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

J Thromb Haemost. 2010 Mar;8(3):463-71. doi: 10.1111/j.1538-7836.2009.03720.x. Epub 2009 Dec 11.

Abstract

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 (> or = 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 > or = 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.

MeSH terms

  • Aged
  • Angioplasty, Balloon, Coronary
  • Apolipoprotein C-III / blood*
  • Biomarkers / blood
  • Blood Coagulation Tests
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / mortality*
  • Chi-Square Distribution
  • Coronary Angiography
  • Coronary Artery Bypass
  • Coronary Artery Disease / blood*
  • Coronary Artery Disease / complications
  • Coronary Artery Disease / diagnostic imaging
  • Coronary Artery Disease / mortality*
  • Coronary Artery Disease / therapy
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Assessment
  • Risk Factors
  • Secondary Prevention
  • Severity of Illness Index
  • Thrombin / metabolism*
  • Time Factors
  • Treatment Outcome
  • Up-Regulation

Substances

  • Apolipoprotein C-III
  • Biomarkers
  • Thrombin