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 β 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.