Remnant cholesterol as a cause of ischemic heart disease: evidence, definition, measurement, atherogenicity, high risk patients, and present and future treatment

TY - JOUR

T1 - Remnant cholesterol as a cause of ischemic heart disease

T2 - evidence, definition, measurement, atherogenicity, high risk patients, and present and future treatment

AU - Varbo, Anette

AU - Benn, Marianne

AU - Nordestgaard, Børge G

N1 - Copyright © 2013 Elsevier Inc. All rights reserved.

PY - 2014/3

Y1 - 2014/3

N2 - 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.

AB - 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.

KW - Animals

KW - Atherosclerosis

KW - Cardiovascular Diseases

KW - Cholesterol

KW - Cholesterol, LDL

KW - Humans

KW - Inflammation

KW - Lipoproteins, HDL

KW - Myocardial Ischemia

KW - Randomized Controlled Trials as Topic

KW - Risk Factors

KW - Triglycerides

U2 - 10.1016/j.pharmthera.2013.11.008

DO - 10.1016/j.pharmthera.2013.11.008

M3 - Journal article

C2 - 24287311

SN - 0163-7258

VL - 141

SP - 358

EP - 367

JO - Pharmacology and Therapeutics, Part A: Chemotherapy, Toxicology and

JF - Pharmacology and Therapeutics, Part A: Chemotherapy, Toxicology and

IS - 3

ER -