Cholesterol and all-cause mortality in Honolulu

Abstract

Irwin Schatz and colleagues1Schatz IJ Masaki K Yano K Chen R Rodriguez BL David Curb J Cholesterol and all-cause mortality in elderly people from the Honolulu Heart Program: a cohort study.Lancet. 2001; 358: 351-355Summary Full Text Full Text PDF PubMed Scopus (352) Google Scholar have no clear explanation for their results. They hint at different homoeostatic mechanisms in the very old participants (>75 years). Other possibilities they suggest are chronic infections with increased proinflammatory cytokines, which would cause hypo-cholesterolaemia. The long follow-up, however, excluded this possibility. Schatz and colleagues do not mention the cause of mortality in their study. It would be interesting to know whether the excess mortality was attributable to death from acute injury—ie, from infections or trauma. Lipoproteins can lessen the toxic effects of various harmful biological and chemical agents. Lipoproteins are directly involved in the host response to infection and tissue destruction. During acute illness, delivery of cholesterol to the liver for excretion is altered to allow cholesterol to remain in the tissues where it is needed for repair and regeneration of damaged membranes. In fact, lipoproteins are potent inhibitors of the infectivity of different viruses and have powerful antiparasitic activity. In animals, LDL and VLDL cholesterol are essential in the survival of infections with gram-negative bacteria.2Harris HW Grunfeld C Feingold KR Rapp JH Human very low density lipoproteins and chylomicrons can protect against endotoxin-induced death in mice.J Clin Invest. 1990; 86: 696-702Crossref PubMed Scopus (271) Google Scholar Circulating cholesterol-rich lipoproteins and triglyceride-rich lipoproteins have the capacity to bind and detoxify bacterial lipopolysaccharide. Daily activities in healthy people, such as tooth brushing and defecating, frequently introduce lipopolysaccharide into the circulation. Lipopoly-saccharide-binding protein (LBP) circulates in association with apo-B-containing lipoproteins. LBP is required to induce a rapid inflammatory response, which is essential for the resistance to bacteria. High concentrations of LBP inhibit lipopolysaccharide effects and prevent mortality induced by endotoxaemia.3Vreugdenhil ACE Snoek AMP van't Veer C Greve JWM Buurman WA. LPS-binding protein circulates in association with apo-B containing lipoproteins and enhances endotoxin-LDL/VLDL interaction.J Clin Invest. 2001; 107: 225-234Crossref PubMed Scopus (109) Google Scholar Lipoproteins also carry the lipopoly-saccharide-binding receptor, CD14, with important functions in triggering host defences. The uptake of lipopolysaccharide into LDL, thought to be beneficial during acute infection, is judged potentially harmful during chronic inflammation. Transport of LDL-lipopolysaccharide complexes into the artery wall might initiate an inflammatory response and provoke an atherosclerotic reaction. This apparent paradox would explain why high cholesterol concentrations are proatherogenic in the long term. People who survive (ie, the elderly population with lower cholesterol concentrations) would be more vulnerable to external factors (infectious agents, poor recovery from trauma) if serum cholesterol concentrations are lower than the security limit. In fact, low cholesterol concentrations have been associated with violence-related mortality and deaths from injuries.4Forette B Tortrat D Wolmark Y Cholesterol as a risk factor for mortality in elderly women.Lancet. 1989; 1: 868-870Summary PubMed Scopus (109) Google Scholar Low cholesterol also predicts an increased risk of death from infection, mainly from the respiratory and digestive tracts.5Jacobs D Blackburn H Higgins M et al.Report of the conference on low blood cholesterol: mortality associations.Circulation. 1992; 86: 1046-1060Crossref PubMed Scopus (610) Google Scholar We purport that people with hypocholesterolaemia display a poor defence in situations of tissue-stress related to external phenomena. Low cholesterol is a marker for decreased antioxidant capacity (vitamin E circulates in lipoprotein) or deficiency in other essential fatty acids.