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May 22, 2020
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Focus on sex-specific risk factors critical in diagnosing, treating CVD in women

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Salim S. Virani

Cardiologists should collaborate with obstetricians, gynecologists and primary care clinicians to identify and treat women at risk for CVD, according to a primer published in Circulation.

“This is a very collaborative, multispecialty kind of issue,” Salim S. Virani, MD, PhD, professor of medicine and director of the cardiovascular disease fellowship program at Baylor College of Medicine in Houston, and staff cardiologist at Michael E. DeBakey Veterans Affairs Medical Center in Houston, told Healio. “The solution is not going to be just one clinical specialty. We’ll have to make sure that all these clinicians pick up on these clues because they all get in touch with a woman in various phases of her life.”

Adverse pregnancy outcomes

Several adverse pregnancy outcomes including hypertensive disorders of pregnancy, preeclampsia and gestational diabetes can increase a woman’s risk for CVD. For example, hypertensive disorders of pregnancy can increase the risk for subsequent diabetes and hypertension, in addition to incident HF and CVD, Anandita Agarwala, MD, third-year fellow in the division of cardiology at Washington University School of Medicine in St. Louis, and colleagues wrote in the primer. Adverse outcomes can also manifest through multiple phenotypes including insulin resistance, endothelial dysfunction and thrombophilia. Studies are currently underway to learn more about molecular mechanisms and heterogeneity in these disorders.

Gestational diabetes increases the risk for developing type 2 diabetes after pregnancy by eightfold compared with women without the condition. This is also linked to a future risk for CVD.

“It is thought that women who develop dysglycemia have an underlying cardiometabolic phenotype that predisposes them to gestational diabetes and CVD,” Agarwala and colleagues wrote. “Glucose screening during pregnancy could identify women at risk for CVD.”

Preterm delivery increases the risk for developing type 2 diabetes, hypertension and hypercholesterolemia, and women are more likely to develop subclinical atherosclerosis, according to the primer. In additional, delivering a baby that is small for their gestational age also increases the risk for future maternal CVD.

“While small for gestational age infants and future maternal CVD appear to be associated, it is unclear as to whether this association is independent of maternal placental syndromes including hypertensive disorders of pregnancy, as many of these factors are interrelated,” Agarwala and colleagues wrote. “Women who deliver small for gestational age infants should be monitored carefully for the development of hypertension in the near future.”

Increased CVD risk is also observed in women with early-onset menopause and premature ovarian failure, defined as loss of ovarian function before age 40 to 45 years, hypergonadotropism, menstruation cessation and hypoestrogenism, according to the primer. Loss of ovarian function is also linked to long-term activation of the renin-angiotensin-aldosterone system, which can lead to immune dysfunction, inflammation and endothelial dysfunction. Estrogen decline can also contribute to a loss in the beneficial effects on atherosclerotic plaque formation and cholesterol metabolism.

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Other factors can affect a woman’s risk for CVD beyond menopause and pregnancy. These include polycystic ovary syndrome, premature menarche, multiple spontaneous miscarriages, hormone-based contraceptive use and breast cancer, according to the primer. Cardiologists should keep this in mind when assessing a woman’s medical history.

Approach to risk stratification

Given all the information detailed in the primer, researchers emphasized the importance of a fourfold approach to risk-stratify women: thorough history on CVD risk factors, early and frequent screening for traditional CVD risk factors if sex-specific risk factors are present, aggressive lifestyle changes and 10-year or lifetime risk calculations based on the woman’s age. The primer mentions the use of the 10-year ASCVD risk calculator for women aged 40 to 75 years, whereas women aged 20 to 59 years can have their lifetime risk assessed.

“There are multiple opportunities to screen women for cardiovascular disorders,” Virani said in an interview. “For example, when a woman is seeing a gynecologist, and once they’ve had their first pregnancy, they’re seeing an obstetrician. At all of those points in time, there are pointers that should raise a red flag that this woman that I’m seeing may have a higher risk for cardiovascular events in the future. There are multiple ways that one can do opportunistic screening to identify women who may be at higher risk for CVD in the future.” – by Darlene Dobkowski

For more information:

Salim S. Virani, MD, PhD, can be reached at virani@bcm.edu; Twitter: @virani_md.

Disclosures: Virani reports he was on the steering committee for the PALM registry at Duke Clinical Research Institute without financial remuneration and received honorarium from the American College of Cardiology for his role as associate editor of innovations at acc.org. Agarwala reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.