Hypertensive Disorders of Pregnancy and 10-Year Cardiovascular Risk Prediction

Abstract

Background: Hypertensive disorders of pregnancy (HDP) affect 10% to 15% of women and are associated with a 2-fold increased risk of cardiovascular disease (CVD).

Objectives: This study sought to determine whether inclusion of HDP in an established CVD risk score improves prediction of CVD events in women.

Methods: The analysis comprised 106,230 ≤10-year observations contributed by 67,406 women, age ≥40 years, free of prior CVD, with data available on model covariates in the Nurses' Health Study II. Participants were followed up for confirmed myocardial infarction, fatal coronary heart disease, or stroke from 1989 to 2013. We fit an established CVD risk prediction model (Model A: age, total cholesterol and high-density lipoprotein cholesterol, systolic blood pressure, antihypertensive medication use, current smoking, diabetes mellitus) and compared it to the same model plus HDP and parity (Model B); Cox proportional hazards models were used to obtain predicted probabilities for 10-year CVD risk.

Results: HDP and parity were associated with 10-year CVD risk independent of established CVD risk factors, overall and at ages 40 to 49 years. However, inclusion of HDP and parity in the risk prediction model did not improve discrimination (Model A: C-index = 0.691; Model B: C-index = 0.693; p value for difference = 0.31) or risk reclassification (net reclassification improvement = 0.4%; 95% confidence interval: -0.2 to 1.0%; p = 0.26).

Conclusions: In this first test of the clinical utility of HDP and parity in CVD risk prediction, additional inclusion of HDP and parity in an established risk score did not improve discrimination or reclassification in this low-risk population; this might be because of the known associations between HDP and established CVD risk factors in the reference model.

Keywords: cardiovascular disease; cardiovascular disease risk factors; pre-eclampsia; pregnancy.

Central Illustration:. Inclusion of hypertensive disorders of pregnancy in an established 10year cardiovascular disease risk prediction model.

* The established CVD risk calculator, based on the Pooled Cohort Risk Equation for white women, was compared across multiple domains of model performance (e.g., discrimination, risk reclassification) with an expanded risk calculator that additionally included history of hypertensive disorders of pregnancy (gestational hypertension or preeclampsia).

Figure 1:. Flow diagram for Nurses’ Health Study II participants by time interval contributed to 10-year cardiovascular disease (CVD) risk prediction.

To fully utilize NHSII data in 10-year CVD risk prediction, we divided active follow-up into three independent time periods—1989–1993, 1994–2003, and 2004–2013—and allowed each woman to contribute person-time to the analysis from one or more periods. Exclusion criteria were applied sequentially at the beginning of each time period and 67,406 women contributed 106,230 observations across the three time periods. * Current smoking, systolic blood pressure, and predicted total and HDL cholesterol. ^† n=38,324 women contributed person-time to the analysis drawn from one time period, n=19,340 contributed person-time from two time periods, and n=9,742 contributed person-time from all three time periods.

Online Figure 1:

Calibration plot of observed and predicted 10-year probabilities of CVD by decline of predicted probability based on established CVD risk factors (Model A) and on established CVD risk factors plus hypertensive disorders of pregnancy and parity (Model B)