Approach to Hypertriglyceridemia

Abstract

Hypertriglyceridemia (HTG) is a common biochemical diagnosis, based on fasting plasma triglyceride (TG) concentration above a specified cut point. Many laboratories report that for children the upper limit of normal TG is 1.7 mmol/L (150 mg/dL), a level that is associated with increased future risk of atherosclerotic cardiovascular disease. Severe HTG is diagnosed when fasting plasma TG concentration is >10 mmol/L (>885 mg/dL) and is associated with increased risk of pancreatitis. In children with a form of severe HTG called familial chylomicronemia syndrome (FCS), the etiology is monogenic due to biallelic pathogenic variants in genes associated with lipolysis. Genetic testing can be helpful to make the diagnosis of FCS. However, much more common in children is mild-to-moderate HTG, which while polygenic in nature results largely from influence of secondary factors, especially obesity and insulin resistance. For all patients with HTG, secondary factors must be ruled out. Treatment of HTG involves a range of non-pharmacologic interventions and sometimes judicious use of pharmaceutical agents such as fibrates, omega-3 fatty acids, or statins. For FCS or very severe HTG, lifestyle interventions are much stricter, and the limited efficacy of available pharmaceutical agents has necessitated development of new biologic treatments such as inhibitors of apolipoprotein C-III and angiopoietin-like protein 3.