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New targets for medical treatment of lipid disorders
Margaret E Brousseau1, Ernst J Schaefer
1JM-USDA-HNRCA at Tufts University, 711 Washington Street, Boston, MA 02111, USA. mbrousseau@hnrc.tufts.edu
Insights
New treatments are emerging for lipid disorders, offering alternatives to statins for patients with low HDL cholesterol or high triglycerides, common in coronary heart disease patients.
Area of Science:
- Cardiovascular Medicine
- Biochemistry
- Pharmacology
Background:
- Coronary heart disease (CHD) is a leading cause of death globally.
- Key risk factors for CHD include elevated low-density lipoprotein (LDL) cholesterol and low high-density lipoprotein (HDL) cholesterol.
- Statins, inhibitors of HMG-CoA reductase, effectively lower LDL but may not be optimal for all dyslipidemic patients, especially those with low HDL.
Purpose of the Study:
- To review emerging therapeutic options for managing lipid disorders beyond statins.
- To address treatment challenges in patients with low HDL cholesterol and/or hypertriglyceridemia.
- To explore novel drug targets and mechanisms for lipid management.
Main Methods:
- Review of current literature on emerging lipid-lowering therapies.
- Discussion of drug classes targeting cholesterol absorption, esterification, and transport.
- Examination of agents influencing HDL cholesterol levels and triglyceride metabolism.
Main Results:
- Emerging therapies include inhibitors of cholesterol absorption, ACAT, MTP, and CETP.
- Liver X receptor agonists are discussed for their role in up-regulating ABCA1 expression.
- These novel agents offer potential for managing complex dyslipidemias not adequately addressed by statins.
Conclusions:
- Novel therapeutic strategies are crucial for managing lipid disorders, particularly in patients with low HDL cholesterol and hypertriglyceridemia.
- Emerging drug classes provide new avenues for cardiovascular risk reduction in specific patient populations.
- Further research and clinical trials are needed to establish the efficacy and safety of these novel treatments.
Abstract:
Coronary heart disease (CHD) is the leading cause of death and disability in the industrialized world. Included among the risk factors for CHD are an elevated level of low-density lipoprotein (LDL) cholesterol and a low level of high-density lipoprotein (HDL) cholesterol. The discovery of drugs that inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins), the rate-limiting enzyme in cholesterol biosynthesis, constituted a major advance in the treatment of patients with elevated plasma concentrations of LDL cholesterol. However, although the statins are potent LDL-lowering agents, they may not be the therapy of choice for all dyslipidemic patients. This is particularly true for subjects whose primary lipid abnormality is a low level of HDL cholesterol with or without hypertriglyceridemia, a group that includes about one half of patients with CHD. In this report, we review emerging options for the treatment of patients with lipid disorders, including inhibitors of cholesterol absorption, acyl coenzyme A-cholesterol acyltransferase, microsomal triglyceride transfer protein, and cholesteryl ester transfer protein, as well as liver X receptor agonists that up-regulate the expression of ATP-binding cassette transporter A1.