Cholesterol Crystals at the Culprit Lesion in Patients with Acute Coronary Syndrome Are Associated with Worse Cardiovascular Outcomes at Two Years Follow Up - Results from the Translational OPTICO-ACS Study Program

Background: Cholesterol crystals (CCs) represent a feature of advanced atherosclerotic plaque and may be assessed by optical coherence tomography (OCT). Their impact on cardiovascular outcomes in patients presenting with acute coronary syndromes (ACS) is yet unknown. Methods: The culprit lesion (CL) of 346 ACS -patients undergoing preintervention OCT imaging were screened for the presence of CCs and divided into two groups accordingly. The primary end -point was the rate of major adverse cardiac events plus (MACE+) consisting of cardiac death, myocardial infarction, target vessel revascularization and re -hospitalization due to unstable or progressive angina at two years. Results: Among 346 patients, 57.2% presented with CCs at the CL. Patients with CCs exhibited a higher prevalence of ruptured fibrous caps (RFC -ACS) (79.8% vs. 56.8%; p < 0.001) and other high -risk features such as thin cap fibroatheroma (80.8% vs. 64.9%; p = 0.001), presence of macrophages (99.0% vs. 85.1%; p < 0.001) as well as a greater maximum lipid arc (294.0 vs. 259.3; p < 0.001) at the CL as compared to patients without CCs. MACE+ at two years follow-up occurred more often in CC -patients (29.2% vs. 16.1%; p = 0.006) as compared to patients without CCs at the culprit site. Multivariable cox regression analysis identified CCs as independent predictor of MACE+ (HR 1.705; 1.025-2.838 CI, p = 0.040). Conclusions: CCs were associated with conventional high -risk plaque features and associated with increased MACE+ -rates at two years follow up. The identification of CCs might be useful as prognostic marker in patients with ACS and assist "precision prevention" in the future.