Hypertriglyceridaemia: Aetiology, Complications and Management

Abstract

The bulk of plasma triglycerides is carried by chylomicrons in the fed and very low density lipoproteins in the fasted state. These triglyceride-rich lipoproteins are metabolised to remnant lipoproteins by lipoprotein lipase. Hypertriglyceridaemia results if triglyceride-rich lipoproteins accumulate either due to defective clearance, overproduction or a combination of both mechanisms. Genetic and environmental factors interact in the genesis of hypertriglyceridaemia but occasionally a single factor may be dominant. At a molecular level the commonest cause of severe primary hypertriglyceridaemia is loss of function mutations in both alleles of lipoprotein lipase (LPL). The commonest environmental contributors include diabetes, diet, alcohol and medications (oestrogen, steroids, retinoids, rotease inhibitors). Severe hypertriglyceridaemia can trigger acute pancreatitis while mild to moderate hypertriglyceridaemia is an independent cardiovascular risk factor. Treatment strategies are determined by the severity and aetiology of hypertriglyceridaemia as well as the patient’s cardiovascular risk profile. General strategies include lifestyle modifications with restriction of dietary fat intake, cessation of alcohol intake and increased exercise. Contributing metabolic disorders should be controlled and aggravating medications withdrawn or reduced where possible. Moderate hypertriglyceridaemia may be treated with high doses of omega-3 fatty acids (4 grammes/day), fibrates, niacin or statins. Fibrates are the agents of choice in severe hypertriglyceridaemia.