Hypertriglyceridemia (HTG) is defined as a fasting triglyceride (TG) concentration above 1.7 mmol/L, and above the 95th percentile for age- and sex-matched populations.1 HTG is an independent risk factor for a host of chronic diseases, notably type 2 diabetes, metabolic syndrome, and atherosclerotic cardiovascular disease (CVD). Estimates of the prevalence of elevated triglycerides in these populations range from 30% to 50%.1

Given the magnitude and severity of HTG, it is essential that appropriate and targeted treatment be initiated as soon as possible. A recent review article1 summarizes current nonpharmacologic and pharmacologic approaches to hypertriglyceridemia, with particular focus on novel agents.

Pathogenesis of HTG

The pathogenesis of HTG “involves a complex interplay between genetic susceptibility, often involving multiple mutations, and environmental factors that affect the production and clearance of TG-rich lipoproteins (TRLs).”1 There are numerous genetic loci involved in this process. In the case of mild to moderate HTG (1.7-10.0 mmol/L), heterozygous genes appear to be involved, while in severe HTG, either homozygosity or compound heterozygosity may be implicated. In both cases, HTG may manifest only in association with a secondary cause.1 (Table 1)

Lifestyle Interventions

Lifestyle interventions are the first-line approach and typically used as monotherapy in mild HTG, in the absence of secondary causes. (Table 2) While lifestyle interventions remain paramount for those with moderate and severe HTG, these patients often require pharmacotherapy as well.1

Pharmacotherapies for HTG

Fibrates activate peroxisome proliferator-activated receptor-α (PPAR-α), leading to increased β-oxidation of fatty acids (FAs) in the mitochondria and peroxisomes. This, in turn, decreases hepatic biosynthesis of TGs and VLDL secretion.1 A study of fibrates showed that they lowered plasma TG concentrations by 46% to 62% in patients with isolated HTG and by 24% to 36% in patients with mixed dyslipidemia.2 However, their effect on LDL-C tends to be variable and in severe HTG, they may actually increase LDL-C.3,4  

Niacin is a well-established therapeutic treatment for HTG. Nicotinic acid decreases plasma TG concentrations by reducing hepatocyte TG synthesis.1 It has been shown to lower TGs by 5% to 40%, and to lower LDL-C and lipoprotein(a). Additionally, it elevates HDL-C. However, its use is limited by significant side effects, which include flushing, pruritus, and hyperglycemia.1 Prospective studies have failed to show improved CVD outcomes with niacin use.1

3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors (statins) are recommended for the treatment of dyslipidemia in most guidelines.2,5-8 The impact on TG involves enhanced catabolism as well as reduced production of TRLs.9 They have been shown to reduce CVD events in both primary and secondary care, to decreased LDL-C , and to reduce TGs by 22% to 45%, in relation to their potency to lower LDL-C and baseline TGs.1,10