Increase seen in stroke, CAD, arrythmias, kidney disease, multimorbidity

Per-pregnancy derived incidence of hypertensive disorders of pregnancy (HDPs) underestimated how many women were affected by the group of disorders, which conferred lifelong cardiovascular disease and multimorbidity risk, a population cohort study found.

Per-pregnancy HDP and pre-eclampsia rates in residents of Olmstead County, Minnesota, who delivered between 1976 and 1982 were 7.3% and 3.3%, respectively. On a per-woman basis, the rates doubled to 15.3% and 7.5%, respectively, reported Vesna Garovic, MD, PhD, of the Mayo Clinic and coauthors in the Journal of the American College of Cardiology.

In addition to normotensive pregnancies, the study identified HDP subtypes of gestational hypertension, pre-eclampsia, eclampsia, pre-eclampsia superimposed on chronic hypertension, and chronic hypertension. Multiple cardiovascular disorders (CVDs), vascular risk factors, chronic kidney disease, and a multimorbidity marker of accelerated aging were also more common in those who had a pregnancy complicated by HDP.

“Taken together, our findings indicate that the risks for kidney and heart disease in women with HDP histories have been underestimated,” Garovic and colleagues wrote.

“The proportion of women who may be at risk based on their HDP histories (15.3%) is similar to the proportions of women at risk for CVD based on the presence of traditional risk factors, such as smoking (13.7%), hyperlipidemia (14.8%), and diabetes (12%),” they added. “Inclusion of HDP history may substantially reduce misclassification using current CVD risk scores, which are particularly inaccurate in women.”

“These findings provide compelling evidence that HDP heralds a syndrome of accelerated cardiovascular aging,” wrote Michael Honigberg, MD, MPP, and Pradeep Natarajan, MD, MMSC, both of the Massachusetts General Hospital, Boston, in an accompanying editorial. “Because most HDP cases occur in first pregnancies and most with HDP do not experience recurrent HDP in subsequent pregnancies, HDP incidence per woman was greater than incidence per pregnancy.”

HDPs are an important cause of fetal and maternal mortality, and confer long-term maternal risks for cardiovascular events, nearly doubling rates of coronary artery disease and stroke and increasing risks for heart failure, atrial fibrillation, venous thromboembolism, and other conditions. Women with HDP also develop vascular risk factors sooner, with higher rates of chronic hypertension, hypercholesterolemia, and type 2 diabetes than women with normotensive pregnancy.

Elevated risk usually emerges within years of delivery and lasts for decades following hypertensive pregnancy, and HDPs have been incorporated into multiple recommendations including the 2019 American College of Cardiology/American Heart Association primary prevention guideline for statin prescription in intermediate risk women.

“Coupled with a signal of persistently increased arterial stiffness after HDP, this constellation of findings suggests that women with HDP may experience global acceleration of cardiovascular aging,” the editorialists observed.

Garovic and colleagues examined Olmstead County data on deliveries between 1976 and 1982, which gave time for the women to reach menopause. Using a health-records algorithm to determine HDP, they calculated incidence on a per-pregnancy basis in 7,544 women with 9,862 pregnancies, and on a per-woman basis in 1,839 women with 4,322 pregnancies (all at 20 or more weeks gestation).

The authors also followed 571 women with a history of HDP and 1,142 parity- and age-matched controls over a median 36 years for cumulative development of any of 16 conditions recommended by the U.S. Department of Health and Human Services for the study of multimorbidity.

Women with a history of HDP were at increased risk for later:

  • Stroke (HR 2.27, 95% CI 1.37 to 3.76).
  • Coronary artery disease (HR 1.89, 95% CI 1.26 to 2.82).
  • Cardiac arrhythmias (HR 1.62, 95% CI 1.28 to 2.05).
  • Chronic kidney disease (HR 2.41, 95% CI 1.54 to 3.78).
  • Multimorbidity (HR 1.25, 95% CI 1.15 to 1.35).

After correction for multiple comparisons, dementia, which had been a primary endpoint, was no longer significant.

“HDP history may be most useful for risk discrimination among younger women, before development of overt CVD risk factors, serving as an early risk signal to guide primordial prevention to prevent or delay risk factor development,” the editorialists wrote.

“Accelerated development of CVD and multimorbidity among women with HDP in this and other contemporary cohorts implies that previous preventive strategies are insufficient, underused among women with HDP, or both,” the editorialists observed. “These data support existing guideline recommendations to incorporate HDP history in atherosclerotic cardiovascular disease risk assessment for statin allocation.”

Limitations include a predominantly white population, limiting generalizability. Billing codes were used to determine long-term outcomes. While pregnancy data are from 1976-1982 to enable long term follow-up, incidence of HDP may be higher today.

  1. The incidence of hypertensive disorders of pregnancy (HDP) between 1976 and 1982 calculated on a per-woman basis (15.3%) was double the figure calculated per pregnancy (7.5%), in Olmstead County, Minnesota.

  2. Pregnancy complicated by HDP was associated with decades-long increased risk of cardiovascular and other morbidities compared with normotensive pregnancy, and the contribution of HDP-related risk to later life chronic illness in women may be underestimated.

Paul Smyth, MD, Contributing Writer, BreakingMED™

This study was supported by the NIH.

Garovic reported no disclosures.

Honigberg is supported by a grant from the National Heart, Lung, and Blood Institute. Natarajan is supported by grants from the National Heart, Lung, and Blood Institute, Fondation Leducq, and a Hassenfeld award from the Massachusetts General Hospital; has received grant support from Amgen, Apple, and Boston Scientific; and has received consulting income from Apple.

Cat ID: 6

Topic ID: 74,6,730,6,914,41,192,916