Carotid and femoral plaque burden identifies different risk phenotypes among patients with early events of coronary artery disease: the CAFEECOR study

Background Early events in patients with coronary artery disease (eCAD) are increasing, but the underlying mechanisms remain controversial. Studying atherosclerosis plaque burden (PB) non-invasively by vascular ultrasound (VUS) may improve risk characterization and provide insight into the involved processes in each patient. Purpose To study, for the first time, the prevalence and extent of PB in secondary prevention patients using novel 3D-VUS method, and determine the relationship between plaque volume and cardiovascular risk factors (CVRF) with the aim of identifying distinct risk phenotypes in eCAD patients. Methods Consecutive patients with eCAD (<60 years old) were prospectively enrolled in a tertiary center. Conventional, atypical and emergent CVRF and blood biomarkers were systematically studied. Global PB (GPB) was defined as the sum of all plaque volumes in both carotid and femoral arteries, and GPB quartiles were used to classify patients into 3 severity categories (no-or-mild, moderate, and severe GPB). Phenotypic clinical and biochemical variations among GPB categories was studied with Factor Analysis for Mixed Data (FAMD) model; and uni and multivariate associations between CVRF and GPB were determined by ordered logistic regression models. In addition, we compared the results obtained in an age-matched subcohort (N=101) of CAFEECOR patients with those published by the population-based study of reference for GPB, the PESA study. Results We included 231 patients with eCAD (53±5yo; 14% women; 23% with a prior CV event; 52% presented with STEMI). High prevalence of conventional and atypical CVRFs was observed (low HDL 66%, obesity 39%, hypertriglyceridemia 38%, elevated lipoprotein(a) 28%, family history of CV disease 25%, hyperuricemia 25%, and hyperhomocysteinemia 14%). GPB was very high in the cohort, being higher in the femoral compared with the carotid territory (200.6 mm3 [IQR 51.7-420.7] vs 35.2 mm3 [IQR 7.9-96.2], p<0.001), in stable versus unstable CAD (409 mm3 [IQR 166.1-742.1] vs 258.4 mm3 [IQR 71.8-464.6], p=0.008), and increased with age. Compared to the PESA cohort, eCAD patients demonstrated a markedly higher GPB (GBP 50.8 mm3 [18.7 – 121.5] vs 284.1 mm3 [IQR 110-546.8], respectively) even after adjusting for age and number of affected territories. GPB correlated with both conventional and atypical CVRF (Figure 1). FAMD model revealed that severe GPB (p>75) identifies a subgroup patients in whom conventional CVRF and a history of prior CV events predominated, whereas the effect of atypical CVRF was marginal (Figure 2). Conclusion GPB by 3DVUS is a simple marker that allows the identification of different pathophysiological phenotypes in patients with eCAD and has the potential to help design individualized treatment and prevention strategies. For the first time, we established the extent of GPB in eCAD patients compared to asymptomatic individuals, reinforcing its usefulness in identifying patients at risk.