® Omega-3 Index for Heart Health Prof. Dr. C. von Schacky, FAHA, FESC Preventive Cardiology Medizinische Klinik und Poliklinik I Ludwig Maximilians-Universität München [email protected]and Omegametrix, Martinsried [email protected]Newcastle, 07 November 2013
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Meta-Analysis Omega-3 Fatty Acids and Cardiovascular Events
Kotwal et al Circ Cardiovasc Qual Outcome 2012;5:808-18
Meta-Analysis Omega-3 Fatty Acids and Cardiovascular Events
Kotwal et al Circ Cardiovasc Qual Outcome 2012;5:808-18
Meta-Analysis Omega-3 Fatty Acids in Atrial Fibrillation
Mozaffarian et al, JACC 2013, in press
Brouwer et al, Eur Heart J 2009;30:820-26
Meta-Analysis Omega-3 Fatty Acids and ICD-Actions
GISSI-HF, Lancet 2008,372:1231
Total mortality + hospitalizations
AHA Secondary Prevention Guidelines
“omega-3 fatty acids from fish or fish oil capsules (1 g/d) for cardiovascular disease risk
reduction.” Smith et al Circulation 2011;124
ESC Cardiovascular Prevention Guidelines
“Fish at least twice a week, one of which to be oily fish.”
Perk et al, Eur Heart J 2012;33:1635
ESC Treatment after myocardial infarction
Not specifically mentioned Steg et al, Eur Heart J 2012;33:2569
ESC Atrial Fibrillation Guidelines
Not mentioned Camm et al Eur Heart J 2010;31:2369
AHA/ESC Ventricular Arrhythmia Guidelines
“omega-3 may be considered for patients with ventr. arrhythmias and underlying CHD”
Outdated, but B IIb Zipes DP et al. Eur Heart J 2006, 27:2099
ESC Heart Failure
„An n-3 PUFA preparation may be considered“
IIb B McMurray et al, Eur Heart J 2012;33:1787
My fellow cardiologists:
Omega-3‘s not effective
Euro Market 15% of US
Hu F et al, JAMA 2002, 287:1815
Limited Plausibility of nutritional surveys…
Archer et al PlosONE 2013;8:76632
Siscovick D et al, Am J Clin Nutr 2000; 71:208S
Better: standardized procedure
A B C D E
…one sample in 5 Labs…
HS-Omega-3 Index®
measured in Erythrocytes
% Eicosapentaenoic + Docosahexaenoic Acid
Standardized and validated Method
in Europe only with Omegametrix®
®
1. Harris WS and von Schacky C. The Omega-3 Index: A New Risk Factor for Death from CHD? Preventive Medicine 2004;39:212-20
2. Harris WS, et al. Omega-3 Fatty Acid Levels in Transplanted Human Hearts: Effect of Supplementation and Comparison with Erythrocytes. Circulation
2004;110;1645-9
3. Sands SA, et al. The impact of age, body mass index, and fish intake on the EPA and DHA content of human erythrocytes. Lipids 2005;40:343-7
4. Harris WS, et al. Effects of Omega-3 Fatty Acids on Heart Rate in Cardiac Transplant Recipients. Am J Cardiol 2006;98:1393-5
5. von Schacky C. Omega-3 Fettsäuren in der Kardiologie – neueste Entwicklungen. Münch Med Wochenschr 2007;149:97-101
6. Harris WS. Omega-3 Fatty Acids and Cardiovascular Disease. A case for the Omega-3 Index as a New Risk Factor. Pharmacol Res 2007;55:217-23
7. Harris WS, et al. Stearidonic Acid Supplementation Increases Red Blood Cell and Heart Omega 3 Index in Dogs. Lipids 2007;42:325-333
8. Harris WS, et al. Tissue n-3 and n-6 fatty acids and risk for coronary heart disease events. Atherosclerosis 2007;193:1-10
9. von Schacky C, Harris WS. Cardiovascular Risk and the Omega-3 Index. J Cardiovasc Med 2007;8 (suppl 1):S46-9
10. Harris WS, et al. Blood Omega-3 and Trans Fatty Acids in Middle-Aged Acute Coronary Syndrome Patients. Am J Cardiol 2007;99:154-8
11. Harris WS, et al. Comparison of the effects of fish and fish oil capsules on the n-3 fatty acid content of blood cells and plasma phospholipids. Am J Clin Nutr
2007;86:1621-25.
12. Aarsetoey H, et al. Low levels of cellular omega-3 increases the risk of ventricular fibrillation during the acute ischaemic phase of a myocardial infarction.
Resuscitation 2008;78:258-64
13. Hwang I, et al. n-3 Polyunsaturated Fatty Acids and Atopy in Korean Preschoolers. Lipid 2007;42,345-349
14. Harris WS, von Schacky C N-3 Fatty Acids, Acute Coronary Syndrome, and Sudden Death. Curr Cardiovasc Risk Rpt 2008;2:161-6
15. Lee E, et al. n-3 Polyunsaturated fatty acids and trans fatty acids in patients with the metabolic syndrome: a case-control study in Korea. Br J Nutr. 2008;100:609-
14
16. von Schacky C. Omega-3 fatty acids pro-arrhythmic, anti-arrhythmic or both ? Curr Op Nutr Metab Care 2008;11:94-99
17. Amin AA, et al. Acute Coronary Syndrome Patients With Depression Have Low Blood Cell Membrane Omega-3 Fatty Acid Levels. Psychosom Med. 2008;70:856-
62.
18. Block RC, et al. EPA and DHA in blood cell membranes from acute coronary syndrome patients and controls. Atherosclerosis 2008;197:821
19. Block RC, et al. Omega-6 and trans fatty acids in blood cell membranes: a risk factor for acute coronary syndromes? Am Heart J. 2008;156:1117-23
20. Block RC, et al. Determinants of blood cell omega-3 fatty acid content. The Open Biomarkers J 2008;1:1-6
21. Cohen BE, et al. Red blood cell EPA and DHA concentrations are positively associated with Socioeconomic status in patients with established coronary artery
disease: Data from the Heart and Soul Study. J Nutrition 2008;138:1135-40
22. Farzaneh-Far R, et al. Inverse association of erythrocyte n-3 fatty acid levels with inflammatory biomarkers in stable coronary artery disease: The Heart and Soul
Study. Atherosclerosis 2009;205:538-43
23. Larson MK, et al. Effects of Omega-3 Acid Ethyl Esters and Aspirin, Alone and in Combination, on Platelet Function in Healthy Subjects. J Thromb Haemost
2008;100:634-41.
24. Harris WS, et al. Stearidonic Acid-Enriched Soybean Oil Increased the Omega-3 Index, an Emerging Cardiovascular Risk Marker. Lipids 2008;43:805-811.
25. von Schacky C. Use of red cell fatty acid profiles as biomarkers in cardiac disease Biomark Med 2009;3:25-32
Publications based on Omega-3 Index
26. Ali S, et al. Association between omega-3 fatty acids and depressive symptoms among patients with established coronary artery disease: Data from the Heart and
27. Shearer GC, et al. Red Blood Cell Fatty Acid Patterns and Acute Coronary Syndrome. PLoS ONE 2009;4: e5444. doi:10.1371/journal.pone.0005444
28. Aarsetoey H, et al. (n-3) fatty acid content of red blood cells does not predict risk of future cardiovascular events following an acute coronary syndrome. J Nutr
2009;139:1–7.
29. Park Y, et al. Erythrocyte fatty acid profiles can predict acute non-fatal myocardial infarction. Br J Nutr. 2009;102:1355-6
30. von Schacky C. Cardiovascular disease prevention and treatment. Prostaglandins Leukot Essent Fatty Acids 2009;81:193-8
31. Park Y, et al. Low level of n-3 polyunsaturated fatty acids in erythrocytes is a risk factor for both acute ischemic and hemorrhagic stroke in Koreans. Nutr Res.
2009;29:825-30
32. Duda MK, et al. Fish oil but not flaxseed oil decreases inflammation and prevents pressure-overload induced cardiac dysfunction. Cardiovasc Res 2009;81:319
33. Harris WS, Thomas RM Biological variability of blood omega-3 biomarkers. Clin Biochem 2009;Sep, e-pub, 2010;43:338-40
34. An WS, et al. Comparison of fatty acid contents of erythrocyte membrane in hemodialysis and peritoneal dialysis patients. J Ren Nutr. 2009;19:267-74.
35. Harris WS The Omega-3 Index: From Biomarker to Risk Marker to Risk Factor. Curr Athero Rep 2009;11:411-7
36. Park Y, et al. Correlation of erythrocyte fatty acid composition and dietary intakes with markers of atherosclerosis in patients with myocardial infarction. Nutr Res.
2009;29:391-6.
37. Carney et al Omega-3 Augmentation of Sertaline in Treatment of Depression in Patients with Coronary Heart Disease JAMA 2009;302:1651-3
38. Shearer GC et al Myocardial infarction does not affect fatty acid profiles in rats. Prostaglandins Leukot Essent Fatty Acids2009; 81:411-6
39. Farzneh-Far et al, Association of marine omega-3 fatty acid levels with telomeric aging in patients with coronary heart disease JAMA 2010;303:250-7
40. von Schacky C Omega-3 fatty acids vs. cardiac disease: the contribution of the omega-3 index. Cell Mol Biol 2010;56:90-98
41. von Schacky C. Omega-3 Index and Sudden Cardiac Death. Nutritives 2010;2:375-8
42. Köhler A, et al. Effects of a convenience drink fortified with n-3 fatty acids on the n-3 index. Br J Nutr 2010; 104:729-36
43. Billman GE, et al. Effects of dietary omega-3 fatty acids on ventricular function in dogs with healed myocardial infarctions: in vivo and in vitro studies. Am J Physiol
Heart Circ Physiol. 2010;298:H1219-28
44. Ebbesson SO, et al. Heart rate is associated with red blood cell fatty acid concentration: the Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN)
study.Am Heart J. 2010;159:1020-5.
45. Pottala JV, et al.Blood Eicosapentaenoic and Docosahexaenoic Acids Predict All-Cause Mortality in Patients With Stable Coronary Heart Disease: The Heart and
Soul Study. Circ Cardiovasc Qual Outcomes. 2010;3:406-12
46. von Schacky C. Omega-3 Index and cardiovascular disease prevention: principle and rationale. Lipid Technology 2010;22:151-4
47. Arnold C, et al. Arachidonic acid-metabolizing cytochrome P-450 enzymes are targets of omega-3 fatty acids. J Biol Chem 2010; 285:32720-33
48. Carney RM, et al Effect of Omega-3 Fatty Acids on Heart Rate Variability in Depressed Patients With Coronary Heart Disease. Psychosom Med 2010;72:748-54
49. Lemke SL, et al. Dietary intake of stearidonic acid-enriched soybean oil increases the omega-3 index: randomized, double-blind clinical study of efficacy and
safety. Am J Clin Nutr. 2010; 92:766-75
50. Harris WS. The Omega-3 Index: Clinical Utility for Therapeutic Intervention. Curr Cardiol Rep 2010;12:503-8
Publications based on Omega-3 Index
51. von Schacky C. Schwangerschaft, kindliche Entwicklung, Omega-3-Fettsäuren und HS-Omega-3 Index. J Frauengesundheit 2010;3:10-21 52. Neubronner J, et al. Enhanced increase of omega-3 index in response to long-term n-3 fatty acid supplementation from triacylglycerides versus ethyl
esters. Eur J Clin Nutr. 2011;65:247-54 53. Kim M et al. Erythrocyte α-linolenic acid is associated with the risk for mild dementia in Korean elderly. Nutr Res 2010;30:756-761 54. Baghai TC, et al. Major depressive disorder is associated with cardiovascular risk factors and low Omega-3 index. J Clin Psy 2011;72:1242-7 55. Skulas-Ray AC, et al. Dose-response effects of omega-3 fatty acids on triglycerides, inflammation, and endothelial function in healthy persons with
moderate hypertriglyceridemia. Am J Clin Nutr 2011;93:243- 52 56. Park Y, et al. Association between 24-hour ambulatory blood pressure and erythrocyte n-3 polyunsaturated fatty acids in Korean subjects with
hypertension. Nutr Res 2010;30:807-14 57. Yang R, et al. Pre-feeding with omega-3 fatty acids suppresses inflammation following hemorrhagic shock. J Parenter Enteral Nutr. 2010;34:496-502. 58. Chen J, et al. Omega-3 fatty acids prevent pressure overload-induced cardiac fibrosis through activation of cGMP/PKG signaling in cardiac fibroblasts.
Circulation 2011;123:584-93 59. Aarsetoey H, et al. Low Levels of the Omega-3 Index are Associated with Sudden Cardiac Arrest and Remain Stable in Survivors in the Subacute Phase.
Lipids. 2011;46:151-61 60. Moyers B, et al. Relation of Whole Blood n-3 Fatty Acid Levels to Exercise Parameters in Patients With Stable Coronary Artery Disease (from the Heart and
Soul Study). Am J Cardiol. 2011;107:1149-54 61. Harris WS, Klurfeld DM. Twentieth-century trends in essential fatty acid intakes and the predicted omega-3 index: evidence versus estimates. Am J Clin
Nutr. 2011;93:907-8 62. Sala-Vila A, et al. Determinants of the omega-3 index in a Mediterranean population at increased risk for CHD. Br J Nutr. 2011;106:425-31 63. Billman GE, Harris WS. Effect of Dietary Omega-3 Fatty Acids on the Heart Rate and the Heart Rate Variability Response to Myocardial Ischemia or
Submaximal Exercise. Am J Physiol Heart Circ Physiol. 2011;300:H2288-99 64. An WS, et al. Association of adiponectin and leptin with serum lipids and erythrocyte omega-3 and omega-6 fatty acids in dialysis patients. Clin Nephrol.
2011;75:195-203. 65. Salisbury AC et al. Predictors of omega-3 index in patients with acute myocardial infarction. Mayo Clin Proc. 2011;86:626-32 66. Son YK, et al. Association Between Vascular Calcification Scores on Plain Radiographs and Fatty Acid Contents of Erythrocyte Membrane in Hemodialysis
Patients. J Ren Nutr. 2012;22:58-66 67. Park Y, Kim M. Serum 25-hydroxyvitamin D concentrations are associated with erythrocyte levels of n-3 PUFA but not risk of CVD. Br J Nutr.
2011;106:1529-34 68. von Schacky C. The Omega-3 Index as a Risk Factor for Cardiovascular Diseases. Prostaglandins and Other Lipid Mediators. 2011;96:94–8 69. Park Y, et al. N-3 polyunsaturated fatty acid consumption produces neurobiological effects associated with prevention of depression in rats after the forced
swimming test. J Nutr Biochem 2012;23:924-928 70. Schuchardt JP, et al. Moderate doses of EPA and DHA from re-esterified triacylglycerols but not from ethyl-esters lower fasting serum triacylglycerols in
statin-treated dyslipidemic subjects: Results from a six month randomized controlled trial. Prostaglandins Leukot Essent Fatty Acids 2011;85:381-6 71. Ladesich JB, et al. Membrane levels of omega-3 docosahexaenoic acid is associated with obstructive sleep apnea. J Clin Sleep Med 2011;7:391-6 72. Maki KC, et al. Effects of prescription omega-3-acid ethyl esters, coadministered with atorvastatin, on circulating levels of lipoprotein particles,
apolipoprotein CIII, and lipoprotein-associated phospholipase A2 mass in men and women with mixed dyslipidemia. J Clin Lipidol. 2011;5:483-92 73. Salisbury AC, et al. Relation Between Red Blood Cell Omega-3 Fatty Acid Index and Bleeding During Acute Myocardial Infarction. Am J Cardiol.
2012;109:13-8 74. Dewell A, et al. Dose-Dependent Effects of Plant and Marine Omega-3 Fatty Acids on Inflammatory Markers in Insulin Resistant Adults. A Randomized
Controlled Trial. J Nutrition 2011;141:2166-71 75. Harris WS. Stearidonic Acid-Enhanced Soybean Oil: A Plant-Based Source of (n-3) Fatty Acids for Foods. J Nutr 2012;142:600S-4S
Publications based on Omega-3 Index
76. Harris WS. Stearidonic Acid as a ‘Pro-Eicosapentaenoic Acid’. Curr Opin Lipidol 2012;23:30-4, 77. Shearer GC, et al. Fish oil: How does it reduce plasma triglycerides? Biochim Biophys Acta 2012;1821:843-51 78. Krul ES, et al. Effects of duration of treatment and dosage of eicosapentaenoic acid and stearidonic acid on red blood cell eicosapentaenoic acid content.
Prostaglandins Leukot Essent Fatty Acids 2012;86:51-9, e-pub 2011 Nov 5 79. An WS, et al. Effect of omega-3 fatty acids on the modification of erythrocyte membrane fatty acid content including oleic acid in peritoneal dialysis patients.
Prostaglandins Leukot Essent Fatty Acids. 2012;86:29-34, e-pub 2011 Nov 7 80. Billman GE, et al. Dietary Omega-3 Fatty Acids and Susceptibility to Ventricular Fibrillation: Lack of Protection and A Proarrhythmic Effect. Circ Arrhythm
Electrophysiol. 2012 Feb 14. [Epub ahead of print] 81. Hussey EK, Portelli S, Fossler MJ, Gao F, Harris WS, Blum RA, Lates CD, Gould E, Abu-Baker O, Johnson S, Reddy KK. Relative bioavailability of an Emulsion
Formulation for Omega-3-Acid Ethyl Esters Compared to theCommercially Available Formulation : A Randomized, Parallel-Group, Single-Dose Study Followed by Repeat dosing in healthy volunteers. Clin Pharm Drug Develop 2012;1:14-2
82. Tan ZS, et al. Red Blood Cell Omega-3 Fatty Acid Levels and Markers of Accelerated Brain Aging. Neurology 2012;78:658-64 . 83. Pottala JV, et al. Red Blood Cell Fatty Acids are Associated with Depression in a Case-Control Study of Adolescents. Prostaglandins Leukot Essent Fatty Acids
2012;86:161-5 e-pub 2012 Mar 28 84. Kim YJ, et al. Omega-3 index and smoking in patients with acute ST-elevation myocardial infarction taking statins: a case-control study in Korea. Lipids Health Dis.
2012;11:43 85. Moon HJ, et al. Positive correlation between erythrocyte levels of n-3 polyunsaturated fatty acids and bone mass in postmenopausal Korean women with
osteoporosis. Ann Nutr Metab 2012;60:146-53 86. von Schacky C. Omega-3 fatty acids: anti-arrhythmic, pro-arrhythmic, or both? Frontiers in Cardiac Electrophysiology, 2012;3: 98 87. Block RC, et al. The Effects of EPA+DHA and Aspirin on Inflammatory Cytokines and Angiogenesis Factors. World J Cardiovasc Dis. 2012;2:14-19. 88. Park YS, et al. Erythrocyte n-3 polyunsaturated fatty acid and seafood intake decrease the risk of depression: case-control study in Korea. Ann Nutr Metab
2012;61:25-31 89. Harris WS, et al. Changes in Erythrocyte Membrane Trans and Marine Fatty Acids between 1999 and 2006 in Older Americans. J Nutr. 2012;142:1297-303 90. Voruganti VS, et al. Variants in CPT1A, FADS1, and FADS2 are associated with higher levels of estimated plasma and erythrocyte delta-5 desatureases in Alaskan
Eskimos. Front Genet 2012;3:86. 91. Harris WS, et al. Clinical correlates and heritability of erythrocyte eicosapentaenoic and docosahexaenoic acid content in the Framingham Heart Study.
Atherosclerosis. 2012;225:425-31 92. Johnston DT, et al. Red blood cell omega-3 fatty acid levels and neurocognitive performance in deployed U.S. Servicemembers. Nutr Neurosci. 2013;16:30-8 93. Keenan AH, et al. Basal omega-3 fatty acid status affects fatty acid and oxylipin responses to high-dose n3-HUFA in healthy volunteers. J Lipid Res. 2012;53:1662-
9 94. Pottala JV, et al. Correcting the Effects of -20 °C Storage and Aliquot Size on Erythrocyte Fatty Acid Content in the Women's Health Initiative. Lipids. 2012;47:835-
46 95. Shearer GC, et al. Effects of prescription niacin and omega-3 fatty acids on lipids and vascular function in metabolic syndrome: a randomized controlled trial. J
Lipid Res. 2012;53:2429-35] 96. Schmidt S, et al. Transcriptome-based identification of antioxidative gene expression after fish oil supplementation in normo- and dyslipidemic men. Nutr Metab
(Lond). 2012 23;9:45 97. Skulas-Ray AC, et al. Effects of Marine-Derived Omega-3 Fatty Acids on Systemic Hemodynamics at Rest and During Stress: a Dose-Response Study. Ann Behav
Med. 2012;44:301-8 98. An WS, et al . Omega-3 fatty acid supplementation increases 1,25-dihydroxyvitamin D and fetuin-A levels in dialysis patients. Nutr Res. 2012;32:495-502 99. von Schacky C. Die Bedeutung des Omega-3 Index für den Sportler. Vitalstoffe 2012;2:47-51 100. Schmidt S, et al. Different gene expression profiles in normo- and dyslipidemic men after fish oil supplementation: results from a randomized controlled trial. Lipids
Health Dis. 2012 Aug 29;11:105
Publications based on Omega-3 Index
101. Harris WS, et al. Red blood cell fatty acid levels improve GRACE score prediction of 2-yr mortality in patients with myocardial infarction.Int J Cardiol. 2012 Oct 5. pii: S0167-5273(12)01182-5. doi: 10.1016/j.ijcard.2012.09.076.
102. von Schacky C. Omega-3 Fettsäuren – HS-Omega-3 Index und Gesundheit von Herz und Hirn. Vitalstoffe 2012;2/4:28-36 103. von Schacky C. Meta-Analysing randomised controlled trials with omega-3 fatty acids in cardiovascular disease. Evidence based medicine, ebmed-2012-100960, 104. Harris WS. Are n-3 fatty acids still cardioprotective? Curr Opin Clin Nutr Metab Care. 2013;16:141-9 105. Oh JS, et al. Comparison of erythrocyte membrane Fatty Acid contents in renal transplant recipients and dialysis patients. Transplant Proc. 2012;44:2932-5. 106. Harris WS, et al. Erythrocyte omega-3 fatty acids increase and linoleic acid decreases with age: Observations from 160,000 patients. Prostaglandins Leukot Essent
Fatty Acids. 2013;88:257-63 107. Oelrich B, et al. Effect of fish oil supplementation on serum triglycerides, LDL cholesterol and LDL subfractions in hypertriglyceridemic adults. Nutr Metab Cardiovasc
Dis. 2013;23:350-7 108. Schuchardt JP, Hahn A. Bioavailability of long-chain omega-3 fatty acids. Prostaglandins Leukot Essent Fatty Acids 2013;89:1-8 109. Schuchardt JP, et al. Comparison of free serum oxylipin concentrations in hyper- vs. normolipidemic men. Prostaglandins Leukot Essent Fatty Acids. 2013;89:19-29 110. Metkus T, et al. Omega-3 fatty acid therapy reduces triglycerides and interleukin-6 in hypertriglyeridemic HIV patients. HIV Med. 2013;14:530-9 111. Grenon SM, et al. Association between n-3 polyunsaturated fatty acid content of red blood cells and inflammatory biomarkers in patients with peripheral artery
disease. J Vasc Surg. 2013;8:176-84 112. Park Y, et al. Effect of n-3 polyunsaturated fatty acid supplementation in patients with rheumatoid arthritis: a 16-week randomized, double-blind, placebo-controlled,
parallel-design multicenter study in Korea. J Nutr Biochem 2013; 24:1367–1372 113. Kim TH, et al. Differences in omega-3 and fatty acid profiles between patients with endometriosis and those with a functional ovarian cyst. J Obstet Gynaecol.
2013;33:597-600 114. Lemke SL, . Consumption of stearidonic Acid-rich oil in foods increases red blood cell eicosapentaenoic Acid. J Acad Nutr Diet. 2013;113:1044-56 115. Udani JK, Ritz BW. High potency fish oil supplement improves omega-3 fatty acid status in healthy adults: an open-label study using a web-based, virtual platform.
Nutr J. 2013;12:112. [Epub ahead of print] 116. Lee AL, Park Y. The association between n-3 polyunsaturated fatty acid levels in erythrocytes and the risk of rheumatoid arthritis in Korean women. Ann Nutr Metab
2013;63:88-95 117. Grenon SM, et al. n-3 Polyunsaturated fatty acids supplementation in peripheral artery disease: the OMEGA-PAD trial. Vasc Med. 2013 Sep 19. [Epub ahead of print] 118. Ammann EM, et al. Omega-3 fatty acids and domain-specific cognitive aging: Secondary analyses of data from WHISCA. Neurology. 2013 Sep 25. [Epub ahead of
print] 119. Harris WS, et al. The Comparative Effects Of An Acute Dose Of Fish Oil On Omega-3 Fatty Acid Levels in Red Blood Cells Versus Plasma: Implications for Clinical
Utility. J Clin Lipidol 2013;7:433-440 120. Baek D, Park Y. Association between erythrocyte n-3 polyunsaturated fatty acids and biomarkers of inflammation and oxidative stress in patients with and without
depression. Prostaglandins Leukot Essent Fatty Acids. E-pub 2013 Sep 21 121. Harris WS. Assessing Fatty Acid Biostatus: Red Blood Cells or Plasma? Lipid Technol 2013 (in press). 122. Jo S, et al. Erythrocyte n-3 Polyunsaturated Fatty Acids and the Risk of Type 2 Diabetes in Koreans: A Case-control Study. Ann Nutr Metab 2013 (in press).
Publications based on Omega-3 Index
Chapters in Books / Buchkapitel von Schacky C. Prevention of cardiovascular disease – what can we learn from epidemiology? In Omega-3 Fatty Acids and Cardiovascular Diseases; von Schacky C, ed., Uni-Med Verlag, Bremen, London, Boston, 2010, p 22-25 Harris WS, von Schacky C. The omega-3 index in clinical research and medicine. In Omega-3 Fatty Acids and Cardiovascular Diseases; von Schacky C, ed., Uni-Med Verlag, Bremen, London, Boston, 2010, p 72-80 von Schacky C. Mechanisms of action of omega-3 fatty acids. Effects on cardiac rhythm. In Omega-3 Fatty Acids and Cardiovascular Diseases; von Schacky, C, ed., Uni- Med Verlag, Bremen, London, Boston, 2010, p 32-35 von Schacky C. Large clinical trials in patients with coronary artery disease or equivalent risk. In Omega-3 Fatty Acids and Cardiovascular Diseases; von Schacky, C, ed., Uni-Med Verlag, Bremen, London, Boston, 2010, p 44-50 von Schacky C. Prävention kardiovaskulärer Erkrankungen – was lehrt uns die Epidemiologie? In Omega-3 Fettsäuren und kardiovaskuläre Erkrankungen; von Schacky C, ed., Uni-Med Verlag, Bremen, London, Boston, 2012, p 12-25 von Schacky C. Wirkmechanismen von Omega-3 Fettsäuren und Interventionsstudien mit < 200 Teilnehmern. In Omega-3 Fettsäuren und kardiovaskuläre Erkrankungen; von Schacky C, ed., Uni-Med Verlag, Bremen, London, Boston, 2012, p 26-49 von Schacky C. Große Klinische Interventionsstudien bei Patienten mit kardialen Erkrankungen. In Omega-3 Fettsäuren und kardiovaskuläre Erkrankungen; von Schacky C, ed., Uni-Med Verlag, Bremen, London, Boston, 2012, p 50-67 von Schacky C. HS-Omega-3 Index in Forschung und Klinik. In Omega-3 Fettsäuren und kardiovaskuläre Erkrankungen; von Schacky C, ed., Uni-Med Verlag, Bremen, London, Boston, 2012, p 82-97 von Schacky C. Andere Wirkungen von Omega-3 Fettsäuren. In Omega-3 Fettsäuren und kardiovaskuläre Erkrankungen; von Schacky C, ed., Uni-Med Verlag, Bremen, London, Boston, 2012, p 98-101 von Schacky C. Optimal Omega-3 Levels for different age groups In Omega-6/3 Fatty acids – Functions, Sustainability Strategies, and Perspectives; De Meester F, Watson RR, Zidadi S, ed., Humana Press, Nutrition and Health Series (Bendich A ed.), 2013, p 53-64 Harris WS, von Schacky C, Park Y. Standardizing Methods for Assessing Omega-3 Fatty Acid Biostatus. In The Omega-3 Fatty Acid Deficiency Syndrome; McNamara RK ed., Nova Science Publishers 2013 von Schacky C. Convenience Drinks Fortified with n-3 Fatty Acids: A Systematic Review. In Nutrition and Health (Series Editor: Adrianne Bendich), Handbook of Food Fortification – From Concepts to Public Health Applications Volume 2, Preedy VR, Srirajaskanthan R, Patel VB, eds., Humana Press, 2013, p 95-103
Publications based on Omega-3 Index
Biological and analytial Variability of EPA+DHA in various Compartments
Harris WS, Thomas R Clin Biochem 2009;43:338-40
0%
2%
4%
6%
8%
10%
12%
14%
16%
CV analytical CV biological
RBC
Whole blood
Whole plasma
Plasma PL
*
* *
* p<0.03 vs RBC
Correlation Heart / Erythrocytes
Harris WS et al Circulation 2004;110:1645
HS-Omega-3 Index
In the experimental animal also true for
Kidneys
Brain cortex
Liver
Lung
Pancreas
Arnold et al, JBC, 2010; 285:32720-33
Marchioli and Harris, unpublished
0
20
40
60
80
100
120
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ate
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Approximate Omega-3 Index (%)
Japan
Korea
USA
Germany
Norway
Spain
*http://circ.ahajournals.org/content/123/4/e18
CHD Death Rates* and the Omega-3 Index
Unadjusted Kaplan Meier Survival Curve
Number at Risk
Logrank p=0.02
3,6 % whole blood EPA+DHA equivalent to
4,6 % Omega-3 Index
Potalla et al, Circ Cardiovasc Qual Outcomes 2010;3:406-12
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ard
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DPA(w-6)
Hazard Ratio (HR)
0.25 0.50 1 2 4 8
Baseline Creatinine
History of congestive heart failure
History of Revascularization
In-Hospital Revascularization
Current Smoker
History of diabetes
White
Male
Age (10 years)
Economic burden: Moderate vs. None
Economic burden: High vs. None
Economic burden: High vs. Moderate
Omega-3 index <4%
Hazard Ratio (HR)
0.25 0.50 1 2 4 8
Baseline Creatinine
History of congestive heart failure
History of Revascularization
In-Hospital Revascularization
Current Smoker
History of diabetes
White
Male
Age (10 years)
Economic burden: Moderate vs. None
Economic burden: High vs. None
Economic burden: High vs. Moderate
Omega-3 index <4%
1.2 (1.1, 1.4)
2.4 (1.4, 4.2)
1.4 (0.9, 2.3)
0.7 (0.4, 1.1)
1.2 (0.7, 2.0)
1.0 (0.6, 1.7)
0.3 (0.2, 0.6)
1.2 (0.8, 2.0)
1.8 (1.4, 2.2)
1.3 (0.7, 2.3)
1.8 (1.1, 3.2)
1.4 (0.8, 2.5)
2.0 (1.2, 3.3)
Variable HR (95% CI)
Mohammad Abuannadi et al, Poster, AHA QCOR Meeting, May 19-21, 2010
Predictors 1-Year Mortality after myocardial infarction - TRIUMPH • 1424 Pat., 27% (387) omega-3 index <4%.
Block RC et al, Atherosclerosis 2008;197:821
HS-Omega-3 Index and ACS
Plasma-PL Omega-3 and subsequent Atrial Fibrillation
Wu et al, Circulation 2012;125:1084
Plasma-PL Omega-3 and subsequent Congestive Heart Failure
Mozaffarian et al, Ann Int Med 2011;155:160
Plasma-PL Omega-3 and survival with Congestive Heart Failure
Masson et al Am Heart J 2013;165:208
Framingham Score
Fatty acid spectrum
Fatty acid spectrum + FRS
Chance
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Reclassification:
Improvement of individual Risk assessment
on statins
Increasing the Omega-3 Index –
Some Effects on Surrogate Parameters
Heart rate q (Harris et al Am J Cardiol 2006; 98:1393-5)
Heart rate variability p (Carney et al Psychosom Med 2010;72:748)
Platelet function q (Larsson et al, Thromb Haemost 2008;100:
634;Harris et al, Lipids 2008;43:805)
Inflammatory biomarkers q (Duda et al Cardiovasc Res 2009;81:319
Dewell et al J Nutrition 2011;141:2166
Blocket al World J Cardiovasc Dis2012;2:14
Triglycerides q (Skulas-Ray Am J Clin Nutr 2011;93:243,
Schuchardt et al PLEFA 2011;85:381
Shearer et al J Lipid Res. 2012;53:2429)
Small dense LDL q (Maki et al J Clin Lipidol 2011;5:483)
Large bouyant LDL p (Maki et al J Clin Lipidol 2011;5:483)
2418121 6
6
4
2
SCIMO – Erythrocyte phospholipid fatty acids
3 mo 3.3 g / day, 21 mo 1.65 g / day EPA+DHA
von Schacky et al. Ann Int Med 1999, 130:554
EPA
DHA
EPA+DHA=3.4 % EPA+DHA=8.3 %
Coronary Lesions changed
Placebo EPA+DHA
(n=48) (n=55)
n (%) n (%)
moderate progression (+2) 5 (10.4) 4 (7.1)
mild progression (+1) 36 (75.0) 35 (63.6)
mild regression (-1) 7 (14.6) 14 (25.5)
moderate Regression (-2) 0 (0.0) 2 (3.6)
p=0.041* * Wilcoxon rank sum test, comparison between groups
SCIMO - Primary endpoint
von Schacky et al, Ann Int Med 1999; 130:554
AHA, USPSTF Criteria for new Biomarkers as Risk Factors
1. Method
2. Independent
3. Reclassification
4. Therapetic Consequence
Hlatky et al, Circulation 2009;119:2408
Helfand et al, USPTFS Ann Int Med 2009;151:496
von Schacky C, Lipid Tech 2010;22:151
HS-Omega-3 Index
+
+
+
(+)
Missing:
Large intervention trial with clinical endpoints
A low Omega-3 Index is associated with increased risk for