Emergence of Nonobstructive Coronary Artery Disease: A Woman's Problem and Need for Change in Definition on Angiography

Abstract

Recognition of ischemic heart disease (IHD) is often delayed or deferred in women. Thus, many at risk for adverse outcomes are not provided specific diagnostic, preventive, and/or treatment strategies. This lack of recognition is related to sex-specific IHD pathophysiology that differs from traditional models using data from men with flow-limiting coronary artery disease (CAD) obstructions. Symptomatic women are less likely to have obstructive CAD than men with similar symptoms, and tend to have coronary microvascular dysfunction, plaque erosion, and thrombus formation. Emerging data document that more extensive, nonobstructive CAD involvement, hypertension, and diabetes are associated with major adverse events similar to those with obstructive CAD. A central emerging paradigm is the concept of nonobstructive CAD as a cause of IHD and related adverse outcomes among women. This position paper summarizes currently available knowledge and gaps in that knowledge, and recommends management options that could be useful until additional evidence emerges.

Keywords: adverse outcomes; ischemia; sex-specific pathophysiology.

Central Illustration. Nonobstructive CAD in Women: Sex-Specific CAD and Need for Ischemic Cardiac Disease Definition Changes

Among patients presenting with symptoms/signs suspect for IHD, the presence of obstructive CAD (e.g., identifying a flow-limiting lesion, FFR <0.80) is highly prevalent in men (and older women), and often associated with reduced LV systolic function. Diagnosis and risk stratification are prompt because guideline-specific diagnostic, preventive, and/or treatment strategies are available. In contrast, nonobstructive CAD (e.g., FFR ≥80) is highly prevalent among women (mostly younger and middle-aged women) with preserved LV systolic function. Additionally, pharmacological testing with acetylcholine and adenosine distinguishes those with macrovascular or microvascular spasm, endothelial dysfunction, and/or coronary microvascular dysfunction (CMD). These latter findings are associated with increased risk of adverse outcomes that include heart failure with preserved systolic function (HFpEF), acute coronary syndromes, and cardiovascular-related hospitalizations, as well as repeated testing, Unfortunately, no guideline-recommended assessment or management is available, except for symptom relief and CVD risk factor management. CAD = coronary artery disease; CVD = cardiovascular disease; IHD = ischemic heart disease; LV = left ventricular.