Publique en esta revista
Información de la revista
Vol. 6. Núm. D.
Utilidad terapéutica de los ácidos grasos omega-3
Páginas 52D-61D (Junio 2006)
Compartir
Compartir
Descargar PDF
Más opciones de artículo
Vol. 6. Núm. D.
Utilidad terapéutica de los ácidos grasos omega-3
Páginas 52D-61D (Junio 2006)
Utilidad terapéutica de los ácidos grasos omega-3
DOI: 10.1016/S1131-3587(06)74826-9
Acceso a texto completo
Tratamiento de la hipertrigliceridemia: fibratos frente a ácidos grasos omega-3
Treatment of Hypertriglyceridemia: Fibrates Versus Omega-3 Fatty Acids
Visitas
...
Emilio Rosa,??
Autor para correspondencia
eros@clinic.ub.es

Correspondencia: Dr. E. Ros. Unidad de Lípidos. Hospital Clínic. Villarroel, 170. 08036 Barcelona. España.
, Juan C. Lagunab
a Unidad de Lípidos. Servicio de Endocrinología y Nutrición. IDIBAPS. Hospital Clínic. Barcelona. España
b Unidad de Farmacología. Facultad de Farmacia. Universidad de Barcelona. Barcelona. España
Información del artículo
Resumen
Bibliografía
Descargar PDF
Estadísticas

Por ser un componente del síndrome metabólico y de la diabetes, entidades que en la actualidad son epidémicas, la hipertrigliceridemia (HTG) asociada con valores bajos de colesterol unido a lipoproteínas de alta densidad (cHDL) es la dislipidemia de presentación clínica más frecuente. Además, es la alteración lipídica característica de pacientes con enfermedad cardiaca coronaria. La HTG se debe a un aumento de la síntesis hepática de las lipoproteínas de muy baja densidad (VLDL), en general por un exceso de grasa visceral, o a un defecto en el aclaramiento de VLDL por hipoactividad de la lipoproteinlipasa (LPL) de causa genética o adquirida, y con frecuencia hay un defecto doble. Además del cHDL bajo, la HTG se asocia con la formación de partículas LDL densas y pequeñas, que son muy aterogénicas. Esto justifica que la HTG sea un factor de riesgo cardiovascular independiente y deba tratarse con la misma intensidad que la hipercolesterolemia. Actualmente, se recomiendan como deseables unas cifras de triglicéridos (TG) <150mg/dl. El tratamiento conservador de la HTG con dieta y normalización del peso es muy eficaz, pero difícil de realizar en la práctica. El tratamiento farmacológico convencional de la HTG son los fibratos, agentes que activan el factor de transcripción PPAR-α. Esto promueve la oxidación de ácidos grasos y estimula la actividad LPL, lo que reduce los TG, y aumenta la síntesis de apoproteínas de las HDL, lo que incrementa las cifras de cHDL. En promedio, los fibratos reducen los TG un 36% y aumentan el cHDL un 8%. En dosis de 2-4 g/día, los ácidos grasos n-3 (AGn-3) de origen marino son tan eficaces como los fibratos en la reducción de TG y carecen de efectos secundarios. Los AGn-3 también son ligandos de PPAR-α, pero reducen la síntesis de ácidos grasos por mecanismos independientes, lo cual justifica que su efecto de reducción de los TG sea complementario del de los fibratos. La eficacia de los AGn-3 en la reducción de TG se ha demostrado en monoterapia y en tratamiento combinado con estatinas. En la HTG grave del síndrome de quilomicronemia, los AGn-3 añaden su efecto al de los fibratos, con lo que se consiguen reducciones adicionales de los TG de hasta un 50% y se minimiza el riesgo de pancreatitis. Por tanto, los fibratos y los AGn-3 no están enfrentados, sino que son complementarios.

Palabras clave:
Triglicéridos
Hipertrigliceridemia
Síndrome metabólico
Fibratos
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.

Key words:
Triglycerides
Hypertriglyceridemia
Metabolic syndrome
Fibrates
Omega-3 fatty acids
El Texto completo está disponible en PDF
Bibliografía
[1.]
E.J. Schaefer, R.I. Levy, D.W. Anderson, R.N. Danner, H.B. Brewer Jr, W.C. Blackwelder.
Plasma triglycerides in the regulation of HDL.
Lancet, 2 (1978), pp. 391-393
[2.]
W. Jaros, G. Assmann, S. Bergmann, DRECAN Team.
Comparison of risk factors for coronary heart disease in Dresden and Munster.
Eur J Epidemiol, 10 (1994), pp. 307-315
[3.]
J.D. Brunzell, A.F. Ayyobi.
Dyslipidemia in the metabolic syndrome and type 2 diabetes.
Am J Med, 115 (2003), pp. S24-S28
[4.]
R. Carmena, J.M. Ordovás.
Hiperlipoproteinemias. Clínica y tratamiento.
Doyma, (1999),
[5.]
J. Genest.
Lipoprotein disorders and cardiovascular risk.
J Inherit Metab Dis, 26 (2003), pp. 267-287
[6.]
R.J. Havel, J.P. Kane.
Structure and metabolism of plasma lipoproteins.
The metabolic bases of inherited disease, 7th ed., pp. 1841-1851
[7.]
P.O. Kwiterovich.
The metabolic pathways of high-density lipoprotein, low-density lipoprotein, and triglycerides: a current review.
Am J Cardiol, (2000), pp. L5-L10
[8.]
M.A. Austin, J.E. Hokanson, K.L. Edwards.
Hypertriglyceridemia as a cardiovascular risk factor.
Am J Cardiol, 81 (1998), pp. B7-B12
[9.]
G. Assmann, H. Schulte, H. Funke, A. Von Eckardstein.
The emergency of triglycerides as a significant independent risk factor in coronary artery disease.
Eur Heart J, (1998), pp. M8-M14
[10.]
J. Ribalta, M. Castro-Cabezas, N. Plana, L. Masana.
Visión actualizada de la hiperlipemia familiar combinada aplicada a la mejora de su diagnóstico.
Clin Invest Arterioscler, 17 (2005), pp. 35-47
[11.]
M.J. Veerkamp, J. De Graaf, J.C. Hendriks, P.N. Demacker, A.F. Stalenhoef.
Nomogram to diagnose familial combined hyperlipidemia on the basis of results of a 5-year follow-up study.
Circulation, 109 (2004), pp. 2980-2985
[12.]
M.C. Carr, J.D. Brunzell.
Abdominal obesity and dyslipidemia in the metabolic syndrome: importance of type 2 diabetes and familial combined hyperlipidemia in coronary artery disease risk.
J Clin Endocrinol Metab, 89 (2004), pp. 2601-2607
[13.]
R.W. Mahley, Y. Huang, S.C. Rall Jr.
Pathogenesis of type III hyperlipoproteinemia (dysbetalipoproteinemia): questions, quandaries, and paradoxes.
J Lipid Res, 40 (1999), pp. 1933-1949
[14.]
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults.
Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III).
JAMA, 285 (2001), pp. 2486-2497
[15.]
S.M. Grundy, J.I. Cleeman, C.N.B. Merz, H.B. Brewer, L.T. Clark, D.B. Hunninghake, et al.
NCEP Report. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines.
Circulation, 110 (2004), pp. 227-239
[16.]
I. Lemieux, A. Pascot, C. Couillard, B. Lamarche, A. Tchernof, N. Almeras, et al.
Hypertriglyceridemic waist: A marker of the atherogenic metabolic triad (hyperinsulinemia; hyperapolipoprotein B; small, dense LDL) in men?.
Circulation, 102 (2000), pp. 179-184
[17.]
A.M. Dattilo, P.M. Kris-Etherton.
Effects of weight reduction on blood lipids and lipoproteins: a meta-analysis.
Am J Clin Nutr, 56 (1992), pp. 320-328
[18.]
D. Zambón, E. Ros, E. Casals, C. Sanllehy, A. Bertomeu, I. Campero.
Effect of apolipoprotein E polymorphism on the serum lipid response to a hypolipidemic diet rich in monounsaturated fatty acids.
Am J Clin Nutr, 61 (1995), pp. 141-148
[19.]
E. Stein, M. Lane, P. Laskarzewski.
Comparison of statins in hypertriglyceridemia.
Am J Cardiol, 81 Suppl 4A (1998), pp. B66-B69
[20.]
G.F. Watts.
Inhibition of cholesterogenesis decreases hepatic secretion of apo B-100 in normolipidemic subjects.
Am J Physiol, 273 (1997), pp. E462-E470
[21.]
A.M. Xydakis, C.M. Ballantyne.
Management of metabolic syndrome: statins.
Endocrinol Metab Clin North Am, 33 (2004), pp. 509-523
[22.]
J. McKenney.
New perspectives on the use of niacin in the treatment of lipid disorders.
Arch Intern Med, 164 (2004), pp. 697-707
[23.]
R.S. Birjmohun, B.A. Hutten, J.J.P. Kastelein, E.S.G. Stroes.
Efficacy and safety of high-density lipoprotein cholesterol-increasing compounds. A meta-analysis of randomized controlled trials.
J Am Coll Cardiol, 45 (2005), pp. 185-197
[24.]
S.J. Robins.
Cardiovascular disease with diabetes or the metabolic syndrome: should statins or fibrates be first line of therapy?.
Curr Opin Lipidol, 14 (2003), pp. 575-583
[25.]
I. Isseman, S. Green.
Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators.
Nature, 347 (1990), pp. 645-650
[26.]
M. Vázquez, J.C. Laguna.
Receptores activados por proliferadores peroxisómicos (PPAR), metabolismo energético y aterosclerosis.
Endocrinol Nutr, 47 (2000), pp. 301-310
[27.]
B. Staels, J. Dallongeville, J. Auwerx, K. Schoonjans, E. Leitersdorf, J.C. Fruchart.
Mechanism of action of fibrates on lipid and lipoprotein metabolism.
Circulation, 98 (1998), pp. 2088-2093
[28.]
F. Blaschke, Y. Takata, E. Caglayan, R.E. Law, W.A. Hsueh.
Obesity, peroxisome proliferator-activated receptor, and atherosclerosis in type 2 diabetes.
Arterioscler Thromb Vasc Biol, 26 (2006), pp. 28-40
[29.]
G. Chinetti-Gbaguidi, J.C. Fruchart, B. Staels.
Pleiotropic effects of fibrates.
Curr Atheroscler Rep, 7 (2005), pp. 396-401
[30.]
D.B. Miller, J.D. Spence.
Clinical pharmacokinetics of fibric acid derivatives (Fibrates).
Clin Pharmacokinet, 34 (1998), pp. 156-162
[31.]
A. Corsini, S. Bellosta, M.H. Davidson.
Pharmacokinetic interactions between statins and fibrates.
Am J Cardiol, (2005), pp. 44-49
[32.]
N. Roglans, A. Bellido, C. Rodríguez, A. Cabrero, F. Novell, D. Zambón, et al.
Fibrate treatment does not modify the expression of acyl coenzyme A oxidase in human liver.
Clin Pharmacol Ther, 72 (2002), pp. 692-701
[33.]
P.H. Jones, M.H. Davidson.
Reporting rate of rhabdomyolysis with fenofibrate + statin versus gemfibrozil + any statin.
Am J Cardiol, 95 (2005), pp. 120-122
[34.]
P. Maison, L. Mennen, D. Sapinho, B. Balkau, J. Sigalas, M.C. Chesnier, DESIR Study Group, et al.
A pharmacoepidemiological assessment of the effect of statins and fibrates on fibrinogen concentration.
Atherosclerosis, 160 (2002), pp. 155-160
[35.]
G. Steiner.
Fibrates and coronary risk reduction.
Atherosclerosis, 182 (2005), pp. 199-207
[36.]
The FIELD study investigators.
Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial.
Lancet, 366 (2005), pp. 1849-1861
[37.]
E. Sanguino, M. Ramón, L. Michalik, W. Wahli, M. Alegret, R.M. Sánchez, et al.
Lack of hypotriglyceridemic effect of gemfibrozil and age-related changes in rat liver PPARα.
Biochem Pharmacol, 67 (2004), pp. 157-166
[38.]
J. Dyerberg, K.A. Jorgensen.
Marine oils and thrombogenesis.
Progr Lipid Res, 21 (1982), pp. 255-269
[39.]
W.S. Harris.
Fish oils and plasma lipid and lipoprotein metabolism in humans: a critical review.
J Lipid Res, 30 (1989), pp. 785-807
[40.]
W.S. Harris.
n-3 Fatty acids and serum lipoproteins: human studies.
Am J Clin Nutr, (1997), pp. S1645-S1654
[41.]
L. Hooper, R. Thompson, R. Harrison, C. Summerbell, H. Moore, H. Worthington, et al.
Omega 3 fatty acids for prevention and treatment of cardiovascular disease.
Cochrane Database Syst Rev, (2004),
[42.]
H.M. Roche, M.J. Gibney.
Effect of long-chain n-3 polyunsaturated fatty acids on fasting and postprandial triacylglycerol metabolism.
Am J Clin Nutr, (2000), pp. S232-S237
[43.]
V.M. Montori, A. Farmer, P.C. Wollan, S.F. Dinneen.
Fish oil supplementation in type 2 diabetes: a quantitative systematic review.
Diabetes Care, 23 (2000), pp. 1407-1415
[44.]
S. Grimsgaard, K.H. Bonaa, J.B. Hansen, A. Nordoy.
Highly purified eicosapentaenoic acid and docosahexaenoic acid in humans have similar triacylglycerol-lowering effects but divergent effects on serum fatty acids.
Am J Clin Nutr, 66 (1997), pp. 649-659
[45.]
Y. Park, W.S. Harris.
Omega-3 fatty acid supplementation accelerates chylomicron triglyceride clearance.
J Lipid Res, 44 (2003), pp. 455-463
[46.]
W.S. Harris, W.E. Connor, R.D. Illingworth, D.W. Rothrock, D.M. Foster.
Effects of fish oil on VLDL triglyceride kinetics in humans.
J Lipid Res, 31 (1990), pp. 1549-1558
[47.]
M.S. Weintraub, R. Zechner, A. Brown, S. Eisenberg, J.L. Breslow.
Dietary polyunsaturated fats of the W-6 and W-3 series reduce postprandial lipoprotein levels.
J Clin Invest, 82 (1988), pp. 1884-1893
[48.]
S. Khan, A.M. Minihane, P.J. Talmud, J.W. Wright, M.C. Murphy, C.M. Williams, et al.
Dietary long-chain n-3 PUFAs increase LPL gene expression in adipose tissue of subjects with an atherogenic lipoprotein phenotype.
J Lipid Res, 43 (2002), pp. 979-985
[49.]
D.B. Jump, D. Botolin, Y. Wang, J. Xu, B. Christian, O. Demeure.
Fatty acid regulation of hepatic gene transcription.
J Nutr, 135 (2005), pp. 2503-2506
[50.]
B. Ren, A.P. Thelen, J.M. Peters, F.J. González, D.B. Jump.
Polyunsaturated fatty acid suppression of hepatic fatty acid synthase and S14 gene expression does not require peroxisome proliferator-activated receptor alpha.
J Biol Chem, 272 (1997), pp. 26827-26832
[51.]
G.W. Power, E.A. Newsholme.
Dietary fatty acids influence the activity and metabolic control of mitochondrial carnitine palmitoyltransferase I in rat heart and skeletal muscle.
J Nutr, 127 (1997), pp. 2142-2150
[52.]
J. Dallongeville, E. Baugé, A. Tailleux, J.M. Peters, F.J. González, J.C. Fruchart, et al.
Peroxisome proliferator-activated receptor α is not rate-limiting for the lipoprotein-lowering action of fish oil.
J Biol Chem, 276 (2001), pp. 4634-4639
[53.]
A. Mishra, A. Chaudhary, S. Sethi.
Oxidized omega-3 fatty acids inhibit NFkB activation via a PPAR?-dependent pathway.
Arterioscl Thromb Vasc Biol, 24 (2004), pp. 1621-1627
[54.]
P.M. Kris-Etherton, W.S. Harris, L.J. Appel, for the Nutrition Committee.
AHA Scientific Statement. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease.
Circulation, 106 (2002), pp. 2747-2757
[55.]
E.B. Schmidt, H. Arnesen, R. De Caterina, L.H. Rasmussen, S.D. Kristensen.
Marine n-3 polyunsaturated fatty acids and coronary heart disease. Part I. Background, epidemiology, animal data, effects on risk factors and safety.
Thromb Res, 115 (2005), pp. 163-170
[56.]
B.A. Griffin.
The effect of n-3 fatty acids on low density lipoprotein subfractions.
Lipids, (2001), pp. S91-S97
[57.]
C.E. Friedberg, M.J. Janssen, R.J. Heine, D.E. Grobbee.
Fish oil and glycemic control in diabetes: a meta-analysis.
Diabetes Care, 21 (1998), pp. 494-500
[58.]
C.H. MacLean, S.J. Newberry, W.A. Mojica, P. Khanna, A.M. Issa, M.J. Suttorp, et al.
Effects of omega-3 fatty acids on cancer risk. A systematic review.
JAMA, 295 (2006), pp. 403-415
[59.]
A.F.H. Stalenhoef, J. De Graaf, M.E. Wittekoek, S.J.H. Bredie, P.N.M. Demacker, J.J.P. Kastelein.
The effect of concentrated n-3 fatty acids versus gemfibrozil on plasma lipoproteins, low density lipoprotein heterogeneity and oxidizability in patients with hypertrygliceridemia.
Atherosclerosis, 153 (2000), pp. 129-138
[60.]
W.O. Richter, B.G. Jacob, M.M. Ritter, P. Schwandt.
Treatment of primary chylomicronemia due to familial hypertriglyceridemia by ω-3 fatty acids.
Metabolism, 10 (1992), pp. 1100-1105
[61.]
W.S. Harris, H.N. Ginsberg, N. Arunakul, N.S. Shachter, S.L. Windsor, M. Adams, et al.
Safety and efficacy of Omacor in severe hypertriglyceridemia.
J Cardiovasc Risk, 4 (1997), pp. 385-391
[62.]
M. Rouis, K.A. Dugi, L. Previato, A.P. Patterson, J.D. Brunzell, H.B. Brewer, et al.
Therapeutic response to medium-chain triglycerides and ω-3 fatty acids in a patient with the familial chylomicronemia syndrome.
Arterioscler Thromb Vasc Biol, 17 (1997), pp. 1400-1406
[63.]
A. Nordoy, J.B. Hansen, J. Brox, B. Svensson.
Effects of atorvastatin and omega-3 fatty acids on LDL subfractions and postprandial hyperlipemia in patients with combined hyperlipemia.
Nutr Metab Cardiovasc Dis, 11 (2001), pp. 7-16
[64.]
P.N. Durrington, D. Bhatnagar, M.I. Mackness, J. Morgan, K. Julier, M.A. Khan, et al.
An omega-3 polyunsaturated fatty acid concentrate administered for one year decreased triglycerides in simvastatin treated patients with coronary heart disease and persisting hypertriglyceridaemia.
Heart, 85 (2001), pp. 544-548
[65.]
D.C. Chan, G.F. Watts, T.A. Mori, P.H. Barrett, L.J. Beilin, T.G. Redgrave.
Factorial study of the effects of atorvastatin and fish oil on dyslipidaemia in visceral obesity.
Eur J Clin Invest, 32 (2002), pp. 429-436
Copyright © 2006. Sociedad Española de Cardiología
Idiomas
Revista Española de Cardiología

Suscríbase a la newsletter

Opciones de artículo
Herramientas
es en

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?