New approaches to triglyceride reduction: Is there any hope left?

Abstract

Triglycerides play a crucial role in the efficient storage of energy in the body. Mild and moderate hypertriglyceridemia (HTG) is a heterogeneous disorder with significant association with atherosclerotic cardiovascular disease (ASCVD), including myocardial infarction, ischemic stroke, and peripheral artery disease and represents an important component of the residual ASCVD risk in statin treated patients despite optimal low-density lipoprotein cholesterol reduction. Individuals with severe HTG (>1,000 mg/dL) rarely develop atherosclerosis but have an incremental incidence of acute pancreatitis with significant morbidity and mortality. HTG can occur from a combination of genetic (both mono and polygenic) and environmental factors including poor diet, low physical activity, obesity, medications, and diseases like insulin resistance and other endocrine pathologies. HTG represents a potential target for ASCVD risk and pancreatitis risk reduction, however data on ASCVD reduction by treating HTG is still lacking and HTG-associated acute pancreatitis occurs too rarely to effectively demonstrate treatment benefit. In this review, we address the key aspects of HTG pathophysiology and examine the mechanisms and background of current and emerging therapies in the management of HTG.

Keywords: Atherosclerosis; Fibrates; Mortality; Omega-3; Statins; Triglycerides.

Fig. 1

Absorption, transport, and metabolism of triglycerides.

Fig. 2

Pathophysiology of triglyceride pro-atherogenic effects.

Fig. 3

Suggested HTG treatment algorithm.

Central 1

Illustration. APO=apolipoprotein; ANGPTL=angiopoietin-like proteins; ASCVD=Atherosclerotic Cardiovascular Disease; CAD=coronary artery disease; CVA=cerebral vascular accident; CVD=cardiovascular disease; DM=diabetes mellitus; FA=fatty acid; FGF=fibroblast growth factor; Hx=history; LDL-C=low-density lipoprotein-cholesterol; PAD=peripheral artery disease; TG=triglycerides; HoFH=homozygous familial hypercholesterolemia; siRNA=small interfering RNA; mRNA=messenger RNA.