Shedding new light on heart health: Examining recent data on fatty acids

Transcription

1 Shedding new light on heart health: Examining recent data on fatty acids London, 18 November 2015 Prof. Dr. C. von Schacky, FESC Preventive Cardiology Medizinische Klinik und Poliklinik I Ludwig Maximilians-Universität München Clemens.vonSchacky@med.uni-muenchen.de and Omegametrix, Martinsried c.vonschacky@omegametrix.eu

2 Limited Plausibility of nutritional surveys Archer et al PlosONE 2013;8:76632

3

4 Fabian et al, Breast Canc Res 2015;17:62

5 HS-Omega-3 Index Effect of 0.5 g EPA+DHA / day, 8 weeks R1 Mean before %, after 8 Weeks % in Intervention Group, p<0.0001, paired t-test Variability in Response: Factor 13 Köhler et al, Br J Nutr 2010, 104:729-36

6 Single-dose study, metabolic cage Köhler et al, Lipids Health Dis 2015, 15:10

7 HS-Omega-3 Index Biomarker measured in Erythrocytes (low biologic variability) Standardized and validated Method for 26 Fatty Acids (low analytical variability) 165 publications, >50 ongoing research projects QM according to DIN ISO in Europe only with Omegametrix

8 one sample in 5 Labs A B C D E Better: standardized Analysis 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

9 In humans representative for tissue Heart Breast In experimental animals representative for tissue Kidney, Cerebral Cortex, Liver, Lung, Gut, asf. Almost no correlation with intake Harris WS et al Circulation 2004;110:1645 Arnold et al, JBC, 2010; 285: ; ; Gurzell et al, PLEFA 2014;91:87 Roy et al, Int J Canc 2015; e-pub July 2 u.a. Köhler et al, Br J Nutr 2010;104:729

10 Target range for HS-Omega-3 Index 8 11%

11 HS-Omega-3 Index in 1000 Koreans No Supplementation, Mean 10,4 + 3,0 % Park et al, unpublished

12 HS-Omega-3 Index HS-Omega-3 Index last Results Personen Mean (+SD): 6.72 (+2.12) %. Range: 1.89 bis 20.74% (Normal Distribution) Individuals in target range (8 11%): 19.5% Below: 76.4%, above: 4.1% von Schacky, J Lab Med, 2014;38:167

13 Heart Health

14 HS-Omega-3 Index and Risk for all-cause Mortality in LURIC 3259 Patients with CAD, Follow-up 11 years Risk of all-cause mortality per 1-SD increase in ALA, EPA, DPA and DHA. Model 1: adjusted for age and gender; model 2: additionally adjusted for BMI, LDL-C, HDL-C, logtg, diabetes, smoking and lipid lowering therapy. Kleber et al, submitted

15 HS-Omega-3 Index and Risk for all-cause Mortality in LURIC: 3259 patients with CAD, Follow-up 11 years Men Women Risk of all-cause mortality per 1-SD increase in ALA, EPA and DHA. Model 1: adjusted for age and gender; model 2: additionally adjusted for BMI, LDL-C, HDL-C, logtg, diabetes, smoking and lipid lowering therapy. Kleber et al, submitted

16 Increasing the HS-Omega-3 Index 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) Blood Pressure q (Dewell et al J Nutr Res 2011;141:2166; Skulas-Ray et al Ann Behav Med 2012;44:301 Platelet Function q (Larsson et al, Thromb Haemost 2008;100: 634 Harris et al, Lipids 2008;43:805) Inflammator. Biomarker 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)

17 Effects on Intermediate Parameters SCIMO Erythrocyte Fatty Acids 3 Mon 3.3 g / day, 21 Mon 1.65 g / day EPA+DHA DHA EPA EPA+DHA=3.4 % EPA+DHA=8.3 % von Schacky et al. Ann Int Med 1999, 130:554

18 SCIMO Primary End Point 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 von Schacky et al, Ann Int Med 1999; 130:554

19 AHA, USPSTF Criteria for novel Biomarkers as Risk factors our Omega-3 Index 1. Method 2. Independent 3. Reclassification 4. Therapy (+) 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

20 A low HS-Omega-3 Index is associated with increased risk for - Total mortality - fatal myocardial infarction - non-fatal myocardial infarction (acute coronary syndrome) - sudden cardiac death - (development of) and death from congestive heart failure The HS-Omega-3 Index provides incremental information to conventional risk factors (c-statistic, reclassification). The HS-Omega-3 provides a basis for a therapeutic decision. Therefore, a low HS-Omega-3 Index is a cardiovascular risk factor according to the criteria of AHA and USPSTF.

21 Meta-Analysis Intervention Trials with Omega-3 Fatty Acids Risk&Prevention (2013) EE 0.9 g / day 0.97 (0.88, 1.08) 733/ /6266 RR 0.96 ( ) Kotwal et al Circ Cardiovasc Qual Outcome 2012;5:808-18

22 Meta-Analysis Intervention Trials with Omega-3 Fatty Acids Kotwal et al Circ Cardiovasc Qual Outcome 2012;5:808-18

23

24 Meta-Analysis Omega-3 s and cardiovascular Events # * * * Fish EE TG EE EE EE EE TG TG EE TG EE ca. 0.9 g / day 0.9 g / day 1.6 g / day 1.8 g / day 1.8 g / day 1.8 g EPA / day 0.9 g / day 0.6 g / day 0.4 g / day 0.9 g / day 2.4 g / day 0.9 g / day Risk&Prevention (2013) EE 0.9 g / day 0.97 (0.88, 1.08) 733/ /6266 * = Breakfast # = Nighttime + = three times daily Kotwal et al Circ Cardiovasc Qual Outcome 2012;5: The Risk & Prevention, N Engl J Med 2013;368:1800-8

25 Bioavailability

26 Modified after Schuchardt PLEFA 2013;89:1

27 Davidson et al J Clin Lipidol. 2012;6: Absorption of EPA+DHA Ethyl-Ester (Omacor, Lovaza, Zodin ) High-Fat Meal Factor 13! Low-Fat Meal

28 Study Design

29 HS-Omega-3 Index HS-Omega-3 Index Measurements Personen Mean (+SD): 6.72 (+2.12) %. Range: 1.89 bis 20.74% (Normal Distribution) Individuals in target range (8 11%): 19.5% Below: 76.4%, above: 4.1% von Schacky, J Lab Med, 2014;38:167

30 HS-Omega-3 Index Effect of 0.5 g EPA+DHA / day, 8 weeks R1 Mean before %, after 8 Weeks % in Intervention Group, p<0.0001, paired t-test Variability in Response: Factor 13 Köhler et al, Br J Nutr 2010, 104:729-36

31 Domino Muhlhausler et al, PLEFA 2014, e-pub July 30

32 Brain & Deficit

33 Low HS-Omega-3 Index or low levels of EPA+DHA associated with - Post Partum Depression - Poor Brain Development (Structure and Function) in Infancy - Poor Brain Development (Structure and Function) in Childhood - ADHD - Poor Social Behaviour - Emotional Lability - Depression in Adolescents and Adults - Suicide - Poor Brain Structure - Poor Cognition: Memory, Reaction Time, Executive Function in all Age Groups studied so far, asf.

34 Increasing the HS-Omega-3 Index or intake of EPA+DHA improves - Post Partum Depression - Poor Brain Development (Structure and Function) in Infancy - Poor Brain Development (Structure and Function) in Childhood - ADHD - Poor Social Behaviour - Emotional Lability - Depression in Adolescents and Adults - Suicide - Poor Brain Structure - Poor Cognition: Memory, Reaction Time, Executive Function in all Age Groups studied so far, asf.

35 EPA and DHA and other brain functions Haast RA, PLEFA 2015;92C:3

36 Slowing age-dependent loss of brain tissue Witte et al, Cereb Cortex 2014;24:

37 EPA + DHA Looks like a deficit Can only be diagnosed with HS-Omega-3 Index Deficit frequent and increasing. In those with deficit: supplementation necessary. Trials in healthy individuals show effects Sources disappear Endogenous Synthesis of DHA impossible Levels go down In brain and muscle: age-dependent decay can be slowed by omega-3 s Symptoms of a deficit become more frequent

38 Trans Fatty Acids

39 Trans Oleic Acid in Erythrocytes and Risk for Acute Coronary Syndrome Method: HS-Omega-3 Index odds ratio per 1 SD higher C18:2n-6: 1.10 (95% CI; ) Block et al, Am J Cardiol 2008;156:

40 Trans Fatty Acids in the USA Method: HS-Omega-3 Index Harris et al, PLEFA 2013; 88:257

41 Trans Fatty Acids and Mortality in LURIC Method: HS-Omega-3 Index Kleber et al, Eur Heart J 2015, e-pub Sep 23, 2015

42 Trans Fatty Acid from Ruminants (C16:1n7t) and Sudden Cardiac Death Kleber et al, Eur Heart J 2015, e-pub

43 HS-Omega-3 Index: Trans Fatty Acids and Mortality Kleber et al, Eur Heart J 2015, e-pub

44 Mean Erythrocyte Trans Fatty Acid Concentrations in % in Germany , and percentage of Persons with the sum of 18:1t + trans isomers of 18:2n-6 >1.04% ( %>1.04% ). Data from routine analyses; mean+standard deviation, n= number of samples analysed, t=trans, c=cis. n 16:1n-7t 18:1t+18:2n-6t %>1.04% % % % % % % % % All columns p < (one-way ANOVA). Except for C18:2n-6ct (n.s.), all concentrations in 2015 lower than in 2008 (p<0.0001, t-test) von Schacky et al, submitted

45 Conclusions Trans Fatty Acids: - Natural Sources associated with lower mortality - From Food Production: Low Levels no problem - Measures in US successful, Levels reached safe - In Germany no need for action on trans fatty acids from Food Production - In Germany levels of trans fatty acids from natural sources decreasing, mortality issue

46 Summary Conventional nutritional studies are inadequate for fatty acids The HS-Omega-3 Index represents an individual s status on Omega-3 s In large parts of European, but not Korean or Japanese populations, the HS-Omega-3 Index is below the target range of 8 11% A low HS-Omega-3 Index is cardiovascular risk factor, however, other risk factors are also important Methodologic issues precluded effects to be demonstrated in large cardiovascular intervention trials A low HS-Omega-3 Index predisposes for issues of complex brain function like ADHD, memory, depression, behaviour problems and others These issues can improved by increasing the HS-Omega-3 Index or intake of EPA+DHA, establishing causality. Low levels of IP-trans fatty acids are not hazardous, and are no problem in Germany, while natural trans fatty acids appear beneficial Using the HS-Omega-3 Index provides a clear picture of fatty acids

47

48 Shedding new light on heart health: Examining recent data on fatty acids London, 18 November 2015 Prof. Dr. C. von Schacky, FESC Preventive Cardiology Medizinische Klinik und Poliklinik I Ludwig Maximilians-Universität München Clemens.vonSchacky@med.uni-muenchen.de and Omegametrix, Martinsried c.vonschacky@omegametrix.eu

49 Natural Sources of EPA + DHA disappear Plants Brain Eggs Fish -, no conversion ALA to DHA -, BSE, no longer eaten -, fish meal no longer used less omega-3 in aquaculture

50 Lopez AD & Murray CCJL Nature Medicine 1998;4:1241

51 HS-Omega-3 Index HS-Omega-3 Index - first 5000 Results HS-Omega-3 Index 5000 randomly selected measurements in Europe Measurements Mean (+SD): 7.15 (+2.19%) %. Range: 1.89 to 20.74% (Normal Distribution) Individuals in target range (8 11%): 1210 (24.4%) Below: 70%, Above: 5.5% von Schacky, Handbook of Food Fortification, 2013

52 HS-Omega-3 Index HS-Omega-3 Index last Results Personen Mean (+SD): 6.72 (+2.12) %. Range: 1.89 bis 20.74% (Normal Distribution) Individuals in target range (8 11%): 19.5% Below: 76.4%, above: 4.1% von Schacky, J Lab Med, 2014;38:167