Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dyslipidemia is a potent cardiovascular (CV) risk factor in the general population. Elevated low-density lipoprotein cholesterol (LDL-C) and/or low high-density lipoprotein (HDL-C) are well-established CV risk factors, but more precise determinants of risk include increased apoprotein B (ApoB), lipoprotein(a) [Lp(a)], intermediate and very low-density lipoprotein (IDL-C, VLDL-C; "remnant particles"), and small dense LDL particles. Lipoprotein metabolism is altered in association with declining glomerular filtration rate such that patients with non dialysis-dependent chronic kidney disease (CKD) have lower levels of HDL-C, higher triglyceride, ApoB, remnant IDL-C, remnant VLDL-C, and Lp(a), and a greater proportion of oxidized LDL-C. Similar abnormalities are prevalent in hemodialysis (HD) patients, who often manifest proatherogenic changes in LDL-C in the absence of increased levels. Patients treated with peritoneal dialysis (PD) have a similar but more severe dyslipidemia compared to HD patients due to stimulation of hepatic lipoprotein synthesis by glucose absorption from dialysate, increased insulin levels, and selective protein loss in the dialysate analogous to the nephrotic syndrome. In the dialysis-dependent CKD population, total cholesterol is directly associated with increased mortality after controlling for the presence of malnutrition-inflammation. Treatment with statins reduces CV mortality in the general population by approximately one third, irrespective of baseline LDL-C or prior CV events. Statins have similar, if not greater, efficacy in altering the lipid profile in patients with dialysis-dependent CKD (HD and PD) compared to those with normal renal function, and are well tolerated in CKD patients at moderate doses (<or=20 mg/day atorvastatin or simvastatin). Statins reduce C-reactive protein as well as lipid moieties such as ApoB, remnants IDL and VLDL-C, and oxidized and small dense LDL-C fraction. Large observational studies demonstrate that statin treatment is independently associated with a 30%-50% mortality reduction in patients with dialysis-dependent CKD (similar between HD- and PD-treated patients). One recent randomized controlled trial evaluated the ability of statin treatment to reduce mortality in type II diabetics treated with HD ("4D"); the primary end point of death from cardiac cause, myocardial infarction, and stroke was not significantly reduced. However, results of this trial may not apply to other end-stage renal disease populations. Two ongoing randomized controlled trials (SHARP and AURORA) are underway evaluating the effect of statins on CV events and death in patients with CKD (including patients treated with HD and PD). Recruitment to future trials should be given a high priority by nephrologists and, until more data are available, consideration should be given to following published guidelines for the treatment of dyslipidemia in CKD. Additional consideration could be given to treating all dialysis patients felt to be at risk of CV disease (irrespective of cholesterol level), given the safety and potential efficacy of statins. This is especially relevant in patients treated with PD, given their more atherogenic lipid profile and the lack of randomized controlled trials in this population.
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PMID:Statins for treatment of dyslipidemia in chronic kidney disease. 1729 64

Patients with chronic kidney disease (CKD) have significantly increased risks of cardiovascular (CV) morbidity and mortality. Dyslipidemia is a common disorder in CKD patients. CKD patients have a different lipid profile with increased atherogenic lipid fractions, and serum low-density lipoprotein cholesterol (LDL-C) levels may underestimate the atherogenic effect of LDL-C in these patients. Dyslipidemia may contribute to the increased CV morbidity and mortality, and to the progression of kidney disease in CKD patients. Currently, statins are the pharmacologic intervention of first choice, if lifestyle changes fail adequately to lower LDL-C levels in the setting of normal or moderately elevated triglycerides. Statins have been extensively studied in a large variety of patient populations and have proven efficacy in the treatment of dyslipidemia, and in reducing CV mortality. Although much evidence supports the CV benefits of statins in patients with normal renal function, there are contradictory results for the beneficial effect of statin therapy on CV morbidity and mortality in CKD patients. While post hoc subgroup analyses of multiple randomized trials support statin use in early CKD patients, the only randomized trial conducted in diabetic dialysis patients found no evidence of benefit in overall mortality. Post transplant there is some definite CV benefit, albeit in a patient cohort selected to be at reduced CV risk by virtue of being eligible for organ transplant. The results from the AURORA and SHARP studies are awaited anxiously.
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PMID:Statin treatment for dyslipidemia in chronic kidney disease and renal transplantation: a review of the evidence. 1980 92

Ezetimibe is a unique inhibitor of intestinal cholesterol absorption. Ezetimibe selectively inhibits intestinal cholesterol absorption by blocking Niemann-Pick C1-like 1 (NPCIL1). Ezetimibe accelerates VLDL and TG degradation. Therefore, ezetimibe ameliorates postprandial hyperlipidemia. Ezetimibe inhibited the progression of nonalcoholic fatty liver disease (NAFLD) by correcting insulin resistance and decreasing small dense LDL-C in human subjects. In clinical study, ezetimibe administration combined with statin failed to inhibit progression of IMT thickness in ENHANCE (Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression) study. In this study baseline IMT thickness (0.7 mm) of patients was within normal range. Therefore only two years observation was too short to demonstrate anti-atherogenic effects of ezetimibe. SEAS(Simvastatin and Ezetimibe in Aortic Stenosis) trial examined effects of combination therapy with ezetimibe and statin in patients with aortic stenosis. Combination therapy could not inhibit progression of aortic stenosis. However, events of ischemic heart disease, especially CABG were significantly decreased only in combination group. Statin was not reported to reduce CVD(cardiovascular disease) in moderate to severe CKD patients. In SHARP(Study of Heart and Renal Protection) study, patients with severe renal disease were allocated either for statin alone group or combination therapy group with statin and ezetimibe. Combination therapy significantly decreased non-hemorrhagic stroke by 25 % compared with statin alone group in severe CKD and HD(hemodialysis) patients. Ezetimibe has unique lipid lowering profile increasing HDL-C concomitant with decreasing LDL-C and TG. Ezetimibe should be initiated first in patients with insulin resistant metabolic syndrome. Ezetimibe should be combined with statin to reduce not only LDL-C but RLP-C(remnant like lipoprotein particle choletserol) in type IIb dyslipidemia.
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PMID:[An inhibitor of intestinal cholesterol transporter]. 2420 31