Shedding new light on heart health: Examining...

®

Shedding new light on heart health:

Examining recent data on fatty acids

Prof. Dr. C. von Schacky, FESC

Preventive Cardiology

Medizinische Klinik und Poliklinik I

Ludwig Maximilians-Universität München

[email protected]

and Omegametrix, Martinsried

[email protected]

London, 18 November 2015

Limited Plausibility of nutritional surveys…

Archer et al PlosONE 2013;8:76632

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

0

2

4

6

8

10

12

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 R1

Mean before 4.37 + 0.51%, after 8 Weeks 6.80 + 1.45 %

in Intervention Group, p<0.0001, paired t-test

Variability in Response: Factor 13

HS-Omega-3 Index

Effect of 0.5 g EPA+DHA / day, 8 weeks

Köhler et al, Br J Nutr 2010, 104:729-36

Single-dose study, „metabolic cage“

Köhler et al, Lipids Health Dis 2015, 15:10

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 15189

in Europe only with Omegametrix®

®

Better: standardized Analysis

A B C D E

…one sample in 5 Labs…

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

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; 285:32720-33; ;

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

Target range for HS-Omega-3 Index

8 – 11%

HS-Omega-3 Index in 1000 Koreans

No Supplementation, Mean 10,4 + 3,0 %

Park et al, unpublished

0

5

10

15

20

25

1 419 837 1255 1673 2091 2509 2927 3345 3763 4181 4599 5017 5435 5853 6271 6689 7107 7525 7943 8361 8779 9197 9615

Personen

HS

-Om

eg

a-3

In

dex

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

HS-Omega-3 Index – last 10 000 Results

Heart

Health

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.

HS-Omega-3 Index and Risk for all-cause Mortality

in LURIC 3259 Patients with CAD, Follow-up 11 years

Kleber et al, submitted

Women Men

Kleber et al, submitted

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 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.

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)

2418121 6

6

4

2

Effects on Intermediate Parameters SCIMO –

Erythrocyte Fatty Acids 3 Mon 3.3 g / day, 21 Mon 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 End Point

von Schacky et al, Ann Int Med 1999; 130:554

AHA, USPSTF Criteria for novel Biomarkers as Risk factors

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

our Omega-3 Index

+

+

+

(+)

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.

Meta-Analysis Intervention Trials

with Omega-3 Fatty Acids

Kotwal et al Circ Cardiovasc Qual Outcome 2012;5:808-18

Risk&Prevention (2013) EE 0.9 g / day 0.97 (0.88, 1.08) 733/6239 745/6266

RR 0.96 (0.90-1.03)


Meta-Analysis Intervention Trials

with Omega-3 Fatty Acids

EE

EE

EE

EE

EE

EE

TG

TG


The Risk & Prevention, N Engl J Med 2013;368:1800-8

EE

Fish

TG

ca. 0.9 g / day

0.9 g / day

0.9 g / day

0.9 g / day

0.9 g / day

0.4 g / day

1.6 g / day

1.8 g / day

2.4 g / day

1.8 g / day

1.8 g EPA / day

0.6 g / day

*

* * *

* = Breakfast

*

#

# = Nighttime

+

+ = three times daily

TG

Risk&Prevention (2013) EE 0.9 g / day 0.97 (0.88, 1.08) 733/6239 745/6266

Meta-Analysis Omega-3‘s and cardiovascular Events

Bioavailability

Modified after Schuchardt PLEFA 2013;89:1

High-Fat Meal

Low-Fat Meal

Absorption of EPA+DHA Ethyl-Ester (Omacor®, Lovaza®, Zodin®)

Factor 13!

Davidson et al J Clin Lipidol. 2012;6:573-84

Study Design

0

5

10

15

20

25

1 419 837 1255 1673 2091 2509 2927 3345 3763 4181 4599 5017 5435 5853 6271 6689 7107 7525 7943 8361 8779 9197 9615

Personen

HS

-Om

eg

a-3

In

dex

Mean (+SD): 6.72 (+2.12) %.




HS-Omega-3 Index – 10 000 Measurements

0

2

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8

10

12

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 R1

Mean before 4.37 + 0.51%, after 8 Weeks 6.80 + 1.45 %

in Intervention Group, p<0.0001, paired t-test

Variability in Response: Factor 13

HS-Omega-3 Index

Effect of 0.5 g EPA+DHA / day, 8 weeks

Köhler et al, Br J Nutr 2010, 104:729-36

Domino

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

Brain &

Deficit

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.

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.

Haast RA, PLEFA 2015;92C:3

EPA and DHA and other brain functions

Slowing „age-dependent“ loss of brain tissue

Witte et al, Cereb Cortex 2014;24:3059-68

EPA + DHA

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

Looks like a deficit

Can only be diagnosed with HS-Omega-3 Index

Deficit frequent and increasing. In those with

deficit: supplementation necessary.

Trans Fatty Acids

Trans Oleic Acid in Erythrocytes and Risk for Acute Coronary Syndrome

Method: HS-Omega-3 Index

Block et al, Am J Cardiol 2008;156:1117-23

odds ratio per 1 SD higher C18:2n-6: 1.10 (95% CI; 0.93–1.30)

2006 2012

Trans Fatty Acids in the USA


Harris et al, PLEFA 2013; 88:257

Trans Fatty Acids and Mortality in LURIC


Kleber et al, Eur Heart J 2015, e-pub Sep 23, 2015

Trans Fatty Acid from Ruminants (C16:1n7t) and Sudden Cardiac Death

Kleber et al, Eur Heart J 2015, e-pub 23.09.15

Kleber et al, Eur Heart J 2015, e-pub 23.09.15

HS-Omega-3 Index: Trans Fatty Acids and Mortality

Mean Erythrocyte Trans Fatty Acid Concentrations in % in Germany 2008-2015,

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%

2008 511 0.25+0.33 0.99+0.62 29.5%

2009 720 0.15+0.12 0.78+0.34 9.3%

2010 657 0.22+0.2 0.75+0.25 5.9%

2011 812 0.20+0.09 0.70+0.27 3.8%

2012 872 0.18+0.07 0.71+0.24 5.2%

2013 1017 0.15+0.06 0.65+0.23 4.4%

2014 1256 0.15+0.05 0.56+0.21 1.3%

2015 909 0.15+0.05 0.59+0.19 1.3%

All columns p <0.0001 (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

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

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

®

Shedding new light on heart health:

Examining recent data on fatty acids

Prof. Dr. C. von Schacky, FESC

Preventive Cardiology

Medizinische Klinik und Poliklinik I

Ludwig Maximilians-Universität München

[email protected]

and Omegametrix, Martinsried

[email protected]

London, 18 November 2015

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

Lo

pez A

D &

Mu

rray C

CJL

Natu

re M

ed

icin

e 1

998;4

:1241

HS-Omega-3 Index

5000 randomly selected measurements in Europe

0

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1 146 291 436 581 726 871 1016 1161 1306 1451 1596 1741 1886 2031 2176 2321 2466 2611 2756 2901 3046 3191 3336 3481 3626 3771 3916 4061 4206 4351 4496 4641 4786 4931

Measurements

HS

-Om

eg

a-3

In

de

x

HS-Omega-3 Index - first 5000 Results

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

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1 419 837 1255 1673 2091 2509 2927 3345 3763 4181 4599 5017 5435 5853 6271 6689 7107 7525 7943 8361 8779 9197 9615

Personen

HS

-Om

eg

a-3

In

dex

Mean (+SD): 6.72 (+2.12) %.




HS-Omega-3 Index – last 10 000 Results

Shedding new light on heart health: Examining...

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