Gender-Related Differences in Chest Pain Syndromes in the Frontiers in CV Medicine Special Issue: Sex & Gender in CV Medicine

Abstract

Coronary artery disease (CAD) is the leading cause of morbidity and mortality among both women and men, yet women continue to have delays in diagnosis and treatment. The lack of recognition of sex-specific biological and socio-cultural gender-related differences in chest pain presentation of CAD may, in part, explain these disparities. Sex and gender differences in pain mechanisms including psychological susceptibility, the autonomic nervous system (ANS) reactivity, and visceral innervation likely contribute to chest pain differences. CAD risk scores and typical/atypical angina characterization no longer appear relevant and should not be used in women and men. Women more often have ischemia with no obstructive CAD (INOCA) and myocardial infarction, contributing to diagnostic and therapeutic equipoise. Existing knowledge demonstrates that chest pain often does not relate to obstructive CAD, suggesting a more thoughtful approach to percutaneous coronary intervention (PCI) and medical therapy for chest pain in stable obstructive CAD. Emerging knowledge regarding the central and ANS and visceral pain processing in patients with and without angina offers explanatory mechanisms for chest pain and should be investigated with interdisciplinary teams of cardiologists, neuroscientists, bio-behavioral experts, and pain specialists. Improved understanding of sex and gender differences in chest pain, including biological pathways as well as sociocultural contributions, is needed to improve clinical care in both women and men.

Keywords: INOCA; chest pain; coronary artery disease; gender; sex.

Figure 1

Prevalence of “Normal” and non-obstructive coronary arteries in women and men. Normal (no visible angiographic disease) or non-obstructive coronary arteries (luminal irregularities <50%) is found more often in women than men who undergo invasive coronary angiography for acute coronary syndrome and ST-segment elevation myocardial infarction. Reprinted with permission (14).

Figure 2

Psychological stress, risk factors, and cardiovascular disease. Acute episodes of mental stress superimposed on chronic stress influence the cardiovascular stress response involving autonomic dysfunction, cardiometabolic dysfunction, endothelial dysfunction, and inflammatory pathways. These pathways are modulated by cardiac risk factors leading to adverse cardiovascular outcomes.

Figure 3

Calibration plots of risk score-specific predicted vs. observed rate of events. Commonly used cardiovascular risk scores significantly underestimate risk in women with ischemia and no obstructive CAD. Dotted line is the reference line for equal predicted and observed risk. Solid line is the observed risk. ASCVD, Atherosclerotic Cardiovascular Disease risk score; ATP III-FRS, Adult Treatment Panel III risk score; FRS, Framingham Risk Score; QRISK2, cardiovascular risk score; RRS, Reynolds Risk Score; and SCORE, Systematic Coronary Risk Evaluation. Reprinted with permission (66).

Figure 4

Stomach and chest angina symptoms in black women vs. white women with suspected CAD. Symptom clusters were derived from a cohort of 466 women (69 black,397 white) undergoing coronary angiography for suspected CAD. Chest symptoms included chest discomfort, pressure, tightness, fatigue, and shortness of breath. Stomach symptoms included indigestion, esophagus, throat, and abdomen symptoms. Mean adjusted chest and stomach scores stratified by race (black vs. white) and presence vs. absence of obstructive CAD. Reprinted with permission (76).

Figure 5

The economic burden of angina in women with suspected ischemic heart disease. Estimated lifetime costs (including sensitivity analyses ranges) of pharmacologic therapy and hospitalization for cardiovascular disease in women with non-obstructive and 1-vessel to 3-vessel CAD. Reprinted with permission (103).

Figure 6

Event-free survival from cardiovascular events by coronary artery disease and persistent chest pain. Cardiovascular events for women with and without persistent chest pain (PChP) in subgroups with and without obstructive CAD. Cardiovascular events defined as cardiovascular death, MI, CHF, or stroke. Reprinted with permission (105).

Figure 7

Angina hospitalization rates in women with signs and symptoms of ischemia but no obstructive CAD. Angina hospitalization event-free survival in women with no CAD (<20% stenosis) and non-obstructive CAD (≥20 to <50% stenosis). Reprinted with permission (104).