Dyslipidemia is a broad category of diseases involving elevation of plasma cholesterol and/or triglyceride, and reduced high-density-lipoprotein bound cholesterol (HDL-C) which generally contribute to atherosclerosis. The most common forms of dyslipidemia include hypertriglyceridemia, mixed dyslipidemia, and hypercholesterolemia. Hypertriglyceridemia is characterized by elevation of serum triglycerides and very-low-desnisty-lipoprotein bound cholesterol (VLDL-C). Mixed dyslipidemia is characterized by elevation of serum triglycerides, total cholesterol, low-density-lipoprotein bound cholesterol (LDL-C), and VLDL-C. Hypercholesterolemia is characterized by elevated total cholesterol and LDL-C.

The majority of cases of dyslipidemia do not have a clear genetic basis, but are due to secondary causes including: sedentary lifestyle, excessive intake of dietary saturated fat and cholesterol, diabetes mellitus and excessive alcohol consumption.

Management and treatment of dyslipidemia involves changes in diet and lifestyle, and often includes pharmacotherapy when diet and lifestyle changes are ineffective in treating the disease.

The National Cholesterol Education Program (NCEP) in the Adult Treatment Program III (ATP III) guidelines provide the following classification of Risk Reduction Targets for treatment:

Very High Triglycerides and the Risk of Acute Pancreatitis

Acute pancreatitis is associated with significant mortality and morbidity. Although two-thirds of the cases present with minimal organ dysfunction, the remainder of cases are associated with intra and extrapancreatic necrosis, shock, multiple organ failure, and results in death in up to 20% of patients who present with severe symptoms. Approximately 80% of deaths in acute pancreatitis are associated with septic complications.

There are several causes for acute pancreatitis, including substantially elevated triglycerides, alcoholism and biliary tract disease.  Very high triglycerides (>500 mg/dL) is a well characterized risk factor for acute pancreatitis, accounting for up to 7% of all cases.  The clinical course of acute pancreatitis in subjects with very high triglycerides is not different from that of pancreatitis due to other causes. 

Triglycerides have both exogenous and endogenous sources. Triglycerides obtained from dietary sources are initially packaged in chylomicrons, while endogenous triglycerides synthesized by the liver are packaged in VLDL. These two lipoproteins are the predominant source of triglycerides in blood and interact with lipoprotein lipase and hepatic triglyceride lipase in peripheral tissue in order to to clear the bloodstream of these particles and store triglycerides in muscle and adipose tissue. The development of hypertriglyceridemia is dependent on a balance between the synthesis and clearance of these lipoproteins. Primary hypertriglyceridemia is a category of rare hereditary diseases which include Familial Hypertriglyceridemia (Type IV Hyperlipidemia), and Familial Combined Hyperlipidemia (Type V Hyperlipidemia). Secondary hypertriglyceridemia has numerous etiologies such as alcohol, diet, obesity, estrogen, pregnancy, chronic renal failure, diabetes, hypothyroidism, and drugs (tamoxifen, estrogen replacement therapy and antiretroviral therapy).

The exact mechanism by which very high triglycerides contributes to increased risk of acute pancreatitis is unclear, but it is thought to be the result of both genetic and acquired causes colluding to increase concentrations of chylomicrons in the blood since there is competition between VLDL and chlyomicrons for clearance by lipoprotein lipase. Chylomicrons are usually formed 1-3 hours post-prandially and cleared within 8 hours. When triglycerides levels exceed 500 mg/dL and approach 1,000mg/dL, chylomicrons are almost always present. These low density particles are very large and may obstruct capillaries leading to local ischemia and acidemia. This local damage can expose triglycerides to pancreatic lipases. The degradation of triglycerides to free fatty acids can lead to local cytotoxic injury that increases inflammatory mediators and free radicals, eventually manifesting as pancreatitis.

Marked reduction of triglyceride levels in patients who had had at least one episode of acute pancreatitis effectively prevents further episodes (2).  Dietary restriction of fat is a critical component of management of triglycerides.  Additionally, increases in physical activity, cessation of smoking, reductions in alcohol consumption and weight loss all may contribute to management of elevated triglycerides.   In some instances, drug therapy contributes to the elevated triglycerides and discontinuation of these treatments results in reductions in triglycerides.  Further, pharmacological interventions that rapidly and markedly reduce triglycerides in patients with very high triglycerides have value in the prevention of pancreatitis.  Even though risk of pancreatitis rises rapidly in patients with triglycerides above 1000 mg/dL, the variable nature of triglyceride measurements, both intraday and from day to day, leads to the recommendation that treatment should be initiated at triglycerides of 500 mg/dL.  According to NCEP ATP III guidelines (4), triglycerides reduction should be a primary target of therapy in patients with triglycerides greater than 500 mg/dL because of the increased risk of acute pancreatitis.  The Kidney Foundation currently provides the same guidance for patients with chronic kidney disease with very high triglycerides.