P1758The novel small leucin-rich repeat protein podocan is an independent predictor of major adverse cardiac events in patients with angiographically-defined coronary artery disease

Abstract

Abstract Background Smooth muscle cell (SMC) function determines the clinical course of vascular disease via fibrous cap stability. Podocan is an inhibitor of SMC function and is circulating in peripheral blood rendering it a candidate biomarker to predict MACE in patients with Coronary Artery Disease (CAD). Purpose We designed a prospective cohort study assessing the predictive value of Podocan for cardiovascular outcome (MI, CVA or death) in patients with CAD. Methods 308 patients with angiographic evidence of CAD were enrolled. At index cardiac catheterization Syntax Score was calculated. For patient baseline characteristics see Table. Podocan and CRP-1 were measured using a human Podocan and CRP-1 ELISA. The Kaplan-Meier method was used to construct survival curves, which were compared using the log-rank test. Cox proportional hazard modeling was used for all univariate/multivariate analyses. Statistical analysis was performed using STATA. Results Podocan was detected in 212 patients (69%) with a detection threshold of 0.01 ng/ml. The median Podocan level observed was 1.4±8.2 ng/ml. 96 patients did not have a detectable Podocan level. Mean CRP-1 was 0.117±0.15 mg/ml. Mean Syntax Score was 12±9. Podocan did not correlate with CRP-1. There was also no association between Podocan and Syntax Score, age, BMI, smoking, LDL, and HDL, HgbA1c, LVEF and GFR. At the univariate level, presence of Podocan was associated with an increased rate of MACE (17% Podocan present vs. 7% Podocan absent, p=0.02). Kaplan-Meier survival analysis showed higher event free survival in patients with no detectable Podocan vs. detectable Podocan level (Figure). In a limited multivariate Cox proportional Hazard analysis, Podocan remained an independent predictor of MACE (HR: 2.5; P=0.042) in addition to diabetes, and LV ejection fraction. Baseline Characteristics Total (N=308) Chronic ischemic heart disease (N=273) Acute coronary syndrome (N=35) Age (Year) 66.5±9.5 67±9 61±11 Female (Sex) 106 (33%) 90 (31%) 16 (46%) Hypertension 282 (89%) 244 (89%) 26 (74%) Diabetes 142 (44%) 124 (45%) 11 (31%) Hyperlipidemia 269 (87%) 243 (89%) 26 (74%) CRP (mg/dL) 0.11±0.14 0.10±0.13 0.18±0.19 LVEF (%) 49±10 49±10 48±9.5 CRP, C-reactive protein; LVEF, Left ventricular ejection fraction. Kaplan Meier Survival Curves by Podocan Conclusion Podocan is a novel biomarker independently predicting MACE in secondary prevention of CAD warranting to be further studied in a Multicenter Clinical Trial.