Does pregnancy complication history improve cardiovascular disease risk prediction? Findings from the HUNT study in Norway

Abstract

Aim To evaluate whether history of pregnancy complications [pre-eclampsia, gestational hypertension, preterm delivery, or small for gestational age (SGA)] improves risk prediction for cardiovascular disease (CVD). Methods and results This population-based, prospective cohort study linked data from the HUNT Study, Medical Birth Registry of Norway, validated hospital records, and Norwegian Cause of Death Registry. Using an established CVD risk prediction model (NORRISK 2), we predicted 10-year risk of CVD (non-fatal myocardial infarction, fatal coronary heart disease, and non-fatal or fatal stroke) based on established risk factors (age, systolic blood pressure, total and HDL-cholesterol, smoking, anti-hypertensives, and family history of myocardial infarction). We evaluated whether adding pregnancy complication history improved model fit, calibration, discrimination, and reclassification. Among 18 231 women who were parous, ≥40 years of age, and CVD-free at start of follow-up, 39% had any pregnancy complication history and 5% experienced a CVD event during a median follow-up of 8.2 years. While pre-eclampsia and SGA were associated with CVD in unadjusted models (HR 1.96, 95% CI 1.44–2.65 for pre-eclampsia and HR 1.46, 95% CI 1.18–1.81 for SGA), only pre-eclampsia remained associated with CVD after adjusting for established risk factors (HR 1.60, 95% CI 1.16–2.17). Adding pregnancy complication history to the established prediction model led to small improvements in discrimination (C-index difference 0.004, 95% CI 0.002–0.006) and reclassification (net reclassification improvement 0.02, 95% CI 0.002–0.05). Conclusion Pre-eclampsia independently predicted CVD after controlling for established risk factors; however, adding pre-eclampsia, gestational hypertension, preterm delivery, and SGA made only small improvements to CVD prediction among this representative sample of parous Norwegian women.

Association of Conventional Cardiovascular Risk Factors With Cardiovascular Disease After Hypertensive Disorders of Pregnancy

“…This linked data resource has previously been used to examine the added value of pregnancy complications in clinical CVD risk prediction. 7 See the eAppendix and eFigure in the Supplement for a description of the sample selection and an overview of the study timeline with associated data sources.…”

Cardiometabolic Risk Factors in Pregnancy and Implications for Long-Term Health: Identifying the Research Priorities for Low-Resource Settings

“…Robust data collection systems are needed for the long-term follow-up of women in LMICs to study the true prevalence and impact of high-risk conditions in pregnancy on future CMDs, and enable accurate risk stratification of high-risk women. It is unclear if existing cardiovascular risk prediction models could be improved through the addition of history of pregnancy complications (41,42). There is a need for prognostic models using sample populations reflecting the diversity of target populations, and involving both nulliparous and multiparous women to better identify women at high-risk of CMD during and after pregnancy (40).…”

“…Research associating pregnancy complications with CVD risk have, to date, been derived from linkage of large national data sets from high income countries (HIC) (41,59,60). Unlike HICs, the majority of CVD deaths in sub-Saharan Africa are due to stroke rather than ischemic heart disease (61), which may reflect differences in etiology.…”

Cardiovascular risk after hypertensive disorders of pregnancy in women with and without inheritable Thrombophilia

“…In the Netherlands, CVD are the second largest cause of death for women (2). It is widely established that there is a correlation between hypertensive disorders of pregnancy (HDP, including pregnancy-induced hypertension and preeclampsia (3)) and developing risk factors for CVD later in life, such as hypertension, metabolic syndrome, hypercholesterolemia, diabetes mellitus (DM), and body mass index (BMI) > 25 kg/m2 (4)(5)(6)(7)(8)(9)(10)(11)(12). Within the group of women who develop HDP, some women are diagnosed with inheritable thrombophilia; a group of genetic disorders including: factor V Leiden (FVL), prothrombin gene G2021A mutation, protein C deficiency, protein S deficiency, and common polymorphisms (C677 T and A1298 C) of the gene for methylenetetrahydrofolate reductase (MTHFR) (13).…”