Topic
High cholesterol
About: High cholesterol is a research topic. Over the lifetime, 1227 publications have been published within this topic receiving 38290 citations.
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TL;DR: Direct evidence is provided that cholesterol-lowering therapy is beneficial for people with diabetes even if they do not already have manifest coronary disease or high cholesterol concentrations and statin therapy should now be considered routinely for all diabetic patients at sufficiently high risk of major vascular events, irrespective of their initial cholesterol concentrations.
2,827 citations
TL;DR: Proposed mechanisms include favorable effects on plasma lipoproteins, endothelial function, plaque architecture and stability, thrombosis, and inflammation, which may ultimately broaden their indication from lipid-lowering to antiatherogenic agents.
Abstract: Statins (HMG-CoA reductase inhibitors) are used widely for the treatment of hypercholesterolemia. They inhibit HMG-CoA reductase competitively, reduce LDL levels more than other cholesterol-lowering drugs, and lower triglyceride levels in hypertriglyceridemic patients. Statins are well tolerated and have an excellent safety record. Clinical trials in patients with and without coronary heart disease and with and without high cholesterol have demonstrated consistently that statins reduce the relative risk of major coronary events by approximately 30% and produce a greater absolute benefit in patients with higher baseline risk. Proposed mechanisms include favorable effects on plasma lipoproteins, endothelial function, plaque architecture and stability, thrombosis, and inflammation. Mechanisms independent of LDL lowering may play an important role in the clinical benefits conferred by these drugs and may ultimately broaden their indication from lipid-lowering to antiatherogenic agents.
1,201 citations
TL;DR: The results demonstrate that statin therapy rapidly reduces the incidence not only of coronary events but also of ischaemic strokes, with no apparent effect on cerebral haemorrhage, even among individuals who do not have high cholesterol concentrations.
1,034 citations
TL;DR: The inverse association of total cholesterol level with mortality in dialysis patients is likely due to the cholesterol-lowering effect of systemic inflammation and malnutrition, not to a protective effect of high cholesterol concentrations.
Abstract: ContextTotal cholesterol level is inversely associated with mortality in dialysis
patients, a group at high risk of cardiovascular disease (CVD). This paradox
may be explained by systemic inflammation and/or malnutrition, which are associated
with lower cholesterol levels and higher mortality.ObjectiveTo determine the relationship between cholesterol level and outcome
in patients undergoing dialysis, accounting for inflammation and malnutrition.Design, Setting, and ParticipantsProspective study of 823 patients enrolled from October 1995 to June
1998 who recently initiated dialysis, from 79 clinics, classified by absence
or presence of inflammation and/or malnutrition (defined as serum albumin
levels <3.6 mg/dL, C-reactive protein ≥10 mg/L, or interleukin 6 ≥3.09
pg/mL).Main Outcome MeasuresAll-cause and cardiovascular disease mortality.ResultsDuring a median follow-up of 2.4 years, 324 deaths (159 CVD deaths),
153 renal transplantations, and 10 losses to follow-up occurred. Average serum
cholesterol level was lower in the presence of inflammation/malnutrition than
in its absence. In a Cox model adjusted for age, race, and sex, a 40-mg/dL
(1.0-mmol/L) increment in baseline total serum cholesterol level was associated
with a decreased risk of all-cause mortality overall (relative hazard [RH],
0.92; 95% confidence interval [CI], 0.87-0.98) and in the presence of inflammation/malnutrition
(RH, 0.89; CI, 0.84-0.95). In contrast, serum cholesterol level was associated
with an increased risk in the absence of inflammation/malnutrition (RH, 1.32;
95% CI, 1.07-1.63). For CVD mortality, an inverse trend was not statistically
significant in the presence of inflammation/malnutrition, and a positive association
was evident in the absence of inflammation/malnutrition (RH, 1.41; 95% CI,
1.04-1.89). Further adjustment for traditional CVD risk factors, dialysis
modality, comorbidity, and inflammatory markers attenuated the inverse association
but strengthened the positive association.ConclusionsThe inverse association of total cholesterol level with mortality in
dialysis patients is likely due to the cholesterol-lowering effect of systemic
inflammation and malnutrition, not to a protective effect of high cholesterol
concentrations. These findings support treatment of hypercholesterolemia in
this population.
665 citations
TL;DR: The data suggest that a significant part of cell-derived cholesterol is transferred specifically to a pre-beta-migrating lipoprotein A-I species as part of a cholesterol transport transfer sequence in plasma.
Abstract: Cultures of human skin fibroblasts were labeled to high cholesterol specific activity with [3H]cholesterol and incubated briefly (1-3 min) with normal human plasma. The plasma was fractionated by two-dimensional agarose-polyacrylamide gel electrophoresis and the early appearance of cholesterol label among plasma lipoproteins determined. A major part of the label at 1-min incubation was in a pre-beta-migrating apo A-I lipoprotein fraction with a molecular weight of ca. 70,000. Label was enriched about 30-fold in this fraction relative to its content of apo A-I (1-2% of total apo A-I). The proportion of label in this lipoprotein was strongly correlated with its concentration in plasma. Further incubation (2 min) in the presence of unlabeled cells demonstrated transfer of label from this fraction to a higher molecular weight pre-beta apo A-I species, to low-density lipoprotein, and to the alpha-migrating apo A-I that made up the bulk (96%) of total apo A-I in plasma. The data suggest that a significant part of cell-derived cholesterol is transferred specifically to a pre-beta-migrating lipoprotein A-I species as part of a cholesterol transport transfer sequence in plasma.
645 citations