Premyodhin N, Fan W, Younus M, et al. - According to findings, discordance between low-density lipoprotein cholesterol (LDL-C) levels and acute coronary syndrome (ACS) risk is common. The highest risk of developing ACS despite controlled LDL-C could exist in men with diabetes and a family history of myocardial infarction who are actively smoking.

• ACS can occur in people with no history of coronary artery disease often in the absence of major risk factors including LDL-C.

• In this study, a novel validated coronary artery disease predictive algorithm (CADPA) including biomarkers of endothelial injury was employed to determine risk factors and biomarkers that can aid detect those at discordantly high risk of ACS with normal LDL-C.

• In 6,392 persons, 5-year predicted ACS risk was estimated using CADPA.

• Participants classified as low (<3.5%), intermediate (3.5–<7.5%) and at high risk (≥7.5%) were 31%, 27%, and 42%, respectively.

• Those identified in the low LDL discordant risk group (LDL-C< 130 mg/dL but 5-year CADPA predicted risk ≥7.5%) were 28% and those in the high LDL discordant risk group (LDL-C ≥ 130 mg/dL but 5-year CADPA risk of <7.5%) were 19%.

• Compared with other risk factors, following factors predicted low LDL risk discordance more: diabetes (odds ratio [OR], 2.84), male gender (OR, 2.83), family history (OR, 2.23) and active smoking (OR, 1.99).

• The biomarkers that were most independently linked with elevated risk were: increased serum soluble FAS, hemoglobin A1c and interleukin-16.