Women and Coronary Heart Disease: A Century after Herrick; Understudied, Underdiagnosed, and Undertreated
Authors: Wenger Nanette 
Published: April 2024

In 1912, James B. Herrick, an icon for the clinician/scientist, postulated and documented coronary thrombosis as the mechanism for myocardial infarction (MI), highlighted that sudden death was not inevitable in MI, and later explored the diagnostic potential of the electrocardiogram for MI recognition.
Once viewed as a “man's disease,” coronary heart disease (CHD) is currently the leading cause of mortality for women, with more coronary deaths occurring annually among U.S. women than men. Despite their burden of cardiovascular disease, women remain underrepresented in clinical trials (27% in mixed-gender NIH trials) and when included are disadvantaged by absence of gender-specific analyses. Lack of public and professional awareness of women's coronary risk; lack of knowledge regarding women's symptom presentation, optimal screening and diagnostic procedures; and gender disparities in application of evidence-based therapies all contribute to adverse outcomes.
Angina is the major initial and subsequent presentation of CHD among women. Despite their excess of angina and its consequent morbidity and mortality, women have less severe obstructive coronary disease at angiography than men. Yet the male model of CHD, i.e., obstructive atherosclerosis of the epicardial coronary arteries, constitutes the basis for diagnostic and therapeutic strategies for both sexes. Comparative effectiveness research is requisite to select optimal strategies to evaluate symptoms of suspected myocardial ischemia in women. Anginal equivalents, the non-chest pain symptoms encountered in both genders but predominating in women, remain underrecognized and understudied. Myocardial ischemia with adverse outcomes, in the absence of coronary obstructive disease, is an emerging paradigm for women, with data derived from the NHLBI Women's Ischemia Syndrome Evaluation (WISE) study.
But insights are needed into the underlying mechanism(s) and optimal recognition and therapy for microvascular disease. What do we do when disease discriminates? In numerous clinical settings, women with CHD have more unfavorable outcomes than men. The young woman (< age 50) with CHD, particularly after MI and after CABG surgery, has substantially greater mortality than her male peers. With all coronary presentations, women sustain an excess of bleeding complications; to date, investigations have failed to elucidate mechanisms of gender differences in blood vessels or in blood function underlying women's bleeding risk. In the Get with the Guidelines database, undertreatment of women with ST-elevation MI with evidence-based therapies and delayed reperfusion was associated with increased early mortality, but its remediation offers the opportunity to improve outcomes.
Does a woman's heart beat to the tune of a different drummer? Women with heart failure far more frequently than men have intact ventricular systolic function. Effective treatments for diastolic heart failure remain elusive, likely accounting for its unchanged prognosis, in contrast to decreased hospitalizations and improved survival with systolic heart failure. Peripartum cardiomyopathy remains poorly understood. Women with systolic heart failure benefit preferentially from cardiac resynchronization therapies, yet these procedures are underutilized in women. Although atrial fibrillation is more likely associated with stroke and mortality in women, undertreatment with anticoagulation is pervasive.
Nonetheless, awareness campaigns and application of evidence-based therapies underlie the dramatic decrease in CV mortality for U.S. women since 2000, due both to preventive interventions and to improved management of established disease. Gender-specific basic and clinical research studies and application of emerging knowledge offer promise to improve CHD outcomes for women, just as Herrick's scholarly observations constituted the underpinnings for a century of antithrombotic strategies for CHD.