Clinical measures and blood biomarkers collected during pregnancy could offer early insight into a woman’s long-term cardiovascular health, according to new research.

An analysis of Danish registry-linked data from pregnancies between 2010 and 2013, published in JAMA Cardiology, tracked participants for over a decade to examine associations between pregnancy biomarkers and subsequent cardiovascular outcomes.

Out of 38,455 pregnancies reaching at least 22 weeks of gestation, excluding cases with pre-existing cardiovascular disease (CVD), a nested biomarker cohort of 2,056 women from the Odense Child Cohort provided blood samples during pregnancy at around 12 weeks’ and 29 weeks’ gestation.

For predictive modelling, analytic cohorts were created from women with complete data: 1,379 women at week 12 and 1,389 women at week 29. The median maternal age was 30.4 years, and the median pre-pregnancy body mass index was 23.4 kg/m².

Several biomarkers, including soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), high-sensitivity cardiac troponin I (hs-cTnI) and N-terminal pro–B-type natriuretic peptide (NT-proBNP) were measured alongside clinical characteristics such as maternal age, blood pressure, lipid levels and hypertensive disorders of pregnancy (HDPs).

Participants were followed until 31 December 2023, with a median follow-up of 11.9 years, to identify incident cardiovascular events including stroke, coronary artery disease, atrial fibrillation and heart failure.

Pregnancy-related factors, biomarkers and CVD risk

During follow-up, 28 women (1.4%) in the biomarker cohort developed CVD and several pregnancy-related factors were associated with increased long-term cardiovascular risk.

Adverse pregnancy outcomes overall were linked to a 76% higher risk of CVD (adjusted hazard ratio [aHR] 1.76; 95% CI 1.38–2.24), while HDPs were associated with a 119% higher likelihood of developing CVD during follow-up (aHR 2.19; 95% CI 1.55–3.08).

In analyses restricted to the index pregnancy within the biomarker cohort, maternal age and HDPs also remained independently associated with later CVD. These associations were observed over a median follow-up period of 11.9 years.

Biomarker analyses indicated that measurements taken later in pregnancy were the most informative. At 29 weeks’ gestation, higher concentrations of hs-cTnI and sFlt-1 were independently associated with increased CVD risk (aHRs 1.33 and 1.50 per 1-standard deviation increase, respectively).

Other biomarkers, including NT-proBNP and PlGF, were not significantly associated with future CVD.

When evaluated in risk prediction models, maternal age alone yielded an area under the receiver operating characteristic curve (AUC) of 0.60, comparable to the background cohort.

A clinical model incorporating age, systolic blood pressure and non-high-density lipoprotein cholesterol achieved an AUC of 0.67; however, combining maternal age with third-trimester sFlt-1 levels further improved predictive performance (AUC = 0.75).

Implications of biomarker testing for CVD risk

The relatively small number of cardiovascular events limited the study’s statistical power and precluded detailed analyses of specific outcomes. The study population was also largely of Northern European origin, which may restrict generalisability to other populations.

Furthermore, although biomarkers were linked to later CVD, the study design could not establish whether they caused the disease or merely indicated a common vulnerability to both pregnancy complications and CVD.

Nevertheless, the authors concluded that pregnancy presents a valuable opportunity for early cardiovascular risk assessment.

If confirmed by further studies, biomarkers – especially sFlt-1 measured in the third trimester – could help to identify women who may benefit from earlier cardiovascular monitoring and preventive strategies throughout their lives.

Reference
Bacmeister L et al. Clinical Factors and Biomarkers During Pregnancy and Risk of Cardiovascular Disease. JAMA Cardiol 2026;Feb 18:e255595.