Sex Hormones and Incident Heart Failure in Men and Postmenopausal Women: The Atherosclerosis Risk in Communities Study

Abstract

Context Sex differences exist in heart failure (HF) phenotypes, but there is limited research on the role of sex hormones in HF and its subtypes. Objective To examine the associations of total testosterone, dehydroepiandrosterone sulfate (DHEA-S), and sex hormone binding globulin (SHBG) with incident HF, HF with preserved ejection fraction (HFpEF), and HF with reduced ejection fraction (HFrEF). Design Atherosclerosis Risk in Communities (ARIC) study (prospective cohort study). Median follow-up is 19.2 years. Setting General community. Participants 4,107 men and 4,839 post-menopausal women, with mean age of 63.2 (SD 5.7) and 62.8 (5.5) years, respectively. Exposure Plasma sex hormone levels were measured at Visit 4 (1996–1998). Main Outcome Measures Incident HF events were identified through hospital discharge codes and death certificates. Results The HRs for HF associated with 1 SD decrease in log-transformed total testosterone, DHEA-S, and SHBG were 1.10 (95% CI 1.03, 1.17), 1.07 (1.00, 1.15), and 1.04 (0.96, 1.11) in men, and 1.05 (0.99, 1.13), 1.17 (1.09, 1.24), and 0.93 (0.85, 1.01) in women, respectively. The associations between sex hormones with subtypes of HF had similar patterns but were attenuated and became statistically insignificant. Conclusion In this prospective cohort, lower levels of endogenous testosterone and DHEA-S in men, and DHEA-S in post-menopausal women, were associated with the development of HF. Similar directions of association in both sexes and both HF subtypes suggest that sex hormones play a role in the development of HF through common pathways regardless of sex.

Low testosterone concentrations and prediction of future heart failure in men and in women: evidence from the large FINRISK97 study

“…Our results reflect rigorous adjustment for conventional cardiovascular risk factors, which are independently associated with testosterone status. Moreover, our report is in contrast to a very recent report from the ARIC study: the authors found a statistically significant association between testosterone and incident heart failure in a general American community 6 . The HR for heart failure associated with 1‐SD decrease in log‐transformed total testosterone was 1.10 (95% CI: 1.03–1.17) in men and 1.05 (95% CI: 0.99–1.13) in women, respectively.…”

“…Most of these studies suffer limitations like small sample size, limited follow‐up, and incomplete statistical adjustment 5 . Nevertheless, just recently, a new report from the ARIC Study reported a weak, although statistically significant association between testosterone and incident heart failure in a general American community 6 . This borderline finding was only evident in overall analyses and needs to be replicated in further studies and populations 6 .…”

Association between oral contraceptive use and incident heart failure

“…Ejection fraction measurement information was recorded for events diagnosed as HF by MESA cardiac reviewers. Based on LV ejection fraction (LVEF) (≥50% or <50%), HF was further classified as either HF with preserved ejection fraction or HF with reduced ejection fraction 26,27 …”

Endocrine Challenges in Patients with Continuous-Flow Left Ventricular Assist Devices

“…Low levels are associated with an increased risk of morbidity, as well as all-cause mortality and cardiovascular death among the general population. Recently the Atherosclerosis Risk in Communities (ARIC) study was published, which specifically studied the risk for heart failure in both men and women, and showed that lower levels of endogenous testosterone in men, DHEA-sulphate in men, and post-menopausal women were associated with subsequent development of HF [ 84 , 85 , 86 , 87 , 88 ]. Within the group of patients with HF, Jankowska et al and Wehr et al showed that, indeed, below normal androgen levels in HF patients were an independent predictor of mortality [ 79 , 89 ].…”