Pregnancy Complication History and CVD Risk Prediction

Study Questions:

Does history of pregnancy complications (pre-eclampsia, gestational hypertension, preterm delivery, small for gestational age [SGA]) improve risk prediction for cardiovascular disease (CVD)?

Methods:

This Norwegian population-based, prospective cohort study used data from the HUNT Study, Medical Birth Registry, hospital records, and Norwegian Cause of Death Registry. Ten-year risk of CVD (myocardial infarction, fatal coronary disease, stroke) was predicted using the NORRISK 2 model based on age, systolic blood pressure, total and high-density lipoprotein cholesterol, smoking, antihypertensives, and family history of myocardial infarction. Pregnancy complications were added to the risk-prediction model to determine if this improved model fit, calibration, discrimination, and reclassification.

Results:

Of 18,231 women who were parous, age 40 or older, and without CVD at the start of follow-up, 39% had pregnancy complications and 5% had CVD events during median follow-up of 8.2 years. Unadjusted models showed that pre-eclampsia and SGA were associated with CVD (hazard ratio [HR], 1.96; 95% confidence interval [CI], 1.44–2.65 and HR, 1.46; 95% CI, 1.18–1.81, respectively) but only pre-eclampsia remained significant after adjustment for established risk factors (HR, 1.60; 95% CI, 1.16–2.17). The addition of pregnancy complications to the NORRISK 2 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).

Conclusions:

After controlling for established risk factors, pre-eclampsia independently predicted CVD, but the addition of several pregnancy-related complications (pre-eclampsia, gestational hypertension, preterm delivery, and SGA) made only a small improvement to overall CVD risk prediction.

Perspective:

Several prior studies have demonstrated the association between pregnancy-related complications (pre-eclampsia, gestational hypertension, preterm delivery, and SGA) and subsequent risk of CVD, even when adjusted for other CVD risk factors. This study reported only a small incremental change in risk prediction when these factors were added to the NORRISK 2 risk prediction model. Approximately 2% of women with CVD events were reclassified into higher risk categories when the obstetric risk factors were added; although the magnitude is small, future studies might show that different populations or subgroups could have higher reclassification rates, such as younger women, cohorts with higher CVD rates, or when heart failure is included as a CVD event. The findings from this study remind us that the traditional CVD risk factors are powerful predictors, but the results should not negate the importance of taking an obstetric history, especially since pre-eclampsia remained a significant predictor. Although this study did not show a substantial change in the overall 10-year risk prediction model, identification of obstetric-related complications remains important for counseling individual patients.

Keywords: Antihypertensive Agents, Blood Pressure, Cardiovascular Diseases, Cholesterol, HDL, Coronary Disease, Heart Failure, Hypertension, Pregnancy-Induced, Infant, Small for Gestational Age, Myocardial Infarction, Pre-Eclampsia, Pregnancy, Primary Prevention, Risk Factors, Smoking, Stroke, Vascular Diseases, Women


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