Identification of Specific Coronary Artery Disease Phenotypes Implicating Differential Pathophysiologies

Background and Aims: The roles of multiple risk factors of coronary artery disease (CAD) are well established. Commonly, CAD is considered as a single disease entity. We wish to examine whether coronary angiography allows to identify distinct CAD phenotypes associated with major risk factors and differences in prognosis. Methods: In a cohort of 4,344 patients undergoing coronary angiography at Heidelberg University Hospital between 2014 and 2016, cluster analysis of angiographic reports identified subgroups with similar patterns of spatial distribution of high-grade stenoses. Clusters were independently confirmed in 3,129 patients from the LURIC study. Results: Four clusters were identified: cluster one lacking critical stenoses comprised the highest percentage of women with the lowest cardiovascular risk. Patients in cluster two exhibiting high-grade stenosis of the proximal RCA had a high prevalence of the metabolic syndrome, and showed the highest levels of inflammatory biomarkers. Cluster three with predominant proximal LAD stenosis frequently presented with acute coronary syndrome and elevated troponin levels. Cluster four with high-grade stenoses throughout had the oldest patients with the highest overall cardiovascular risk. All-cause and cardiovascular mortality differed significantly between the clusters. Conclusions: We identified four phenotypic subgroups of CAD bearing distinct demographic and biochemical characteristics with differences in prognosis, which may indicate multiple disease entities currently summarized as CAD.