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Relationship between age at natural menopause and risk of heart failure

Rahman, Iffat PhD; Åkesson, Agneta PhD; Wolk, Alicja DrMedSci

doi: 10.1097/GME.0000000000000261
Original Articles

Objective We investigated whether younger age at natural menopause confers a risk of heart failure. We also examined a possible modifying effect of tobacco smoking.

Methods This study used the population-based Swedish Mammography Cohort; 22,256 postmenopausal women with information on age at natural menopause were followed from 1997 through 2011. First event of heart failure was ascertained through the Swedish National Patient Register and the Cause of Death Register. Cox proportional hazards regression analyses were conducted to estimate multivariable-adjusted hazard ratios (HRs) and 95% CIs.

Results During a mean follow-up of 13 years, we ascertained 2,532 first events of heart failure hospitalizations and deaths. The mean age at menopause was 51 years. Early natural menopause (40-45 y), compared with menopause at ages 50 to 54 years, was significantly associated with heart failure (HR, 1.40; 95% CI, 1.19 to 1.64). In analyses stratified by smoking status, similar HRs were observed for this age group among never smokers (HR, 1.33; 95% CI, 1.06 to 1.66) and ever smokers (HR, 1.39; 95% CI, 1.09 to 1.78). Among ever smokers, increased incidence (HR, 1.25; 95% CI, 1.06 to 1.47) of heart failure could be detected even among those who entered menopause at ages 46 to 49 years. We found a significant interaction between age at natural menopause and smoking (P = 0.019).

Conclusions This study indicates that women who experience early natural menopause are at increased risk for developing heart failure and that smoking can modify the association by increasing the risk even among women who enter menopause around ages 46 to 49 years.

From the Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

Received February 7, 2014; revised and accepted March 20, 2014.

Funding/support: This work was supported by the Swedish Research Council Committee for Medicine and the Swedish Research Council Committee for Infrastructure.

Financial disclosure/conflicts of interest: None reported.

Address correspondence to: Iffat Rahman, PhD, Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, Stockholm 17177, Sweden. E-mail:

© 2015 by The North American Menopause Society.