Higher concentrations in the third trimester of the pregnancy-specific biomarker soluble fms-like tyrosine kinase-1 (sFlt-1) and the cardiovascular-specific biomarker high-sensitivity cardiac troponin I (hs-cTnI) were both independently associated with subsequent cardiovascular disease, according to research published Feb. 18 in JAMA Cardiology, suggesting that pregnancy may be a unique and important opportunity for cardiovascular risk assessment.

In a study of Denmark’s Odense Child Cohort, a population-registry of all pregnancies reaching at least 22 weeks in southern Denmark from 2010-2013, Lucas Bacmeister, MD, et al., focused on 2,056 women without preexisting cardiovascular disease who had biomarker data at either week 12 (n=1,379) or week 29 (n=1,389) of their pregnancy. Their median age was 30 years and median prepregnancy BMI was 23.4; 62% were nulliparous, and 16% had adverse pregnancy outcomes, including fetal growth restriction, preterm delivery and stillbirth.

Results found that 28 women (1.4%) had developed cardiovascular disease over a median follow-up of 11.9 years. Maternal age, hypertensive disorders of pregnancy (HDPs) and third-trimester concentrations of sFlt-1 and hs-cTnI were all independently associated with higher long-term risk – while earlier pregnancy biomarkers were not.

A combined model of age and sFlt-1 at week 29 improved discrimination for cardiovascular disease compared to age alone (Δ area under the curve, 0.16) whereas a combination of age, systolic blood pressure and non–HDL-C did not. These results were consistent in women without prior births, hypertension or HDPs.

“Here, we extend the relevance of third-trimester sFlt-1 levels from obstetric risk stratification to long-term [cardiovascular] risk assessment,” write the authors. “The ability of sFlt-1 to inform both short-term obstetric outcomes as well as long-term [cardiovascular disease] risk suggests that a single antepartum measurement could yield insights into 2 pivotal stages of women’s health.”

In an accompanying editorial, Sadiya S. Khan, MD, FACC, and Lynn M. Yee, MD, MPH, note the troubling rise of adverse pregnancy outcomes in the U.S. and their association with increased maternal cardiovascular risk. HDPs as a cardiovascular risk enhancer was a connection noted in both the 2019 ACC/AHA Primary Prevention Guideline and 2025 AHA/ACC/Multisociety High Blood Pressure Guideline.

“The present study is a welcome addition to the epidemiologic evidence supporting the importance of adverse pregnancy outcomes as a clinical red flag or risk enhancer to warrant improved counseling, support for transitions from obstetric to primary care, and development of payer and health systems strategies to ensure postpartum individuals receive appropriate longitudinal care after delivery,” they write. “Moreover, these findings highlight the role of pregnancy as a life stage when individuals regularly interact with clinicians and the health care system to optimize pregnancy outcomes as well as long-term cardiovascular health.”