Long-Term Cardiovascular Risk in Women With Hypertension During Pregnancy

Abstract

Background: History of a hypertensive disorder of pregnancy (HDP) among women may be useful to refine atherosclerotic cardiovascular disease risk assessments. However, future risk of diverse cardiovascular conditions in asymptomatic middle-aged women with prior HDP remains unknown.

Objectives: The purpose of this study was to examine the long-term incidence of diverse cardiovascular conditions among middle-aged women with and without prior HDP.

Methods: Women in the prospective, observational UK Biobank age 40 to 69 years who reported ≥1 live birth were included. Noninvasive arterial stiffness measurement was performed in a subset of women. Cox models were fitted to associate HDP with incident cardiovascular diseases. Causal mediation analyses estimated the contribution of conventional risk factors to observed associations.

Results: Of 220,024 women included, 2,808 (1.3%) had prior HDP. The mean age at baseline was 57.4 ± 7.8 years, and women were followed for median 7 years (interquartile range: 6.3 to 7.7 years). Women with HDP had elevated arterial stiffness indexes and greater prevalence of chronic hypertension compared with women without HDP. Overall, 7.0 versus 5.3 age-adjusted incident cardiovascular conditions occurred per 1,000 women-years for women with versus without prior HDP, respectively (p = 0.001). In analysis of time-to-first incident cardiovascular diagnosis, prior HDP was associated with a hazard ratio (HR) of 1.3 (95% CI: 1.04 to 1.60; p = 0.02). HDP was associated with greater incidence of CAD (HR: 1.8; 95% CI: 1.3 to 2.6; p < 0.001), heart failure (HR: 1.7; 95% CI: 1.04 to 2.60; p = 0.03), aortic stenosis (HR: 2.9; 95% CI: 1.5 to 5.4; p < 0.001), and mitral regurgitation (HR: 5.0; 95% CI: 1.5 to 17.1; p = 0.01). In causal mediation analyses, chronic hypertension explained 64% of HDP's association with CAD and 49% of HDP's association with heart failure.

Conclusions: Hypertensive disorders of pregnancy are associated with accelerated cardiovascular aging and more diverse cardiovascular conditions than previously appreciated, including valvular heart disease. Cardiovascular risk after HDP is largely but incompletely mediated by development of chronic hypertension.

Keywords: cardio-obstetrics; cardiovascular epidemiology; hypertension in pregnancy; preeclampsia; pregnancy; women’s health.

Figure 1.. Prevalence of chronic hypertension stratified by age at study enrollment among women with and without prior hypertensive disorders of pregnancy.

Women with prior HDP had increased prevalence of chronic hypertension across age groups. HDP = hypertensive disorder or pregnancy.

Figure 2.. Age-specific unadjusted rates of incident cardiovascular diagnoses per 1,000 woman-years of follow-up in women with and without prior hypertensive disorders of pregnancy.

Women with prior HDP had increased incidence of cardiovascular diagnoses into their 60s. Incident cardiovascular disease diagnoses included coronary artery disease, heart failure, aortic stenosis, mitral regurgitation, atrial fibrillation or flutter, ischemic stroke, peripheral artery disease, and venous thromboembolism. HDP = hypertensive disorder of pregnancy.

Figure 3.. Hazard ratios for incident cardiovascular diagnoses in women with prior hypertensive disorders of pregnancy.

Women with prior hypertensive pregnancy had increased hazards of coronary artery disease, heart failure, aortic stenosis, and mitral regurgitation. Cox proportional hazards models begin follow-up at study enrollment and are adjusted for age at enrollment and race. X-axis is presented in log scale. HR = hazard ratio. CI = confidence interval.

Central Illustration.. Hypertensive disorders of pregnancy are associated with long-term risk of chronic hypertension and diverse cardiovascular diseases.

Women with a history of hypertensive disorders of pregnancy had greater prevalence of hypertension and elevated arterial stiffness indices compared to women without prior hypertensive pregnancy. Hypertensive pregnancy was associated with long-term risk of incident coronary artery disease, heart failure, aortic stenosis, and mitral regurgitation. HDP = hypertensive disorder of pregnancy. ASI = arterial stiffness index. HR = hazard ratio. The cumulative incidence plots on the right reflect incident cardiovascular disease diagnoses plotted against the age at the time of diagnosis on the x-axis. The hazard ratios displayed reflect results of the primary survival (Cox proportional hazards) analysis, which were adjusted for age at study enrollment and race.