- In a large, prospective, population-based cohort of middle-aged women, those who previously had a hypertensive disorder of pregnancy (HDP) were at increased risk of a range of cardiovascular conditions later in life
- Specifically, HDP was associated with significantly greater risk of incident coronary artery disease, heart failure, aortic stenosis and mitral regurgitation
- A history of HDP was also associated with persistently increased arterial stiffness
- The relationship between HDP and long-term cardiovascular risk was largely mediated by an increased prevalence of chronic hypertension
- Blood pressure control may be especially important in these women
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Hypertensive disorders of pregnancy (HDP) are known to increase the risk of cardiovascular disease in affected women. This group of disorders comprises preterm delivery, gestational diabetes, gestational hypertension, preeclampsia, eclampsia and the HELLP syndrome (hemolysis, elevated liver enzymes and low platelet count).
It's unclear whether the elevated risk of cardiovascular disease persists to midlife and beyond because very few studies have followed women after age 60. In addition, the risk of nonatherosclerotic cardiovascular diseases in women with a history of HDP is unknown.
Michael Honigberg, MD, MPP, cardiology fellow, Pradeep Natarajan, MD, MMSc, director of the Cardiovascular Disease Prevention Center at Massachusetts General Hospital, and colleagues have found that prior HDP is associated with a range of cardiovascular conditions later in life, including valvular heart disease. In the Journal of the American College of Cardiology, they report that the increased risk is largely mediated by the development of chronic hypertension.
This is the first study of cardiovascular risk after HDP that began prospective follow-up in midlife. The researchers analyzed data from the UK Biobank, a prospective, observational, population-based cohort study that recruited >500,000 adults between 2006 and 2010. They identified 220,024 women who at the baseline study visit were age 40 to 69 (average, 57), did not have congenital heart disease and reported at least one prior live birth. Of the total cohort, 2,808 women (1.3%) had prior HDP.
The cohort was followed for a median of seven years. The primary outcome was a new diagnosis of coronary artery disease (CAD), heart failure, aortic stenosis, mitral regurgitation, atrial fibrillation or flutter, ischemic stroke, peripheral artery disease or venous thromboembolism.
Prevalent Cardiovascular Disease
At the baseline study visit, after adjustment for age and race, women with prior HDP were more likely than those without to have:
- Hypertension (OR, 11.6; 95% CI, 10.6–12.7; P < .001)
- Heart failure (OR, 2.4; 95% CI, 1.3–4.2; P = .002)
- CAD (OR, 1.6; 95% CI, 1.1–2.2; P = .008)
- Venous thromboembolism (OR, 1.5; 95% CI, 1.2–1.9; P < .001)
Women with prior HDP were also significantly more likely than those without to have hyperlipidemia, diabetes mellitus and chronic kidney disease.
Arterial Stiffness Index
Arterial stiffness index (ASI) data derived from finger photoplethysmography were available for 42% of women with HDP and 37% without HDP. Prior HDP was significantly associated with higher ASI after adjustment for age at enrollment and menopausal status. The association persisted after additional adjustment for diabetes, ever-smoking and body mass index, although not after adjustment for prevalent hypertension.
Incident Cardiovascular Disease
Per 1,000 woman-years of follow-up and after adjustment for age, seven new cardiovascular diagnoses occurred in women with prior HDP versus 5.3 in women without (P = .001). Persistent differences were observed among women in their early 60s.
After adjustment for age at enrollment and race, significant associations were observed between prior HDP and new diagnoses of:
- Mitral regurgitation (HR, 5.0; 95% CI, 1.5–17.1; P = .01)
- Aortic stenosis (HR, 2.9; 95% CI, 1.5–5.4; P < .001)
- CAD (HR, 1.8; 95% CI, 1.3–2.6; P < .001)
- Heart failure (HR, 1.7; 95% CI, 1.04–2.60; P = .03)
HDP was not associated with incident atrial fibrillation or flutter, ischemic stroke, peripheral artery disease or venous thromboembolism.
Causes of the Associations
Mediation analyses suggest that chronic hypertension at baseline accounted for 64% of the association between HDP and incident CAD and 49% of the association between HDP and incident heart failure. No significant effects were observed for prevalent hyperlipidemia or diabetes mellitus.
Applying the Findings to Practice
The finding of increased arterial stiffness decades after pregnancy, along with the increased risk of both vascular and valvular pathology, suggests that HDP is associated with a syndrome of accelerated cardiovascular aging. Women with prior HDP should be counseled that they face increased early risk of certain cardiovascular diseases and retain increased risk of CAD, heart failure, mitral regurgitation and aortic stenosis into midlife.
Because cardiovascular disease risk after HDP was largely mediated by the development of chronic hypertension, blood pressure control may be especially important in these women.
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