Sex Hormones and Change in N-Terminal Pro-B-Type Natriuretic Peptide Levels: The Multi-Ethnic Study of Atherosclerosis

J Clin Endocrinol Metab. 2018 Nov 1;103(11):4304-4314. doi: 10.1210/jc.2018-01437.

Abstract

Context: Sex hormones may influence sex differences in cardiovascular disease (CVD). N-terminal pro-B-type natriuretic peptide (NT-proBNP), a predictor of CVD, is higher in women than men, which may relate to sex hormones.

Objective: To evaluate whether total testosterone (T), bioavailable T, free T, estradiol, dehydroepiandrosterone (DHEA), and SHBG are associated with NT-proBNP.

Design: Cohort study.

Participants: Cross-sectional sample included 2371 postmenopausal women and 2688 men free of CVD, of which 2041 women and 2348 men were included longitudinally.

Main outcome measures: NT-proBNP at baseline (2000 to 2002) and one or more repeat NT-proBNPs (through 2012). Analyses adjusted for CVD risk factors.

Results: Women had higher NT-proBNP than men (median 79.9 vs 38.5 pg/mL). Cross-sectionally, higher bioavailable T, free T, DHEA, and lower SHBG levels were independently associated with lower NT-proBNP among both women and men (all P < 0.05). Higher total T in women and estradiol in men were also associated with lower NT-proBNP (both P < 0.05). Longitudinally, in women, higher total T, bioavailable T, free T, DHEA, and lower estradiol and SHBG were associated with greater 10-year increase in NT-proBNP (all P < 0.05). In men, higher free T and estradiol were associated with greater NT-proBNP increase (both P < 0.05).

Conclusions: A more androgenic sex hormone pattern was inversely associated with NT-proBNP cross-sectionally and may contribute to sex differences in NT-proBNP. Longitudinally, a more androgenic sex hormone pattern was associated with greater increase in NT-proBNP in women, which may reflect a mechanism for CVD risk after menopause.

Trial registration: ClinicalTrials.gov NCT00005487.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Atherosclerosis / blood*
  • Cross-Sectional Studies
  • Female
  • Gonadal Steroid Hormones / blood*
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood*
  • Peptide Fragments / blood*
  • Prospective Studies
  • Sex Factors

Substances

  • Gonadal Steroid Hormones
  • Peptide Fragments
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain

Associated data

  • ClinicalTrials.gov/NCT00005487