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Patients with very high levels of serum triglycerides (greater than 1000 mg/dL) are at risk for pancreatitis. The pathophysiology is not certain, since pancreatitis never develops in some patients with very high triglyceride levels. Most patients with congenital abnormalities in triglyceride metabolism present in childhood; hypertriglyceridemia-induced pancreatitis first presenting in adults is more commonly due to an acquired problem in lipid metabolism.

Although there are no clear triglyceride levels that predict pancreatitis, most clinicians treat fasting levels above 500 mg/dL (5 mmol/L). The risk of pancreatitis may be more related to the triglyceride level following consumption of a fatty meal. Because postprandial increases in triglyceride are inevitable if fat-containing foods are eaten, fasting triglyceride levels in persons prone to pancreatitis should be kept well below that level.

The primary therapy for high triglyceride levels is dietary, avoiding alcohol, simple sugars, refined starches, and saturated and trans fatty acids, and restricting total calories. Control of secondary causes of high triglyceride levels (see eTable 28–1) may also be helpful. In patients with fasting triglycerides greater than or equal to 500 mg/dL (5 mmol/L) despite adequate dietary compliance—and certainly in those with a previous episode of pancreatitis—therapy with a triglyceride-lowering drug (eg, statins, omega-3 preparations, or fibric acid derivatives) is indicated. Combinations of these medications may also be used.

Currently, drug treatment for patients with triglycerides greater than 150 mg/dL (1.5 mmol/L) is reserved for those with established CVD with well-controlled LDL cholesterol on maximally tolerated therapy with statins or other agents. Currently, data are strongest for icosapent ethyl.

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