Menopause Before 50 Could Predict Increased Cardiovascular Disease Risk

Dr. Ga Eun Nam

Entering menopause before 40 years of age could signal an increased risk of atrial fibrillation and heart failure, according to the results of a new study of more than 1.4 million women.

Using data from 1,401,175 postmenopausal women within the Korean National Health Insurance Service, investigators found women with a history of premature menopause had a 33% greater risk of heart failure and 9% greater risk of atrial fibrillation compared to those without early menopause in adjusted analyses, with further analysis indicating all patients entering menopause prior to 50 years of age had an increased risk of both conditions.

“Women with premature menopause should be aware that they may be more likely to develop heart failure or atrial fibrillation than their peers,” said study author Dr. Ga Eun Nam of Korea University College of Medicine, Seoul, Republic of Korea, in a statement from the European Society of Cardiology. “This may be good motivation to improve lifestyle habits known to be linked with heart disease, such as quitting smoking and exercising.”

To further the existing knowledge base related to early menopause and cardiovascular risk, Eun Nam and a team of colleagues designed the current study with the aim of estimating the associations of premature menopause and age at menopause with risk of heart failure and atrial fibrillation using data from the Korean National Health Insurance Service and multivariable Cox proportional hazard models. From the Korean National Health Insurance Service, investigators identified 1,401,175 postmenopausal women with had undergone health examinations and had full data related to their reproductive histories collected.

Of the 1,401,175 women included in the study, 2% (n=28,111) had a history of premature menopause. The mean age at menopause for those without premature menopause was 50.2±3.7 years compared to 36.7±2.2 years among those with a history of premature menopause. Compared to their counterparts without premature menopause, those with premature menopause were more likely to report having been an ever-smoker (6.0% vs 3.8%; P <.001) and use alcohol (14.8% vs 12.5%; P <.001) and less likely to report regular exercise (15.3% vs 18.5%; P <.001).

The overall study cohort had a mean follow-up duration of 9.1 years. During this time, 42,699 new cases of heart failure and 44,834 new cases of atrial fibrillation were identified using ICD codes. In multivariable analyses, results indicated women with history of premature menopause had an increased risk of both heart failure (HR, 1.33, [95% CI, 1.26-1.40]; P <.001) and atrial fibrillation (HR, 1.09 [95% CI, 1.02-1.16]; P=.008) compared to women without history of premature menopause.

Additional analyses according to age shed further light on the associations between premature menopause and increased risk of both conditions. For heart failure, further analysis indicated those aged 45-49, 40-44, and less than 40 years at menopause had increases in risk for incident heart failure of 11% (HR, 1.11 [95% CI, 1.08-1.13]), 23% (1.23, 1.19−1.28), and 39% (1.39, 1.31−1.47) incident HF, respectively, compared to those who entered menopause at 50 years or later (P <.001). For atrial fibrillation, those aged 45-49, 40-44, and less than 40 years at menopause had increases in risk for incident atrial fibrillation of a 4% (HR, 1.04 [95% CI, 1.02-1.06), 10% (HR, 1.10 [95% CI, 1.06-1.14]), and 11% (HR, 1.11 [95% CI, 1.04-1.18]), respectively, compared to those who entered menopause at 50 years or later (P <.001).

“The misconception that heart disease primarily affects men has meant that sex-specific risk factors have been largely ignored. Evidence is accumulating that undergoing menopause before the age of 40 may increase the likelihood of heart disease later in life. Our study indicates that reproductive history should be routinely considered in addition to traditional risk factors such as smoking when evaluating the future likelihood of heart failure and atrial fibrillation.”

This study, “Age at menopause and risk of heart failure and atrial fibrillation: a nationwide cohort study,” was published in the European Heart Journal.