Why Are Women Underrepresented in Heart Failure Clinical Studies?

Women are underrepresented in heart failure (HF) studies, and the ones they are included in do not adequately account for important sex-specific risk factors, such as pregnancy, reproductive lifespan, and hormone therapy use, according to a research letter published in the American Heart Journal.¹

For the study, “Female Sex-Specific Cardiovascular Risk Factors and Heart Failure Practice Guidelines,” researchers systematically reviewed clinical studies cited by the 2017 American College of Cardiology/American Heart Association/Heart Failure Society of America Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure.² The investigators categorized sex-specific cardiovascular risk factors as pregnancy, menopausal, reproductive, and female-predominant risk factors. Of 205 articles cited in the 2017 Guideline report, 188 studies met the inclusion criteria for further review. However, while most of the studies included women participants, only 3 studies (1.6%) reported any female sex-specific cardiovascular risk factors in either their data analysis or results sections.

The cardiovascular risk factors specific to women from the 3 studies included oral contraceptive use (n=1), menopausal status (n=2) and hormone replacement therapy (n=2). Researchers noted that oral contraceptive use was often reported as part of a combined category that encompassed both oral contraceptive use and hormone replacement therapy. The eligible studies did not include any other female-specific cardiovascular risk factors.

“Our work highlights that in addition to the need for proportional representation of women in [HF] clinical studies, inclusion of female sex-specific and predominant risk factors in data collection and analysis is of paramount importance to guide [HF] care in the female population,” the study authors wrote.

To gain more insights, we spoke with 2 of the study authors: Sofia Ahmed, MD, MMSc, of the Cumming School of Medicine, University of Calgary in Alberta, the Libin Cardiovascular Institute, and the Alberta Kidney Disease Network, Alberta, Canada, and Rana Hassan, MD, also of the Cumming School of Medicine and the Libin Cardiovascular Institute. They spoke about their findings and offered suggestions on how cardiologists and endocrinologists can work together to diagnose and treat potential heart health issues in their patients.

Why are women underrepresented in cardiovascular clinical trials, and why is it important for researchers to make a greater effort to include them?

Dr Ahmed: Study participation often reflects the population, so studies that inform our treatments are often done with men, and the findings are then extrapolated to women. There is often a “one-size-fits-all” approach to cardiovascular medicine, and this is not the right approach when the No. 1 killer of women in the US and worldwide is cardiovascular disease (CVD). Death rates from CVD are going down, but at rates much faster in men than in women. They’re actually going up in women under 55 years old. There needs to be a paradigm shift.

Dr Hassan: Female physiology is very unique and complex, so studies need to integrate female-specific risk factors which are related to cardiovascular and other health risks. Gestational diabetes is an example. Blood sugars go back to normal after delivery, but the lifetime risk of developing diabetes is still raised in these women by 50%.

What issues that are unique to women are linked to CVD?

Dr Ahmed: Menopause is one of them. There is evidence that a shorter reproductive lifespan—the time between menarche and menopause—can cause an increase in cardiovascular events. This stems from the fact that estrogen can be cardioprotective. But another big trial, the 2002 Women’s Health Initiative Study, showed more heart attacks in women taking hormonal therapy. This is not what we expected to see.

[Editor’s Note: this study was discontinued early when investigators observed the overall risk of hormonal treatment outweighed the benefits, including an increased risk of venous thromboembolism].³

How can cardiologists and endocrinologists work together in the early detection and treatment of disease in their female patients?

Dr Hassan: Managing traditional risk factors in diabetes, such as glycemic control, is essential. And patients with polycystic ovarian syndrome are at an increased risk for cardiac events.

Dr Ahmed: The American College of Obstetricians and the Endocrine Society have some good guidelines regarding the role of endocrinologists in cardiac health. Endocrinologists and their patients would benefit from making cardiovascular health screening a part of their routine clinical practice.

Reference

1. Hassan R, Riehl-Tonn, V, Dumanski SM, Lyons KJ, Ahmed SB. Female sex-specific cardiovascular risk factors and heart failure practice guidelines. Am Heart J. Published online February 4, 2022. doi:10.1016/j.ahj.2022.01.007

2. Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017;136(6):e137-e161. doi:10.1161/CIR.0000000000000509

3. Stjernquist M and the North American Menopause Society Advisory Panel. After the early termination of the Women’s Health Initiative Study. New American recommendations for postmenopausal hormone therapy. Läkartidningen. 2003;100(20):1790-1797.