A longitudinal study found that third-trimester levels of sFlt-1 and hs-cTnI were an independently associated with higher long-term CVD risk.
Research published in JAMA Cardiology revealed that specific blood-based biomarkers measured during pregnancy could serve as early indicators of a woman’s long-term risk for cardiovascular disease (CVD). The study found that third-trimester concentrations of soluble fms-like tyrosine kinase 1 (sFlt-1) and high-sensitivity cardiac troponin I (hs-cTnI) were each independently associated with the development of CVD across a median 12-year follow-up period.
According to the researchers, CVD remains the primary cause of death for women globally, representing approximately 30% of total mortality. While hypertensive disorders of pregnancy (HDPs) are known independent predictors of premature cardiovascular events—leading to a roughly a 2-fold increased relative risk—conventional risk scores often fail to identify high risk in younger women. Researchers hypothesized that utilizing biomarkers during the unique physiological stress of pregnancy could improve risk stratification beyond traditional clinical profiles.
The investigation utilized data from the Odense Child Cohort in the Region of Southern Denmark. The analysis included 2,056 women with a median age of 30.4 years and a median pre-pregnancy body mass index of 23.4 (21.2-26.4; calculated as weight in kilograms divided by height in meters squared). Participants were required to have at least 22 weeks of gestation between June 2010 and October 2013 and no history of CVD prior to the index pregnancy.
The study followed participants through December 31, 2023, with a median follow-up of 11.9 years. The primary endpoint was incident CVD, defined as a composite of stroke, coronary artery disease, vascular disease, atrial fibrillation, and heart failure. During the follow-up period, 28 women (1.4%) developed incident CVD. Adverse pregnancy outcomes occurred in 15.5% of the cohort, with HDPs observed in 193 (9.4%) of participants.
The researchers found that adverse pregnancy outcomes and HDPs were significantly associated with long-term CVD risk. Specifically, adverse outcomes were linked to a 76% higher risk (adjusted HR [aHR], 1.76; 95% CI, 1.38-2.24), while HDPs were associated with a 119% higher risk (aHR, 2.19; 95% CI, 1.55-3.08).
Beyond clinical history, the study highlighted the role of third-trimester biomarkers. When integrated with age, sFlt-1 improved risk stratification for future CVD. Notably, a model combining age and sFlt-1 performed better than age alone, whereas a traditional clinical model including systolic blood pressure and non-HDL cholesterol did not.
Additionally, hs-cTnI concentrations were independently associated with subsequent CVD, even though many values fell below the limit of detection. The median third-trimester concentration was 1.1 pg/mL. In contrast, NT-proBNP measured at week 29 was not significantly associated with future CVD in this population.
The ability of sFlt-1 to inform both short-term obstetric risk and long-term cardiovascular health suggests that a single measurement during the third trimester could provide insights into 2 pivotal stages of women’s health. The study suggested that pregnancy offers a unique window for initiating cardiovascular risk assessment and prevention in women who might otherwise be clinically overlooked due to their young age.
The researchers noted that these biomarkers should complement, rather than replace, postpartum surveillance measures like blood pressure monitoring.
The study authors concluded that pregnancy-derived risk indicators, including circulating biomarkers, could inform more targeted preventive strategies across a woman’s life course.
“Pending further validation, pregnancy-derived risk indicators, including circulating biomarkers and clinical profiles, could inform earlier and more targeted preventive strategies across the life course of women,” the authors wrote.
Reference:
Bacmeister L, Glintborg D, Kjer-Møller J, et al. Clinical Factors and Biomarkers During Pregnancy and Risk of Cardiovascular Disease. JAMA Cardiol. Published online February 18, 2026. doi:10.1001/jamacardio.2025.5595
