Does hypertension during pregnancy signal CVD risk later in life?

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Research suggests that there is an association between preeclampsia and major cardiovascular disorders (CVD) in later life, but it has not been investigated at scale in a large-scale population. A recent study in Circulation aimed to investigate the association between preeclampsia, hypertensive disorders of pregnancy, and subsequent diagnosis of 12 different cardiovascular disorders. 

Using linked electronic health records, the authors were able to create a large-scale contemporaneous pregnancy cohort of approximately 1.3 million UK participants over a 20-year period (1997-2016). Women were selected from the CALIBER resource (Cardiovascular Research using Linked Bespoke Studies and Electronic Health Records), which contains verified and reproducible health phenotypes for hundreds of variables.  Because preeclampsia is a syndrome of the second half of pregnancy, non-preeclamptic pregnancies at least 20 weeks’ gestation were considered as the non-exposed group. A record of preeclampsia was identified through ICD10 codes. 

The 12 cardiovascular disorders selected as outcomes were ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, stroke not otherwise specified, myocardial infarction, stable angina, unstable angina, coronary heart disease not otherwise specified, peripheral arterial disease, abdominal aortic aneurysm, atrial fibrillation and heart failure. 

The study cohort included 1,899,150 pregnancies from 1,303,365 women. A total of 434,955 (33.37%) women had more than one pregnancy during the follow-up period. A total of 31,478 (2.42%) women had 33,344 preeclamptic pregnancies. Of those pregnancies, 25,554 (76.64%) occurred in the first pregnancy, 5,811 (17.43%) occurred in the second pregnancy, and 1,979 (5.93%) occurred in the third pregnancy or later. 

Women who had preeclampsia were more likely to be nulliparous, diabetic, hypertensive, overweight or obese, and less likely to be smokers (all P< 0.001). Pregnancies affected by preeclampsia were more likely to be delivered preterm (compared to those without) and to have a lower mean infant birthweight (both P< 2.2x10^-16).

During the study period, 18,624 incident cardiovascular disorders were observed, 65% of which had occurred in women younger than 40. While women with preeclampsia had fewer cardiovascular events than those without preeclampsia in absolute numbers (861 vs 17,1763), in relative terms, the proportion in the preeclamptic group was approximately double that in the non-preeclamptic cohort (2.77% vs 1.40%). 

Compared to women without hypertension in pregnancy, women with one or more pregnancies affected by preeclampsia had a hazard ratio of 1.9 (95% CI 1.53-2.35) for any stroke, 1.67 (95% CI 1.54-1.81) for cardiac atherosclerotic events, 1.82 (95% CI 1.34-2.46) for peripheral events, 2.13 (95% CI 1.64-2.76) for heart failure, 1.73 (95% CI 1.38-2.16) for atrial fibrillation, 2.12 (95% CI 1.49-2.99) for cardiovascular deaths, and 4.47 (95% CI 4.32-4.62) for chronic hypertension. According to preeclampsia status, the differences in cumulative incidence curves were evident within 1 year of the first index pregnancy. 

The authors believe their study illustrates that preeclampsia, preterm preeclampsia, and hypertensive disorders of pregnancy all have a similar pattern of increased risk for the 12 most common cardiovascular disorders observed in women in UK. Although more research is necessary to determine how many cardiovascular events could be avoided by implementing interventions, this study highlights the opportunity of hypertensive disorders of pregnancy as a naturally occurring screening tool to detect women at high risk of cardiovascular events.