Abstract
Background: The risk of cardiovascular disease (CVD) differs between men and women, and sex hormones are thought to play a key role. N-terminal pro-brain natriuretic peptide (NT-proBNP) is a sensitive biomarker of ventricular wall stress and a strong predictor of incident cardiovascular disease (CVD) and heart failure (HF). It can thus be seen as an early marker of CVD. We evaluated whether sex hormones levels were associated with change in NT-proBNP concentrations over 10 years in MESA. Methods: We studied 2348 men and 2041 post-menopausal women. Serum testosterone (T), estradiol, dehydroepiandrosterone (DHEA), and sex hormone binding globulin (SHBG) were measured at Exam 1 (2000-02); free T and bioavailable T were calculated. NT-proBNP was measured by Roche assay at Exam 1, plus Exam 3 (2004-05) and/or Exam 5 (2010-12). Multivariable-adjusted linear mixed effects models were used to study associations between sex hormone levels and change in NT-proBNP over an approximately 10-year period. Results: Mean (SD) age (years) at baseline was 65 (9) for women and 62 (10) for men. Women had higher NT-proBNP than men (median 76.6 vs 37.1 pg/ml). Among women, after adjusting for demographic, socioeconomic, and CVD risk factors, higher total T, bioavailable T, and free T were independently associated with a greater increase in NT-proBNP over 10 years, whereas estradiol and SHBG were inversely associated with change in NT-proBNP ( Table ). When sex hormones were analyzed together in the same model, total T was positively associated and SHBG was inversely associated with change in NT-proBNP. In men, higher estradiol was associated with greater 10-year increase in NT-proBNP. These associations were preserved after excluding individuals with ejection fraction <50%. Conclusion: A more androgenic sex hormone profile in post-menopausal women and a more estrogenic profile in men were independently associated with 10-year change in NT-proBNP levels. Sex hormone patterns may thus explain in part sex differences in the development of CVD and HF.
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