High BMI Before Pregnancy Tied to Greater CVD Risk Later in Life

Overweight or obesity prior to pregnancy may be an important marker of the trajectory of CVD risk in midlife, new data suggest.

Among healthy pregnant adults with a mean age of 30, having a prepregnancy body mass index (BMI) in the overweight or obesity range was associated with a twofold greater risk of hypertensive disorders of pregnancy (HDP) and gestational diabetes, which in turn were associated with the development of several CVD risk factors by the time they reached their early 40s.

“Pregnancy has often been termed nature’s stress test [and] potentially a window into future health,” said lead investigator Jaclyn D. Borrowman, PhD (Northwestern University, Chicago, IL). “Understanding whether this link between adverse pregnancy outcomes and cardiovascular disease is related to factors that could be targeted before pregnancy, such as the presence of overweight or obesity, may help to inform preventative strategies.”

The data from Borrowman and colleagues’ study add to prior reports showing that women who have HDP are at increased risk of developing CAD earlier in life than those who are normotensive during pregnancy, and that a woman’s pregnancy and reproductive history should be considered in CV risk factor assessment.

The stakes are high—in the United States alone, more than one-third of all women are classified as having obesity, recent data suggest, with nearly one in five pregnancies involving an adverse outcome like HDP or diabetes.

“The results of the study underscore the value in addressing excess adiposity in the peripartum period, particularly with the emergence of new anti-obesity medications,” Garima Sharma, MD (Inova Schar Heart and Vascular, Falls Church, VA), and colleagues write in an accompanying editorial. Pregnant women have historically been barred from participating in drug trials, they say, so “it is imperative to determine the safety, efficacy, and potential role of these medications in reducing both adverse pregnancy outcomes and future CVD risk.”

Other important targets for ongoing research, the study authors say, involve determining whether pregnancy-associated weight gain and shifts in BMI over a woman’s reproductive lifespan are able to impact risk prediction for future CVD.

Looking Back to Look Ahead

For the study, published online today in the Journal of the American College of Cardiology, researchers analyzed data from 4,269 pregnant women (mean age 30.1 years; mean gestation 28 weeks) from 10 countries who had no history of hypertension or diabetes before pregnancy and were enrolled in the Hyperglycemia and Adverse Pregnancy Outcomes Follow-Up Study. BMI, as calculated by self-reported prepregnancy weight, was within normal range in 67.7%, overweight in 21.7%, and obese in 10.6%. Participants were followed for a mean of 11.6 years after delivery.

Gestational diabetes and new-onset HDP occurred in 13.8% and 10.7% of participants, respectively. Overweight, classified as a BMI before pregnancy of 25-30 kg/m², was associated with a twofold increase in both gestational diabetes and in preeclampsia/eclampsia compared with normal BMI. The odds of developing these adverse pregnancy outcomes were even higher for those with obesity prior to pregnancy.

Developing gestational diabetes or HDP was associated with higher mean arterial pressure, triglycerides, fasting glucose, and HbA1c over the follow-up period.

In addition, those who developed gestational diabetes had increased odds of developing type 2 diabetes (adjusted OR 7.01; 95% CI 5.53-8.88) and diabetes or prediabetes (adjusted OR 4.30; 95% CI 3.18-5.81) over the follow-up period compared with those who did not have gestational diabetes. The same was seen for those who developed HDP, with type 2 diabetes (adjusted OR 1.88; 95% CI 1.21-2.92) and diabetes or prediabetes (adjusted OR 1.44; 95% CI 1.20-1.74) more likely to emerge in these women over the next 10 to 14 years than in those with a normotensive pregnancy.

Having a gestational diabetes diagnosis mediated the associations between prepregnancy overweight BMI and measurements of fasting glucose as well as HbA1c over the follow-up period, while having new-onset HDP mediated the association between prepregnancy overweight BMI and median arterial pressure.

The findings were similar for obesity prior to pregnancy, with gestational diabetes mediating about 25% of the association with later-life HbA1c levels. New-onset HDP mediated the association with later-life mean arterial pressure by about 12%.

Borrowman told TCTMD she was surprised by the minimal role that APOs played in the link between pregnancy BMI and CVD later in life, noting, “I thought it would be greater, but I think it highlights how important prepregnancy health is in the context of this broader issue of cardiovascular disease burden.”

Potential Role for GLP-1s

The editorialists acknowledge that the study “provides insightful information about the extent to which preconception risk factors and those that present during pregnancy may affect downstream risk,” but note some limitations of this type of research. One is that BMI is increasingly being recognized as an imprecise definition of obesity, with a recent Lancet commission report suggesting the need to reframe how obesity is diagnosed.

The other limitation, Sharma and colleagues say, is the impact that aging, menopause, and lifestyle have on women’s weight gain throughout life.

“Postpartum weight changes, which are not captured in this study, may play an important role in mediating CVD risk given the dose- and time-dependent nature of the exposure,” they write.

While data on GLP-1 use are still in early stages, at least one retrospective analysis suggests that prescribing them within 24 months before conception may lead to a lower incidence of gestation diabetes and HDP, the editorial highlights

Borrowman added that GLP-1 receptor agonists could potentially be a game changer for women in whom high BMI interferes with fertility.

She noted that one of the most exciting things about this type of research is “the move toward thinking about maternal health in the context of chronic disease prevention” and promotion of family health.