Are we there yet? Closing the gender gap in coronary heart disease recognition, management and outcomes

Keywords::

• acute coronary syndromes
• cardiovascular disease
• coronary heart disease
• coronary revascularization
• gender gap
• prevention guideline
• risk factors
• women

Cardiovascular disease is the major contributor to both morbidity and mortality among US women and men, but the absolute numbers of women living with and dying from cardiovascular disease (CVD) and stroke are greater than for men [1]. A stunning advance in the past decade has been the decline by almost half in total CVD mortality for women, ascribed to improved control of major cardiovascular risk factors and improved management of established CVD, including secondary prevention. Concomitant, with this mortality decline, has been the near doubling of awareness of CVD as the major health problem for women; the heightened awareness resulted from initiatives of the National Heart, Lung, and Blood Institute (Heart Truth Campaign) and the American Heart Association (Red Dress Campaign). A new challenge is the increase in coronary heart disease (CHD) mortality among young women, 35 to 44 years of age [2], mandating increased CHD preventive efforts at younger age. Although women remain underrepresented in clinical trials of cardiovascular therapies [3], transformation of the research arena and results of recent landmark clinical trials arguably contributed to improvements in CHD care for women.

Even with recognition of gender differences in CHD burden, women are not a homogenous group. As an example, age-adjusted CHD mortality is 122 per 100,000 black women versus 94 per 100,000 white women. Hypertension, more common among black women, is currently increasing in prevalence, accounting for mortality of 37 per 100,000 black compared with 14 per 100,000 white women [1].

Prevention

The 2011 Cardiovascular Prevention Guideline for women [4], highlighted risk assessment and risk-based interventions, and also emphasized that global underestimation of cardiovascular risk for women resulted in adverse outcomes. The recurring finding that physician assessment of a woman's cardiovascular risk guides the intensity and quality of preventive therapies likely reflects the provider's misinterpretation of lower CVD risk for women.

Landmark research has changed CVD preventive care for women, initially with the documented lack of effectiveness of menopausal hormone therapy in preventing incident or recurrent CVD but with increased stroke risk [5–7]. Antioxidant supplementation with vitamins C, E and β-carotene and folic acid therapy with and without vitamin B supplementation (despite homocysteine lowering) have also been shown not to prevent incident or recurrent CVD in women [8–11]. Neither vitamin D nor calcium supplementation in the Women's Health Initiative decreased the risk of cardiovascular events or mortality [12–13]. Studies in women (in contrast to findings in men) showed that aspirin failed to lessen myocardial infarction (MI) below age 65, but decreased stroke risk (albeit accompanied by increased bleeding events) [14,15]. As for men, intensive diabetic control did not prevent CVD events in women [16]. Reduction of LDL cholesterol levels in women, with studies primarily involving statin drugs, dramatically decreased recurrent CVD events and likely decreased incident events [17,18].

Women have unique gender-specific risk characteristics. Pregnancy is now recognized as a 'stress test' for CVD, and hypertensive complications of pregnancy are established to confer future cardiovascular risk [19]. Of note is that successful fertility therapy did not increase cardiovascular risk later in life [20].

Acute coronary syndromes

Data from randomized clinical trials in acute coronary syndromes (ACS) have defined benefit of an early invasive strategy for intermediate and high-risk women, but highlighted women's increased bleeding risk related to antiplatelet therapy, predominantly due to lack of weight or creatinine-based dosage adjustment. It also highlighted that more women than men, and particularly in younger women, have non-chest-pain presentations of an ACS [21], information that requires intensive dissemination. Gender differences in ACS pathophysiology require elucidation. About half of women with a documented ACS do not have obstructive disease in their epicardial coronary arteries, hence such women are not candidates for revascularization procedures; however, application of guideline-directed secondary prevention measures are underutilized in these ACS women who do not undergo coronary revascularization.

The 30-day mortality in women with ACS is increased with ST elevation MI (STEMI), with predominant increase in the initial 24 h. This likely reflects differences in presentation and late recognition of MI [22]. The paradox of increased mortality in younger women [23] despite decreased risk remains unexplained. Recent data from the VIRGO study suggest that younger women had more medical problems, physical limitations and poorer mental health prior to MI than men. Women are under-referred to cardiac rehabilitation; they are more likely to die than men in the first year following MI [24].

Coronary revascularization

Although procedural and clinical success rates are essentially comparable with percutaneous coronary revascularization for women and men, in contrast to less favorable findings for women in earlier years, women continue to have excess procedural bleeding risks, and are more likely to incur procedure-related acute renal insufficiency. Drug-eluting stents are more effective and safe, long-term for women than bare metal stents [25].

Hospital mortality remains elevated for women with coronary artery bypass graft surgery (CABG), despite better long-term outcomes than their male peers. The potential benefit of off-pump CABG for women [26] requires further confirmation/ascertainment. Women experience less relief from angina with CABG than do men.

Unmet needs

Although both the Institute of Medicine [3] and the Agency for Healthcare Quality (AHRQ) have emphasized the necessity for parity in the enrollment of women in clinical trials of CVD, the median enrollment of women in randomized trials has remained unchanged since 2004 [27]. This challenge is compounded by failure to present disaggregated data regarding gender which challenges the clinician to define gender-specific safety and effectiveness.

Unquestionably, our journey to gender parity has begun. It has effected improvement in CVD outcomes for women. However, the odyssey must continue – we are not there yet!

Expert commentary

Despite the striking improvement in women's cardiovascular mortality during the past decade, CHD remains the leading cause of death among US women, whose survival is less favorable than that for men. More cardiovascular deaths continue to occur annually among US women than men, with coronary deaths in women exceeding those from all forms of cancer combined. Although we have witnessed increased public and professional awareness for CHD among women, this problem remains understudied, underdiagnosed and undertreated. Contributors to adverse CHD outcomes for women include the limited public and professional awareness of women's coronary risk burden; gaps in knowledge regarding women's symptom presentation, optimal screening and diagnostic procedures and inadequate application of guideline-directed preventive, lifestyle, medical and interventional therapies. As I delineated in a previous publication [24], my major recommendations to improve coronary outcomes in women include:

• • to increase the inclusion of women in CHD trials, with analysis and reporting of gender-stratified data;

• • to delineate the biologic mechanism(s) underlying the pathophysiology of ischemic heart disease in women, with emphasis on microvascular disease;

• • to increase the awareness of CHD risk by women and their healthcare providers;

• • to increase the application of evidence-based data to guide prevention, recognition and management strategies for CHD in women, including focus on microvascular disease;

• • to explore psychosocial/environmental/sociocultural disciplines and their relationship(s) to CHD and cardiovascular illness, including differential impacts by gender;

• • to explore political (including public policy), economic, business, ethical, legal and regulatory, community (global, regional, local), faith-based and cultural associations and interrelationships with women's coronary and cardiovascular health.

Five-year view

Attention to gender disparities will improve the awareness, prevention, recognition, treatment and outcomes of CHD in women. Closing the research gap will elucidate gender-specific coronary pathophysiology, identify optimal diagnostic strategies, effective lifestyle, pharmacologic and invasive interventions, explore genomic issues and focus attention on subpopulations of women socially disadvantaged because of race or ethnicity, income level or educational attainment. We must appreciate that women's heart health is not solely a medical issue but also an economic, legal and regulatory, psychosocial, ethical, faith-based, cultural, environmental, community, health systems and political and public policy issue, globally. Thus, women's cardiovascular health research will involve not only basic and clinical research scientists, but healthcare providers, women and their families, governmental officials and agencies and members of Congress.

Key issues

• • Despite a striking decline in cardiovascular mortality for women during the past decade, more US women than men are currently living with and dying from cardiovascular disease.

• • Women remain underrepresented in clinical research studies of cardiovascular disease and cardiovascular therapies; and reported studies often fail to provide gender-specific analyses.

• • Landmark research has substantially altered cardiovascular preventive recommendations for women. This new information requires effective communication to women, to the public, to healthcare providers and to policymakers.

• • Coronary heart disease remains under-recognized in women. Diagnostic procedures are often deferred or suboptimally selected, likely owing to the misperception of lesser coronary risk for women.

• • Women have a less favorable prognosis with acute coronary syndromes. Despite their higher risk characteristics and higher in-hospital risks, they are less likely to receive coronary interventions and guideline-directed medical therapies.

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.