Clinical Investigation
Electrophysiology
Age of natural menopause and atrial fibrillation: The Framingham Heart Study

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Background

Early menopausal age is associated with risk of cardiovascular events including myocardial infraction, stroke, and increased mortality. Relations between menopausal age and atrial fibrillation (AF) have not been investigated. We examined the association between menopausal age and AF.

Methods

Framingham Heart Study women ≥60 years old without prevalent AF and natural menopause were followed up for 10 years or until incident AF. Menopausal age was modeled as a continuous variable and by categories (<45, 45-53, and >53 years). We used Cox proportional hazards regression to determine associations between menopausal age and AF risk.

Results

In 1,809 Framingham women (2,662 person-examinations, mean baseline age 71.4 ± 7.6 years, menopausal age 49.8 ± 3.6 years), there were 273 unique participants with incident AF. We did not identify a significant association between the SD of menopausal age (3.6 years) and AF (hazard ratio [HR] per SD 0.94, 95% CI 0.83-1.06; P = .29). In a multivariable model with established risk factors for AF, menopausal age was not associated with incident AF (HR per SD 0.97, 95% CI 0.86-1.09; P = .60). Examining categorical menopausal age, earlier menopausal age (<45 years) was not significantly associated with increased AF risk compared with older menopausal age >53 years (HR 1.20, 95% CI 0.74-1.94; P = .52) or menopausal age 45 to 53 years (HR 1.38, 95% CI 0.93-2.04; P = .11).

Conclusion

In our moderate-sized, community-based sample, we did not identify menopausal age as significantly increasing AF risk. However, future larger studies will need to examine whether there is a small effect of menopausal age on AF risk.

Section snippets

Study sample

The Framingham Heart Study is a longitudinal, community-based study designed to investigate cardiovascular disease and its risk factors.9 Original cohort participants were enrolled in the Framingham Heart Study starting in 1948 and attend examinations every 2 years. Offspring cohort participation started in 1971 and consists of examinations every 4 to 8 years. To have 10-year follow-up, the present study used data from women attending the original cohort examination cycles 11 (1968-1971), 17

Results

The study cohort consisted of 1,809 unique Framingham Heart Study participants with 2,662 examinations. The mean age was 71.4 ± 7.6 years, and the mean age at natural menopause was 49.8 ± 3.6 years (Table I). There were 273 incident AF events in follow-up. The unadjusted incidence rates per 1000 person-years were 15.8 in the menopausal age <45 years category, compared with 11.5 and 13.3 in the menopausal age 45 to 53 and >53 years categories (P = .24 between different age categories) (Table II).

Discussion

We hypothesized an association between menopausal age and 10-year risk of incident AF in a prospective, community-based cohort and, specifically, that decreased age of menopause would result in increased incident AF risk. Our hypothesis stemmed from the established association between earlier menopausal age and augmented risk for cardiovascular events.

A second rationale was the cardiovascular adaptation and remodeling by complex vascular and endocrinologic pathways resulting from menopause.17

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  • Cited by (0)

    Dr. Magnani is supported by American Heart Association Award 09FTF219028. This work was supported by grants from the NIH to Drs. Benjamin and Ellinor (HL092577), Dr. Benjamin (RO1AG028321, RC1-HL01056, 1R01HL102214) and Dr. Ellinor (5R21DA027021, 1RO1HL104156, 1K24HL105780) and 6R01-NS17950, N01-HC25195. This work was partially supported by the Evans Center for Interdisciplinary Biomedical Research ARC on “Atrial Fibrillation at Boston University (http://www.bumc.bu.edu/evanscenteribr/).

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