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Published on: November 10, 2017
Evidence to support aggressive management of high-density lipoprotein cholesterol: implications of recent imaging
1Cardiology Service, Department of Medicine, Walter Reed Army Medical Center, Washington, District of Columbia 20307-5001, USA. allen.taylor@na.amedd.army.mil
Insights
Raising high-density lipoprotein (HDL) cholesterol with niacin can help regress atherosclerosis. However, solely increasing HDL may not guarantee clinical benefit, necessitating further research for novel HDL therapies.
Area of Science:
- Cardiovascular Medicine
- Lipidology
- Pharmacology
Background:
- High-density lipoprotein (HDL) is recognized as a
- regression particle
- due to its unique lipid particle biology.
- Therapies designed to elevate HDL cholesterol are theoretically expected to promote atherosclerosis regression.
- Niacin is the primary pharmacotherapy currently used to increase HDL cholesterol levels.
Purpose of the Study:
- To evaluate the role of HDL-raising therapies in atherosclerosis regression.
- To assess the efficacy of niacin, alone and in combination therapies, for inducing atherosclerosis regression.
- To determine the predictive value of HDL-raising effects for clinical benefit of novel HDL therapies.
Main Methods:
- Review of existing literature on niacin and HDL-raising therapies.
- Analysis of imaging studies, including quantitative coronary angiography, carotid ultrasound, and intravascular ultrasound.
- Examination of clinical trial data for novel HDL therapeutics, particularly those involving cholesterol ester transfer protein inhibition.
Main Results:
- Niacin has demonstrated efficacy in regressing atherosclerosis when used as monotherapy or in combination with statins, non-statin therapies, and fibrates.
- Imaging studies show a modest inverse correlation between the extent of HDL increase and atherosclerosis regression.
- Adverse effects observed with cholesterol ester transfer protein inhibitors suggest that HDL-raising effects alone are insufficient to predict clinical benefit.
Conclusions:
- While niacin effectively promotes atherosclerosis regression, novel HDL therapies require rigorous clinical trial evidence for safety and efficacy.
- Atherosclerosis imaging is crucial for preclinical assessment of new HDL-raising agents and for comparative treatment strategy testing.
- The predictive value of solely increasing HDL levels for clinical outcomes needs further investigation.
Abstract:
High-density lipoprotein (HDL) is a "regression particle" based on its unique lipid particle biology. This unique property predicts that, in theory, therapies that raise HDL cholesterol should be able to induce regression of atherosclerosis. Presently, the principle pharmacotherapy for increasing HDL cholesterol is niacin. Niacin has been shown to regress atherosclerosis when used as monotherapy, in combination with a statin, and in combination with nonstatin therapies (including cholesterol-binding resins) and fibrates. Insights into the atherosclerosis benefits of combination lipid-lowering therapy with niacin have come from imaging studies utilizing quantitative coronary angiography, carotid ultrasound, and intravascular ultrasound showing modest inverse correlations between the extent of HDL increase and atherosclerosis regression. Recent adverse atherosclerosis and clinical effects seen with cholesterol ester transfer protein inhibition indicate that HDL-raising effects alone are insufficient to predict clinical benefit of new HDL therapies. Thus, although clinical trial evidence is necessary to understand the full scope of the safety and efficacy profile of novel HDL therapeutics, atherosclerosis imaging will be an important component of preclinical testing of these agents as they emerge and in head-to-head testing of treatment strategies.
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