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Higher on-statin CETP mass predicts fewer recurrent coronary events in the PROVE IT-TIMI 22 trial (Am J Cardiol 2010)
Original title: On-statin cholesteryl ester transfer protein mass and risk of recurrent coronary events (from the pravastatin or atorvastatin evaluation and infection therapy-thrombolysis in myocardial infarction 22 [PROVE IT-TIMI 22] study)
In 3,218 patients from the PROVE IT-TIMI 22 statin trial, researchers measured plasma CETP mass after four months of pravastatin or atorvastatin therapy and related it to recurrent coronary events over a mean 1.8-year follow-up. Higher on-statin CETP mass was inversely associated with coronary risk, both unadjusted (hazard ratio per SD increase 0.77, 95% CI 0.65 to 0.92) and after adjustment for traditional risk factors (HR 0.81, 95% CI 0.67 to 0.98). The protective association was concentrated in patients with LDL cholesterol below the study median, revealed by a significant CETP-by-LDL interaction, suggesting higher CETP mass on statin therapy is not simply harmful and may even track with lower recurrent risk in some patients.
Original abstract
Although cholesteryl ester transfer protein (CETP) plays an important role in human lipoprotein metabolism, its relation to coronary artery disease remains controversial. The present study evaluated the relation between on-statin CETP mass and recurrent coronary events. The plasma CETP mass, measured after 4 months of statin therapy, was quantified in 3,218 patients enrolled in the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) study. Of the 3,218 patients, 150 experienced the combined end point of recurrent myocardial infarction or death from coronary causes during a mean follow-up of 1.8 years. An increasing on-statin CETP mass was inversely related to the risk of coronary events in both unadjusted (hazard ratio [HR] per SD increase 0.77, 95% confidence interval 0.65 to 0.92, p = 0.005) and fully adjusted (HR per SD increase 0.81, 95% confidence interval 0.67 to 0.98, p = 0.027) analyses that included traditional cardiovascular risk factors. A similar trend was observed across increasing CETP mass quartiles (p trend = 0.07). A significant interaction between the CETP mass and on-treatment low-density lipoprotein (LDL) cholesterol was noted (p interaction = 0.007). A CETP mass greater than the median was associated with a decreased risk in patients with LDL cholesterol less than the median of 80 mg/dl (HR 0.52, 95% confidence interval 0.31 to 0.89, p = 0.02), but not in patients with LDL cholesterol greater than the median. In conclusion, an increasing on-statin CETP mass was inversely related to the coronary outcomes in this large clinical trial-based cohort, particularly among those with low LDL cholesterol levels. This finding is consistent with CETP facilitating reverse cholesterol transport in the setting of robust LDL clearance and might have important implications for efforts to optimally target patients with pharmacologic CETP inhibition.
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Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.