Any one of five adverse pregnancy outcomes (APOs) significantly increase the risk for atherosclerotic cardiovascular disease (ASCVD) later in life, a new Women’s Health Initiative analysis suggests.
The added risk associated with gestational diabetes, low birth weight, high birth weight, preterm delivery, and hypertensive disorders of pregnancy was independent of traditional ASCVD risk factors such as age, hyperlipidemia, hypertension, diabetes, and smoking.
Moreover, the results did not change appreciably after further controlling for race/ethnicity, income, education, body mass index, breastfeeding, and parity, the authors, led by Marc Meller Søndergaard, Bscmed, Aalborg University School of Medicine and Health, Aalborg, Denmark, reported this week in JAMA Cardiology.
“We were actually surprised we found an association in the sense that these adverse pregnancy outcomes would have happened five to eight decades before the CVD event,” senior author Nisha Parikh, MD, MPH, told theheart.org | Medscape Cardiology. “So in some way we were surprised they were still robust that many years after the exposure.”
Although several studies have shown that APOs can elevate risk for future CVD in women, the new study extends those findings to a large, well characterized, multi-ethnic cohort that also accounted for other pregnancy factors.
“Many studies have looked at each of these adverse pregnancy outcomes by themselves but we’ve really felt strongly that our reproductive and pregnancy history is something that clinically is taken all together. We don’t ask about these factors in isolation,” said Parikh, an associate professor of medicine at the University of California San Francisco School of Medicine.
When the model was further adjusted for all five APOs as well as traditional risk factors, both hypertensive disorders of pregnancy (defined as gestational hypertension and/or preeclampsia) and low birth weight were independently associated with late ASCVD. The adjusted odds ratios were 1.34 (95% CI, 1.15-1.54) and 1.18 (95% CI, 1.03-1.35), respectively.
“We finally have an answer to whether or not these gestational hypertensive disorders actually are a unique and independent risk factor for future cardiovascular disease, and the answer is yes, where [in] prior studies it was mostly ‘no’ or ‘we don’t know’ but they were underpowered and were not accurately collected. So it’s better science to an incredibly important question,” C. Noel Bairey Merz, MD, director of the Barbra Streisand Women’s Heart Center at Cedars-Sinai Smidt Heart Institute, Los Angeles, and coauthor of a linked commentary, said in an interview.
Future studies, however, will need to separate gestational hypertension and preeclampsia because they have different associations with CVD, with outcomes consistently worse for preeclampsia, she noted.
Data also suggest that preeclampsia has increased in the United States, specifically in Black women, observed Parikh. “Because of our health disparities and racial/ethnic disparities that have really come to the light in this era of COVID, for many of the adverse pregnancy outcomes we are actually seeing increases and that includes preeclampsia, whereas that is going down in other developed countries.”
In their related editorial, Bairey Merz and colleagues pointed out that 86% of US women bear at least one child and studies consistently show that 1 in 5 pregnancies are affected by an adverse outcome.
“In short, a risk factor readily found in nearly all women — literally under our collective noses — might be harnessed for relevant, sex-specific atherosclerotic CVD (ASCVD) risk information to address the preventive, diagnostic, and treatment gaps that adversely affect women,” write Bairey Merz, Odayme Quesada, MD, and Chrisandra Shufelt, MD, also with the Streisand Women’s Heart Center.
The American College of Obstetricians and Gynecologists guidelines recommend routine screening of body mass index, lipids, and blood pressure in all women with a history of APO. The latest American Heart Association (AHA)/American College of Cardiology (ACC) cholesterol guidelines include APOs as potential “risk enhancers” for ASCVD risk.
The societies trigger guidelines when there’s enough evidence to support action, but the problem lies in operationalizing this now, said Bairey Merz, who recently led the ACC’s CVD in Women Committee. Primary care physicians may have 7 minutes and subspecialists roughly double that to spend with a patient from the time the office door opens to the time it closes. In addition, pregnancy history — unlike medical and surgical history — is not a mandatory element in the electronic health record.
“This is the time to get the electronic health records to stop disparaging women,” she said in an interview. “This is just another: women and children always take it in the shorts. And why do we allow that? That’s not okay.”
Both Parikh and Bairey Merz contend the new findings are strong enough that hypertensive disorders of pregnancy and low birth weight should be incorporated in ASCVD risk stratification.
The recent Nurses’ Health Study II reported that adding hypertensive disorders of pregnancy did not improve discrimination or risk reclassification. But the women were surveyed at a much younger age, resulting in a low CVD risk and lack of power, it was noted.
The current analysis considered 46,805 active Women’s Health Initiative participants recruited between the ages of 50 and 79 years at baseline who responded to an APO survey in 2017. Their median age at enrollment was 60 years, 90% were White, 5.2% Black, 2.4% Hispanic, and 2.5% other race/ethnicity.
At least one APO was reported by 13,482 women, or nearly one in three women (28.8%). Nearly 5000 women had two or more APOs. The most common combination of APOs was preterm delivery and low birth weight.
Between study entry and the time of the survey, 7.6% of women with an APO had developed ASCVD compared with 5.8% without an APO.
The odds ratios and 95% confidence intervals for late ASCVD risk adjusted for ASCVD risk factors only and for ASCVD risk factors plus all APOs were:
gestational diabetes: 1.32 (1.02-1.67) and 1.19 (0.91-1.52)
low birth weight: 1.25 (1.12-1.39) and 1.18 (1.03-1.35)
high birth weight: 1.07 (0.91-1.25) and 1.06 (0.89-1.24)
preterm delivery: 1.23 (1.10-1.36) and 1.07 (0.94-1.21)
hypertensive disorders: 1.38 (1.19-1.58) and 1.34 (1.15-1.54).
The biggest unanswered question is whether women with APOs have preexisting subclinical vascular conditions that are simply unmasked during pregnancy that increase CVD risk, or if APOs result in de novo damage that results in subsequent CVD, Bairey Merz said.
Of note, her team recently reported that a history of APOs was associated with abnormally low microvascular coronary flow reserve up to 30 years after an index pregnancy in women with evidence of ischemia without obstructive coronary artery disease, raising the hypothesis that APOs may be associated with microvascular dysfunction.
The Women’s Health Initiative program was funded by the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, and US Department of Health and Human Services through various contracts. This study was also supported, in part, by a NHLBI grant. Parikh has disclosed no relevant financial relationships.
The editorial was supported by contracts from the NHLBI; grants from the National Institute on Aging, National Center for Research Resources, and National Center for Advancing Translational Sciences; and by the Edythe L. Broad Women’s Heart Research Fellowship and the Constance Austin Women’s Heart Health Fellowship (both at Cedars-Sinai Medical Center), the Barbra Streisand Women’s Cardiovascular Research and Education Program at Cedars-Sinai, the Linda Joy Pollin Women’s Heart Health Program, and the Erika Glazer Women’s Heart Health Project.