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Hypertriglyceridemia: a review beyond low-density lipoprotein
1Little Rock Diagnostic Clinic, Little Rock, Arkansas 72205, USA.
Insights
Elevated triglycerides play a key role in atherosclerosis development, contributing to coronary artery disease risk. Detailed lipid analysis is crucial for aggressive hypertriglyceridemia management and identifying at-risk patients.
Area of Science:
- Cardiovascular Medicine
- Lipid Metabolism
- Atherosclerosis Research
Background:
- Hypertriglyceridemia is a complex dyslipidemia often associated with low high-density lipoprotein cholesterol.
- The independent predictive value of triglycerides in coronary artery disease (CAD) is debated due to particle diversity and confounding factors.
- Recent evidence highlights the primary role of triglycerides in atherogenesis.
Purpose of the Study:
- To re-evaluate the role of elevated triglycerides in coronary artery disease.
- To emphasize the atherogenic potential of triglyceride-rich lipoproteins (TRLs) and altered low-density lipoprotein (LDL) phenotypes.
- To advocate for more comprehensive lipid analysis in managing hypertriglyceridemia.
Main Methods:
- Review of recent data on triglyceride metabolism and atherosclerosis.
- Analysis of the impact of cholesterol ester transfer protein (CETP) on TRLs.
- Examination of LDL particle size and density in hypertriglyceridemia states.
Main Results:
- Triglyceride-rich lipoprotein particles, especially those enriched with cholesterol via CETP, are highly atherogenic.
- Hypertriglyceridemia is associated with the atherogenic small, dense LDL phenotype (Pattern B), increasing CAD risk threefold.
- This small, dense LDL phenotype is not detected by routine lipid testing.
Conclusions:
- Elevated triglycerides are a primary driver of atherosclerosis, not merely a statistical correlate.
- Aggressive management of hypertriglyceridemia necessitates detailed lipid profiling beyond standard tests.
- Broader risk assessment including triglycerides can expand eligibility for lipid-lowering therapies, benefiting more patients at risk for CAD.
Abstract:
Hypertriglyceridemia is made up of a complex array of dyslipidemias. Difficulties in establishing the independent predictive value of elevated triglycerides in coronary artery disease arise because the triglyceride-rich lipoprotein particles that accumulate are diverse, with differential atherogenic potential, and because hypertriglyceridemia states are typically associated with low high-density lipoprotein cholesterol. When high-density lipoprotein cholesterol is considered in multivariate analysis of the role of hypertriglyceridemia in coronary artery disease, the importance of elevated triglycerides pales, emerging as a statistical second fiddle. However, recent data have affirmed the primary role of triglycerides in the genesis of atherosclerosis. This process involves the overabundance of triglyceride-rich lipoprotein particles, which, paradoxically, can be enriched with cholesterol through the action of cholesterol ester transfer protein. These particles appear to be especially atherogenic. Also, low-density lipoproteins become smaller and denser-small, dense phenotype or pattern B-in hypertriglyceridemia states. This profile is associated with a threefold increase in coronary artery disease risk and is not evident on routine lipid testing. Aggressive management of hypertriglyceridemia requires more detailed lipid analyses to identify patients at risk. In treating hypertriglyceridemia, a risk factor beyond low-density lipoprotein would allow a broader definition of patients at risk for coronary artery disease so that more people would benefit from lipid-lowering initiatives.