The emerging evidence for the role of elevated levels of triglyceride-rich lipoprotein remnants (TLRs) in raising the risk of atherosclerotic cardiovascular disease (ASCVD) events, along with emerging lipid-lowering therapies for cardiovascular risk management, were the subject of a Focus Seminar published Oct. 25 in the Journal of the American College of Cardiology.
Robert S. Rosenson, MD, FACC; Aleesha Shaik, MD, MPH; and Wenliang Song, MD, reviewed evidence from epidemiological, biological mechanism, genomic and clinical studies that suggest TLRs from hepatic and intestinal sources contribute to a “pro-atherogenic environment that augments cardiovascular risk.”
Risk assessment of TLR-related ASCVD disease risk begins with assessment of cardiovascular history and risk factors and an evaluation of clinical and subclinical atherosclerosis. Ensuring the optimal management of low-density lipoprotein cholesterol (LDL-C) and other major modifiable risk factors are important.
“Our approach to patients with mild to moderate hypertriglyceridemia (fasting triglycerides [TGs] ³150 mg/dL to <880 mg/dL) involves a low fat and low glycemic index diet with caloric restriction in overweight patients, regular exercise, including aerobic and muscle strengthening, and guideline-directed management of major cardiovascular risk factors including intensive control of dysglycemia,” write Rosenson, et al.
Evidence supporting treatment of high concentrations of TLRs for ASCVD prevention is limited. Aggressive reduction of LDL-C based on high-intensity statin therapy is recommended but trials of TG-lowering therapies in statin-treated patients have not shown clinical benefit, with the exception of icosapent ethyl. The authors consider its use in patients with fasting triglycerides ³135 mg/dL. A clinical algorithm for assessment and treatment of high levels of TLR is provided by the authors.
They also recognize the importance of angiopoietin-like 3 (ANGPLT3) inhibitor that lower both TLRs and LDL-C. They note that an apolipoprotein C-III (Apo-CIII) inhibitor is an option for patients with severe hypertriglyceridemia (>880 mg/dL). Looking ahead, they conclude that more trials of these agents are needed to provide guidance on their contribution to cardiovascular risk management in patients with elevated remnant cholesterol.
Clinical Topics: Arrhythmias and Clinical EP, Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Genetic Arrhythmic Conditions, Hypertriglyceridemia, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Diet, Exercise
Keywords: Angiopoietins, Heart Disease Risk Factors, Cardiology, Risk Assessment, Exercise, Genomics, Atherosclerosis, Lipoproteins, Triglycerides, Hypertriglyceridemia, Eicosapentaenoic Acid, Risk Factors, Centers for Medicare and Medicaid Services, U.S., Glycemic Index, Caloric Restriction, Cardiovascular Diseases, Apolipoprotein C-III, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cholesterol, LDL