Abstract
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 situation is termed the multifactorial chylomicronemia 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.
Highlights
The chylomicronemia syndrome (CS) is a term that is used to describe individuals with either intermittent or persistent fasting chylomicronemia causing severe hypertriglyceridemia (HTG)
Patients with familial chylomicronemia syndrome (FCS) are younger and less likely to have any of the aggravating factors for HTG compared to those with multifactorial chylomicronemia syndrome (MFCS), but are more likely to develop pancreatitis probably because of life-long, sustained chylomicronemia [8]
They are less like to have cardiovascular disease (CVD) than those with MFCS because of the severe reduction in lipoprotein lipase (LPL) activity, which reduces atherogenic chylomicron and very low density lipoprotein (VLDL) remnant formation and accumulation which may occur in MFCS [7]
Summary
The chylomicronemia syndrome (CS) is a term that is used to describe individuals with either intermittent or persistent fasting chylomicronemia causing severe hypertriglyceridemia (HTG). 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. Most cases with CS occur in individuals with a polygenic form of hypertriglyceridemia (HTG) that typically manifests with moderately elevated triglyceride levels (500–999 mg/dl), in whom severe HTG and CS may develop as a result of the underlying genetic tendency being complicated by one or more conditions or medications that aggravate HTG and is termed the multifactorial chylomicronemia syndrome (MFCS) [3]. Because the principal health risk of the CS is pancreatitis, which can be prevented if triglyceride levels are maintained below 500 mg/dl, clinical recognition of polygenic HTG and the factors that can aggravate it are key to the prevention of much of the morbidity and mortality associated with the CS and is the major focus of this review
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