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Clinical Factors and Biomarkers During Pregnancy and Risk of Cardiovascular Disease
Lucas Bacmeister1,2, Dorte Glintborg3,4, Jens-Jakob Kjer-Møller4
1University Heart Center Freiburg - Bad Krozingen, Clinic for Cardiology and Angiology, Medical Center, University of Freiburg, Freiburg, Germany.
Insights
Pregnancy biomarkers like hs-cTnI and sFlt-1, along with maternal age and hypertensive disorders of pregnancy, can identify women at higher risk for long-term cardiovascular disease (CVD). This highlights pregnancy as a key time for CVD risk assessment in women.
Area of Science:
- Reproductive Medicine and Cardiology
- Women's Health and Cardiovascular Risk Assessment
Background:
- Cardiovascular disease (CVD) is a leading global cause of death in women.
- Pregnancy offers a unique opportunity to assess a woman's cardiovascular health.
- Current methods often fail to leverage pregnancy insights for long-term CVD risk prediction.
Purpose of the Study:
- To investigate if clinical measures and biomarkers from pregnancy can predict long-term CVD risk in women.
- To identify specific pregnancy markers associated with future cardiovascular events.
Main Methods:
- Population-based cohort study in Southern Denmark involving over 38,000 pregnancies.
- Analysis of a nested subcohort (n=2056) with available pregnancy biomarkers (sFlt-1, hs-cTnI) at weeks 12 or 29.
- Long-term follow-up (median 11.9 years) to assess incident maternal CVD using Cox proportional hazards models.
Main Results:
- Maternal age, hypertensive disorders of pregnancy (HDPs), and third-trimester hs-cTnI and sFlt-1 levels were independently associated with increased long-term CVD risk.
- A model combining maternal age and week 29 sFlt-1 improved CVD prediction compared to age alone (ΔAUC, 0.16).
- Clinical models including blood pressure and cholesterol did not enhance CVD prediction as effectively as pregnancy biomarkers.
Conclusions:
- Pregnancy serves as a critical window for sex-specific cardiovascular risk assessment.
- Specific biomarkers measured during pregnancy can significantly enhance long-term CVD risk prediction in women.
- Findings support integrating pregnancy data into lifelong cardiovascular health strategies.
Importance:
Cardiovascular disease (CVD) is the leading cause of death among women worldwide. Pregnancy serves as a natural cardiovascular stress test and universal clinical encounter, yet few approaches leverage its insights to inform long-term cardiovascular risk.
Objective:
To determine whether clinical measures and biomarkers obtained during pregnancy may identify women at risk of long-term CVD.
Design, Setting, And Participants:
This was a registry-linked, population-based cohort study of all pregnancies reaching at least 22 weeks between June 2010 and October 2013 in Southern Denmark. Primary analyses were performed in a nested prospective subcohort of Odense Child Cohort participants with available pregnancy biomarker data. Women with preexisting CVD were excluded (n = 114). Follow-up was done through December 31, 2023. Among 38 455 eligible women, 2056 had biomarker data at week 12 or week 29. Analytic subsets with complete data were used for prognostic modeling at week 12 (n = 1379) and week 29 (n = 1389).
Exposures:
Clinical characteristics, obstetric outcomes, and pregnancy biomarkers including 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.
Main Outcomes And Measures:
Incident maternal CVD, evaluated using Cox proportional hazards models.
Results:
In the biomarker cohort (median [IQR] age, 30.4 [27.4-33.8] years), 28 women (1.4%) developed CVD during a median (IQR) follow-up of 11.9 (11.2-12.5) years. Maternal age, hypertensive disorders of pregnancy (HDPs), and third-trimester concentrations of hs-cTnI and sFlt-1 were each independently associated with higher long-term CVD risk. A combined model including age and sFlt-1 measured at week 29 improved discrimination for CVD compared with a base model of age alone (ΔAUC, 0.16; 95% CI, 0.02-0.30), whereas a clinical model consisting of age, systolic blood pressure, and non-high-density lipoprotein cholesterol did not. Results were consistent in women without prior hypertension or HDPs and in nulliparous women. CVD incidence and the predictive value of the base model were comparable between the biomarker and the contemporaneous background cohorts (n = 36 274).
Conclusions And Relevance:
These findings support pregnancy as an opportunistic window for sex-specific cardiovascular risk assessment and prevention throughout a woman's life course. Further studies are warranted to validate these findings.
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