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Serum uric acid (SUA) has been associated with cardiovascular disease, but up to now whether SUA is an independent cardiovascular risk factor or merely a disease-related epiphenomenon remains still controversial. within the framework of the Verona Heart Study, we prospectively followed 703 subjects with angiographically demonstrated and clinically stable coronary artery disease between May 1996 and March 2007. At baseline, SUA levels were measured in all the patients. Genotype data of SCL2A9 rs7442295 polymorphism, which has been associated with SUA by genome-wide association studies, were available for 686 subjects (97.6%). After a median follow-up of 57 months, 116 patients (16.5%) had died, 83 (11.8%) because of cardiovascular causes. Patients with hyperuricemia, defined by SUA levels above the 75th percentile (≥0.41 mmol/L), had an increased total and cardiovascular mortality rate than those with SUA below this threshold level (23.3% vs 14.1%, P = 0.048 and 19.4% vs 9.2%, P = 0.001, respectively, by Kaplan-Meier with Log-Rank test). These associations were confirmed by Cox regression after adjustment for sex, age, other predictors of mortality, coronary revascularization, and drug therapies at discharge (hazard ratio for total mortality 1.87 [1.05-3.34], P = 0.033; hazard ratio for cardiovascular mortality 2.09 [1.03-4.25], P = 0.041). Although associated with SUA levels, rs7442295 polymorphism did not predict total or cardiovascular mortality. our data support that SUA may be a prognostic cardiovascular biomarker, predicting total and cardiovascular mortality in the setting of secondary prevention of coronary artery disease. On the other hand, SCL2A9 gene polymorphism, notwithstanding a clear influence on SUA levels, was not associated with mortality.

Activated factor VII–anti-thrombin (FVIIa-AT) complex is a potential biomarker of pro-thrombotic diathesis reflecting FVIIa–tissue factor (TF) interaction and has been associated with mortality in patients with coronary artery disease (CAD). Previous data indicated plasma lipids as predictors of FVIIa-AT variability, and plasma lipoproteins as potential stimulators of the coagulation cascade. Our aim was to evaluate the relationships between FVIIa-AT plasma concentration and a broad apolipoprotein profile (including ApoA-I, ApoB, ApoC-III and ApoE). Within the framework of the observational Verona Heart Study, we selected 666 subjects (131 CAD-free and 535 CAD, 75.4% males, mean age: 61.1 ± 10.9 years) not taking anticoagulant drugs and for whom plasma samples were available for both FVIIa-AT assay and a complete lipid profile. Plasma concentration of FVIIa-AT levels significantly and directly correlated with total and high-density lipoprotein cholesterol, triglycerides, ApoA-I, ApoC-III and ApoE levels. ApoC-III showed the strongest correlation (R = 0.235, p = 7.7 × 10−10), confirmed in all the sub-group analyses (males/females and CAD/CAD-free). Only ApoC-III remained associated with FVIIa-AT plasma concentration, even after adjustment for sex, age, CAD diagnosis, body mass index, renal function, smoking status, lipid-lowering therapies and FVIIa levels. The APOC3 gene locus-tagging polymorphism rs964184, previously linked with cardiovascular risk and plasma lipids by genome-wide association studies, was associated with both ApoC-III and FVIIa-AT plasma concentration. Our results indicate a strong association between ApoC-III and FVIIa-AT levels, thereby suggesting that an increased ApoC-III concentration may identify subjects with a pro-thrombotic diathesis characterized by an enhanced TF-FVIIa interaction and activity.