Pregnancy loss and risk of incident CVD within 5 years: Findings from the Women's Health Initiative

Front Cardiovasc Med. 2023 Feb 21;10:1108286. doi: 10.3389/fcvm.2023.1108286. eCollection 2023.


Background: Previous studies have demonstrated an increased risk of cardiovascular disease (CVD) in women with a history of pregnancy loss. Less is known about whether pregnancy loss is associated with age at the onset of CVD, but this is a question of interest, as a demonstrated association of pregnancy loss with early-onset CVD may provide clues to the biological basis of the association, as well as having implications for clinical care. We conducted an age-stratified analysis of pregnancy loss history and incident CVD in a large cohort of postmenopausal women aged 50-79 years old.

Methods: Associations between a history of pregnancy loss and incident CVD were examined among participants in the Women's Health Initiative Observational Study. Exposures were any history of pregnancy loss (miscarriage and/or stillbirth), recurrent (2+) loss, and a history of stillbirth. Logistic regression analyses were used to examine associations between pregnancy loss and incident CVD within 5 years of study entry in three age strata (50-59, 69-69, and 70-79). Outcomes of interest were total CVD, coronary heart disease (CHD), congestive heart failure, and stroke. To assess the risk of early onset CVD, Cox proportional hazard regression was used to examine incident CVD before the age of 60 in a subset of subjects aged 50-59 at study entry.

Results: After adjustment for cardiovascular risk factors, a history of stillbirth was associated with an elevated risk of all cardiovascular outcomes in the study cohort within 5 years of study entry. Interactions between age and pregnancy loss exposures were not significant for any cardiovascular outcome; however, age-stratified analyses demonstrated an association between a history of stillbirth and risk of incident CVD within 5 years in all age groups, with the highest point estimate seen in women aged 50-59 (OR 1.99; 95% CI, 1.16-3.43). Additionally, stillbirth was associated with incident CHD among women aged 50-59 (OR 3.12; 95% CI, 1.33-7.29) and 60-69 (OR 2.06; 95% CI, 1.24-3.43) and with incident heart failure and stroke among women aged 70-79. Among women aged 50-59 with a history of stillbirth, a non-significantly elevated hazard ratio was observed for heart failure before the age of 60 (HR 2.93, 95% CI, 0.96-6.64).

Conclusions: History of stillbirth was strongly associated with a risk of cardiovascular outcomes within 5 years of baseline in a cohort of postmenopausal women aged 50-79. History of pregnancy loss, and of stillbirth in particular, might be a clinically useful marker of cardiovascular disease risk in women.

Keywords: cardiovascular disease; epidemiology; miscarriage; pregnancy loss; stillbirth.

Grant support

The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, and HHSN268201600004C.