Cardiovascular events with increased lipoprotein-associated phospholipase A(2) and low high-density lipoprotein-cholesterol: the Veterans Affairs HDL Intervention Trial.
OBJECTIVE
Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), a proinflammatory enzyme that predominantly circulates with low-density lipoprotein (LDL), has been shown in general populations to predict cardiovascular (CV) events. We sought to determine whether increased Lp-PLA(2) would also predict CV events in the absence of high LDL-cholesterol (LDL-C), in a population with low high-density lipoprotein-cholesterol (HDL-C).


RESULTS
Plasma Lp-PLA(2) activity was measured at baseline and after 6 months on-trial in 1451 men with low HDL-C (mean, 32 mg/dL) and low LDL-C (mean 110 mg/dL), randomized to either placebo or gemfibrozil therapy in the Veterans Affairs HDL Intervention Trial (VA-HIT). Over a quartile range of increasing Lp-PLA(2) there was a significant increase in LDL-C and decrease in HDL-C (P < 0.0001), and an increased percentage of myocardial infarction (MI), stroke, or CHD death (P=0.03 for trend). In Cox models, adjusted for major CV risk factors, a 1-SD increase in Lp-PLA(2) was associated with a significant increase in CV events (hazard ratio [HR] 1.17 95% CI 1.04 to 1.32). Although gemfibrozil reduced Lp-PLA(2) only modestly (6.6%), at higher levels of Lp-PLA(2) gemfibrozil produced a significant reduction in CV events.


CONCLUSIONS
In VA-HIT, a population with low HDL-C and LDL-C, high Lp-PLA(2) independently predicted CV events that were reduced by gemfibrozil.
Robins
Sander J
SJ
Framingham Heart Study, 73 Mt Wayte Avenue, Framingham, MA 01702, USA. sjrobins@bu.edu
Collins
Dorothea
D
Nelson
Jeanenne J
JJ
Bloomfield
Hanna E
HE
Asztalos
Bela F
BF
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood*; D000368:Aged; D001055:Apolipoproteins B / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000209:etiology* / Q000517:prevention & control; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood*; D005500:Follow-Up Studies; D015248:Gemfibrozil / Q000627:therapeutic use; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000209:etiology / Q000517:prevention & control; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D020521:Stroke / Q000097:blood / Q000209:etiology / Q000517:prevention & control; D014280:Triglycerides / Q000097:blood
D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D000960:Hypolipidemic Agents; D014280:Triglycerides; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D015248:Gemfibrozil