Cholesteryl Ester Transfer Protein and Mortality in Patients Undergoing Coronary Angiography

Abstract

Background-The role of cholesteryl ester transfer protein (CETP) in the development of atherosclerosis is still open to debate. In the Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events (ILLUMINATE) trial, inhibition of CETP in patients with high cardiovascular risk was associated with increased high-density lipoprotein levels but increased risk of cardiovascular morbidity and mortality. In this report, we present a prospective observational study of patients referred to coronary angiography in which CETP was examined in relation to morbidity and mortality. Methods and Results-CETP concentration was determined in 3256 participants of the Ludwigshafen Risk andCardiovascular Health (LURIC) study who were referred to coronary angiography at baseline between 1997 and 2000. Median follow-up time was 7.75 years. Primary and secondary end points were cardiovascular and all-cause mortality, respectively. CETP levels were higher in women and lower in smokers, in diabetic patients, and in patients with unstable coronary artery disease, respectively. In addition, CETP levels were correlated negatively with high-sensitivity C-reactive protein and interleukin-6. After adjustment for age, sex, medication, coronary artery disease status, cardiovascular risk factors, and diabetes mellitus, the hazard ratio for death in the lowest CETP quartile was 1.

Dysfunctional high-density lipoproteins in coronary heart disease: implications for diagnostics and therapy

“…201 Population studies that investigated CETP plasma concentrations as a biomarker also yielded results that contradict the initial genetic studies: Low rather than high CETP concentrations were associated with increased cardiovascular mortality in a nearly 8 years long follow-up of more than 3000 patients who underwent coronary angiography. 202 In the PROVE IT-TIMI 22 study, plasma CETP levels were not associated with differences in cardiovascular event rates. In the 50% of patients who reached the lowest concentrations of LDL-cholesterol by pravastatin treatment, a low CETP concentration was associated with excess cardiovascular event rates.…”

Farnesoid X receptor activation increases cholesteryl ester transfer protein expression in humans and transgenic mice

“…In brief, incubation media contained 4 µl of donor liposomes and 10 µl of total plasma, as a source of CETP and endogenous lipoprotein substrates, in a fi nal volume of 200 µl TBS. Incubations were performed in triplicate for 1 h at 37°C in a FL600 Microplate Fluorescence Reader (Bio-Tek, Winooski, not all ( 7,8 ) human studies consequently reported a positive association between plasma CETP activity and atherosclerotic cardiovascular disease (CVD) morbidity and mortality. Especially in the setting of the metabolic syndrome, including type 2 diabetes mellitus and hypertriglyceridemia, the predictive value of increased CETP mass and activity for CVD events is particularly strong ( 9 ).…”

Is Cholesteryl Ester Transfer Protein Inhibition an Effective Strategy to Reduce Cardiovascular Risk?

“…In 3 of these studies there was a significant inverse relationship between ASCVD and CETP concentration, [35][36][37] whereas in another there was no statistically significant association. 32 The fifth study identified a significant positive relationship between the concentration of CETP and ASCVD in people with elevated levels of plasma triglyceride but not in those with low triglyceride levels.…”