A 52-year-old female with an elevated fasting triglyceride level and familial cardiac risk

Hypertriglyceridaemia can be primary or secondary. Primary hypertriglyceridaemia is a genetic defect in triglyceride metabolism as a result of abnormal apolipoproteins, lipoprotein lipase deficiency, apo C-II deficiency, or enhanced hepatic triglyceride synthesis. Triglyceride levels are often severely elevated (>500 mg/dL) and may be associated with normal to elevated total cholesterol levels (Fredrickson dyslipidaemia type IV).

Secondary hypertriglyceridaemia is associated with a number of conditions, including diabetes mellitus, obesity, metabolic syndrome, renal disease (e.g. nephrotic syndrome, uremia), hypothyroidism, glucocorticoid therapy, medications (e.g. antiretroviral therapy, oestrogen therapy, retinoic acid), systemic lupus erythematosus, and even sepsis.

Hypertriglyceridaemia is also associated with insulin resistance, even in non-obese, non-diabetic patients [1]. This appears to be the result of increased very low-density lipoprotein production and decreased HDL production by the liver in response to elevated serum insulin levels [2].

The diagnosis of hypertriglyceridaemia is made on the basis of laboratory findings of a fasting triglyceride level >150 mg/dL. Levels of 150-199 mg/dL are considered mild or borderline, and levels of 200-499 mg/dL are high. Levels >500 mg/dL are considered very high or severe. Most cases are diagnosed through routine screening laboratory tests, as was the situation for this patient.

In patients with very high levels of triglycerides, physical manifestations include eruptive xanthomas, pancreatitis, and lipid-related changes in the retinal blood vessels. Eruptive xanthomas are small, yellowish papules on the skin that commonly occur on the upper chest and back.

When hypertriglyceridaemia is discovered, a patient should be evaluated for associated conditions, particularly hypothyroidism, metabolic syndrome, and diabetes. The association between hypertriglyceridaemia and cardiovascular disease is not clear and is confounded by the fact that elevated triglyceride levels often accompany other cholesterol abnormalities as well as other factors that contribute to atherosclerotic disease such as obesity, insulin-resistance, and diabetes. In addition, treatment of hypertriglyceridaemia can lead to improvements in HDL, a protective factor in atherosclerotic disease. However, it is clear that a diet that is high in saturated fatty acids leads to hypertriglyceridaemia and endothelial activation with oxidation of the LDL, factors known to contribute to atherogenic plaque formation [3]. Hypertriglyceridaemia has also been found to have a higher predictive value for metabolic syndrome than even central obesity [4].

The initial treatment for mild hypertriglyceridaemia is a lifestyle intervention. Increased exercise and achieving an ideal weight are the first steps and can lead to normalization of the triglyceride levels. Dietary changes should include reducing saturated fat intake to <7% of caloric intake and reducing carbohydrates to <60% of the daily caloric intake. Patients can be encouraged to eat oily fish and should be discouraged from drinking alcoholic beverages. Patients should be encouraged to exercise most days of the week for at least 30 minutes.

Other contributing factors, if present, should be treated. This includes treatment for other cholesterol abnormalities if they are present.

If the hypertriglyceridaemia is severe or the initial lifestyle changes do not lead to improvements within the first few months of therapy, additional medication therapy can be instituted. Extended-release niacin therapy is a useful adjunct that can lower triglycerides and increase HDL levels. The extended-release formulation is better tolerated than the immediate-release formulations of niacin. Fish oil in doses of 2-4 g/day can reduce triglyceride levels but does not have the benefit of increasing the HDL levels. At higher doses, the reduction in triglyceride levels can be dramatic [5]. Taking the capsules at bedtime or with meals improves tolerance of the fishy reflux or burping that can follow dosing.

If first-line therapies are not effective, fibric acid derivatives can be considered. If LDL elevations are present, treatment with statins is effective at reducing the LDL and may effectively reduce the triglycerides as well. Bile-binding resin drugs are not recommended for hypertriglyceridaemia, as these drugs can actually lead to increased triglyceride levels.

Follow-up with repeated blood levels for triglycerides and a lipid panel should be done monthly until the levels are normal and then should be monitored every 6 months. If the patient is initiating therapy with fibric acid derivatives or statins, liver enzymes should also be checked periodically. Because hypertriglyceridaemia is associated with the metabolic syndrome and diabetes, regular screening for these conditions should also be done and treatment initiated if indicated.