Effects Of Cholesterol-lowering Treatment Research Articles

Effect of cholesterol lowering treatment on plasma markers of endothelial dysfunction in chronic kidney disease

The elevated cardiovascular morbidity and mortality in chronic kidney disease (CKD) is linked with endothelial dysfunction secondary to the pro-inflammatory and pro-oxidative state typical of this pathology. In consideration of the well-known pleiotropic effect of statins, we investigated the effect of cholesterol lowering treatment on endothelial dysfunction markers (MED), asymmetric dimethylarginine (ADMA), vascular cell (VCAM) and intercellular (ICAM) adhesion molecule. Plasma MED concentrations, inflammation and oxidative stress indices [Kynurenine/Tryptophan (Kyn/Trp) ratio, malondialdehyde (MDA) and allantoin/uric acid (All/UA) ratio] were measured in 30 CKD patients randomized to three cholesterol lowering regimens for 12 months (simvastatin 40mg/day, ezetimibe/simvastatin 10/20mg/day, or ezetimibe/simvastatin 10/40mg/day). Treatment significantly reduced ADMA concentrations in all patients [0.694μmol/L (0.606–0.761) at baseline vs. 0.622μmol/L (0.563–0.681) after treatment, p<0.001]. ADMA reduction was paralleled by a significant decrease of MDA, All/AU ratio and Kyn/Trp ratio, but not VCAM and ICAM plasma concentrations. Cholesterol lowering treatment was associated with a significant reduction in plasma ADMA concentrations in CKD patients. This might be mediated by reduced oxidative stress and inflammation.

Alterations of cholesterol precursor levels in Alzheimer's disease

Cerebral and extracerebral cholesterol metabolism are altered in Alzheimer's disease (AD) as indicated by reduced plasma levels of the cholesterol elimination products 24S-hydroxycholesterol, which is of cerebral origin, and of 27-hydroxycholesterol, which is formed extracerebrally. However, it has to be evaluated, if changes of cholesterol metabolism in the whole body or in the CNS are exclusively due to the altered elimination of cholesterol or are also due to altered de novo synthesis in AD. We investigated CSF and plasma levels of cholesterol and of its precursors lanosterol, lathosterol and desmosterol in AD patients and non-demented controls. We found CSF levels of cholesterol ( p = 0.011), absolute levels of all investigated cholesterol precursors (each p < 0.001) and ratios of cholesterol precursors/cholesterol (each < 0.01) to be lower in AD patients as compared to controls. In plasma, the absolute levels of lanosterol ( p = 0.026) and lathosterol ( p < 0.001) and the ratio of lathosterol/cholesterol ( p = 0.002) but none of the other investigated parameters were reduced in AD patients ( p > 0.1). Furthermore, ratios of desmosterol/lathosterol in CSF ( p = 0.023) and plasma ( p = 0.009) were higher in AD patients as compared to controls. Our data support the hypothesis that cholesterol metabolism is altered in AD and further suggest that especially cholesterol de novo synthesis within the CNS of AD patients might be reduced. These findings raise doubt on a beneficial effect of cholesterol lowering treatment in manifest AD.

Mortality and incidence of cancer during 10-year follow-up of the Scandinavian Simvastatin Survival Study (4S)

The effects of cholesterol-lowering treatment with statins on mortality and risk of cancer beyond the usual 5-6-year trial periods are unknown. We extended post-trial follow-up of participants in the Scandinavian Simvastatin Survival Study (4S) to investigate cause-specific mortality and incidence of cancer 5 years after closure of the trial. 4S was a randomised double-blind trial of simvastatin or placebo in patients with coronary heart disease, serum total cholesterol 5.5-8.0 mmol/L, and serum triglycerides 2.5 mmol/L or lower. The double-blind period lasted for a median of 5.4 years (range for survivors 4.9-6.3) and ended in 1994. After the trial, most patients in both groups received open-label lipid-lowering treatment. National registers were used to assess mortality and causes of death and cancer incidence in the original treatment groups for a median total follow-up time of 10.4 years (range for survivors 9.9-11.3). Analysis was by intention to treat. 414 patients originally allocated simvastatin and 468 assigned placebo died during the 10.4-year follow-up (relative risk 0.85 [95% CI 0.74-0.97], p=0.02), a difference largely attributable to lower coronary mortality in the simvastatin group (238 vs 300 deaths; 0.76 [0.64-0.90], p=0.0018). 85 cancer deaths arose in the simvastatin group versus 100 in the placebo group (0.81 [0.60-1.08], p=0.14), and 227 incident cancers were reported in the simvastin group versus 248 in the placebo group (0.88 [0.73-1.05], p=0.15). Incidence of any specific type of cancer did not rise in the simvastatin group. Simvastatin treatment for 5 years in a placebo-controlled trial, followed by open-label statin therapy, was associated with survival benefit over 10 years of follow-up compared with open-label statin therapy for the past 5 years only. No difference was noted in mortality from and incidence of cancer between the original simvastatin group and placebo group.

Effect of cholesterol lowering treatment on positive exercise tests in patients with hypercholesterolaemia and normal coronary angiograms

AIMTo assess the impact of cholesterol lowering on positive exercise stress tests in hypercholesterolaemic patients with normal coronary angiograms.METHODS43 non-diabetic patients aged 43–61 years, with total serum cholesterol concentrations of...

Effect of Cholesterol-Lowering Treatment on Coronary Heart Disease Morbidity and Mortality: The Evidence from Trials, and Beyond

Evidence from controlled clinical trials shows convincingly that reducing serum cholesterol levels by diet or drug treatment reduces the incidence of coronary heart disease. On a population basis, the most important effect of cholesterol lowering might be postponement of the first symptoms of disease rather than postponement of death, because most cardiac deaths occur at an advanced age. No enhanced cancer mortality is seen either in populations with low serum cholesterol levels or in patients who, through a genetic defect, have a low-density-lipoprotein cholesterol of zero. This makes it unlikely that cholesterol-lowering treatment as such promotes cancer. Still, specific side effects and toxicity of drugs need careful scrutiny, and diet remains the treatment of choice for mild hypercholesterolemia.