title: The endotoxin-lipoprotein hypothesis.
abstract: The advent of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) has revolutionised the treatment of hypercholesterolaemia. Statin treatment, by lowering the atherogenic lipoprotein profile, reduces morbidity and mortality in patients with cardiovascular disease. Treatment with simvastatin causes a reduction of events of new-onset heart failure, but this may be attributable to properties other than its lipid-lowering effects. There is some evidence that lower serum cholesterol concentrations (as a surrogate for the totality of lipoproteins) relate to impaired survival in patients with chronic heart failure (CHF). Inflammation is a feature in patients with CHF and increased lipopolysaccharide may contribute substantially. We postulate that higher concentrations of total cholesterol are beneficial in these patients. This is potentially attributable to the property of lipoproteins to bind lipopolysaccharide, thereby preventing its detrimental effects. We hypothesise there is an optimum lipoprotein concentration below which lipid reduction would, on balance, be detrimental. We also propose that, in patients with CHF, a non-lipid-lowering statin (with ancillary properties such as immune modulatory and anti-inflammatory actions) could be as effective or even more beneficial than a lipid-lowering statin.
authors.affiliation: Department of Clinical Cardiology, National Heart and Lung Institute, London, UK. m.rauchhaus@ic.ac.uk
authors.forename: M
authors.initials: M
authors.lastname: Rauchhaus
authors.forename: A J
authors.initials: AJ
authors.lastname: Coats
authors.forename: S D
authors.initials: SD
authors.lastname: Anker
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002784:Cholesterol / Q000097:blood / Q000502:physiology*; D004731:Endotoxins / Q000494:pharmacology*; D006333:Heart Failure / Q000503:physiopathology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000188:drug therapy; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology; D011485:Protein Binding; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000924:Anticholesteremic Agents; D004731:Endotoxins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008070:Lipopolysaccharides; D020011:Protective Agents; D002784:Cholesterol; D019821:Simvastatin