The Yentl syndrome and gender inequality in ischemic HD

Issue: August 2011

ByC. Noel Bairey Merz, MD, FACC, FAHA

C. Noel Bairey Merz, MD
C. Noel Bairey Merz

More women than men die annually of ischemic heart disease, which represents a reversal of fortune from prior decades and places women firmly as the new majority now affected. The adverse ischemic heart disease (HD) gender gap is the widest in relatively young women, where MI mortality is twofold higher in women younger than 50 years compared with age-matched men. Although it is clear that there are many gender differences in ischemic HD outcomes, including more frequent angina diagnosis, more office visits, more avoidable hospitalizations, higher MI mortality, and higher rates of HF in women compared with men, the contributing etiologies to these differences are unclear.

Gender differences highlighted

A number of contradictory findings are evident with regard to sex differences in ischemic HD: Women have a higher prevalence of angina compared with men, yet have an overall lower prevalence of obstructive CAD; symptomatic women undergoing coronary angiography have less extensive and severe obstructive CAD, despite being older with higher risk factor burden compared with men; and despite relatively less obstructive CAD, women have a more adverse prognosis compared with men. We have hypothesized an alternative, female-specific pattern of ischemic HD due to the relatively high frequency of microvascular coronary dysfunction in symptomatic women with and without obstructive CAD, which we have linked with symptoms, ischemia and adverse outcomes. This alternative “female-pattern” of ischemic HD is not easily recognized, given our male-pattern strategies aimed at detection and treatment of obstructive CAD.

What relevance does this have to the adverse gender gaps for ischemic HD in women? The literature suggests that when women look like men (with “male-pattern” obstructive CAD), they are more likely to be diagnosed and treated as men are treated. As characterized by the “Yentl” syndrome, depicted in the Barbra Streisand movie of the same name, Bernadine Healy, MD, used this term in 2001 to call attention to the paradox of adverse outcomes of women with ischemic HD, as well as the under-diagnosis and under-treatment of women.

Ten years later, recent analyses published in the European Heart Journal suggest that Yentl syndrome remains evident in 2011. Johnson and colleagues compared diagnostic coronary angiography, medication usage, and outcomes in 12,200 women and men with stable signs and symptoms of ischemic HD and 2-year outcomes in Sweden between 2006 and 2008. Bugiardini and colleagues summarized medication usage and outcomes in 6,558 women and men with ACS with 1-year outcomes from the Canadian ACS Registry I and II between 1999 and 2003. Both studies demonstrate under-treatment of women with medication, including lower rates of aspirin and ACE inhibitor use in stable women compared with men, as well lower rates of ACE inhibitor, beta-blocker and statin medication in ACS women compared with men. Both studies also show gender differences in use of procedures, where interestingly, stable women undergo more repeat angiography, whereas ACS women undergo fewer index angiograms, percutaneous coronary interventions and CABG compared with their male counterparts. The adverse outcomes described in these new works are consistent with prior literature. Both studies demonstrate adverse gender differences for women; Stable women have more MIs while ACS women have higher death rates compared with men.

Women remain undertreated

The Swedish data report equivalent use of the four life-saving medication strategies (ACE inhibitors, beta-blockers, aspirin and statins) among stable women and men after angiographic diagnosis of obstructive CAD. Importantly, appropriate medication utilization was accompanied by equivalent mortality between the sexes, although event rates were predictably lower in this stable lower-risk population. Prior work has shown an improvement of ischemic HD prognosis in women over time. Nevertheless, other contemporary data demonstrate persistently more adverse outcomes for women compared with men. The Canadian Registry analysis adds to the accumulated literature that women with ACS remain less likely than men to receive indicated diagnostic tests, guideline-indicated medication and procedures and subsequently suffer predictable higher rates of adverse outcomes.

Given the emphasis on guidelines therapy, why are women still undertreated with appropriate ischemic HD guidelines therapy? Both of these new studies provide similar clues. The Canadian Registry data demonstrate that female sex, despite adjustment for multiple associated variables, independently remains associated with under-utilization of guidelines therapy for ACS patients. The Swedish data demonstrate that the relatively large differences in medication between women and men before coronary angiography vanished following demonstration of obstructive CAD at angiography. These findings, which are consistent with prior literature, argue against cultural, “gender-based” factors, including misogyny and sexism, as a driving force for drug under-utilization in women, and suggest alternatively that biological, “sex-based” differences are key contributors. We can conclude from these studies and the prior literature that the presence or absence of obstructive CAD (eg, “male-pattern” ischemic HD) remains a key decision point in medication prescription for practicing physicians. Because higher proportions of women with ischemic HD present without obstructive CAD or undergo less coronary angiography, relatively fewer women will be treated, including those with evident ACS (for which guideline medication is not linked to angiography).

Toward improved outcomes

We have estimated the prevalence of signs and symptoms of ischemic HD in the absence of obstructive CAD using the NCDR database to be between 2 and 3 million women, placing it as a larger health care threat to women than breast cancer, and comparable to the highly prevalent 6 million women with clinically documented obstructive CAD in the US alone. Accordingly, two guidelines now specify strategies for women, including the AHA/ACC Prevention of Cardiovascular Disease in Women, and the AHA/ACC Management of Patients with Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction. Moreover, ischemic HD strategies that provide guideline-driven infrastructure support to physicians such as the AHA Get with the Guidelines and the ACC Guidelines Applied in Practice initiatives appear to have the largest impact on closing therapeutic gender-gaps that disadvantage women.

While increasing knowledge exists regarding pathophysiological mechanistic pathways for “female-pattern” ischemic HD, translational studies aimed at developing practical diagnosis and therapeutics with both traditional and novel treatments are needed. Further closure of knowledge gaps related to the paradox and the pathophysiology of ischemic HD in women is one of our highest priorities to improve the health of the 51% of the population that is female and who currently represent the majority of deaths.

C. Noel Bairey Merz, MD, is director of the Women’s Heart Center at Cedars Sinai Medical Center in Los Angeles and a member of the Cardiology Today Editorial Board.

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Disclosure: Dr. Bairey Merz reports no relevant financial disclosures.