Hypertension in Pregnancy Linked to Early Death

Women who had hypertensive disorders of pregnancy were at higher risk of dying before reaching age 70 whether or not they developed chronic hypertension, a retrospective study showed.

Among nearly 90,000 women who were pregnant from 1989 to 2009, gestational hypertension or pre-eclampsia was linked to a higher likelihood of premature death (adjusted HR 1.31, 95% CI 1.18-1.46), according to Jorge Chavarro, MD, ScD, of Harvard T.H. Chan School of Public Health in Boston, and colleagues.

The uptick in premature deaths was driven by differences in mortality due to:

• Cardiovascular disease (CVD; HR 2.26, 95% CI 1.67-3.07)
• Infectious diseases (HR 2.77, 95% CI 1.38-5.54)
• Respiratory diseases (HR 2.26, 95% CI 1.29-3.98)
• Nervous system diseases (HR 2.51, 95% CI 1.33-4.72)
• Metabolic/immunity disorders (HR 4.85, 95% CI 2.29-10.27)

The association between hypertensive disorders of pregnancy (HDPs) and premature all-cause death persisted whether the women developed chronic hypertension after pregnancy (adjusted HR 2.02, 95% CI 1.75-2.33) or not (adjusted HR 1.20, 95% CI 1.02-1.40), Chavarro’s group reported in the March 16 issue of the Journal of the American College of Cardiology.

“Together, these findings suggest that although the previously described progression of HDPs to chronic hypertension to increased cardiovascular morbidity and mortality is undoubtedly important, it may not be the primary pathway through which HDPs affect health and, ultimately, mortality,” the authors concluded.

“It is also noteworthy that the elevated risk of premature mortality appeared to be driven by the small number of women who experienced HDPs in two or more pregnancies and those who simultaneously reported HDPs and low birth weight,” they said.

Associations with all-cause and cause-specific mortality were similar when gestational hypertension and pre-eclampsia were examined separately.

The investigators “should be applauded on raising a biologic plausibility of the independent association of HDPs with premature all-cause mortality,” according to an accompanying editorial by Garima Sharma, MD, and colleagues of Johns Hopkins University School of Medicine in Baltimore.

“In summary, we have identified an at-risk population of young women who may benefit from early screening and intervention for chronic diseases to prevent early mortality. We must not pull the shade on this unique window,” the editorialists said.

Sharma’s group suggested developing better risk assessment tools that incorporate hypertensive disorders of pregnancy, and algorithms for early intervention in women deemed at high risk of premature CVD.

For now, “available tools to predict the risk of CVD lack the accuracy to identify high-risk women <40 years of age because these tools were developed and validated in predominantly older populations (>50 years of age),” according to the group.

Study participants were 88,395 U.S. women in the Nurses’ Health Study II who underwent 28 years of follow-up. Mean age at first birth was 26.7 years.

Hypertensive disorders of pregnancy occurred in at least one pregnancy in 14.0% of women. Participants who reported gestational hypertension or pre-eclampsia had a greater baseline BMI and higher baseline prevalence of gestational diabetes and parental history of diabetes, MI, or stroke.

Chavarro’s group noted that cancer mortality rates were not elevated with gestational hypertension or pre-eclampsia (HR 0.97, 95% CI 0.82-1.15).

Incidence of gestational hypertension and pre-eclampsia was self-reported in the study, a potential source of bias and misclassification of disease.

Other limitations included the possibility of residual confounding in the analyses and the preponderance of professional, non-Hispanic white women in the cohort.

“Future studies exploring the biological links between HDPs and premature mortality are needed. The association between HDPs and mortality from some causes that are not intuitively related (such as nervous system disease) may be representative of unmeasured confounding; however, an HDP is a systemic process with well-known end-organ effects,” Sharma’s group wrote.