Hypertriglyceridemia

In medicine, hypertriglyceridemia denotes high (hyper-) blood levels (-emia) of triglycerides, the most abundant fatty molecule in most organisms. It has been associated with atherosclerosis, even in the absence of hypercholesterolemia (high cholesterol levels). It can also lead to pancreatitis in excessive concentrations (i.e. when the triglyceride concentration is greater, and often very much greater, than 1000 mg/dl or 12 mmol/l). Very high triglyceride levels may also interfere with blood tests; hyponatremia may be reported spuriously (pseudohyponatremia).

A related term is "hyperglyceridemia" which refers to a high level of all glycerides, including monoglycerides, diglycerides and triglycerides.

Signs and symptoms
Modestly elevated triglyceride levels do not lead to any physical symptoms. Higher levels are associated with lipemia retinalis (white appearance of the retina), eruptive xanthomas (small lumps in the skin, sometimes itchy).

Causes

 * High carbohydrate diet
 * Idiopathic (constitutional)
 * Obesity
 * Diabetes mellitus and insulin resistance - it is one of the defined components of metabolic syndrome (along with central obesity, hypertension, and hyperglycemia)
 * Excess alcohol intake
 * renal failure, Nephrotic syndrome
 * Genetic predisposition; some forms of familial hyperlipidemia such as familial combined hyperlipidemia i.e. Type II hyperlipidemia
 * Lipoprotein lipase deficiency - Deficiency of this water soluble enzyme, that hydrolyzes triglycerides in lipoproteins, leads to elevated levels of triglycerides in the blood.
 * Lysosomal acid lipase deficiency or Cholesteryl ester storage disease
 * Certain medications e.g. isotretinoin, estrogen, hydrochlorothiazide diuretics, beta blockers, protease inhibitors
 * Hypothyroidism (underactive thyroid)
 * Systemic Lupus Erythematosus
 * Glycogen storage disease type 1.

Relationship of Hypertriglyceridemia to Atherosclerosis
Since triglycerides are not a component of the atherosclerotic plaque, it is not intuitively obvious whether hypertriglyceridemia promotes atherosclerosis. Numerous studies (summarized in references ) have examined the relationship between hypertriglyceridemia and atherosclerosis with a definitive answer still not apparent. In large part, the conflicting results reflect whether various other relevant risk factors for atherosclerosis were examined and taken into account. Specifically, the following are all risk factors for atherosclerosis and all are also associated with (not necessarily in a causal way) hypertriglyceridemia:


 * obesity
 * diabetes and insulin resistance
 * metabolic syndrome
 * presence of other dyslipidemias associated themselves both with high triglycerides and atherosclerosis (e.g. mixed hyperlipidemia, low HDL (hypoalphalipoproteinemia), Familial dysbetalipoproteinemia (type III hyperlipoproteinemia), etc.)
 * high levels of small, dense LDL
 * high levels of apolipoprotein B (apoB)

In other words, any study purporting to demonstrate an association of hypertriglyceridemia and atheroslerosis must not only have controlled for the classic atherosclerosis risk factors but also for the more recently recognized risk factors such as insulin resistance, levels of small, dense LDL, and apoB levels. The relationship among hypertriglyceridemia, atherosclerosis, and apoB is particularly instructive. Specifically, those forms of hypertriglyceridemia associated with high levels of apoB, but not those associated with low levels of apoB, are associated with atherosclerosis.

Treatment
Treatment of hypertriglyceridemia is by restriction of carbohydrates and fat in the diet, as well as with niacin, fibrates and statins (three classes of drugs). Increased fish oil intake may substantially lower an individual's triglycerides.

Clinical practice guidelines by the National Cholesterol Education Program (NCEP) suggest that pharmacotherapy should be considered for a triglycerides level over 200 mg/dL. The guidelines state "the sum of LDL + VLDL cholesterol (termed non-HDL cholesterol [total cholesterol - HDL cholesterol]) as a secondary target of therapy in persons with high triglycerides (200 mg/dL). The goal for non-HDL cholesterol in persons with high serum triglycerides can be set at 30 mg/dL higher than that for LDL cholesterol (Table 9) on the premise that a VLDL cholesterol level 30 mg/dL is normal."

Non–HDL cholesterol contains the highly atherogenic, small, dense lipoproteins that are associated with a high incidence of cardiovascular disease (CVD). Studies subsequent to the NCEP report have shown that the non–HDL cholesterol level predicts CVD in people who have diabetes. It may be superior to LDL cholesterol in this regard, and should be used as the primary lipid target in persons with diabetes.

Primary prevention
Omega-3 fatty acid supplementation in the form of fish oil has been found to be effective in decreasing levels of triglycerides and all cardiovascular events by 19% to 45%.

Gemfibrozil twice daily in asymptomatic men ages 40–55 without heart disease was also found to be effective at reducing cardiac endpoints at 5 years (4.14% to 2.73%). This means that 71 people must take the treatment for five years to prevent one cardiac event (number needed to treat of 71).

Secondary prevention
A randomized controlled trial of men with known heart disease and HDL cholesterol of 40 mg/dl or less, 600 mg of gemfibrozil twice daily reduced cardiac endpoints (non-fatal myocardial infarction or death from coronary causes) at 5 years from 21.7% to 17.3%. This means that 23 patients must be treated for five years to prevent one cardiac event (number needed to treat is 23).