Association of Age at Menopause With Incident Heart Failure: A Prospective Cohort Study and Meta‐Analysis

<jats:sec xml:lang="en"> <jats:title>Background</jats:title> <jats:p xml:lang="en"> Early age (<45 years) at menopause has been postulated to be associated with increased cardiovascular disease risk; however, evidence of its relation with heart failure ( <jats:styled-content style="fixed-case">HF</jats:styled-content> ) incidence is limited. We examined whether age at menopause is associated inversely with <jats:styled-content style="fixed-case">HF</jats:styled-content> incidence in the Atherosclerosis Risk In Communities ( <jats:styled-content style="fixed-case">ARIC</jats:styled-content> ) study and summarized all existing data in a meta‐analysis. </jats:p> </jats:sec> <jats:sec xml:lang="en"> <jats:title>Methods and Results</jats:title> <jats:p xml:lang="en"> In <jats:styled-content style="fixed-case">ARIC</jats:styled-content> , data were obtained from 5629 postmenopausal women (mean age 56 years, 26% with bilateral oophorectomy) without <jats:styled-content style="fixed-case">HF</jats:styled-content> . During a median follow‐up of 21.4 years, 965 incident <jats:styled-content style="fixed-case">HF</jats:styled-content> events occurred. In a Cox regression model adjusted for reproductive health and <jats:styled-content style="fixed-case">HF</jats:styled-content> risk factors, the hazard ratios for incident <jats:styled-content style="fixed-case">HF</jats:styled-content> across categories of age at menopause (<45, 45–49, 50–54, and ≥55 years) were 1.32, 1.17, 1.00 (referent), and 1.12, respectively. Compared with women with later onset of menopause (aged ≥45 years), those with early menopause had elevated <jats:styled-content style="fixed-case">HF</jats:styled-content> risk (hazard ratio 1.20, 95% <jats:styled-content style="fixed-case">CI</jats:styled-content> 1.01–1.43). For the meta‐analysis, we searched Medline and Embase for articles published through December 2015 that prospectively evaluated age at menopause and <jats:styled-content style="fixed-case">HF</jats:styled-content> risk. Summarized estimates from the 3 included studies (3568 events) showed higher <jats:styled-content style="fixed-case">HF</jats:styled-content> risk among women with early menopause compared with those with later menopause (hazard ratio 1.33, 95% <jats:styled-content style="fixed-case">CI</jats:styled-content> 1.15–1.53). </jats:p> </jats:sec> <jats:sec xml:lang="en"> <jats:title>Conclusions</jats:title> <jats:p xml:lang="en"> These results provided evidence that early age at menopause is associated with a modestly greater risk of <jats:styled-content style="fixed-case">HF</jats:styled-content> . Identification of women with early menopause offers a window of opportunity to implement interventions that will improve overall cardiovascular health during the postmenopausal years. </jats:p> </jats:sec>