Association Between Statin Use and Sex Hormone in the Multi-Ethnic Study of Atherosclerosis Cohort.

PURPOSE: Based on the 2018 American College of Cardiology/American Heart Association cholesterol guidelines, the number of individuals eligible for statin therapy to reduce atherosclerotic cardiovascular disease risk has greatly expanded. Statins inhibit cholesterol biosynthesis, which can impair gonadal steroidogenesis. We evaluated the effect of statins on endogenous sex hormones in a large epidemiological study. METHODS: A total of 6814 Multi-Ethnic Study of Atherosclerosis (MESA) participants underwent the baseline examination. Of these, 6171 had measurements of serum sex hormones available: dehydroepiandrosterone (DHEA), SHBG, estradiol, and total and bioavailable testosterone. Multivariable linear regression models were used to assess the relationship of statin use with each sex hormone. RESULTS: A total of 345 women (17.4%) and 464 men (14.7%) were statin users (mean age, 67 years; 41% white, 29% black, 11% Chinese, and 19% Hispanic). Among the users vs nonusers of statins, the mean SHBG was 3.54 nmol/L (P < 0.01) lower in women and 3.37 nmol/L (P < 0.001) lower in men; the mean DHEA was 1.06 nmol/L (P < 0.05) lower in women and 0.70 nmol/L (P < 0.01) lower in men, after adjustment for potential confounders. With further propensity score adjustment, the mean DHEA and SHBG levels were 0.67 nmol/L (P < 0.05) and 3.49 nmol/L (P < 0.001) lower, respectively, for statin users vs nonusers. No statistically significant association was noted between estradiol, total testosterone, and bioavailable testosterone and statin use. CONCLUSION: Statin users have lower levels of SHBG and DHEA. This is especially relevant owing to the increasing use of statin therapy.

History of atrial fibrillation as a risk factor in patients with heart failure and preserved ejection fraction.

BACKGROUND: Atrial fibrillation (AFib) is common in heart failure (HF) with preserved ejection fraction (HFpEF). Current AFib stroke risk prediction models include the presence of HF but do not specifically include HFpEF as a risk factor. Whether a history of AFib should be used to identify patients with HFpEF who are at risk has not been established. METHODS AND RESULTS: Baseline characteristics and outcomes of patients with HFpEF in the Irbesartan in Heart Failure with Preserved Ejection Fraction Trial were analyzed in relation to AFib. At baseline, 1209 (29.3%) had a history of AFib. Of these 557 (13.5%) had history of AFib alone, whereas 670 (16.2%) had both a history and AFib on ECG; 2901 (70.3%) had neither. There were no significant differences in the risk of stroke between the 2 groups with a history of AFib who did or did not have AFib present on baseline ECG. During a median follow-up of 53 months, a fatal or nonfatal stroke occurred in 6.5% (79/1209) patients with history of AFib compared with 3.9% (114/2901) with no AFib. Having a history of AFib was independently associated with higher risk of stroke (hazard ratio, 2.2; 95% confidence interval, 1.6-3.2; P<0.0001) compared with those with no history of AFib. CONCLUSIONS: In patients with HFpEF, a history of AFib was common and independently associated with increased risk of stroke, regardless of whether AFib was present on ECG. Patients with HFpEF and a history of AFib should be considered at risk. Further studies are needed to determine whether this risk can be safely reduced. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT000095238.

Troponin T, N-terminal pro-B-type natriuretic peptide, and incidence of stroke: the atherosclerosis risk in communities study.

BACKGROUND AND PURPOSE: Increased levels of plasma troponins and natriuretic peptides are associated with increased risk of cardiovascular disease, but only limited information exists on these biomarkers and stroke occurrence. In a prospective epidemiological study, we tested the hypothesis that high-sensitivity troponin T (TnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are associated positively with incidence of stroke. METHODS: The Atherosclerosis Risk in Communities (ARIC) Study measured plasma TnT and NT-proBNP in 10 902 men or women initially free of stroke and followed them for a mean of 11.3 years for stroke occurrence (n=507). RESULTS: Both biomarkers were associated positively with total stroke, nonlacunar ischemic, and especially cardioembolic stroke, but not with lacunar or hemorrhagic stroke. For example, after adjustment for prevalent risk factors and cardiac diseases, the hazard ratios (95% CIs) for jointly high values of TnT and NT-proBNP (versus neither biomarker high) were 2.70 (1.92-3.79) for total stroke and 6.26 (3.40-11.5) for cardioembolic stroke. Associations with stroke appeared somewhat stronger for NT-proBNP than TnT. Strikingly, ≈ 58% of cardioembolic strokes occurred in the highest quintile of prestroke NT-proBNP, and 32% of cardioembolic strokes occurred in participants who had both NT-proBNP in the highest quintile and were known by ARIC to have atrial fibrillation sometime before their cardioembolic stroke occurrence. CONCLUSIONS: In the general population, elevated plasma TnT and NT-proBNP concentrations are associated with increased risk of cardioembolic and other nonlacunar ischemic strokes.

Troponin T, B-type natriuretic peptide, C-reactive protein, and cause-specific mortality.

PURPOSE: We sought to evaluate the associations of high-sensitivity troponin T (Hs-TnT), N-terminal pro-brain natriuretic peptide (NT-proBNP), and high sensitivity C-reactive protein (Hs-CRP) with mortality from any cause, cardiovascular disease (CVD), coronary heart disease (CHD), stroke, cancer, and respiratory disease in the Atherosclerosis Risk in Communities cohort. METHODS: We included 11,193 participants aged 54 to 74 years, initially free of the conditions being studied, and who had biomarkers measured. Participants were followed for a mean of 9.9 years. RESULTS: Hazard ratios (HR), adjusted for multiple risk factors, for mortality in participants in the highest Hs-TnT category compared with those with undetectable levels were: Total 3.42 (95% confidence interval [CI], 2.75-4.26); CVD, 7.34 (95% CI, 4.64-11.6); CHD, 6.06 (95% CI, 2.91-12.6); stroke, 3.31 (95% CI, 1.26-8.66); cancer, 1.60 (95% CI, 1.08-2.38); and respiratory, 3.85 (95% CI, 1.39-10.7). Comparing the highest NT-proBNP quintile with those in the lowest quintile, the adjusted HRs for mortality were: Total, 3.05 (95% CI, 2.46-3.77); CVD, 7.48 (95% CI, 4.67-12.0); CHD, 4.07 (95% CI, 2.07-7.98); and stroke, 10.4 (95% CI, 2.26-47.7). Comparing extreme Hs-CRP quintiles, the adjusted HRs for mortality were: Total, 1.61 (95% CI, 1.32-1.97); CVD, 1.76 (95% CI, 1.19-2.62); and respiratory, 3.36 (95% CI, 1.34-8.45). Having multiple markers elevated simultaneously greatly increased cause-specific mortality risks. CONCLUSIONS: Greater levels of Hs-TnT, NT-proBNP and Hs-CRP are associated with increased risk of death, not just from CVD, but also from some noncardiovascular causes.