title: Remnant cholesterol as a cause of ischemic heart disease: evidence, definition, measurement, atherogenicity, high risk patients, and present and future treatment.
abstract: This review focuses on remnant cholesterol as a causal risk factor for ischemic heart disease (IHD), on its definition, measurement, atherogenicity, and levels in high risk patient groups; in addition, present and future pharmacological approaches to lowering remnant cholesterol levels are considered. Observational studies show association between elevated levels of remnant cholesterol and increased risk of cardiovascular disease, even when remnant cholesterol levels are defined, measured, or calculated in different ways. In-vitro and animal studies also support the contention that elevated levels of remnant cholesterol may cause atherosclerosis same way as elevated levels of low-density lipoprotein (LDL) cholesterol, by cholesterol accumulation in the arterial wall. Genetic studies of variants associated with elevated remnant cholesterol levels show that an increment of 1mmol/L (39mg/dL) in levels of nonfasting remnant cholesterol associates with a 2.8-fold increased risk of IHD, independently of high-density lipoprotein cholesterol levels. Results from genetic studies also show that elevated levels of remnant cholesterol are causally associated with both low-grade inflammation and IHD. However, elevated levels of LDL cholesterol are associated with IHD, but not with low-grade inflammation. Such results indicate that elevated LDL cholesterol levels cause atherosclerosis without a major inflammatory component, whereas an inflammatory component of atherosclerosis is driven by elevated remnant cholesterol levels. Post-hoc subgroup analyses of randomized trials using fibrates in individuals with elevated triglyceride levels, elevated remnant cholesterol levels, show a benefit of lowering triglycerides or remnant cholesterol levels; however, large randomized trials with the primary target of lowering remnant cholesterol levels are still missing.
authors.affiliation: Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Denmark; The Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Anette
authors.initials: A
authors.lastname: Varbo
authors.affiliation: The Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; Department of Clinical Biochemistry, Gentofte Hospital, Copenhagen University Hospital, Denmark.
authors.forename: Marianne
authors.initials: M
authors.lastname: Benn
authors.affiliation: Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Denmark; The Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Denmark. Electronic address: Boerge.Nordestgaard@regionh.dk.
authors.forename: Børge G
authors.initials: BG
authors.lastname: Nordestgaard
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000209:etiology* / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000209:etiology / Q000503:physiopathology; D002784:Cholesterol / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000503:physiopathology; D008075:Lipoproteins, HDL / Q000378:metabolism; D017202:Myocardial Ischemia / Q000209:etiology* / Q000503:physiopathology; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D014280:Triglycerides / Q000378:metabolism
chemical_list: D008078:Cholesterol, LDL; D008075:Lipoproteins, HDL; D014280:Triglycerides; D002784:Cholesterol
keywords: Atherosclerosis; Cardiovascular disease; Causal; Cholesterol; HDL; IDL; IHD; LDL; LDL receptor-related protein; LRP; Lipoprotein; Remnants; VLDL; high-density lipoprotein; intermediate-density lipoprotein; ischemic heart disease; low-density lipoprotein; very-low-density lipoprotein