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.


OBJECTIVE
(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.


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.
Olivieri
O
O
Department of Clinical and Experimental Medicine, Unit of Internal Medicine, University of Verona, Verona, Italy. oliviero.olivieri@univr.it
Martinelli
N
N
Girelli
D
D
Pizzolo
F
F
Friso
S
S
Beltrame
F
F
Lotto
V
V
Annarumma
L
L
Corrocher
R
R
D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D053305:Apolipoprotein C-III / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001780:Blood Coagulation Tests; D002318:Cardiovascular Diseases / Q000097:blood* / Q000209:etiology / Q000401:mortality*; D016009:Chi-Square Distribution; D017023:Coronary Angiography; D001026:Coronary Artery Bypass; D003324:Coronary Artery Disease / Q000097:blood* / Q000150:complications / Q000000981:diagnostic imaging / Q000401:mortality* / Q000628:therapy; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D055502:Secondary Prevention; D012720:Severity of Illness Index; D013917:Thrombin / Q000378:metabolism*; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation
D053305:Apolipoprotein C-III; D015415:Biomarkers; D013917:Thrombin