Reproductive Risk Factors and Coronary Heart Disease

Study Questions:

Are reproductive factors associated with coronary heart disease (CHD) in women?


Data from the Women’s Health Initiative Observational Study were used for the present analysis. Multivariate models included age, pregnancy status, number of live births, age at menarche, menstrual irregularity, age at first birth, stillbirths, miscarriages, and infertility ≥1 year, as well as traditional CHD risk factors. Each candidate reproductive factor was examined by adding the variable to an established CHD risk factor model. A final model was created with the significant reproductive factors and the established CHD risk factors. Improvement in C-statistic, net reclassification index (NRI) (or NRI with risk categories of <5%, 5-<10%, and ≥10% 10-year CHD risk), and integrated discriminatory index were assessed.


Among 72,982 women with a median follow-up of 12 years, 4,607 CHD events occurred. Mean age of the participants was 63.2 years. After adjustment for established CHD risk factors, younger age at first birth, number of still births, number of miscarriages, and lack of breastfeeding were positively associated with CHD. Reproductive factors modestly improved model discrimination, with an increase in the C-statistic from 0.726 to 0.73, p value < 0.0001. Net reclassification for women with CHD events was not improved (NRI events = 0.007, p = 0.18). Among women without events, net reclassification was marginally improved (NRI events = 0.002, p = 0.04).


The investigators concluded that key reproductive factors are associated with CHD events, independent of established CHD risk factors. Model discrimination improved modestly with the addition of reproductive factors; however, net reclassification did not improve for women who experienced CHD events.


These results support the assessment of traditional risk factors to identify women at increased risk for CHD.

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