Abstract 2260: On-treatment Cholesteryl Ester Transfer Protein Mass and Risk for MI in the PROVE-IT Study
Background: Cholesteryl ester transfer protein (CETP) transfers cholesteryl esters from HDL to apoB containing lipoproteins in exchange for triglyceride and is a therapeutic target to raise HDL-C levels. Plasma levels of CETP mass have been shown to positively predict cardiovascular events in observational longitudinal studies. Statins are known to reduce CETP mass, but the relationship of CETP mass to CV events in statin treated patients is unknown.
Methods: We measured 4 month on-treatment plasma CETP mass in the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction (PROVE-IT) study to determine whether on-treatment CETP levels were associated with subsequent cardiovascular events. The PROVE-IT study recruited a total of 4,162 subjects with acute coronary syndrome and randomized them to aggressive (atorvastatin 80mg) or standard (pravastatin 40mg) statin therapy. CETP mass was measured in plasma obtained at the 4 month blood draw using a commercially available ELISA (Wako Chemicals, USA).
Results: Using the Spearman rank-order correlation coefficient, on-treatment CETP mass levels were directly correlated to LDL-cholesterol (r=0.18; p<0.0001) but not to HDL-cholesterol (r=0.0002; p=0.99). Subjects treated with atorvastatin 80 mg had significantly lower CETP levels than subjects treated with pravastatin 40 mg (median 0.70 versus 0.77; p<0.001). In the overall group, subjects who experienced a myocardial infarction (MI) in follow-up had lower CETP levels compared to those who did not have an MI (median 0.68 versus 0.74; p=0.026). In a Cox regression analysis subjects in with baseline LDL cholesterol below the median (107 mg/dL), subjects in the highest quartile of CETP were less likely to have an MI in follow up compared to subjects in the lowest quartile of CETP (hazard ratio 0.39; 95% CI 0.17 to 0.88; p=0.022). A similar result was seen using the combined endpoint of death/MI (hazard ratio 0.48; 95% CI 0.26 to 0.91; p=0.024) in subjects with LDL below the median.
Conclusions: In this study of subjects with acute coronary syndrome on statin therapy, on-treatment CETP mass levels appear to be inversely associated with risk for MI, particularly in those subjects who had a baseline LDL-C level below the median.