Hypertriglyceridemia: its etiology, effects and treatment

Abstract

Elevated plasma triglyceride concentration is a common biochemical finding, but the evidence for the benefit of treating this lipid disturbance remains less robust than that for treating elevated low-density lipoprotein-cholesterol. Part of the difficulty in the provision of specific recommendations has been the frequent coexistence of elevated triglycerides with other conditions that affect cardiovascular disease risk, such as depressed high-density lipoprotein-cholesterol, obesity, metabolic syndrome, proinflammatory and prothrombotic biomarkers, and type 2 diabetes. Recent investigations of outcomes of cardiovascular disease when medications are used to reduce triglyceride levels suggest that, although a net benefit probably exists, both relative and absolute risk reductions seem underwhelming when compared with the benefit of reducing low-density lipoprotein-cholesterol levels with treatment. However, the totality of evidence suggests that elevated triglyceride levels likely contribute independently to increased risk of cardiovascular disease, although there is no consensus about appropriate target levels. Furthermore, severe hypertriglyceridemia is associated with an increased risk of acute pancreatitis, irrespective of its effect on risk of cardiovascular disease. We review the causes and classification of elevated triglyceride levels, the clinical manifestations of primary hypertriglyceridemia and the management of patients with elevated triglyceride levels.

Fig. 1: Clinical manifestations of primary hypertriglyceridemia. A: Eruptive cutaneous xanthomas (here on a patient's knee) are filled with foam cells that appear as yellow morbiliform eruptions 2–5 mm in diameter, often with erythematous areolae. Most often associated with markedly elevated plasma chylomicrons in cases of familial chylomicronemia (hyperlipoproteinemia type 1) or primary mixed dyslipidemia (hyperlipoproteinemia type 5), they usually occur in clusters on the skin of the trunk, buttocks or extremities. B: Lipemic plasma. Whole blood has been allowed to stand at 4°C overnight. The sample on the left comes from a patient whose fasting total cholesterol result was 14.2 mmol/L and triglyceride concentration was 41.8 mmol/L. The sample on the right comes from a normolipidemic subject. C: Lipemia retinalis. A milky appearance of the retinal vessels and pink retina can be seen when plasma triglyceride concentration exceeds 35 mmol/L. D: Tuberous xanthomas, filled with foam cells, appear as reddish or orange, often shiny nodules, up to 3 cm in diameter. They are usually moveable and nontender. In patients with familial dysbetalipoproteinemia (hyperlipoproteinemia type 3), they usually appear on extensor surfaces; these are on a patient's elbows. E: Palmar crease xanthomas are filled with foam cells and appear as yellowish deposits within palmar creases. These skin lesions are pathognomonic for familial dysbetalipoproteinemia (hyperlipoproteinemia type 3). Photo by: Panels A, B and D are courtesy of Robert A. Hegele; panel C is courtesy of Ted M. Montgomery; and panel E is courtesy of Jean Davignon.

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