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Introduction:Plasma soluble form of the receptor for advanced glycation end products (sRAGE) is a splice variant of the full-length receptor neutralizes RAGE ligands. A decrease in sRAGE may lead to increased accumulation of deleterious pro-apoptotic and/or pro-inflammatory RAGE ligands and contribute to diabetic complications in the cardiovascular system.Hypothesis:We aimed to determine whether the concentration of sRAGE in patients without diabetes is associated with evolution to coronary artery disease (CAD).Methods:72 asymptomatic patients (mean age: 60.6?6.8 years, 55 male) without diabetes but with suspected CAD due to risk factor profile and noninvasive testing underwent coronary arteriography and recording of individual risk factors. Titers of sRAGE were measured by enzyme-linked immunosorbent assay in plasma.Results:CAD was diagnosed in 30 patients by invasive testing (mean age: 60.2?7.5, 29 male) and excluded in the remaining 42 patients (mean age: 59.9?6.9 yrs, 26 male). Plasma levels of sRAGE were decreased in patients with the presence of CAD (Non-CAD 717.9+67.1 vs. CAD 447.1+38.9 pg/mL, p=.002). In multivariable regression analysis sRAGE and conventional risk factors (age, smoking, HDL-C, HbA1c, triglycerides) were independent determinants of CAD in nondiabetic patients. Moreover, sRAGE consistently remained to be independently associated with CAD in nondiabetic patients, so did other major conventional risk factors. Interestingly, the plasma levels of the RAGE ligands S100B, calgranulins A/B (S100A8/A9) and C (S100A12) were not different between Non and CAD nondiabetic patients.Conclusion:This study demonstrates that decreased plasma sRAGE level is associated with CAD in nondiabetic patients and as such may act as a novel biomarker for predicting CAD in nondiabetic patients.