity and mortality,” Dr. Pajewski said.
 

In SPRINT, CVD mortality reduced 43%

In the 9,631-patient SPRINT trial, the intensive treatment group achieved a mean SBP of 121.4 mm Hg versus 136.2 mm Hg in the standard treatment group at the end of 1 year. The trial was stopped early after 3.26 years because of strength of the benefit in the intensive treatment arm. At that time, the reductions by hazard ratio were 25% (HR, 0.75; P < .001) for a composite major adverse cardiovascular event (MACE) endpoint, 43% for CVD mortality (P = .005), and 27% for all-cause mortality (P = .003).

In the new observational follow-up, mortality data were drawn from the National Death Index, and change in SBP from electronic health records in a subset of 2,944 SPRINT trial participants. Data were available and analyzed through 2020.

The newly published long-term observational analysis showed that the median SBP in the intensive treatment arm was already climbing by the end of the end of the trial. It reached 132.8 mm Hg at 5 years after randomization and then 140.4 mm Hg by 10 years.

This latter figure was essentially equivalent to the SBP among those who were initially randomized to the standard treatment arm.
 

Factors driving rising BP are unclear

There is limited information on what medications were taken by either group following the end of the trial, so the reason for the regression in the intensive treatment arm after leaving the trial is unknown. The authors speculated that this might have been due to therapeutic inertia among treating physicians, poor adherence among patients, the difficulty of keeping blood pressures low in patients with advancing pathology, or some combination of these.

“Perhaps the most important reason was that providers and patients were not aiming for the lower goals since guidelines did not recommend these targets until 2017,” Dr. Cushman pointed out. He noted that Healthcare Effectiveness Data and Information Set (HEDIS) “has still not adopted a performance measure goal of less than 140 mm Hg.”

In an accompanying editorial, the authors focused on what these data mean for population-based strategies to achieve sustained control of one of the most important risk factors for cardiovascular events. Led by Daniel W. Jones, MD, director of clinical and population science, University of Mississippi, Jackson, the authors of the editorial wrote that these data emphasized “the challenge of achieving sustained intensive BP reductions in the real-world setting.”

Basically, the editorial concluded that current approaches to achieving meaningful and sustained blood pressure control are not working.

This study “should be a wakeup call, but other previously published good data have also been ignored,” said Dr. Jones in an interview. Despite the compelling benefit from intensive blood pressure control the SPRINT trial, the observational follow-up emphasizes the difficulty of maintaining the rigorous reductions in blood pressure needed for sustained protection.

“Systemic change is necessary,” said Dr. Jones, reprising the major thrust of the editorial he wrote with Donald Clark III, MD, and Michael E. Hall, MD, who are both colleagues at the University of Mississippi.

“My view is that health care providers should be held responsible for motivating better compliance of their patients, just as a teacher is accountable for the outcomes of their students,” he said.

The solutions are not likely to be simple. Dr. Jones called for multiple strategies, such as employing telehealth and community health workers to monitor and reinforce blood pressure control, but he said that these and other data have convinced him that “simply trying harder at what we currently do” is not enough.

Dr. Pajewski and Dr. Jones report no potential conflicts of interest. Dr. Cushman reports a financial relationship with ReCor.

The substantial reductions in cardiovascular disease (CVD) and all-cause mortality achieved with intensive blood pressure lowering in the landmark SPRINT trial were not sustained in a newly released long-term follow-up.

The loss of the mortality benefits corresponded with a steady climb in the average systolic blood pressures (SBP) in the intensive treatment group after the trial ended. The long-term benefit serves as a call to develop better strategies for sustained SBP control.

“We were disappointed but not surprised that the blood pressure levels in the intensive goal group were not sustained,” acknowledged William C. Cushman, MD, Medical Director, department of preventive medicine, University of Tennessee Health Science Center, Memphis. “There are many trials showing no residual or legacy effect once the intervention is stopped.”
 

Long-term results do not weaken SPRINT

One of the coinvestigators of this most recent analysis published in JAMA Cardiology and a member of the SPRINT writing committee at the time of its 2015 publication in the New England Journal of Medicine, Dr. Cushman pointed out that the long-term results do not weaken the main trial result. Long-term adherence was not part of the trial design.

“After the trial, we were no longer treating these participants, so it was up to them and their primary care providers to decide on blood pressure goals,” he noted in an interview. Based on the trajectory of benefit when the study was stopped, “it is possible longer intensive treatment may lead to more benefit and some long-term residual benefits.”

The senior author of this most recent analysis, Nicholas M. Pajewski, PhD, associate professor of biostatistics and data science, Wake Forest University, Winston-Salem, N.C., generally agreed. However, he pointed out that the most recent data do not rule out meaningful benefit after the study ended.

For one reason, the loss of the SBP advantage was gradual so that median SBP levels of the two groups did not meet for nearly 3 years. This likely explains why there was still an attenuation of CVD mortality for several years after the all-cause mortality benefit was lost, according to Dr. Pajewski.

“It is important to mention that we were not able to assess nonfatal cardiovascular events, so while the two groups do eventually come together, if one thinks about the distinction of healthspan versus lifespan, there was probably residual benefit in terms of delaying CVD morbidity and mortality,” Dr. Pajewski said.
 

In SPRINT, CVD mortality reduced 43%

In the 9,631-patient SPRINT trial, the intensive treatment group achieved a mean SBP of 121.4 mm Hg versus 136.2 mm Hg in the standard treatment group at the end of 1 year. The trial was stopped early after 3.26 years because of strength of the benefit in the intensive treatment arm. At that time, the reductions by hazard ratio were 25% (HR, 0.75; P < .001) for a composite major adverse cardiovascular event (MACE) endpoint, 43% for CVD mortality (P = .005), and 27% for all-cause mortality (P = .003).

In the new observational follow-up, mortality data were drawn from the National Death Index, and change in SBP from electronic health records in a subset of 2,944 SPRINT trial participants. Data were available and analyzed through 2020.

The newly published long-term observational analysis showed that the median SBP in the intensive treatment arm was already climbing by the end of the end of the trial. It reached 132.8 mm Hg at 5 years after randomization and then 140.4 mm Hg by 10 years.

This latter figure was essentially equivalent to the SBP among those who were initially randomized to the standard treatment arm.
 

Factors driving rising BP are unclear

There is limited information on what medications were taken by either group following the end of the trial, so the reason for the regression in the intensive treatment arm after leaving the trial is unknown. The authors speculated that this might have been due to therapeutic inertia among treating physicians, poor adherence among patients, the difficulty of keeping blood pressures low in patients with advancing pathology, or some combination of these.

“Perhaps the most important reason was that providers and patients were not aiming for the lower goals since guidelines did not recommend these targets until 2017,” Dr. Cushman pointed out. He noted that Healthcare Effectiveness Data and Information Set (HEDIS) “has still not adopted a performance measure goal of less than 140 mm Hg.”

In an accompanying editorial, the authors focused on what these data mean for population-based strategies to achieve sustained control of one of the most important risk factors for cardiovascular events. Led by Daniel W. Jones, MD, director of clinical and population science, University of Mississippi, Jackson, the authors of the editorial wrote that these data emphasized “the challenge of achieving sustained intensive BP reductions in the real-world setting.”

Basically, the editorial concluded that current approaches to achieving meaningful and sustained blood pressure control are not working.

This study “should be a wakeup call, but other previously published good data have also been ignored,” said Dr. Jones in an interview. Despite the compelling benefit from intensive blood pressure control the SPRINT trial, the observational follow-up emphasizes the difficulty of maintaining the rigorous reductions in blood pressure needed for sustained protection.

“Systemic change is necessary,” said Dr. Jones, reprising the major thrust of the editorial he wrote with Donald Clark III, MD, and Michael E. Hall, MD, who are both colleagues at the University of Mississippi.

“My view is that health care providers should be held responsible for motivating better compliance of their patients, just as a teacher is accountable for the outcomes of their students,” he said.

The solutions are not likely to be simple. Dr. Jones called for multiple strategies, such as employing telehealth and community health workers to monitor and reinforce blood pressure control, but he said that these and other data have convinced him that “simply trying harder at what we currently do” is not enough.

Dr. Pajewski and Dr. Jones report no potential conflicts of interest. Dr. Cushman reports a financial relationship with ReCor.

The substantial reductions in cardiovascular disease (CVD) and all-cause mortality achieved with intensive blood pressure lowering in the landmark SPRINT trial were not sustained in a newly released long-term follow-up.

The loss of the mortality benefits corresponded with a steady climb in the average systolic blood pressures (SBP) in the intensive treatment group after the trial ended. The long-term benefit serves as a call to develop better strategies for sustained SBP control.

“We were disappointed but not surprised that the blood pressure levels in the intensive goal group were not sustained,” acknowledged William C. Cushman, MD, Medical Director, department of preventive medicine, University of Tennessee Health Science Center, Memphis. “There are many trials showing no residual or legacy effect once the intervention is stopped.”
 

Long-term results do not weaken SPRINT

One of the coinvestigators of this most recent analysis published in JAMA Cardiology and a member of the SPRINT writing committee at the time of its 2015 publication in the New England Journal of Medicine, Dr. Cushman pointed out that the long-term results do not weaken the main trial result. Long-term adherence was not part of the trial design.

“After the trial, we were no longer treating these participants, so it was up to them and their primary care providers to decide on blood pressure goals,” he noted in an interview. Based on the trajectory of benefit when the study was stopped, “it is possible longer intensive treatment may lead to more benefit and some long-term residual benefits.”

The senior author of this most recent analysis, Nicholas M. Pajewski, PhD, associate professor of biostatistics and data science, Wake Forest University, Winston-Salem, N.C., generally agreed. However, he pointed out that the most recent data do not rule out meaningful benefit after the study ended.

For one reason, the loss of the SBP advantage was gradual so that median SBP levels of the two groups did not meet for nearly 3 years. This likely explains why there was still an attenuation of CVD mortality for several years after the all-cause mortality benefit was lost, according to Dr. Pajewski.

“It is important to mention that we were not able to assess nonfatal cardiovascular events, so while the two groups do eventually come together, if one thinks about the distinction of healthspan versus lifespan, there was probably residual benefit in terms of delaying CVD morbidity and mortality,” Dr. Pajewski said.
 

In SPRINT, CVD mortality reduced 43%

In the 9,631-patient SPRINT trial, the intensive treatment group achieved a mean SBP of 121.4 mm Hg versus 136.2 mm Hg in the standard treatment group at the end of 1 year. The trial was stopped early after 3.26 years because of strength of the benefit in the intensive treatment arm. At that time, the reductions by hazard ratio were 25% (HR, 0.75; P < .001) for a composite major adverse cardiovascular event (MACE) endpoint, 43% for CVD mortality (P = .005), and 27% for all-cause mortality (P = .003).

In the new observational follow-up, mortality data were drawn from the National Death Index, and change in SBP from electronic health records in a subset of 2,944 SPRINT trial participants. Data were available and analyzed through 2020.

The newly published long-term observational analysis showed that the median SBP in the intensive treatment arm was already climbing by the end of the end of the trial. It reached 132.8 mm Hg at 5 years after randomization and then 140.4 mm Hg by 10 years.

This latter figure was essentially equivalent to the SBP among those who were initially randomized to the standard treatment arm.
 

Factors driving rising BP are unclear

There is limited information on what medications were taken by either group following the end of the trial, so the reason for the regression in the intensive treatment arm after leaving the trial is unknown. The authors speculated that this might have been due to therapeutic inertia among treating physicians, poor adherence among patients, the difficulty of keeping blood pressures low in patients with advancing pathology, or some combination of these.

“Perhaps the most important reason was that providers and patients were not aiming for the lower goals since guidelines did not recommend these targets until 2017,” Dr. Cushman pointed out. He noted that Healthcare Effectiveness Data and Information Set (HEDIS) “has still not adopted a performance measure goal of less than 140 mm Hg.”

In an accompanying editorial, the authors focused on what these data mean for population-based strategies to achieve sustained control of one of the most important risk factors for cardiovascular events. Led by Daniel W. Jones, MD, director of clinical and population science, University of Mississippi, Jackson, the authors of the editorial wrote that these data emphasized “the challenge of achieving sustained intensive BP reductions in the real-world setting.”

Basically, the editorial concluded that current approaches to achieving meaningful and sustained blood pressure control are not working.

This study “should be a wakeup call, but other previously published good data have also been ignored,” said Dr. Jones in an interview. Despite the compelling benefit from intensive blood pressure control the SPRINT trial, the observational follow-up emphasizes the difficulty of maintaining the rigorous reductions in blood pressure needed for sustained protection.

“Systemic change is necessary,” said Dr. Jones, reprising the major thrust of the editorial he wrote with Donald Clark III, MD, and Michael E. Hall, MD, who are both colleagues at the University of Mississippi.

“My view is that health care providers should be held responsible for motivating better compliance of their patients, just as a teacher is accountable for the outcomes of their students,” he said.

The solutions are not likely to be simple. Dr. Jones called for multiple strategies, such as employing telehealth and community health workers to monitor and reinforce blood pressure control, but he said that these and other data have convinced him that “simply trying harder at what we currently do” is not enough.

Dr. Pajewski and Dr. Jones report no potential conflicts of interest. Dr. Cushman reports a financial relationship with ReCor.

A “high-intensity-care” strategy based on early and rapid uptitration of guideline-directed meds improves postdischarge clinical outcomes for patients hospitalized with decompensated heart failure (HF), suggest topline results from a randomized trial.

The STRONG-HF study was halted early on recommendation from its data safety monitoring board after an interim analysis suggested the high-intensity-care strategy significantly cut risk of death or HF readmission, compared with a standard-of-care approach.

The trial termination was announced  in a press release from one of its sponsors, The Heart Initiative, a nonprofit organization. STRONG-HF was also supported by Roche Diagnostics.

The early termination was based on interim data from the approximately 1,000 patients, out of an estimated planned enrollment of 1,800, who had been followed for at least 90 days. The study’s actual primary endpoint had been defined by death or HF readmission at 6 months.

The announcement did not include outcomes data or P values, or any other indication of the magnitude of benefit from the high-intensity-care approach.

Patients in STRONG-HF who had been assigned to a high-intensity-care strategy had been started in-hospital on a beta blocker, a renin-angiotensin system inhibitor (RASi), and a mineralocorticoid receptor blocker (MRA) with dosages uptitrated at least halfway by the time of discharge.

The meds were uptitrated fully within 2 weeks of discharge guided by clinical and biomarker assessments, especially natriuretic peptides, at frequent postdischarge visits, the press release states.

Patients conducted “safety visits 1 week after any uptitration and follow-up visits at 6 weeks and 3 months,” the announcement notes. “At each visit, patients were assessed by physical examination for congestion and blood tests, including NT-proBNP measurements.”

The “full STRONG-HF trial results” are scheduled for presentation at the American Heart Association annual scientific sessions, the announcement states.

STRONG-HF is sponsored by The Heart Initiative and Roche Diagnostics.

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

A “high-intensity-care” strategy based on early and rapid uptitration of guideline-directed meds improves postdischarge clinical outcomes for patients hospitalized with decompensated heart failure (HF), suggest topline results from a randomized trial.

The STRONG-HF study was halted early on recommendation from its data safety monitoring board after an interim analysis suggested the high-intensity-care strategy significantly cut risk of death or HF readmission, compared with a standard-of-care approach.

The trial termination was announced  in a press release from one of its sponsors, The Heart Initiative, a nonprofit organization. STRONG-HF was also supported by Roche Diagnostics.

The early termination was based on interim data from the approximately 1,000 patients, out of an estimated planned enrollment of 1,800, who had been followed for at least 90 days. The study’s actual primary endpoint had been defined by death or HF readmission at 6 months.

The announcement did not include outcomes data or P values, or any other indication of the magnitude of benefit from the high-intensity-care approach.

Patients in STRONG-HF who had been assigned to a high-intensity-care strategy had been started in-hospital on a beta blocker, a renin-angiotensin system inhibitor (RASi), and a mineralocorticoid receptor blocker (MRA) with dosages uptitrated at least halfway by the time of discharge.

The meds were uptitrated fully within 2 weeks of discharge guided by clinical and biomarker assessments, especially natriuretic peptides, at frequent postdischarge visits, the press release states.

Patients conducted “safety visits 1 week after any uptitration and follow-up visits at 6 weeks and 3 months,” the announcement notes. “At each visit, patients were assessed by physical examination for congestion and blood tests, including NT-proBNP measurements.”

The “full STRONG-HF trial results” are scheduled for presentation at the American Heart Association annual scientific sessions, the announcement states.

STRONG-HF is sponsored by The Heart Initiative and Roche Diagnostics.

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

A “high-intensity-care” strategy based on early and rapid uptitration of guideline-directed meds improves postdischarge clinical outcomes for patients hospitalized with decompensated heart failure (HF), suggest topline results from a randomized trial.

The STRONG-HF study was halted early on recommendation from its data safety monitoring board after an interim analysis suggested the high-intensity-care strategy significantly cut risk of death or HF readmission, compared with a standard-of-care approach.

The trial termination was announced  in a press release from one of its sponsors, The Heart Initiative, a nonprofit organization. STRONG-HF was also supported by Roche Diagnostics.

The early termination was based on interim data from the approximately 1,000 patients, out of an estimated planned enrollment of 1,800, who had been followed for at least 90 days. The study’s actual primary endpoint had been defined by death or HF readmission at 6 months.

The announcement did not include outcomes data or P values, or any other indication of the magnitude of benefit from the high-intensity-care approach.

Patients in STRONG-HF who had been assigned to a high-intensity-care strategy had been started in-hospital on a beta blocker, a renin-angiotensin system inhibitor (RASi), and a mineralocorticoid receptor blocker (MRA) with dosages uptitrated at least halfway by the time of discharge.

The meds were uptitrated fully within 2 weeks of discharge guided by clinical and biomarker assessments, especially natriuretic peptides, at frequent postdischarge visits, the press release states.

Patients conducted “safety visits 1 week after any uptitration and follow-up visits at 6 weeks and 3 months,” the announcement notes. “At each visit, patients were assessed by physical examination for congestion and blood tests, including NT-proBNP measurements.”

The “full STRONG-HF trial results” are scheduled for presentation at the American Heart Association annual scientific sessions, the announcement states.

STRONG-HF is sponsored by The Heart Initiative and Roche Diagnostics.

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