Subfertility and risk of later life maternal cardiovascular disease.

Subfertility shares common pathways with cardiovascular disease (CVD), including polycystic ovarian syndrome, obesity and thyroid disorders. Women with prior 0-1 pregnancies are at an increased risk of incident CVD when compared with women with two pregnancies. It is uncertain whether history of subfertility among women eventually giving birth is a risk factor for CVD. Among Swedish women with self-reported data on subfertility in the Swedish Medical Birth Register (n = 863 324), we used Cox proportional hazards models to relate a history of subfertility to CVD risk after adjustment for age, birth year, highest income, education, birth country, hypertension, diabetes, preterm birth, small for gestational age (SGA), smoking and for BMI in separate models. In additional analyses, we excluded women with: (i) pregnancy-related or non-pregnancy-related hypertension and/or diabetes; and (ii) preterm births and/or SGA babies. Among nulliparous women eventually having a childbirth (between 1983 and 2005, the median follow-up time 11.9; 0-23 years and 9 906 621 person-years of follow-up), there was an increased risk of CVD among women reporting ≥ 5 years of subfertility versus 0 years (hazard ratio 1.19, 95% confidence interval 1.02-1.39). There were not significantly elevated CVD risks for women with 1-2 or 3-4 years of subfertility versus 0 years. Accounting for BMI did not change results. Excluding women with hypertension and/or diabetes attenuated associations, whereas exclusion of women with preterm and/or SGA births did not change findings. CONCLUSIONS Subfertility among women eventually having a childbirth is a risk factor for CVD even upon accounting for cardiovascular risk factors and adverse pregnancy outcomes. Future studies should explore the mechanisms underlying this association.