Tratamiento de la hipertrigliceridemia: fibratos frente a ácidos grasos omega-3

Hypertriglyceridemia (HTG) combined with a low highdensity lipoprotein (HDL) cholesterol level is the characteristic lipid abnormality in two prevalent conditions: the metabolic syndrome and diabetes. Moreover, it is also the commonest dyslipidemia in patients with coronary heart disease. HTG is caused by increased hepatic synthesis of very-low-density lipoprotein (VLDL), usually due to excess visceral fat, or to defective VLDL clearance secondary to genetic or acquired impairment of lipoprotein lipase activity (LPL). Frequently, there is both excess VLDL input to the circulation and reduced clearance. In addition to a low HDL cholesterol level, HTG is also associated with the formation of small dense low-density lipoprotein (LDL) particles that are particularly atherogenic. This explains why HTG is an independent cardiovascular risk factor that must be treated as intensively as hypercholesterolemia. At present, a triglyceride concentration < 150 mg/dL is regarded as desirable. Conservative treatment of HTG by lifestyle modification involving diet and weight loss is very effective but difficult to implement. Fibrates are the conventional pharmacological treatment for HTG. These agents are activators of transcription factor PPAR-α, and consequently promote fatty acid oxidation and enhance LPL. This, in turn, reduces the serum level and stimulates synthesis of HDL apolipoproteins, thereby increasing the HDL cholesterol level. On average, fibrates reduce the level by 36% and increase HDL cholesterol by 8%. Given at a dose of 2-4 g/day, marine omega-3 fatty acids are as effective as fibrates in lowering the triglyceride level. Moreover, they are devoid of side effects. In addition, omega-3 fatty acids also interact with PPAR-α, although they decrease fatty acid synthesis by alternative mechanisms. This explains why the lowering effect of omega-3 fatty acids is complementary to that of fibrates. Omega-3 fatty acids have been found to be effective in lowering the, triglyceride level when given either as monotherapy or in combination with statins. In the severe HTG found with chylomicronemia syndromes, the effect of omega-3 fatty acids is additive to that of fibrates, resulting in an additional reduction in levels of up to 50% beyond that induced by fibrates alone, thereby minimizing the risk of acute pancreatitis. Consequently, fibrates and omega-3 fatty acids do not have opposing actions. Instead, they complement each other when used for the treatment of hypertriglyceridemia.