Apolipoprotein C-III predicts cardiovascular mortality in severe coronary artery disease and is associated with an enhanced plasma thrombin generation

Background: Apolipopoprotein C-III (apo C-III) plays a pivotal role in controlling plasma triglyceride (TG) and contributes to the atherogenic properties of TG-rich lipoproteins. Objectives: (i) To examine the predictive value of serum apo C-III for cardiovascular mortality in the setting of secondary prevention of coronary artery disease (CAD); and (ii) to evaluate possible associations between apolipoprotein levels and the thrombin generation assay, a global test to estimate plasma thrombogenic potential. Methods and results: A cohort of 633 patients with angiographically proven CAD was prospectively followed for a median follow-up of 57 months. The large majority of them (92%) underwent coronary (endovascular or surgical) revascularization. During the follow-up, 91 (14.3%) out of 633 patients died, with 64 events (10.1%) attributed to cardiovascular causes. After adjustment for all the other predictors of mortality during univariate analysis (i.e. age, statin therapy, myocardial infarction history, diabetes, hs-CRP and creatinine), elevated apo C-III levels (>= 10.5 mg dL-1- the median value) significantly predicted both total and cardiovascular mortality (HR for total mortality 2.22 with 95% CI 1.16-4.24; HR for cardiovascular mortality 2.35 with 95% CI 1.19-4.62). In a subgroup of 225 subjects, apo C-III levels were significantly associated with endogenous thrombin potential in regression models (standardized beta coefficient = 0.207, P = 0.002). Conclusions: Basal concentrations of apo C-III levels >= 10.5 mg dL-1 in CAD patients independently predicted cardiovascular mortality during the subsequent 5-year period. Such concentrations were associated with an enhanced plasma endogenous thrombin generation, suggesting a complex interplay between TG-rich particles and the coagulation cascade as well as a new 'thrombogenetic' role for apo C-III.