Sex Differences in Psychosocial Factors and Angina in Patients With Chronic Coronary Disease

Abstract

BACKGROUND: Women with chronic coronary disease have more frequent angina and worse health status than men, despite having less coronary artery disease (CAD). We examined whether perceived stress and depressive symptoms mediate sex differences in angina, and whether this relationship differs in the setting of obstructive CAD or ischemia with no obstructive coronary artery disease (INOCA). METHODS: We analyzed the association between sex, stress (Perceived Stress Scale-4) and depressive symptoms (Patient Health Questionnaire-8) on angina-related health status (Seattle Angina Questionnaire [SAQ]) at enrollment in the ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) trial and CIAO-ISCHEMIA (Changes in Ischemia and Angina Over 1 Year Among ISCHEMIA Trial Screen Failures With No Obstructive CAD on Coronary CT [Computed Tomography] Angiography) ancillary study. RESULTS: Scores for the SAQ, Perceived Stress Scale-4, and Patient Health Questionnaire-8 were available in 1626 participants (N=1439 CAD and N=187 INOCA). Women had lower (worse) SAQ-7 summary scores than men in both CAD and INOCA cohorts (CAD: median 76 [25th, 75th percentiles 60, 90] versus 83 [70, 96], P<0.001; INOCA: 80 [64,89] versus 85 [75, 93], P=0.012). Higher stress and depressive symptoms were associated with worse angina in both cohorts. Female sex, Perceived Stress Scale-4 score, and Patient Health Questionnaire-8 score were each independently associated with lower SAQ summary score, but CAD versus INOCA cohort was not. There was no interaction between sex and stress (−0.39 [95% CI, –1.01 to 0.23]) or sex and depression (−0.00 [95% CI, –0.53 to 0.53]) on SAQ summary score. CONCLUSIONS: High stress and depressive symptoms were independently associated with worse angina and poorer health status, without interaction with sex with or without obstructive CAD. Factors other than stress or depression contribute to worse health status in women with obstructive CAD or INOCA. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02347215, NCT01471522. © 2025 The Author(s). Published on behalf of the American Heart Association, Inc., by Wiley.