Cardiovascular disease (CVD) remains the leading cause of death among women globally, and pregnancy represents a universal cardiovascular stress test. This registry-linked, population-based cohort study, published in JAMA Cardiology, examined pregnancies at ≥22 weeks’ gestation between June 2010 and October 2013 in Southern Denmark.

Women with preexisting CVD were excluded (n = 114). Of 38,455 eligible women, 2,056 had biomarker data available at gestational week 12 or 29 within the Odense Child Cohort. Prognostic modeling was conducted in analytic subsets with complete data at week 12 (n = 1,379) and week 29 (n = 1,389). Follow-up extended through December 31, 2023.

Pregnancy biomarkers assessed included soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor, high-sensitivity cardiac troponin I (hs-cTnI), and N-terminal pro-B-type natriuretic peptide. In the biomarker cohort (median age 30.4 years), 28 women (1.4%) developed incident CVD during a median follow-up of 11.9 years. Maternal age, hypertensive disorders of pregnancy, and third-trimester hs-cTnI and sFlt-1 concentrations were independently associated with higher long-term CVD risk. 

A combined model including age and sFlt-1 at week 29 improved discrimination compared with age alone (ΔAUC 0.16; 95% CI, 0.02-0.30), whereas a clinical model incorporating age, systolic blood pressure, and non-high-density lipoprotein (non-HDL) cholesterol did not. Findings were consistent in women without prior hypertension or hypertensive disorders and in nulliparous women. The overall CVD event rate and the performance of the age-based model were similar in the biomarker subgroup and in the contemporaneous background cohort (n = 36,274).

These data support pregnancy as an opportunity for sex-specific cardiovascular risk assessment. Further studies are warranted to validate these findings.