Genetic data reveal hypertensive disorders of pregnancy, CVD link

Hypertensive disorders of pregnancy were associated with higher risk for coronary artery disease and stroke, which was only partially mediated by cardiometabolic factors, according to findings from a study using mendelian randomization.

“Observational evidence suggests that women who experience hypertensive disorders of pregnancy have a twofold higher long-term risk of future cardiovascular events compared with women who have normotensive pregnancy,” Bilal Rayes, BSc, from the National Heart and Lung Institute at Imperial College London, and colleagues wrote. “In addition, recent data from the Nurses’ Health Study II cohort revealed that women with hypertensive disorders of pregnancy had a significantly higher rate of atherosclerosis in the years following pregnancy. However, causal inference cannot be drawn from such observational associations due to the potential residual impact of confounding.”

Rayes and colleagues conducted a genome-wide association study from Feb. 16 to March 4, 2022. Researchers analyzed associations between hypertensive disorders of pregnancy as a whole and its two subtypes of gestational hypertension and preeclampsia/eclampsia and CVD risk.

The primary outcomes were genetic association estimates from genome-wide association studies of 122,733 cases for coronary artery disease (CAD), 34,217 cases for ischemic stroke, 47,309 cases for heart failure and 60,620 cases for atrial fibrillation.

Genetically predicted hypertensive disorders of pregnancy were associated with a higher risk for CAD (OR = 1.24; 95% CI, 1.08-1.43; P = .002). This association remained for both gestational hypertension (OR = 1.08; 95% CI, 1-1.17; P = .04) and preeclampsia/eclampsia (OR = 1.06; 95% CI, 1.01-1.12; P = .03). Hypertensive disorders of pregnancy were also associated with higher risk for ischemic stroke (OR = 1.27; 95% CI, 1.12-1.44).

In addition, researchers found a partial attenuation of the effect of hypertensive disorders of pregnancy on CAD in the mediation analysis after adjustment for systolic blood pressure (OR = 1.24; 95% CI, 1.02-1.08; P = .02) and type 2 diabetes (OR = 1.24; 95% CI, 1.04-1.29; P = .008).

There were no associations between genetically predicted hypertensive disorders of pregnancy and heart failure (OR = 0.97; 95% CI, 0.76-1.23; P = .79) or atrial fibrillation (OR = 1.11; 95% CI, 0.65-1.88; P= .71).

“Future studies should focus on evaluating the mechanism underlying the direct association between hypertensive disorders of pregnancy and CAD,” the researchers wrote. “Efforts should also focus on increasing genetic studies of obstetric complications in pregnancy to enable comprehensive assessment of the importance of obstetric morbidity on long-term maternal outcomes.”