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Older women's heart disease risk factors were tied to the timing and events of their child-bearing years, researchers found.

Adverse pregnancy outcomes, especially hypertensive disorders of pregnancy and low birth weight, were associated with subsequent maternal atherosclerotic cardiovascular disease (ASCVD) independent of traditional risk factors in one large study.

A separate study showed that the shorter a woman's reproductive life span, the higher the risk of coronary heart disease and stroke after menopause.

Both studies were published online in .

Adverse Pregnancy Outcomes

Certain outcomes of pregnancy should be considered in considering ASCVD risk for postmenopausal women, a suggested.

Older women with a history of pregnancy had a greater risk of MI, stroke, peripheral artery disease, or coronary revascularization if they had had an adverse pregnancy outcome (7.6% vs 5.8%), according to Nisha Parikh, MD, MPH, of the University of California San Francisco School of Medicine, and colleagues.

Four specific pregnancy outcomes were independently associated with maternal ASCVD after adjustment for established risk factors:

• Gestational diabetes: adjusted OR 1.32, 95% CI 1.02-1.67
• Gestational hypertension and preeclampsia: adjusted OR 1.38, 95% CI 1.19-1.58
• Low birth weight (<2.49 kg, 5.49 lb): adjusted OR 1.25, 95% CI 1.12-1.39
• Preterm delivery (by 3 weeks or more): adjusted OR 1.23, 95% CI 1.10-1.36

Hypertensive disorders of pregnancy (OR 1.34, 95% CI 1.15-1.54) and low birth weight (OR 1.18, 95% CI 1.03-1.35) remained significantly associated with ASCVD after researchers tested adverse pregnancy outcomes together in a single model.

"All findings were materially unchanged by additional adjustment for parity, body mass index, and socioeconomic factors," Parikh's group reported. "Our study supports guideline recommendations that clinicians should consider a history of pregnancy-associated disorders when assessing ASCVD risk in older women."

The investigators noted, though, that it is unclear if these adverse outcomes are associated with ASCVD because they are involved in novel pathophysiologic processes or whether they serve as a marker of longer-term and more severe underlying cardiometabolic risk.

There is a possibility that dysfunction of the microvasculature plays a role, according to C. Noel Bairey Merz, MD, and colleagues of Cedars-Sinai Smidt Heart Institute in Los Angeles.

"Emerging but limited data suggest that many affected women are not completely healthy prior to pregnancy, with some reports describing preconception prevalence of obesity, dyslipidemia, dysglycemia, and even overt hypertension that was previously undiagnosed," they added in an .

"Further research is needed to understand the potential mechanisms that might link hypertensive disorders of pregnancy and low birth weight with late ASCVD," study authors said.

Their study was based on the Women's Health Initiative, a large multiethnic cohort of postmenopausal women enrolled in 1994-1998. Eligible individuals had a history of pregnancy for more than 6 months. Exclusion criteria included prior stroke, MI, or a coronary revascularization procedure.

In all, 46,805 participants (median age 60 years) responded to a survey in 2017 and were included in the study.

Nearly 29% reported having experienced one or more adverse pregnancy outcomes.

High birth weight (>4.08 kg, 9.00 lb) was examined but was not associated with postmenopausal ASCVD.

The study had the potential for survival and recall bias, Parikh and colleagues cautioned.

Another limitation was that preeclampsia and gestational hypertension were analyzed together. "These disorders have been shown to have differences in their associations with CVD (e.g., worse outcomes are consistently reported for preeclampsia compared with gestational hypertension), so future studies should be designed to separate them," according to Bairey Merz's group.

Nevertheless, the study is enough to suggest that hypertension during pregnancy "should be incorporated into a new ASCVD risk score for women," she and her colleagues emphasized.

Adverse pregnancy outcomes should be mandatory elements in the electronic health record and made accessible by clinicians and continuity of care systems over women's life courses, the editorialists also urged.

Reproductive Life Span

Women who had less than 30 years between menarche and menopause were at higher risk of coronary heart disease and stroke, .

The incidence of nonfatal CVD events in midlife was higher for these women (adjusted HR 1.71, 95% CI 1.58-1.84), compared with peers with reproductive lifespans of 36 to 38 years. Adjustment for age at menarche did not change the finding, but adjusting for age at menopause did weaken the association (adjusted HR 1.25, 95% CI 1.08-1.45).

Reproductive life span and age at menarche significantly interacted in their association with CVD risk, according to Gita Mishra, PhD, of the University of Queensland in Brisbane, Australia, and colleagues.

"Our study showed that both combinations, early menarche (age ≤11 years) and short reproductive life span (<33 years) as well as late menarche (age ≥15 years) and short reproductive life span (<33 years) were associated with increased risk of CVD events compared with menarche at age 13 years and reproductive life span at 36 to 38 years," Mishra's group said.

"Previous studies have suggested that menarche at age 12 to 14 years was optimal in terms of future CVD risk, but our study has demonstrated that this does not capture the increased risk for women with a short reproductive life span who have an average age at menarche," study authors said.

The study used individual-level data (n=307,855) pooled from 12 studies of the InterLACE consortium. Each study collected prospective or retrospective survey data on women's reproductive health, sociodemographic and lifestyle factors, and chronic disease events.

Participants averaged 13 years at menarche, 50.2 years at menopause, and had a mean reproductive lifespan of 37.2 years.

The association between age at menarche and CVD events followed a U-shaped curve, with increased risk observed in women with early menarche (age ≤10 years) and late menarche (age ≥16 years).

In contrast, was strongly associated with greater risk of CVD.

Investigators noted that study participants were predominantly white women from the U.K., U.S., Australia, Denmark, and Sweden, limiting the generalizability of their findings. Moreover, the data available did not allow for adjustment for genetic factors, early life factors, diet, physical activity, and comorbidities.

"Given the interrelationship between timing of menarche and menopause, we suggest that for women in midlife, CVD risk assessment should take into account the timing of both menarche and menopause," Mishra's team maintained.

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