Spontaneous Coronary Artery Dissection and Fibromuscular Dysplasia Do Not Share the Same Urinary Proteomic Signature

Objective: Spontaneous coronary artery dissection (SCAD) is a frequent but underdiagnosed cause of acute coronary syndrome in young-middle aged women, often associated with Fibromuscular Dysplasia (FMD). We developed a urinary proteomic classifier for discrimination of SCAD from controls, and tested its ability to discriminate SCAD patients from patients with primary FMD and patients with coronary artery disease (CAD). Design and method: The study included 56 patients with SCAD (women: 94.6%, median age: 45 years) with centrally confirmed diagnosis. The cohort was divided based on the absence (n=27) (discovery) or presence (n=29) of FMD (validation). Controls included 1286 individuals from population-based studies, 267 patients with CAD and 33 patients with FMD. Proteomics data were acquired through capillary electrophoresis coupled to mass spectrometry (CE-MS). Results: 190 urinary peptides, mostly related to collagen turnover, were identified in the discovery cohort, of which 114 were included into a classifier based on leave-one-out cross-validation. When applied in the validation cohort, the AUC of the SCAD classifier was 0.998 (100% sensitivity; 96.67% specificity). All patients with primary FMD and 90% of patients with CAD scored negative for the SCAD classifier. Conclusions: A proteomic score has the potential to discriminate between patients with SCAD, with primary FMD and with “classic” CAD. If confirmed in a wider cohort, these findings may pave the way for a non-invasive diagnostic test of SCAD. In SCAD patients, urinary proteomic profile was similar in presence or absence of extra-coronary FMD, and differed substantially from that observed in primary FMD, suggesting that FMD and SCAD are distinct entities.