Heart failure biomarker linked to greater HFrEF risk for women with early menopause
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Risk for heart failure with reduced ejection fraction due to elevated N-terminal pro-B-type natriuretic peptide levels is higher for women with early menopause compared with those without early menopause, according to study data.
Among postmenopausal women participating in the Atherosclerosis Risk in Communities (ARIC) study, the association between elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) level and heart failure with reduced ejection fraction (HFrEF) was greater for women with early menopause compared with those without early menopause, but a significant interaction between the HF biomarker and early menopause was not similarly observed for incident HF with preserved ejection fraction (HFpEF).
“Our results were contrary to our study hypothesis, because we had proposed that NT-proBNP elevation would be associated with a greater risk of incident HF (both preserved and reduced subtypes) in women with early menopause when compared to those without early menopause,” Imo A. Ebong, MD, MS, associate professor in the division of cardiology at the University of California, Davis, told Healio. “However, in analysis that categorized women according to HF subtypes, this assumption was only true for incident HFrEF and did not apply to incident HFpEF.”
Ebong and colleagues analyzed data from 4,352 postmenopausal women who participated in the ARIC study using baseline data collected during the fourth follow-up visit conducted from 1996 to 1998. The cohort included 3,541 women who had natural menopause and 811 who had surgical menopause. Data on demographics, anthropometrics, lifestyle, medical history, cardiovascular risk factors and medications were collected at the visit. Menopause age was self-reported. Sandwich immunoassay was used to measure NT-proBNP levels. Hospital records were analyzed to obtain HF-related hospitalization information. HF events occurring since 2005 were classified by an expert panel as HFpEF or HFrEF.
The findings were published in Menopause.
Of the cohort, 1,174 women reported early menopause. There were 881 HF events over a mean follow-up of 16.5 years. The HF incidence rate was 15.6 per 1,000 person-years for women with early menopause and 11.1 per 1,000 person-years for those without early menopause. Incidence rates for HFpEF and HFrEF were highest among women with early menopause and a NT-proBNP level greater than 600 pg/mL.
The interaction between NT-proBNP and early menopause was not significant for incident HF or incident HFpEF, but there was a significant interaction for incident HFrEF (P = .03). Women with early menopause had a greater risk for HFrEF with each doubling of NT-proBNP levels (HR = 1.68; 95% CI, 1.42-1.99) compared with those without early menopause (HR = 1.36; 95% CI, 1.22-1.52). The risk for HFrEF was greater in women with early menopause compared with those without early menopause at all NT-proBNP levels above 128 pg/mL.
No significant interactions between NT-proBNP and early menopause for incident HF were observed in women with either natural menopause or surgical menopause. The three-way interaction between NT-proBNP, early menopause and type of menopause for incident HF was also not significant.
“Based on our findings, we recommend that the presence of NT-proBNP elevation should trigger aggressive CVD risk factor modification and referral to a HF specialist for further evaluation and management, irrespective of early menopause status,” Ebong said.
Ebong said more studies are needed to examine the mechanisms behind the more robust association between NT-proBNP elevation and incident HFrEF in women with early menopause and to replicate the study findings in adequately powered populations.
For more information:
Imo A. Ebong, MD, MS, can be reached at iaebong@ucdavis.edu.
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