Hypertensive Disorders of Pregnancy and 10-Year Cardiovascular Risk Prediction
Key result
Adding pregnancy complications and parity fails to improve cardiovascular risk discrimination in low-risk women.
- Difference in C-index +0.002
- P=0.31
- n=67,406
Why the study?
Does adding history of hypertensive disorders of pregnancy and parity to an established CVD risk score improve prediction of 10-year CVD events in women?
Key Points
- To determine whether adding hypertensive disorders of pregnancy and parity to an established cardiovascular disease risk score improves 10-year risk prediction in women.
- Analyzed 106,230 ≤10-year observations contributed by 67,406 women aged ≥40 without prior CVD in the Nurses' Health Study II, followed from 1989 to 2013 for incident myocardial infarction, fatal coronary heart disease, or stroke.
- Fitted an established risk model with age, total and HDL cholesterol, systolic blood pressure, antihypertensive medication use, smoking, and diabetes (Model A) and compared it to Model A plus HDP and parity (Model B) using Cox proportional hazards models.
- Across follow-up, 685 first CVD events occurred; women with a history of HDP and two births had elevated 10-year CVD risk compared to normotensive women with two births (HR: 2.02, 95% CI: 1.50, 2.72).
- Inclusion of HDP and parity did not improve model discrimination (Model A C-index=0.691 vs. Model B C-index=0.693; p=0.31 for difference).
- Model B did not significantly improve risk reclassification compared to Model A (net reclassification improvement: 0.4%, 95% CI: -0.2, 1.0%, p=0.26).
Study Design
Type
Cohort (n=67,406)
Structured PICO
Does adding history of hypertensive disorders of pregnancy and parity to an established CVD risk score improve prediction of 10-year CVD events in women?
P
Population
67,406 women aged 40 and older, free of prior cardiovascular disease, followed to assess the utility of adding pregnancy history to 10-year CVD risk prediction.
E
Exposure
Addition of history of hypertensive disorders of pregnancy (HDP) and parity to an established CVD risk prediction model
C
Comparator
Established CVD risk prediction model (Pooled Cohort Equations variables: age, total and HDL cholesterol, systolic blood pressure, anti-hypertensive medication use, current smoking, diabetes)
O
Outcome
Improvement in 10-year CVD risk prediction (discrimination via C-index and reclassification via net reclassification improvement)
Main Result
Effect estimate: Difference in C-index 0.002
Absolute Event Rate: 0.693% vs 0.691%
p-value: p=0.31
Limitations
- Reliance on self-reported systolic blood pressure
- Use of predicted rather than measured total and HDL cholesterol levels
- Self-reported pregnancy history subject to recall bias
- Potential survivor bias due to requirement of survival to 2009
- Primarily white population limiting generalizability
- Reliance on self-reported SBP
- Predicted rather than measured cholesterol
- Self-reported pregnancy history
- Potential survivor bias
- Primarily white nurses limiting generalizability
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Such null results might lead clinicians to abandon APO history in evaluating individual patients' CVD risk. This, however, would overlook differences between population and individual risk prediction and timing of risk prediction. To improve population risk prediction, an exposure must (1) be strongly associated with the outcome, (2) predict the outcome independent of other risk factors in the model, and (3) be prevalent enough to shift population risk. Preeclampsia, for example, presages a doubling of CVD risk that is often diminished (though not always eliminated) when chronic hypertension is included in the model. Even where it retains a clinically significant hazard ratio independent of other risk factors, preeclampsia history may not contribute meaningfully to population risk prediction because relatively few women have a history of preeclampsia (eg, far fewer than have high cholesterol). However, to predict individual risk, a factor needs only to be associated with the outcome independent of other factors that the patient already has.”
Implication
Adding hypertensive disorders of pregnancy to standard risk calculators does not improve 10-year CVD risk prediction in low-risk women, likely because its risk is mediated by traditional factors already in the model.
Abstract
Background: Hypertensive disorders of pregnancy (HDP) affect 10–15% of women and are associated with a two-fold increased risk of cardiovascular disease (CVD). Objective: To determine whether including 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, free of prior CVD, with data available on model covariates in the Nurses’ Health Study II. Participants were followed for confirmed myocardial infarction, fatal coronary heart disease, or stroke from 1989–2013. We fit an established CVD risk prediction model (Model A: age, total and HDL cholesterol, systolic blood pressure, anti-hypertensive medication use, current smoking, diabetes) 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 40–49. However, inclusion of HDP and parity in the risk prediction model did not improve discrimination (Model A: C-index=0.691; Model B: Cindex=0.693; p-value for difference=0.31) or risk reclassification (net reclassification improvement=0.4%, 95% CI: -0.2, 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 may be due to known associations between HDP and established CVD risk factors in the reference model.
Discussion
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Cite This Study
Stuart et al. (2018) conducted a cohort in Free of prior CVD (n=67,406). Hypertensive disorders of pregnancy (HDP) and parity vs. Established CVD risk prediction model (Model A) was evaluated on 10-year CVD risk discrimination (C-index) (Difference in C-index 0.002, p=0.31). The addition of hypertensive disorders of pregnancy and parity to an established cardiovascular risk score did not significantly improve risk discrimination or reclassification in a low-risk population of women.