Later CVD Risk From Hypertension in Pregnancy Vastly Underestimated

The number of women who may be at risk for developing CVD later in life based on their history of hypertension in pregnancy is twice as high as previously thought, new research suggests.

In a population-based analysis, the incidence of hypertensive disorders of pregnancy (HDP) was 7.3% and preeclampsia was 3.3% on a per-pregnancy basis, which matches up with global and regional estimates. However, on a per-woman incidence, both estimates doubled: to 15.3% for HDP and 7.5% for preeclampsia.

The study’s lead author told TCTMD that the findings have significant implications for women’s healthcare long after pregnancy.

“Reproductive history is commonly underrecorded for women of postmenopausal age because it is not considered, in general, to be relevant,” observed Vesna D. Garovic, MD, PhD (Mayo Clinic College of Medicine, Rochester, MN). “This study further underscores the importance of taking the detailed history of reproduction of women who are coming in for either preventive care or who have established cardiovascular disease.”

Garovic added that women need to be reminded of how important it is to report their reproductive history throughout their lives.

“The fact that [hypertension] happened when you were 25 years old is still relevant. We need to get away from the typical thinking that if you had preeclampsia or hypertension in pregnancy and it resolved [then] it doesn’t matter. It does matter,” she said.

In an editorial accompanying the study, Michael C. Honigberg, MD, and Pradeep Natarajan, MD (both Massachusetts General Hospital and Harvard Medical School, Boston, MA), note that the study primarily looked at women who were white and gave birth in the 1970s and 1980s. They hypothesize that “a more ethnically diverse contemporary cohort with inherently greater prevalence of HDP risk factors (eg, obesity, prepregnancy hypertension) and known ethnic disparities in HDP risk is likely to have even higher HDP incidence.”

The study was published this week in the Journal of the American College of Cardiology. Also today, the American Heart Association (AHA) released a scientific statement online in Circulation stressing the importance of cardio-obstetrics teams in managing cardiovascular disease before, during, and after pregnancy.

Significant Future Risk

The study by Garovic and colleagues included data on 9,862 pregnancies among residents of Olmsted County, MN, who were part of the Rochester Epidemiology Project medical record-linkage system.

Among a subset of 571 women with pregnancies complicated by HDP, who had median follow-up of 36 years, risks were increased for stroke (HR 2.27; 95% CI 1.37-3.76), CAD (HR 1.89; 95% CI 1.26-2.82), arrhythmias (HR 1.62; 95% CI 1.28-2.05), chronic kidney disease (HR 2.41; 95% CI 1.54-3.78), and multimorbidity (HR 1.25; 95% CI 1.15-1.35). HDP also was associated with accelerated rates of 16 chronic conditions, primarily related to CVD risks and events. All-cause death, however, did not differ between women with HPD and those who were normotensive during pregnancy.

“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%),” Garovic and colleagues write.

We need to get away from the typical thinking that if you had preeclampsia or hypertension in pregnancy and it resolved [then] it doesn’t matter. It does matter. Vesna Garovic

Presuming that women with HDP develop CVD at higher rates despite receiving similar preventive care as those with no hypertensive reproductive history, Honigberg and Natarajan wonder whether an HDP history should trigger different thresholds for initiating preventive pharmacotherapies and/or different treatment targets. “Dedicated lifestyle and pharmacologic interventions for primordial and primary prevention to improve long-term health trajectories warrant prospective study,” they add.

Accelerated Vascular Aging

The finding that women with a history of HDP developed chronic conditions at an earlier age is consistent with epidemiological studies showing that HPD, especially severe forms of preeclampsia, may accelerate CAD events such that they occur as early as 10 or 15 years after pregnancy, Garovic told TCTMD. The cause is thought to be accelerated vascular aging, possibly as a result of cellular senescence. It has been established that in women with preeclampsia who deliver before 30 weeks gestation, for example, the placenta may be consistent with a 42-week pregnancy, she added.

“It’s really a window into cardiovascular health,” Garovic noted. “Hypertension may be something which is unmasked by the pregnancy and which reflects future risk based on inadequate vascular response during the pregnancy.”

Clearly, there is a need for better understanding of CVD risk in women with HDP, Honigberg and Natarajan note.

“Research is needed to clarify novel pathways, such as derangement in cellular senescence, as the authors hypothesize, and to reveal unique therapeutic targets. Work to elucidate the fundamental maternal and fetal genetic architecture of HDP and metabolomic and proteomic signatures may help elucidate these gaps,” they observe.

Importantly, more research is needed to improve HDP prediction and prevention before pregnancy as well, they conclude. Similarly, the AHA scientific statement, authored by Laxmi S. Mehta, MD (Ohio State University, Columbus), and colleagues, notes that preconception counseling and early involvement of a multidisciplinary cardio-obstetrics team are crucial to controlling maternal mortality, understanding immediate and postdischarge monitoring requirements, and managing specialized long-term cardiovascular follow-up for women with HDP.

“These patients warrant follow-up in the fourth trimester, at which time aggressive risk factor modification should be undertaken and future risk should be discussed with the patient,” Mehta and colleagues write.