Pregnancy complications and fertility issues that occur throughout the course of life may increase a woman’s risk of developing cardiovascular disease (CVD) later on in life, according to an umbrella review.
A wide range of female sex-specific reproductive health factors from first menstruation to menopause were associated with increased risk of composite CVD, stroke, ischemic heart disease, and heart failure (HF), reported Krishnarajah Nirantharakumar, MD, of the University of Birmingham in England, and colleagues.
Preeclampsia, gestational diabetes, stillbirth, and preterm birth had the strongest associations with cardiovascular illness later on in life, with women who had history of preeclampsia at four times the risk of developing HF (relative risk 4.19, 95% CI 2.09-8.38), they wrote in The BMJ.
Breastfeeding reduced the risk of poor cardiovascular health. There were also no observed associations between CVD and use of progesterone-only birth control, non-oral hormonal contraceptives, or fertility treatment, according to the authors.
“Our review increases awareness of female sex-specific risk factors for cardiovascular disease among women and health care workers,” Nirantharakumar told MedPage Today in an email. “It calls for multi-disciplinary collaboration between primary care doctors and specialists (obstetricians, gynecologists, cardiologists, and stroke physicians) in the evaluation and follow-up of women with a history of reproductive risk factors for cardiovascular disease.”
Christopher Nau, MD, a maternal-fetal medicine specialist at University Hospitals in Cleveland, said that while this review does not quantify individualized risk, it highlights a wide range of female-specific reproductive health factors that all physicians should pay attention to when screening patients.
“Pregnancy is a window into the long-term health risks for a woman,” Nau, who was not involved in the study, said in an interview. “A lot of issues with women’s reproductive health can have an impact on other parts of their health, and we need to keep that in mind.”
Recent age and sex-specific trends have shown some increases in cardiovascular illness risk among younger age groups, and specifically women, Nirantharakumar said. Although many studies have investigated female sex-specific cardiovascular risk factors, gaps in the current literature make public health implications unclear.
Nirantharakumar and colleagues conducted an umbrella review to synthesize existing systematic reviews and meta-analyses. They searched databases for studies about women, CVD, and risk factors related to fertility and pregnancy occurring from first menstruation to menopause. The group investigated several cardiovascular health outcomes, including ischemic heart disease, coronary artery disease, stroke, HF, composite CVD, and others.
Narrative reviews, literature reviews, genetic studies, duplicate analyses, and reviews that looked into atherosclerosis, venous thromboembolism, and hormone replacement treatment were excluded from the review. The researchers accepted articles published up to August 2019.
There were 32 articles included in the umbrella review, a majority of which were meta-analyses. The studies that investigated fertility outcomes followed patients for a median of 10 years, while those that looked into adverse pregnancy outcomes followed patients for around 7.5 years.
Women with moderate preeclampsia, stillbirth, and preterm birth were more than twice as likely to develop composite CVD. Those who had preeclampsia, gestational diabetes, and preterm birth had double the likelihood of ischemic heart disease, and patients who used combined oral contraceptives and had preeclampsia were two times as likely to have a stroke.
Researchers also found that starting periods early, polycystic ovary syndrome, miscarriage, low birthweight, and early menopause were all associated with cardiovascular risk.
Certain reproductive health factors that have known associations with cardiovascular risks — including endometriosis, pelvic inflammatory disease, first trimester bleeding, and anemia during pregnancy — were not included in this study, because of a lack of systematic reviews. Nirantharakumar and colleagues also acknowledged that missing metadata, and the nature of observational data included in these analyses, may weaken these findings.
The range of reproductive health factors associated with CVD is important for all clinicians across all specialties to take into account when monitoring female patients at multiple life stages, Nau said. “This reaffirms that it is really important for all healthcare providers to make sure that they take a close look at a woman’s reproductive medical history, and use that to guide their care,” he stated.
Study authors disclosed relevant relationships with AstraZeneca, Sanofi, Merck, and Boehringer Ingelheim.