P0676CHOLESTEROL ABSORPTION JUGDED BY CAMPESTEROL / LATHOSTEROL RATIO AND OUTCOMES IN CHRONIC KIDNEY DISEASE

Abstract

Abstract Background and Aims In dialysis patients, cholesterol-lowering therapy with statins is less effective than in other high-risk patients. This may partly be explained by a shift from cholesterol synthesis, which is inhibited by statin treatment, towards cholesterol absorption, which is inhibited by ezetimibe. In line, markers of cholesterol absorption – such as campesterol - better predict atherosclerotic cardiovascular events than markers of cholesterol synthesis – such as lathosterol - in dialysis patients. We now investigated in our CARE FOR HOMe study whether a similar shift towards cholesterol absorption occurs in non-dialysis chronic kidney disease (CKD), and whether the campesterol / lathosterol ratio predicts outcome in non-dialysis CKD patients. Method Since 2008, 599 participants suffering from chronic kidney disease have been included into the CARE FOR HOME study, an observational cohort study. 555 patients had baseline samples available for analyses of the lathosterol / cholesterol ratio as a marker for cholesterol synthesis, and the campesterol / cholesterol ratio as a marker for cholesterol absorption. We excluded those participants who were currently treated with statins or other lipid lowering drugs, leaving 251 patients for this analysis. Participants were followed annually for major atherosclerotic cardiovascular events (MACE), defined as non-fatal acute myocardial infarction, non-fatal ischemic stroke, cerebrovascular / peripheral arterial or coronary revascularization, major amputation above the ankle and cardiovascular death. Additionally, all-cause death and the composite endpoint MACE and all-cause death were explored. We performed univariate (Model 1) and multivariate Cox regression analysis, adjusting for age, gender (Model 2), estimated glomerular filtration rate (eGFR), log-transformed albuminuria (Model 3), prevalent cardiovascular disease, current smoking, diabetes mellitus, systolic blood pressure and body mass index (Model 4). The primary hypothesis was that patients with a high campesterol / lathosterol ratio had a higher event rate. Results Neither lathosterol / cholesterol ratio (r = 0.022, p = 0.730), nor campesterol / cholesterol ratio (r = 0.042; p = 0.519) nor the campesterol / lathosterol ratio (r = -0.103; p = 0.105) correlated significantly with eGFR. During follow-up of 5.1 ± 2.1 years, 47 participants suffered from MACE, 46 participants died and 61 participants reached the composite endpoint of MACE or all-cause death. In univariate Cox regression analysis, campesterol / lathosterol ratio did not significantly predict atherosclerotic cardiovascular events (HR 0.740; 0.368 – 1.487), all-cause death (HR 0.564; 0.277 – 1.145) or the composite endpoint (HR 0.652; 0.355 – 1.196). After full adjustment, results were not different: Campesterol / lathosterol ratio was not significantly associated with all three endpoints: MACE (HR 1.064; 0.507 – 2.231), all-cause death (HR 0.818; 0.420 – 1.594) and MACE and all-cause death (HR 0.956; 0.525 – 1.744). Conclusion We did not observe a shift from cholesterol synthesis to cholesterol absorption across the spectrum of non-dialysis CKD. Campesterol / lathosterol ratio did not predict future MACE or all-cause death in non-dialysis CKD. These findings do not support the concept that CKD patients may preferentially benefit from ezetimibe rather than from statin treatment.