Sex-Based Disparities in Atherosclerotic Cardiovascular Disease Care

Although the use of lipid-lowering medication is recommended for all patients with an intermediate or high risk for atherosclerotic cardiovascular disease (ASCVD), research has shown that women receive less aggressive lipid management compared with men, despite evidence of similar benefits.^1,2 Consistent with those observations, findings from 2 recent studies demonstrate that women are less likely than men to receive statin therapy for both primary and secondary prevention of ASCVD.^3,4

In a study published in December 2021 in the American Journal of Cardiology, Metser et al analyzed electronic health record data from 7,550 patients who were eligible for primary prevention statin therapy at the time of consultation with a primary care physician or cardiologist. The results showed that 52.9% of eligible patients were prescribed statins, and women were less likely than men to receive a prescription for statin therapy (adjusted odds ratio [aOR], 0.79; 95% CI, 0.71-0.88).³

In a cross-sectional, multicenter study published in July 2021 in JAMA Cardiology, Lee et al examined sex disparities in secondary prevention care among 147,600 patients with premature ASCVD (age ≤55 years; 7.1% women) and extremely premature ASCVD (age ≤40 years; 14.1% women), who were treated by a primary care provider within the Veterans Affairs healthcare system. The sample included patients with ischemic heart disease (IHD), ischemic cerebrovascular disease (ICVD), and peripheral arterial disease (PAD).⁴

Compared with men, women with premature IHD were less likely to receive antiplatelet therapy (aOR, 0.47; 95% CI, 0.45-0.50), any statin (aOR, 0.62; 95% CI, 0.59-0.66), or high-intensity statins (aOR, 0.63; 95% CI, 0.59-0.66) and were less adherent to statin therapy (mean [SD] PDC, 0.68 [0.34] vs 0.73 [0.31]; β coefficient: −0.02; 95% CI, −0.03 to −0.01). Similar disparities in prescription patterns were noted among patients with premature ICVD and premature PAD.⁴

Women with extremely premature ASCVD were also less likely to receive antiplatelet therapy (aOR, 0.61; 95% CI, 0.53-0.70), any statin therapy (aOR, 0.51; 95% CI, 0.44-0.58), and high-intensity statin therapy (aOR, 0.45; 95% CI, 0.37-0.54) compared with men.⁴

These results align with those of earlier research, including a 2019 study of 5,693 statin-eligible patients (43% women) that found that women were less likely than men to receive any statin therapy (67.0% vs 78.4%, P<.001) or to receive statins at the guideline-recommended intensity (36.7% vs 45.2%, P<.001) for both primary and secondary indications.⁵

After adjustment for various demographic, socioeconomic, and clinical confounders, as well as patient beliefs and provider characteristics, these disparities in overall statin prescription (aOR, 0.70; 95% CI, 0.61-0.81; P<.001) and recommended intensity (OR, 0.82; 95% CI, 0.73-0.92; P<.01) persisted. “A combination of [women] being offered statin therapy less frequently, while declining and discontinuing treatment more frequently, accounted for these sex differences in statin use,” the authors wrote.⁵

We learned more about these disparities and implications for clinicians in interviewswithRadmila Lyubarova, MD, FACC, FASE, associate professor of medicine in the division of cardiology at Albany Medical Center in New York and coauthor of a 2021 review² on the topic; and Michael G. Nanna, MD, MHS, assistant professor of medicine in the section of cardiovascular medicine at Yale University School of Medicine in New Haven, Connecticut, and first author of the 2019 study described above.⁵  

What does the literature suggest thus far about sex-related disparities in ASCVD care? What may contribute to these differences?

Dr Lyubarova: I feel the most important factor causing sex-related disparities is underestimation of cardiovascular disease [CVD] risk in women. While heart disease is the leading cause of mortality in women, CVD typically occurs on average 7-10 years later in women than men.² This contributes to a misperception that women develop less heart disease and are somewhat protected from CVD, and thus can be treated less aggressively.

However, as women typically have a longer lifespan, more women have heart disease at older ages. Furthermore, traditional coronary artery disease risk factors often have stronger potency in women. In addition, it is important to recognize unique sex-specific CVD risk factors such as pregnancy-related conditions, hormonal factors, menopause-related syndromes, and inflammatory autoimmune conditions, which more commonly affect women.

Dr Nanna: Sex differences in the prevention, diagnosis, and treatment of CVD have been repeatedly demonstrated across multiple decades. For example, we know that women are less likely to receive statins for primary and secondary prevention and anticoagulation for atrial fibrillation.⁶ These differences are likely related to a confluence of contributors including patient, clinician, and systemic factors.

What measures are needed to reduce these disparities, including specific recommendations for clinicians to address this issue in practice?

Dr Lyubarova: It is important to improve clinician education and awareness of high CVD risk in women, as well sex-specific differences. It is also important to improve self-awareness among female patients. With nationwide efforts and the ongoing Go Red for Women AHA campaign, self-awareness was improving from late 1990s and 2000s, but has been declining in recent years (2009-2019), especially among Hispanic and non-Hispanic Black women.⁷

It is crucial to improve representation of female patients in cardiovascular trials. Historically, women of childbearing age and older patients were excluded from the majority of trials. This, in addition to other factors, led to preferential recruitment of male participants. There have recently been efforts on the government level to mandate adequate representation of women in federally funded research.

In addition to increasing enrollment of women, it is important to incorporate sex-based analysis and women-specific outcomes in cardiovascular research, to have a better understanding of differences in pathophysiology and management of heart disease in women.⁸

Dr Nanna: Every clinician has the responsibility to provide equitable care to their patients. Combatting these health disparities begins at the level of the individual clinician, with an emphasis on raising awareness about sex differences in care and recognizing bias. The responsibility extends to health systems to actively monitor for sex differences in the care provided and leveraging the electronic health record to identify opportunities for improvement in real time. Finally, policy makers at the local, state, and federal level must consider quality metrics and value-based payment models to prioritize closing these gaps.⁶

What are additional remaining needs to address sex-based disparities in ASCVD care?

Dr Nanna: More work must be done across the research, education, and clinical domains to address this important issue. Further research efforts are needed to better understand the underlying drivers of sex differences in cardiovascular care while informing future interventions. Prospective evaluation of these interventions, specifically targeted at fostering equitable care, will also be necessary to determine the optimal approach to eliminate sex differences in care.

References

1. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019;73(24):3168-3209. doi:10.1016/j.jacc.2018.11.002
2. Peterson KA, Kaur G, Gianos E, et al. Challenges in optimizing lipid management in women. Cardiovasc Drugs Ther. Published online October 18, 2021. doi:10.1007/s10557-021-07273-0
3. Metser G, Bradley C, Moise N, Liyanage-Don N, Kronish I, Ye S. Gaps and disparities in primary prevention statin prescription during outpatient care. Am J Cardiol. 2021;161:36-41. doi:10.1016/j.amjcard.2021.08.070
4. Lee MT, Mahtta D, Ramsey DJ, et al. Sex-related disparities in cardiovascular health care among patients with premature atherosclerotic cardiovascular disease. JAMA Cardiol. Published online April 21, 2021. doi:10.1001/jamacardio.2021.0683
5. Nanna MG, Wang TY, Xiang Q, et al. Sex differences in the use of statins in community practice. Circ Cardiovasc Qual Outcomes. 2019;12(8):e005562. doi:10.1161/CIRCOUTCOMES.118.005562
6. Khazanie P, Ho PM. Leveraging value-based payment models to reduce sex differences in care. Circ Cardiovasc Qual Outcomes. 2019;12(8):e006038. doi:10.1161/CIRCOUTCOMES.119.006038
7. Cushman M, Shay CM, Howard VJ, et al; American Heart Association. Ten-year differences in women’s awareness related to coronary heart disease: results of the 2019 American Heart Association National Survey: A Special Report From the American Heart Association. Circulation. 2021.;143(7):e239-e248. doi:10.1161/CIR.0000000000000907
8. Wang SC, Koutroumpakis E, Schulman-Marcus J, Tosh T, Volgman AS, Lyubarova R. Sex differences remain under-reported in cardiovascular publications. J Womens Health (Larchmt). Published online September 15, 2021. doi:10.1089/jwh.2020.8561