Abstract 14606: Endothelial Injury Biomarkers and Risk Factors Associated With Discordant Risk of Acute Coronary Syndrome Despite Controlled Low-density Lipoprotein Cholesterol Identified by a Novel Coronary Artery Disease Predictive Algorithm

Abstract

Background: Individuals with no history of coronary artery disease can develop acute coronary syndrome (ACS), often in the absence of major risk factors including low-density lipoprotein cholesterol (LDL-C). We identified risk factors and biomarkers that can help identify those at discordantly high risk of ACS who have normal LDL-C using a novel coronary artery disease predictive algorithm (CADPA) incorporating biomarkers of endothelial injury validated in the Multi-Ethnic Study of Atherosclerosis cohort. Methods: Five-year predicted ACS risk was calculated using the CADPA for 8589 patients. Common risk factors and serum levels of 9 biomarkers utilized by the CADPA were tracked. We identified a “discordant high ACS” risk group with serum LDL-C < 130 mg/dL but 5-year CADPA predicted risk ≥ 7.5% and a “discordant low ACS” risk group defined as LDL-C ≥ 130 mg/dL but 5-year CADPA risk of < 7.5%. Multiple logistic regression identified risk factors and biomarkers that predicted discordance in two separate models. Results: The average age and percent male of the high ACS discordant group was higher compared to non-discordant (68±10 vs 54±13 years and 61% vs 43%, respectively). Diabetes (OR 2.84 [2.21-3.66]), male sex (OR 2.83 [2.40-3.35]), family history (OR 2.23 [1.88-2.64]) and active smoking (OR 1.99 [1.50-2.62]) exhibited greatest odds of high ACS discordance compared to other risk factors (all p < 0.01). Increased serum soluble FAS (OR 2.12 [1.97-2.29]), Hemoglobin A1c (OR 1.60 [1.48-1.72]) and interleukin-16 (OR 1.40 [1.32-1.48]) were the biomarkers most associated with discordant risk, independent of global risk factors. Conclusion: Men with diabetes and family history of myocardial infarction who are actively smoking may be at highest risk of developing ACS despite controlled LDL-C. Future studies should examine whether using the CADPA can help identify such individuals that could benefit from earlier targeting of risk factor modification for prevention of ACS.