title: Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management.
abstract: Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high-density lipoprotein cholesterol (HDL-C) as cardiovascular risk factors, and (ii) to advise on therapeutic strategies for management. Current evidence supports a causal association between elevated TRL and their remnants, low HDL-C, and cardiovascular risk. This interpretation is based on mechanistic and genetic studies for TRL and remnants, together with the epidemiological data suggestive of the association for circulating triglycerides and cardiovascular disease. For HDL, epidemiological, mechanistic, and clinical intervention data are consistent with the view that low HDL-C contributes to elevated cardiovascular risk; genetic evidence is unclear however, potentially reflecting the complexity of HDL metabolism. The Panel believes that therapeutic targeting of elevated triglycerides (≥ 1.7 mmol/L or 150 mg/dL), a marker of TRL and their remnants, and/or low HDL-C (<1.0 mmol/L or 40 mg/dL) may provide further benefit. The first step should be lifestyle interventions together with consideration of compliance with pharmacotherapy and secondary causes of dyslipidaemia. If inadequately corrected, adding niacin or a fibrate, or intensifying LDL-C lowering therapy may be considered. Treatment decisions regarding statin combination therapy should take into account relevant safety concerns, i.e. the risk of elevation of blood glucose, uric acid or liver enzymes with niacin, and myopathy, increased serum creatinine and cholelithiasis with fibrates. These recommendations will facilitate reduction in the substantial cardiovascular risk that persists in patients with cardiometabolic abnormalities at LDL-C goal.
authors.affiliation: European Atherosclerosis Society, INSERM UMR-S939, Pitié-Salpetriere University Hospital, Paris 75651, France. john.chapman@upmc.fr
authors.forename: M John
authors.initials: MJ
authors.lastname: Chapman
authors.forename: Henry N
authors.initials: HN
authors.lastname: Ginsberg
authors.forename: Pierre
authors.initials: P
authors.lastname: Amarenco
authors.forename: Felicita
authors.initials: F
authors.lastname: Andreotti
authors.forename: Jan
authors.initials: J
authors.lastname: Borén
authors.forename: Alberico L
authors.initials: AL
authors.lastname: Catapano
authors.forename: Olivier S
authors.initials: OS
authors.lastname: Descamps
authors.forename: Edward
authors.initials: E
authors.lastname: Fisher
authors.forename: Petri T
authors.initials: PT
authors.lastname: Kovanen
authors.forename: Jan Albert
authors.initials: JA
authors.lastname: Kuivenhoven
authors.forename: Philippe
authors.initials: P
authors.lastname: Lesnik
authors.forename: Luis
authors.initials: L
authors.lastname: Masana
authors.forename: Børge G
authors.initials: BG
authors.lastname: Nordestgaard
authors.forename: Kausik K
authors.initials: KK
authors.lastname: Ray
authors.forename: Zeljko
authors.initials: Z
authors.lastname: Reiner
authors.forename: Marja-Riitta
authors.initials: MR
authors.lastname: Taskinen
authors.forename: Lale
authors.initials: L
authors.lastname: Tokgözoglu
authors.forename: Anne
authors.initials: A
authors.lastname: Tybjærg-Hansen
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Watts
mesh_terms: D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology* / Q000517:prevention & control; D008076:Cholesterol, HDL / Q000378:metabolism*; D002986:Clinical Trials as Topic; D050171:Dyslipidemias / Q000097:blood / Q000150:complications* / Q000517:prevention & control; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use; D058607:Fibric Acids / Q000627:therapeutic use; D005544:Forecasting; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D008019:Life Style; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000378:metabolism*; D009525:Niacin / Q000627:therapeutic use; D012307:Risk Factors; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D008076:Cholesterol, HDL; D015525:Fatty Acids, Omega-3; D058607:Fibric Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D008074:Lipoproteins; D014280:Triglycerides; C030087:lipoprotein triglyceride; D009525:Niacin