Trans -Fatty Acids and Sudden Cardiac Death
2002; Lippincott Williams & Wilkins; Volume: 105; Issue: 6 Linguagem: Inglês
10.1161/circ.105.6.669
ISSN1524-4539
Autores Tópico(s)Adipose Tissue and Metabolism
ResumoHomeCirculationVol. 105, No. 6Trans-Fatty Acids and Sudden Cardiac Death Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBTrans-Fatty Acids and Sudden Cardiac Death Arnold M. Katz, MD, DMed (Hon) Arnold M. KatzArnold M. Katz From the Cardiology Division, Department of Medicine, University of Connecticut Health Center, Farmington, Conn. A.M.K. is a Professor of Medicine Emeritus at University of Connecticut School of Medicine and a Visiting Professor of Medicine and Physiology at Dartmouth Medical School. Originally published12 Feb 2002https://doi.org/10.1161/circ.105.6.669Circulation. 2002;105:669–671Der Mensch ist, was er isst ("A man is what he eats")— German ProverbA relationship between diet and human disease has been known at least since the time of Hippocrates. Our "modern" understanding of the role of nutrition in heart disease began in 1908, when a diet of meat, milk, or eggs was found to produce atherosclerosis in rabbits; a decade later, cholesterol was identified as causing the experimental lesions. Epidemiological studies that began in the 1930s confirmed this correlation in humans, but the importance of diet in causing atherosclerosis attracted little attention until the 1950s, when a high intake of saturated fats was recognized as a major risk factor for myocardial infarction and stroke. Although the role of dietary lipids in causing vascular disease is now established, an influence of fat intake on cardiac arrhythmias is less well-appreciated.1 The potential importance of this relationship is highlighted by Lemaitre et al,2 who in this issue of Circulation, suggest that dietary trans-fatty acids cause sudden cardiac death. Trans-fatty acids differ from the natural cis-isomers in the conformation around the double bond; in the former, the fatty acyl chains are on opposite (trans) sides of the molecule, whereas they are on the same (cis) side in the latter. Most dietary trans-fatty acids are formed when unsaturated fats are "hardened" by hydrogenation and when vegetable oils become hydrogenated during frying; they occur in hardened margarines, fast foods, and some commercially baked goods and salad dressings.See p 697The possibility that dietary lipids cause cardiac arrhythmias became apparent more than 30 years ago when the severity of ventricular arrhythmias in patients after myocardial infarction was found to correlate with elevated circulating levels of free fatty acids (FFA).3 These observations stimulated experimental studies that confirmed that FFA can be arrhythmogenic,4–9 especially when catecholamine levels are high.10 Clinical studies also showed a direct relationship between high FFA levels, arrhythmias, and sudden cardiac death.11–12 The arrhythmogenic potency of these lipids is determined not only by the amounts that reach the heart, but also by their structure; for example, the ability of different FFA to lower ventricular fibrillation threshold depends on the length and saturation of the fatty acyl chain.9 A role for FFA intake has been shown in experimental animals, where diets rich in polyunsaturated fats and fish oil were found to have antiarrhythmic effects.13–18 Clinical studies also suggest that a diet rich in fish oil and other unsaturated FFA can prevent cardiac death and arrhythmias,19–23 although not all published data support the importance of this relationship.24The mechanisms underlying the pro- and antiarrhythmic effects of FFA are readily explained by their interactions with biological membranes, which are lipid bilayers made up of 2 hydrophilic (lipophobic) surfaces and a hydrophobic (lipophilic) core (Figure). The latter, which is virtually impermeable to charged molecules, contains the fatty acyl chains of the membrane lipids, whereas the 2 surfaces are lined with charged head groups that interact with the aqueous media on either side of the membrane. Most biological activities are mediated by proteins imbedded in the bilayer; these include enzymes, receptors, carriers, pumps, and the voltage-gated ion channels responsible for the cardiac action potential. The bilayer was once viewed simply as a supporting structure for the membrane proteins, much as a sea whose surface can float a variety of ships. It is now apparent, however, that hydrophobic portions of membrane proteins interact specifically with lipids within the core of the bilayer. This specificity is one reason why changes in membrane composition, as occur when FFA and other lipophilic molecules are incorporated into the bilayer, alter such functions as opening, closing, and inactivation of ion channels. Download figureDownload PowerPointModel of a membrane protein within a membrane lipid bilayer. Membrane proteins, like the P-type adenosine triphosphatase depicted here, generally include cytosolic peptide chains (A, green), membrane-spanning α-helices (B, orange), and extracellular peptide chains (C, blue). Hydrophobic surfaces of the membrane-spanning α-helices interact with the bilayer lipids (red). Shown schematically are the consequences of incorporation of a cis-fatty acid (bottom, left) and a trans-fatty acid (bottom, right) into the bilayer. Both interact with hydrophobic regions of the protein to change the conformation around membrane-spanning α-helices (black), but because these fatty acids differ structurally, the conformational changes in the cytosolic and extracellular peptide chains (black dotted lines) are not the same. (Modified from Katz AM. Physiology of the Heart, 3rd ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2001).A likely mechanism by which dietary fat intake might influence cardiac rhythm became apparent in the 1970s, when the hydrophobic surfaces of intrinsic membrane proteins were recognized to interact with hydrophobic regions of the surrounding bilayer lipids.25 These lipids, initially viewed as a long-lived annulus, are now known to exchange readily with lipids elsewhere in the membrane. The functional importance of hydrophobic surfaces on the membrane-spanning α-helices of membrane proteins is underscored by evidence that the binding sites for many drugs and physiological ligands, even ions that are transported across membranes, include these transmembrane segments.26 Hydrophobic interactions with membrane proteins allow FFA, whose hydrocarbon tails are readily incorporated in the bilayer, to exert remarkably specific effects on membrane function. Using as a model the effects of various FFA on calcium pump of rabbit skeletal muscle sarcoplasmic reticulum, we not only found that increasing fatty acyl chain length and the extent of unsaturation potentiated inhibition of calcium transport, but also that the response to many FFAs was highly dependent on the functional state of the calcium pump.27 These and other findings demonstrate a high specificity for the hydrophobic interactions between membrane lipids and membrane proteins (Figure) and so provide a plausible explanation for the ability of different dietary fatty acids to exert specific effects on ion channel function.A correlation between primary cardiac arrest and high membrane content of trans-fatty acids is documented by the population-based case-control study reported by Lemaitre et al,2 which found that the trans-fatty acid content of erythrocyte membranes obtained from survivors of out-of-hospital cardiac arrest was greater than that in membranes from age- and sex-matched controls. Membrane levels of trans-fatty acids in this study did not correlate with such "traditional" risk factors for atherosclerosis as age, sex, hypertension, diabetes, or smoking, but were lower in high school graduates than nongraduates; the latter finding suggests that the healthy lifestyle choices associated with education include avoidance of foods that contain trans-fatty acids. Although an earlier case-control clinical study found no correlation between sudden cardiac death and adipose tissue content of trans-oleic and trans-linoleic acids,28 there is substantial evidence that trans-fatty acid intake is associated with increased coronary heart disease risk.29Although currently available data do not prove that trans-fatty acids cause sudden death, the findings of Lemaitre et al2 fit with other data supporting an important link between dietary fat intake and arrhythmias. In view of solid evidence that the lipids we ingest find their way into our membranes, where some can do a great deal of harm, it seems prudent to minimize the intake of foods that contain a high content of trans-fatty acids.The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.FootnotesCorrespondence to Arnold M. Katz, MD, 1592 New Boston Rd, PO Box 1048, Norwich, VT 05055-1048. E-mail [email protected] References 1 Charnock JS. Lipids and cardiac arrhythmia. Prog Lipid Res. 1994; 33: 355–385.CrossrefMedlineGoogle Scholar2 Lemaitre RN, King IB, Raghunathan TE, et al. Cell membrane trans-fatty acids and the risk of primary cardiac arrest. Circulation. 2002: 105: 697–701.CrossrefMedlineGoogle Scholar3 Oliver MF, Kurien VA, Greenwood TW. Relation between serum-free-fatty-acids and arrhythmias and death after acute myocardial infarction. Lancet. 1968; 1: 710–715.CrossrefMedlineGoogle Scholar4 Opie LH. Effect of fatty acids on contractility and rhythm of the heart. Nature. 1970; 227: 1055–1056.CrossrefMedlineGoogle Scholar5 Kurien VA, Yates PA, Oliver MF. The role of free fatty acids in the production of ventricular arrhythmias after acute coronary artery occlusion. Eur J Clin Invest. 1971; 1: 225–241.CrossrefMedlineGoogle Scholar6 Misra SN, Stanley EL, Kezdi P. Long-chain saturated fatty acid (FFA) and sudden death in myocardial infarction. Am Heart J. 1971; 82: 576–577. Letter.CrossrefMedlineGoogle Scholar7 Soloff LA. Arrhythmias follow infusions of fatty acids. Am Heart J. 1970; 80: 671–674.CrossrefMedlineGoogle Scholar8 Makiguchi M, Kawaguchi H, Tamura M, et al. Effect of palmitic acid and fatty acid binding protein on ventricular fibrillation threshold in the perfused rat heart. Cardiovasc Drugs Ther. 1991; 5: 753–762.CrossrefMedlineGoogle Scholar9 Murnaghan MF. Effect of fatty acids on the ventricular arrhythmia threshold in the isolated heart of the rabbit. Br J Pharmacol. 1981; 73: 909–915.CrossrefMedlineGoogle Scholar10 Opie LH, Norris RM, Thomas M, et al. Failure of high concentrations of circulating free fatty acids to provoke arrhythmias in experimental myocardial infarction. Lancet. 1971; i: 818–822.Google Scholar11 Paolisso G, Gualdiero P, Manzella D, et al. Association of fasting plasma free fatty acid concentration and frequency of ventricular complexes in nonischemic non–insulin-dependent diabetic patients. Am J Cardiol. 1997; 80: 932–937.CrossrefMedlineGoogle Scholar12 Jouven X, Charles M-A, Desnos M, et al. Circulating nonesterified fatty acid level as a predictive risk factor for sudden death in the population. Circulation. 2001; 104: 756–761.CrossrefMedlineGoogle Scholar13 Charnock JS, McLennan PL, Abeywardena MY, et al. Diet and cardiac arrhythmia: effects of lipids on age-related changes in myocardial function in the rat. Ann Nutrition Metab. 1985; 29: 306–318.CrossrefMedlineGoogle Scholar14 McLennan PL, Abeywardena MY, Charnock JS, Dietary fish oil prevents ventricular fibrillation following coronary artery occlusion and reperfusion. Am Heart J. 1988; 116: 709–717.CrossrefMedlineGoogle Scholar15 Riemersma RA, Sargent CA. Dietary fish oil and ischaemic arrhythmias. J Intern Med. 1989; 225 (suppl): 111–116.CrossrefMedlineGoogle Scholar16 McLennan PL, Bridle TM, Abeywardena MY, et al. Dietary lipid modulation of ventricular fibrillation threshold in the marmoset monkey. Am Heart J. 1992; 123: 1555–1561.CrossrefMedlineGoogle Scholar17 Billman GE, Kang JX, Leaf A. Prevention of ischemia-induced cardiac sudden death by n-3 polyunsaturated fatty acids in dogs. Lipids. 1997; 32: 1161–1168.CrossrefMedlineGoogle Scholar18 Billman GE, Kang JX, Leaf A. Prevention of sudden cardiac sudden death by dietary pure omega-3 polyunsaturated fatty acids in dogs. Circulation. 1999; 99: 2452–2457.CrossrefMedlineGoogle Scholar19 de Lorgeril M, Renaud S, Mamelle N, et al. Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease. Lancet. 1994; 343: 1454–1459.CrossrefMedlineGoogle Scholar20 Siscovick DS, Raghunathan TE, King I, et al. Dietary intake and cell membrane levels of long-chain n-3 polyunsaturated fatty acids and the risk of primary cardiac arrest. JAMA. 1995; 274: 1363–1367.CrossrefMedlineGoogle Scholar21 Singh RB, Niaz MA, Sharma JP, et al. Randomized, double-blind, placebo-controlled trial of fish oil and mustard oil in patients with suspected acute myocardial infarction: the Indian experiment of infarct survival. Cardiovasc Drugs Ther. 1997; 11: 485–491.CrossrefMedlineGoogle Scholar22 GISSI-Prevenzione Investigators. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI Prevenzione Trial. Lancet. 1999; 354: 447–455.CrossrefMedlineGoogle Scholar23 Albert CM, Hennekens CH, O'Donnell CJ, et al. Fish consumption and risk of sudden cardiac death. JAMA. 1998; 279: 23–28.CrossrefMedlineGoogle Scholar24 Kromhout D. Fish consumption and sudden cardiac death. JAMA. 1998; 279: 65–70.Editorial.CrossrefMedlineGoogle Scholar25 Griffith OH, Jost PC. Lipid protein interactions.In: Solomon AK, Karnovsky M, ed. Molecular Stabilization and Symmetry in Membrane Function. Cambridge, Mass: Harvard; 1978:31–60.Google Scholar26 Katz AM. Physiology of the Heart, 3rd ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2001.Google Scholar27 Katz AM, Adler PN, Watras J, et al. Fatty acid effects on calcium influx and efflux in sarcoplasmic reticulum vesicles from rabbit skeletal muscle. Biochim Biophys Acta. 1982; 687: 17–26.CrossrefMedlineGoogle Scholar28 Roberts TL, Woods DA, Riemersma RA, et al. Trans isomers of oleic and linoleic acids in adipose tissue and sudden cardiac death. Lancet. 1995; 345: 278–282.CrossrefMedlineGoogle Scholar29 Oomen CM, Ocké CM, Feskens EJM, et al. Association between trans fatty acid intake and 10-year risk of coronary heart disease in the Zutphen Elderly Study: a prospective population-based study. Lancet. 2001; 357: 746–751.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Hadj Ahmed S, Kharroubi W, Kaoubaa N, Zarrouk A, Batbout F, Gamra H, Najjar M, Lizard G, Hininger-Favier I and Hammami M (2018) Correlation of trans fatty acids with the severity of coronary artery disease lesions, Lipids in Health and Disease, 10.1186/s12944-018-0699-3, 17:1, Online publication date: 1-Dec-2018. Qiu B, Wang Q, Du F, Liu L, Zong A, Jia M, Liu W and Xu T (2018) Comparative Proteomics Analysis Reveals Trans Fatty Acid Isomers Activates Different Pathways in Human Umbilical Vein Endothelial Cell, Lipids, 10.1002/lipd.12015, 53:2, (189-203), Online publication date: 1-Feb-2018. Mori K, Ishida T, Yasuda T, Hasokawa M, Monguchi T, Sasaki M, Kondo K, Nakajima H, Shinohara M, Shinke T, Irino Y, Toh R, Nishimura K and Hirata K (2015) Serum Trans-Fatty Acid Concentration Is Elevated in Young Patients With Coronary Artery Disease in Japan, Circulation Journal, 10.1253/circj.CJ-14-0750, 79:9, (2017-2025), . Tejaswi Kumar H, Jeyarani T, Milind and Indrani D (2013) Effects of Fats and Oils on Rheological, Fatty Acid Profile and Quality Characteristics of South Indian Parotta, Journal of the American Oil Chemists' Society, 10.1007/s11746-013-2301-5, 90:10, (1523-1531), Online publication date: 1-Oct-2013. Gürdeniz G, Rago D, Bendsen N, Savorani F, Astrup A, Dragsted L and Oresic M (2013) Effect of trans Fatty Acid Intake on LC-MS and NMR Plasma Profiles, PLoS ONE, 10.1371/journal.pone.0069589, 8:7, (e69589) Soares-Miranda L, Stein P, Imamura F, Sattelmair J, Lemaitre R, Siscovick D, Mota J and Mozaffarian D (2012) Trans-Fatty Acid Consumption and Heart Rate Variability in 2 Separate Cohorts of Older and Younger Adults, Circulation: Arrhythmia and Electrophysiology, 5:4, (728-738), Online publication date: 1-Aug-2012. Govil A, Gupta M, Girish M and Tyagi S (2011) Prediction and Prevention in Sudden Cardiac Death, Apollo Medicine, 10.1016/S0976-0016(11)60078-1, 8:3, (228-237), Online publication date: 1-Sep-2011. Chugh S (2010) Early identification of risk factors for sudden cardiac death, Nature Reviews Cardiology, 10.1038/nrcardio.2010.52, 7:6, (318-326), Online publication date: 1-Jun-2010. Chiuve S, Rimm E, Manson J, Whang W, Mozaffarian D, Stampfer M, Willett W and Albert C (2009) Intake of total trans, trans-18:1, and trans-18:2 fatty acids and risk of sudden cardiac death in women, American Heart Journal, 10.1016/j.ahj.2009.08.015, 158:5, (761-767), Online publication date: 1-Nov-2009. Sherazi S, Kandhro A, Mahesar S, Bhanger M, Talpur M and Arain S (2009) Application of transmission FT-IR spectroscopy for the trans fat determination in the industrially processed edible oils, Food Chemistry, 10.1016/j.foodchem.2008.09.058, 114:1, (323-327), Online publication date: 1-May-2009. Kandhro A, Sherazi S, Mahesar S, Bhanger M, Younis Talpur M and Rauf A (2008) GC-MS quantification of fatty acid profile including trans FA in the locally manufactured margarines of Pakistan, Food Chemistry, 10.1016/j.foodchem.2007.12.029, 109:1, (207-211), Online publication date: 1-Jul-2008. Vareiro M, Tranchant I, Maplin S, Zak K, Gani M, Slevin C, Hailes H, Tabor A, Cameron P, Jenkins A and Williams D (2008) Surface plasmon resonance-enhanced fluorescence implementation of a single-step competition assay: Demonstration of fatty acid measurement using an anti-fatty acid monoclonal antibody and a Cy5-labeled fatty acid, Analytical Biochemistry, 10.1016/j.ab.2008.03.033, 377:2, (243-250), Online publication date: 1-Jun-2008. Edward Hunter J (2007) Safety and Health Effects of Trans Fatty Acids Fatty Acids in Foods and their Health Implications,Third Edition, 10.1201/9781420006902.ch31, (757-790), Online publication date: 19-Nov-2007. Kuhnt K, Kraft J, Vogelsang H, Eder K, Kratzsch J and Jahreis G (2007) Dietary supplementation with trans -11- and trans -12-18 : 1 increases cis -9, trans -11-conjugated linoleic acid in human immune cells, but without effects on biomarkers of immune function and inflammation , British Journal of Nutrition, 10.1017/S0007114507685183, 97:6, (1196-1205), Online publication date: 1-Jun-2007. Zhang B, Hu S, Qiu L, Zhu J, Xie X, Sun J, Zhu Z, Xia Q and Bian K (2007) Effects of Astragalus membranaceus and its main components on the acute phase endothelial dysfunction induced by homocysteine, Vascular Pharmacology, 10.1016/j.vph.2006.11.001, 46:4, (278-285), Online publication date: 1-Apr-2007. Katz A (2006) Should trans fatty acids be viewed as membrane-active drugs?, Atherosclerosis Supplements, 10.1016/j.atherosclerosissup.2006.04.009, 7:2, (41-42), Online publication date: 1-May-2006. Abeywardena M (2006) Dietary Fatty Acids and Cardiovascular Disease Dietary Fats and Risk of Chronic Disease, 10.1201/9781439822418.pt5, (157-167), Online publication date: 13-Mar-2006. Ackman R (2005) Fish Oils Bailey's Industrial Oil and Fat Products, 10.1002/047167849X.bio078 Karupaiah T, Ismail Noor M and Sundram K (2005) Dietary Fatty Acids and Their Influence on Blood Lipids and Lipoproteins Healthful Lipids, 10.1201/9781439822289.pt3, Online publication date: 30-Jan-2005. Bengmark S (2004) Acute and "chronic" phase reaction—a mother of disease, Clinical Nutrition, 10.1016/j.clnu.2004.07.016, 23:6, (1256-1266), Online publication date: 1-Dec-2004. Stachowska E, Dołęgowska B, Chlubek D, Wesołowska T, Ciechanowski K, Gutowski P, Szumiłowicz H and Turowski R (2004) Dietary trans fatty acids and composition of human atheromatous plaques, European Journal of Nutrition, 10.1007/s00394-004-0479-x, 43:5, (313-318), Online publication date: 1-Oct-2004. Dyerberg J, Eskesen D, Andersen P, Astrup A, Buemann B, Christensen J, Clausen P, Rasmussen B, Schmidt E, Tholstrup T, Toft E, Toubro S and Stender S (2004) Effects of trans- and n-3 unsaturated fatty acids on cardiovascular risk markers in healthy males. An 8 weeks dietary intervention study, European Journal of Clinical Nutrition, 10.1038/sj.ejcn.1601934, 58:7, (1062-1070), Online publication date: 1-Jul-2004. Stachowska E, Dołȩgowska B, Olszewska M, Gutowska I and Chlubek D (2004) Isomers of trans fatty acids modify the activity of platelet 12-P lipoxygenase and cyclooxygenase/thromboxane synthase, Nutrition, 10.1016/j.nut.2004.03.013, 20:6, (570-571), Online publication date: 1-Jun-2004. Mauger J, Lichtenstein A, Ausman L, Jalbert S, Jauhiainen M, Ehnholm C and Lamarche B (2003) Effect of different forms of dietary hydrogenated fats on LDL particle size, The American Journal of Clinical Nutrition, 10.1093/ajcn/78.3.370, 78:3, (370-375), Online publication date: 1-Sep-2003. Anderson K (2003) Lipid-lowering therapy for prevention of ventricular tachyarrhythmias, Journal of the American College of Cardiology, 10.1016/S0735-1097(03)00497-2, 42:1, (88-92), Online publication date: 1-Jul-2003. February 12, 2002Vol 105, Issue 6 Advertisement Article InformationMetrics https://doi.org/10.1161/circ.105.6.669PMID: 11839617 Originally publishedFebruary 12, 2002 Keywordslipidsdietarrhythmiafatty acidsEditorialsPDF download Advertisement
Referência(s)