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Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Silbernagel, G; Fauler, G; Genser, B; Drechsler, C; Krane, V; Scharnagl, H; Grammer, TB; Baumgartner, I; Ritz, E; Wanner, C; März, W.
Intestinal cholesterol absorption, treatment with atorvastatin, and cardiovascular risk in hemodialysis patients.
J Am Coll Cardiol. 2015; 65(21):2291-2298
Doi: 10.1016/j.jacc.2015.03.551
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- Leading authors Med Uni Graz
- Silbernagel Günther
- Co-authors Med Uni Graz
- Fauler Günter
- März Winfried
- Scharnagl Hubert
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- Abstract:
- Hemodialysis patients are high absorbers of intestinal cholesterol; they benefit less than other patient groups from statin therapy, which inhibits cholesterol synthesis. This study sought to investigate whether the individual cholesterol absorption rate affects atorvastatin's effectiveness to reduce cardiovascular risk in hemodialysis patients. This post-hoc analysis included 1,030 participants in the German Diabetes and Dialysis Study (4D) who were randomized to either 20 mg of atorvastatin (n=519) or placebo (n=511). The primary endpoint was a composite of major cardiovascular events. Secondary endpoints included all-cause mortality and all cardiac events. Tertiles of the cholestanol-to-cholesterol ratio, which is an established biomarker of cholesterol absorption, were used to identify high and low cholesterol absorbers. A total of 454 primary endpoints occurred. On multivariate time-to-event analyses, the interaction term between tertiles and treatment with atorvastatin was significantly associated with the risk of reaching the primary endpoint. Stratified analysis by cholestanol-to-cholesterol ratio tertiles confirmed this effect modification: atorvastatin reduced the risk of reaching the primary endpoint in the first tertile (hazard ratio [HR]: 0.72; p=0.049), but not the second (HR: 0.79; p=0.225) or third tertiles (HR: 1.21; p=0.287). Atorvastatin consistently significantly reduced all-cause mortality and the risk of all cardiac events in only the first tertile. Intestinal cholesterol absorption, as reflected by cholestanol-to-cholesterol ratios, predicts the effectiveness of atorvastatin to reduce cardiovascular risk in hemodialysis patients. Those with low cholesterol absorption appear to benefit from treatment with atorvastatin, whereas those with high absorption do not benefit. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Aged -
- Atorvastatin Calcium -
- Cardiovascular Diseases - epidemiology Cardiovascular Diseases - prevention & control
- Cholestanol - blood
- Cholesterol - metabolism
- Female -
- Heptanoic Acids - therapeutic use
- Humans -
- Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use
- Intestinal Absorption -
- Kidney Failure, Chronic - complications Kidney Failure, Chronic - metabolism Kidney Failure, Chronic - therapy
- Male -
- Middle Aged -
- Pyrroles - therapeutic use
- Renal Dialysis -
- Find related publications in this database (Keywords)
- cholestanol
- mortality
- randomized controlled trial
- statin