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Long-Term CV Risk After Hypertensive Pregnancy
Study Questions:
What is the long-term incidence of cardiovascular disease (CVD) among middle-aged women with a prior history of hypertensive disorders of pregnancy (HDP)?
Methods:
The prospective, observational UK Biobank was used to analyze data from women aged 40-69 years with ≥1 live birth. Women with self-reported history of HDP (including gestational hypertension, pre-eclampsia, eclampsia, and HELP syndrome [hemolysis, elevated liver enzymes, low platelets]) were compared to those without HDP. A subset also had noninvasive arterial stiffness measurement. The primary outcome was a composite of incident CV conditions including coronary artery disease (CAD), heart failure, aortic stenosis, mitral regurgitation, atrial fibrillation or flutter, ischemic stroke, peripheral artery disease, and venous thromboembolism.
Results:
Of 220,024 women, prior HDP was present in 2,808 (1.3%) women with mean (± standard deviation) age of 57.4 ± 7.8 years and median follow-up of 7 years. Arterial stiffness indices were measured in 81,557 women. HDP were associated with significantly higher arterial stiffness indices after adjustment for age, menopausal status, diabetes, smoking, and body mass index; however, the association was not significant among postmenopausal women, or when adjusted for chronic hypertension. Age-adjusted incident CV conditions occurred in 7.0 versus 5.3 per 1,000 women-years among women with versus without HDP, respectively (p = 0.001). In time-to-first CV diagnosis, HDP were associated with a hazard ratio (HR) of 1.3 (95% confidence interval [CI], 1.04-1.6; p = 0.02). Women with prior HDP had a higher risk of CAD (HR, 1.8; 95% CI, 1.3-2.6; p < 0.001), heart failure (HR, 1.7; 95% CI, 1.04-2.6; p = 0.03), aortic stenosis (HR, 2.9; 95% CI, 1.5-5.4; p < 0.001), and mitral regurgitation (HR, 5.0; 95% CI, 1.5-17.1; p = 0.01). Causal mediation analyses revealed that chronic hypertension explained 64% of the association between HDP and CAD, and 49% of the association between HDP and heart failure.
Conclusions:
HDP are associated with increased risk of diverse CV conditions, including valvular disease. The development of chronic hypertension explains some, but not all, of this associated risk.
Perspective:
Adverse pregnancy outcomes, including HDP, are recognized as risk factors for future CVD in women. This large study of women aged 40-69 demonstrated that HDP are associated with elevated measures of arterial stiffness and increased CV risk that persists for many years after the pregnancy. Novel findings include the association between HDP and valve disease (aortic stenosis and mitral regurgitation). The overall risk of valvular disease is low, but suggests a process of accelerated aging. Also important is that the development of chronic hypertension accounted for one-half to two-thirds of the increased CV risk. This likely explains why population-based risk scores that include hypertension have not been substantially improved with the addition of HDP, particularly in older populations. However, HDP should continue to be considered risk enhancers. Individual attention to young women with HDP, prior to the development of chronic hypertension, could be essential for long-term prevention of CVD. Diagnosis and management of hypertension remains an important therapeutic target. The results of this study underscore the importance of taking an obstetric history when assessing patients’ CV risk.
Keywords: AHA19, AHA Annual Scientific Sessions, Aortic Valve Stenosis, Atrial Fibrillation, Brain Ischemia, Coronary Artery Disease, Diabetes Mellitus, Eclampsia, Heart Failure, Heart Valve Diseases, Hemolysis, Hypertension, Pregnancy-Induced, Mitral Valve Insufficiency, Peripheral Arterial Disease, Postmenopause, Pre-Eclampsia, Pregnancy, Primary Prevention, Risk Factors, Smoking, Stroke, Vascular Stiffness, Venous Thromboembolism, Women
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