Plaque composition in symptomatic versus asymptomatic women and men: data from the CONFIRM2 registry

Background Coronary artery disease (CAD) risk assessment in clinical practice is largely guided by symptom-based strategies. However, a substantial proportion of myocardial infarctions occur without preceding symptoms, and women frequently present with heterogeneous symptoms. This raises questions about the clinical relevance of symptoms for cardiovascular prognosis. Purpose The present study, in a large cohort of patients undergoing clinically indicated coronary computed tomography angiography (CCTA), aimed to evaluate the association between symptom status and coronary plaque burden, including sex-stratified analyses, as a robust predictor of cardiovascular events. Methods CONFIRM2 is a multicenter, international cohort study of subjects undergoing clinically indicated CCTA. Symptomatic and asymptomatic patients with suspected CAD were selected. CCTA scans were analyzed using artificial intelligence–based quantitative computed tomography (AI-QCT). Patients were categorized into three groups based on symptom status: asymptomatic, typical angina, and other symptoms. Outcomes included quantitative plaque burden, composition, and ischemia classification (FFR≤80) from AI-QCT. Multivariable models were adjusted for clinical risk factors (age, sex, diabetes, hypertension, dyslipidemia, smoking status, family history of CAD, atrial fibrillation, and heart failure). Results A total of 7,879 patients were included (mean age 58.7 years; 49% women; mean follow-up 4.5 years). In both men and women, symptom status was not associated with total, noncalcified, or calcified plaque volume (p>0.05 for all comparisons) (Table 1). In adjusted multivariable analysis in men, typical angina was associated with 5.8 percentage-point increase in diameter stenosis severity (p<0.001), a 66% higher risk of ischemia (aOR 1.66, p=0.008) and more than threefold higher odds of high-risk plaque (aOR 3.20, p<0.001) (Tables 1&2). In contrast, symptoms showed no association with these features in women. Conclusion These findings indicate that the presence of symptoms does not reflect the extent of underlying atherosclerosis and thus cardiovascular risk in either women or men. While symptoms were indicative of flow-limiting lesions in men, this association was not observed in women. This adds to growing evidence highlighting the limitations of symptom-based risk stratification—particularly in women—and supports a potential role for objective plaque characterization in CAD risk assessment.