NT-pro B-type natriuretic peptide, early menopause, and incident heart failure in postmenopausal women of the ARIC study

Abstract

Objective: N-Terminal pro B-type Natriuretic Peptide (NT-proBNP), a biomarker of heart failure (HF) has been associated with early menopause. We evaluated the modifying role of early menopause on the association of NT-proBNP with incident HF, and separately for HF subtypes, HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF).

Methods: We included 4,352 postmenopausal women including 1,174 with early menopause, ages 63.5 ± 5.5 years, without prevalent HF at the Atherosclerosis Risk in Communities study Visit 4. Binary log-transformation was performed for NT-proBNP. Cox proportional hazards models were used to examine the association of NT-proBNP with incident HF, and separately for incident HFpEF and incident HFrEF, testing for effect modification by early menopause and adjusting for HF risk factors.

Results: We observed 881 HF events over a mean follow-up of 16.5 years. The interaction terms of NT-proBNP and early menopause were not significant for incident HF (Pinteraction 0.95) and incident HFpEF (Pinteraction 0.17) but were significant for incident HFrEF (Pinteraction 0.03). The adjusted hazard ratios resulting from each doubling of NT-proBNP levels amongst women with and without early menopause were 1.33 (1.20-1.47) and 1.34 (1.24-1.44), respectively, for incident HF; 1.57 (1.34-1.86) and 1.38 (1.24-1.54), respectively, for incident HFpEF; and 1.68 (1.42-1.99) and 1.36 (1.22-1.52), respectively, for incident HFrEF.

Conclusions: The association of NT-proBNP with incident HFpEF is similar irrespective of early menopause status. However, the association of NT-proBNP with incident HFrEF is greater among women with early menopause when compared to those without early menopause.