postavenie omega-3 mastných kyselín pri znižovaní … prezentacie pdf/sala 1/2...slide source...
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Postavenie omega-3 mastných kyselín pri znižovaní rizika kardiovaskulárnych chorôb Štefan Farský, Dom srdca Martin
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COOH C20:5 ω-3 Eikozapentaénová
(EPA)
H3C
Rodina esenciálnych MK
C18:3 ω-3
ω-3 family
α-Linolénová • ľanový olej • repkový olej • sójový olej
C22:6 ω-3 Dokozapentaénová (DHA)
COOH H3C
• rybí olej • kapsuly
H3C COOH
ω-6 family
C20:4 ω-6
C18:2 ω-6 Linolová
Arachidonic
H3C COOH
Protrombotický a
prozápalový účinok
Metabolity: menej sa tvoria tromby, protizápalové
H3C COOH
• kukuričný olej • slnečnicový
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Vzťah medzi pomerom omega-6 : omega-3 v strave a KV mortalitou
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Rybí olej z morských rýb Olej z morských rýb, bohatý na omega-3 MK, znižuje
hladinu triglyceridov a je efektívny v kombinácii so statínmi pri liečbe pac. s kombinovanou dyslipidémiou
Rybí olej plus statín môže byť dobrou alternatívou k th. fibrát plus statín
Rybí olej okrem toho má aj iné kardiovaskulárne účinky: – redukcia maligných komorových dysrytmií a SCD – spomalenie srdcovej frekvencie – antitrombotické účinky – zlepšenie endoteliálnej dysfunkcie a cievnej funkcie – protizápalové účinky – ľahké zníženie krvného tlaku – zlepšenie diastolického plnenia ľavej komory
Bays HE et al. Expert Opin Pharmacother 2003;4:1901-1938. Kris-Etherton PM et al. Circulation 2002;106:2747-2757.
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Total mortality reduced by 28% (p=0.027)
Sudden death reduced by 47% (p=0.0136)
Marchioli R et al. Circulation 2002;105:1897-1903.
GISSI-Prevenzione: Time Course of Clinical Events
>11,300 post-MI patients were given usual care with or without 850 mg EPA+DHA for 3.5 years
Days
Prob
abili
ty
0 30 60 90 120 150 180 210 240 270 300 330 360
Prob
abili
ty
0 30 60 90 120 150 180 210 240 270 300 330 360
n-3 PUFA Control
n-3 PUFA Control
Days
0.59 (0.36–0.97) p=0.037
0.72 (0.54–0.96) p=0.027
0.47 (0.22–0.99) p=0.048 0.53 (0.32–0.88)
p=0.0136
0.95
0.96
0.97
0.98
0.99
1.00
0.95
0.96
0.97
0.98
0.99
1.00
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Omega-3 FA Infusion Prevents Ventricular Tachyarrhythmias in Dogs
Billman GE et al. Proc Natl Acad Sci U S A 1994;91:4427-4430.
Infuse Omega-3 FA
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Možné antiarytmické mechanizmy: >N-3MK v srdcových membránach hyperpolarizácia ischemických
bunkových membrán, predĺženie ERP
väzba na sodíkové kanály, podobne ako Ic trieda
inhibícia influxu Ca do bunky cez L-kanály pri ischemickom Ca overloade
zvýšenie variablity, zníženie frekvencie u pac. po IM s EF < 0,4 (cez ANS?)
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Months
1 2 3 4 5 6
mg/
dL
mg/
dL
Months
1 2 3 4 5 6
mg/
dL
mg/
dL
GISSI-Prevenzione: Effects of 850 mg/d of EPA+DHA on Serum Lipids
Total Cholesterol
HDL Cholesterol
LDL Cholesterol
Triglycerides
n-3 Control
n-3 Control
n-3 Control
n-3 Control
38404244464850
200205210215220225230
140145150155160165170
125130135140145150155
Marchioli R et al. Circulation 2002;105:1897-1903.
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Omega-3 Ethyl Esters and Lipid Levels in Patients with Triglycerides >500 mg/dL
Pooled analysis: Harris WS et al. J Cardiovasc Risk 1997;4:385-391. | Pownall HJ et al. Atherosclerosis 1999;143:285-297.
Placebo Omega-3 Acid Ethyl Esters (4 g/day)
Baseline (mg/dL)
TG 816
HDL-C 22
Non-HDL-C
27
Chol 296
VLDL-C 175
LDL-C 89
P<0.0001 P=0.0002
P=0.0015 P=0.0059
P<0.0001
P<0.0001
-45.0
6.7 0.0
9.1
-3.6 -13.8
-9.7 -1.7 -0.9
-42.0
-4.8
45.0
-60%
-40%
-20%
0%
20%
40%
60%
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Cum
ulat
ive
Inci
denc
e of
M
ajor
Cor
onar
y Ev
ents
(%
)
Yokoyama M. Presented at American Heart Association Scientific Sessions, Dallas, Texas, 14 November 2005.
Japan EPA Lipid Intervention Study (JELIS)
18,645 Japanese (70% women, mean age 61 years) randomized to statin alone or statin + EPA (1.8 g/d) and followed for 5 years
0 1 2 3 4 5 Years
Control EPA
–19%
Hazard ratio = 0.81 (0.69–0.95) p = 0.011
0
1
2
3
4
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0
2
4
6
8
10
12
14
Om
ega-
3 In
dex
(%)
Distribution of Omega-3 Index in 163 Adults Not Taking Omega-3 Supplements
Sands SA et al. Lipids 2005;40:343-347.
9% of sample
47% of sample
44% of sample
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IV AHA Type
V VI Thin Cap
*p<0.05
Omega-3 FA and Plaque Stability: Plaque Characteristics
Perc
ent
Patients awaiting carotid endarterectomy (n=188) were randomized to control, fish oil (omega-3), or sunflower oil (omega-6) supplementation for median 34, 46, and 43 days preprocedure
Plaques in omega-3 patients appeared to be more stable
Control Omega-3 Omega-6
* *
* * * *
Theis F et al. Lancet 2003;361:477-485.
01020304050607080
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AHA Recommendations for Omega-3 FA Intake
Kris-Etherton PM et al. Circulation 2002;106:2747-2757.
Population Recommendation
Patients without documented CHD
Eat a variety of (preferably oily) fish at least twice a week. Include oils and foods rich in α-linolenic acid (flaxseed, canola, and soybean oils; flaxseeds; and walnuts)
Patients with documented CHD
Consume ~1 g of EPA+DHA per day, preferably from oily fish. EPA+DHA supplements could be considered in consultation with the physician
Patients needing triglyceride lowering
2–4 grams of EPA+DHA per day provided as capsules under a physician’s care
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Food sources of long-chain omega-3 polyunsaturated fatty acids Common dietary sources
EPA, mg/100 g
DPA, mg/100 g
DHA, mg/100 g
EPA + DHA mg/100 g
Slede 909 71 1105 2014
Losos z farmy 862 393 1104 1966
Losos voľný 411 368 1429 1840
Pstruh 259 235 677 936
Makrela 504 106 699 1203
Sardinky 473 0 509 982
Morský jazyk 168 34 132 300
Tuniak 91 17 237 328
DHA = docosahexaenoic acid; DPA = docosapentaenoic acid; EPA = eicosapentaenoic acid
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Ako získať 1 g/d EPA+DHA/deň: Rybie mäso
– 60-90g slede, losos, sardinky, makrely Potravinové doplnky a lieky
– Nízky obsah: 300 mg EPA+DHA/g (bežné kapsuly; 3 g/d)
– Stredný obsah: 500–700 mg EPA+DHA/g (účinnejšie kapsuly; 2 g/d)
– Vysoký obsah: 850-1000 mg EPA+DHA/g (Omega-3 acid etyl estery; 1 g/d)
Olej z treščej pečene – 1 čaj.lyž. (RDA vitamín D; 2× RDA vitamín A)