SHTG - FCS 4.pptx, A Comprehensive Update on

The chylomicronemia syndrome is characterized by severe hypertriglyceridemia and fasting chylomicronemia and predisposes affected individuals to acute pancreatitis. When due to very rare monogenic mutations in the genes encoding the enzyme, lipoprotein lipase, or its regulators, APOC2, APOA5, GPIHBP1, and LMF1, it is referred to as the familial chylomicronemia syndrome. Much more frequently, the chylomicronemia syndrome results from a cluster of minor genetic variants causing polygenic hypertriglyceridemia, which is exacerbated by conditions or medications which increase triglyceride levels beyond the saturation point of triglyceride removal systems. This situa syndrome. These aggravating factors include common conditions such as uncontrolled diabetes, overweight and obesity, alcohol excess, chronic kidney disease and pregnancy and several medications, including diuretics, non-selective beta blockers, estrogenic compounds, corticosteroids, protease inhibitors, immunosuppressives, antipsychotics, antidepressants, retinoids, L-asparaginase, and propofol. A third uncommon cause of the chylomicronemia syndrome is familial forms of partial lipodystrophy. Development of pancreatitis is the most feared complication of the chylomicronemia syndrome, but the risk of cardiovascular disease as well as non-alcoholic steatohepatitis is also increased. Treatment consists of dietary fat restriction and weight reduction combined with the use of triglyceride lowering medications such as fibrates, omega 3 fatty acids and niacin. Effective management of aggravating factors such as improving diabetes control, discontinuing alcohol and replacing or reducing the dose of medications that raise triglyceride levels is essential. Importantly, many if not most cases of the chylomicronemia syndrome can be prevented by effective identification of polygenic hypertriglyceridemia in people with conditions that increase its likelihood or before starting medications that may increase triglyceride levels. Several new pharmacotherapeutic agents are being tested that are likely to considerably improve treatment of hypertriglyceridemia in people at risk. INTRODUCTION The chylomicronemia syndrome (CS) is a term that is used to describe individuals with either intermittent or persistent fasting chylomicronemia causing severe hypertriglyceridemia (HTG). It is usually defined as being present when triglyceride values exceed 1,000 mg/dl (1) or 10 mmol/L (885 mg/dl) (2), when the risk for pancreatitis is increased. Fasting chylomicronemia may rarely be due to a monogenic disorder that markedly reduces the activity of lipoprotein lipase (LPL), resulting in decreased clearance of the triglyceride-rich lipoproteins (TRL) from plasma. This is referred to as the familial chylomicronemia syndrome (FCS) and is very resistant to treatment. However most cases with CS occur in individuals with a polygenic form of hypertriglyceridemia (HTG) that typically manifests with moderately elevated triglycerid