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Prepregnancy Obesity, Not Pregnancy Complications, Drives Midlife Cardiovascular Risk in Women, Suggest HAPO FUS Study Findings
Gestational diabetes and hypertensive disorders of pregnancy may be markers for rather than mediators of risk for future CVD, according to new research.
Prepregnancy overweight and obesity appear to be more significant drivers of midlife cardiovascular disease (CVD) risk factors than adverse pregnancy outcomes (APO) themselves, according to recent findings from the HAPO FUS (Hyperglycemia and Adverse Pregnancy Outcomes Follow-Up Study).
The research, published in the Journal of the American College of Cardiology, revealed that gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP), both associated with increased risk of maternal death and heart disease in later life, mediated only a small proportion of the association between prepregnancy body mass index (BMI) and CV risk factors in midlife.1
According to study authors, led by Jaclyn D. Borrowman, PhD, postdoctoral research fellow in the department of preventive medicine at Northwestern University Feinberg School of Medicine, the findings suggest that interventions targeting prepregnancy weight management may be the most valuable strategy to reduce subsequent CVD risk.1
Markers or Mediators?
Specifically, the multinational study found that compared to women with normal prepregnancy BMI, those with obesity before pregnancy had significantly higher mean risk factors for CVD, including arterial pressure (mean difference 7.0 mm Hg; 95% CI, 6.0-8.1 mm Hg), triglycerides (28.5 mg/dL; 95% CI, 21.9-35.1 mg/dL), and HbA1c (0.3%; 95% CI, 0.2%-0.4%) at follow-up approximately 12 years after delivery (mean age 41.7 years).
GDM was found to mediate just 24.6% (95% CI: 20.9%-28.4%) of the association between obesity and HbA1c, while new-onset HDP mediated only 12.4% (95% CI: 10.6%-14.2%) of the link between obesity and mean arterial pressure.1
Adverse pregnancy outcomes, long understood as risk factors for postpartum heart disease, do not appear to explain “a majority of the association between prepregnancy overweight or obesity” and later development of risk factors for CVD," Borrowman and colleagues wrote.
Pregnancy has historically offered a “window into future health,” with complications such as gestational hypertension, preeclampsia, and gestational diabetes harbingers of future poor CVD health, the authors said. Given that adverse pregnancy outcomes occur in 17–20% of all pregnancies in the US,2 the research team set out to better understand whether the association is related to factors that could be mitigated before pregnancy.1
Adverse pregnancy outcomes, long understood as risk factors for postpartum heart disease, do not appear to explain “a majority of the association between prepregnancy overweight or obesity” and later development of risk factors for CVD.
The analysis included 4,269 pregnant participants who were enrolled at approximately 28 weeks' gestation (range: 24-32 weeks) in the HAPO FUS study. Participants had no prepregnancy hypertension or diabetes and underwent follow-up visits at a mean of 11.6 ± 1.3 years after delivery, according to the study. At baseline, the mean maternal age was 30.1 ± 5.6 years, and 10.6% of participants had prepregnancy obesity.
During pregnancy, 13.8% developed gestational diabetes and 10.7% experienced new-onset hypertensive disorders. The analyses were adjusted for maternal and gestational age, parity, field center, alcohol and smoking status during pregnancy, and fetal sex.
In a related editorial,3 Garima Sharma, MD, FAHA, director of preventive cardiology and women’s cardiovascular health at Inova Schar Heart and Vascular in Fairfax, Virginia pointed out that “postpartum weight changes, which are not captured in this study, may [also] play a significant role in mediating CVD risk given the dose- and time-dependent nature of the exposure.” They noted that the distribution of excess adipose tissue impacts cardiovascular risk differently, with visceral adipose tissue being highly associated with CVD, “while subcutaneous adipose tissue (commonly distributed in the gluteofemoral region in women) is not.”3
Nonetheless, the editorial writers emphasized that the study results "underscore the value in addressing excess adiposity in the peripartum period, particularly with the emergence of new anti-obesity medications."3
