Triglyceride-Rich Lipoproteins and Atherosclerotic Cardiovascular Disease
2016/02/18 by Børge G. Nordestgaard · 28 citations
Medicine · Biochemistry, Genetics and Molecular Biology · #Diabetes, Cardiovascular Risks, and Lipoproteins #Lipoproteins and Cardiovascular Health #Cancer, Lipids, and Metabolism
paper · pdf · doi:10.1161/circresaha.115.306249
Abstract
Scientific interest in triglyceride-rich lipoproteins has fluctuated over the past many years, ranging from beliefs that these lipoproteins cause atherosclerotic cardiovascular disease (ASCVD) to being innocent bystanders. Correspondingly, clinical recommendations have fluctuated from a need to reduce levels to no advice on treatment. New insight in epidemiology now suggests that these lipoproteins, marked by high triglycerides, are strong and independent predictors of ASCVD and all-cause mortality, and that their cholesterol content or remnant cholesterol likewise are strong predictors of ASCVD. Of all adults, 27% have triglycerides >2 mmol/L (176 mg/dL), and 21% have remnant cholesterol >1 mmol/L (39 mg/dL). For individuals in the general population with nonfasting triglycerides of 6.6 mmol/L (580 mg/dL) compared with individuals with levels of 0.8 mmol/L (70 mg/dL), the risks were 5.1-fold for myocardial infarction, 3.2-fold for ischemic heart disease, 3.2-fold for ischemic stroke, and 2.2-fold for all-cause mortality. Also, genetic studies using the Mendelian randomization design, an approach that minimizes problems with confounding and reverse causation, now demonstrate that triglyceride-rich lipoproteins are causally associated with ASCVD and all-cause mortality. Finally, genetic evidence also demonstrates that high concentrations of triglyceride-rich lipoproteins are causally associated with low-grade inflammation. This suggests that an important part of inflammation in atherosclerosis and ASCVD is because of triglyceride-rich lipoprotein degradation and uptake into macrophage foam cells in the arterial intima. Taken together, new insights now strongly suggest that elevated triglyceride-rich lipoproteins represent causal risk factors for low-grade inflammation, ASCVD, and all-cause mortality.
Citations
Cited by
- Olezarsen in patients with hypertriglyceridemia at high cardiovascular risk: Rationale and design of the Essence–TIMI 73b trial
- 2020 International Society of Hypertension Global Hypertension Practice Guidelines
- Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel
- Atherosclerosis: Successes, Surprises, and Future Challenges. [europepmc]
- Association of Rare and Common Variation in the Lipoprotein Lipase Gene With Coronary Artery Disease. [europepmc]
- Rationale and design of REDUCE-IT: Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial. [europepmc]
- Gut Microbiota-Dependent Trimethylamine-N-oxide and Serum Biomarkers in Patients with T2DM and Advanced CKD. [europepmc]
- Resident and Monocyte-Derived Macrophages in Cardiovascular Disease. [europepmc]
- Remnant-Like Particle Cholesterol, Low-Density Lipoprotein Triglycerides, and Incident Cardiovascular Disease. [europepmc]
- Endothelial Cell Metabolism in Atherosclerosis. [europepmc]
- The Forgotten Lipids: Triglycerides, Remnant Cholesterol, and Atherosclerotic Cardiovascular Disease Risk. [europepmc]
- Immunity and Inflammation in Atherosclerosis. [europepmc]
- The Discovery and Development of Liraglutide and Semaglutide. [europepmc]
- Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel. [europepmc]
- A New Equation for Calculation of Low-Density Lipoprotein Cholesterol in Patients With Normolipidemia and/or Hypertriglyceridemia. [europepmc]
- Dyslipidemia and cardiovascular disease risk among the MASHAD study population. [europepmc]
- Triglyceride-Rich Lipoprotein Cholesterol, Small Dense LDL Cholesterol, and Incident Cardiovascular Disease. [europepmc]
- Causes and Consequences of Hypertriglyceridemia. [europepmc]
- Vupanorsen, an N-acetyl galactosamine-conjugated antisense drug to ANGPTL3 mRNA, lowers triglycerides and atherogenic lipoproteins in patients with diabetes, hepatic steatosis, and hypertriglyceridaemia. [europepmc]
- The Molecular Basis of Predicting Atherosclerotic Cardiovascular Disease Risk. [europepmc]
- Remnant cholesterol predicts cardiovascular disease beyond LDL and ApoB: a primary prevention study. [europepmc]
- Triglyceride-rich lipoproteins and their remnants: metabolic insights, role in atherosclerotic cardiovascular disease, and emerging therapeutic strategies-a consensus statement from the European Atherosclerosis Society. [europepmc]
- Addressing dyslipidemic risk beyond LDL-cholesterol. [europepmc]
- Lipoprotein(a) in Atherosclerotic Diseases: From Pathophysiology to Diagnosis and Treatment. [europepmc]
- Triglyceride-rich lipoprotein remnants, low-density lipoproteins, and risk of coronary heart disease: a UK Biobank study. [europepmc]
- Women, lipids, and atherosclerotic cardiovascular disease: a call to action from the European Atherosclerosis Society. [europepmc]
- 2023 Chinese guideline for lipid management. [europepmc]
- Inflammation in atherosclerosis: pathophysiology and mechanisms. [europepmc]
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