Nytta och risk med konsumtion av fet fisk Uppsala, okt.2002

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Nytta och risk med konsumtion av fet
fiskUppsala, okt.2002

• Jørn Dyerberg
• Hjärta/kärlaspekter,
• omega-3-fettsyror

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Age standardised death rates in per cent of all
deaths from IHD in males aged 45-64 yearsFigures
in Greenland based on the years 1974-76.
IHD deaths
U.S. 40,4
Denmark 34,7
Greenland 5,3
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Lancet 1971 11143-6
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Fatty acid composition of plasma phospholipids in
Greenland Eskimos GE and Danish controls D.
Values are means as per cent of total (Am J Clin
Nutr 197528958-66)
GE D
80 150 4.2 0.3
160 32.2 30.0
161 4.3 0.8
162 171 - 0.7
180 17.0 14.6
181 14.9 12.4
182 5.4 22.3
183 0.1 0.2
184 203 3.3 0.7
204 3.8 7.4
205 7.4 1.8
220 225 2.2 2.2
226 3.6 2.2
240 241 2.5 4.2
Saturated 54.5 47.3
Monoenes 24.4 15.3
Polyenes 21.1 34.2
205/204 1.95 0.24
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Lancet 1978 21179
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Distribution of fatty acid classes in Danish and
Eskimo food and blood platelets

• Food
• Omega-6 class__________________________________
• Omega-3 class__________________________________
• Platelets
• Arachidonic acid (Omega-6)_______________________
• Eicosapentaenoic acid (Omega-3)___________________
  
• Bleeding Time_____________________________________

Eskimos 5,4 g/day 13,7 g/day 8,5 8,0
8,1 min
Danes 10,0 g/day 2,8 g/day 22,1 0,5 4,7
min
Lancet 19792433-5
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The effect of n-3 PUFA supplementation on
bleeding time (BT) in normals and different
patient groups
n-3 PUFA Duration Median BT (min) Median BT (min)
Patient group n g/day (weeks) before after p value
Angina pectoris1 36 4.5 12 5 5½ N.S.
IDDM2 10 4 6 5 5½ 0.05ltplt0.10
Hyperlipemia3 17 6 6 5 6 lt0.05
Hypertension4 10 4 6 6 6½ N.S.
Normals5 10 4 6 5 6½ lt0.05
Normal6 20 4 4 5 5½ lt0.05

1. Kristiansen et al. Atherosclerosis 1987 13-9
2. Schmidt et al. J Intern Med 1989 (suppl 1)
   201-6
3. Schmidt et al. Thromb Haemostas 1989 62
   797-801
4. Schmidt et al. Clin Chim Acta 1990 189
   25-32
5. Schmidt et al. Thromb Haemostas 1990 63
   1-5
6. Mortensen et al. Thromb Haemostas 1983 30
   543-6.

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Gissi-Prevenzione trial
11324 patients randomised
2830 given vitamin E
2830 given n-3 PUFA
2830 given n-3 PUFA plus vitamin E
2828 controls
3 lost to follow-up 768 discontinued n-3 PUFA
4 lost to follow-up 687 discontinued vitamin E 11
received n-3 PUFA
4 lost to follow-up 848 discontinued n-3 PUFA 808
discontinued vitamin E
2 lost to follow-up 15 received n-3 PUFA 2
received vitamin E
2836 analysed for outcomes
2830 analysed for outcomes
2830 analysed for outcomes
2828 analysed for outcomes
Figure 1 Trial profile
Lancet 1999 354 447-55
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GISSI Preventione TrialResults (RR Four-way
analysis)
n-PUFA
All fatal events 0.80 (p 0.008)
CV deaths 0.70 (p 0.0242)
Sudden death 0.55 (0 0.010)
Death, non-fatal MI, and non-fatal stroke 0.85 (p 0.023)
Cardiovascular death, non-fatal MI, and nonfatal stroke 0.80 (p 0.008)
Lancet 1999 254 4475-5
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Special Report
Heart Rate Variability
Standards of Measurement, Physiological
Interpretation,
and Clinical Use Task Force of the European
Society of Cardiology and the North American
Society of
Pacing and Electrophysiology

• Because 24-hour HRV indices appear to be stable
• and free of placebo effect, they may be
  ideal variables
• to assess intervention therapies
• A powerful predictor of SCD

Circulation 1996931043
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Omega-3 fedtsyrer og pludselig hjertedød

Patienter med AMI og EF lt 0.40
SDNN (ms)

1. kvartil 2.-3. kvartil 4.
kvartil
lav
høj
mellem
DHA i trombocytter
(Am J Cardiol 1997791670)
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HRV and DHA in healthy men
r 0.50, plt0.01 ---------Lowess
regression ______linear regression r 0.68,
plt0.001 in the interval 1.3ltDHAlt2.1
Content of DHA in granulocytes
Am J Clin Nutr 199970333-7
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Am J Clin Nutr 199970331-7
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Marine n-3 Fatty Acids, Wine Intake, and
Heart Rate Variability in Patients Referred for
Coronary Angiography
Circulation 2001103651

• 295 patients referred for elective coronary
  angiography
• Food questionnaire and drinking habits
• Adipose tissue biopsy (n-3 fatty acids)
• Granulocytes and platelets (n-3 fatty acids)
• 24-hour HRV

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Table 2. Fish Consumption (Fish Score) Related to
n-3 PUFA Levels
Fish Score Fish Score Fish Score Fish Score Fish Score
2-4 (n29) 5-6 (n49) 7-8 (n91) 9-10 (n-113) 11-12 (n19)
Granulocytes
EPA, 0.63 (0.3) 0.68 (0.3) 0.77 (0.4) 1.02 (0.5) 1.12 (0.5)
DHA, 1.34 (0.4) 1.52 (0.4) 1.59 (0.4) 1.88 (0.5) 1.81 (0.5)
Total n-3 PUFA 3.30 (0.8) 3.56 (1.0) 3.82 (1.0) 4.56 (1.3) 4.41 (1.2)
Adipose tissue
EPA, 0.09 (0.04) 0.11 (0.04) 0.12 (0.05) 0.14 (0.05) 0.16 (0.05)
DHA, 0.23 (0.09) 0.30 (0.12) 0.34 (0.14) 0.40 (0.16) 0.46 (0.18)
Total n-3 PUFA 0.60 (0.19) 0.71 (0.23) 0.79 (0.25) 0.88 (0.29) 0.96 (0.29)
The mean levels (SD) of the n-3 PUFA eicosapentaenoic acid (EPA) and DHA in granulocyte membranes and in adipose tissue are given plt0.001 (Kruskal-Wallis test) The mean levels (SD) of the n-3 PUFA eicosapentaenoic acid (EPA) and DHA in granulocyte membranes and in adipose tissue are given plt0.001 (Kruskal-Wallis test) The mean levels (SD) of the n-3 PUFA eicosapentaenoic acid (EPA) and DHA in granulocyte membranes and in adipose tissue are given plt0.001 (Kruskal-Wallis test) The mean levels (SD) of the n-3 PUFA eicosapentaenoic acid (EPA) and DHA in granulocyte membranes and in adipose tissue are given plt0.001 (Kruskal-Wallis test) The mean levels (SD) of the n-3 PUFA eicosapentaenoic acid (EPA) and DHA in granulocyte membranes and in adipose tissue are given plt0.001 (Kruskal-Wallis test) The mean levels (SD) of the n-3 PUFA eicosapentaenoic acid (EPA) and DHA in granulocyte membranes and in adipose tissue are given plt0.001 (Kruskal-Wallis test)
Cirkulation 2001 103 651-7
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Table 3. Univariate Nonparametric Correlation
Coefficients Between Levels of n-3 PUFA in
Adipose Tissue and in Granulocyte Membranes and
HRV Indices in the 291 Patients
Adipose Tissue Adipose Tissue Adipose Tissue Granulocyte Membranes Granulocyte Membranes Granulocyte Membranes
EPA DHA Total n-3 PUFA EPA DHA Total n-3 PUFA
RR 0.087 0.121 0.124 0.130 0.166 1.150
SDNN -0.002 0.044 0.028 0.088 0.150 0.132
SDNN index 0.048 0.122 0.101 0.167 0.214 0.191
SDANN index -0.012 0.010 0.000 0.063 0.124 0.113
RMSSD 0.033 0.138 0.115 0.083 0.152 0.101
PNN50 0.035 0.134 0.114 0.071 0.137 0.084
plt0.05 plt0.01 plt0.05 plt0.01 plt0.05 plt0.01 plt0.05 plt0.01 plt0.05 plt0.01 plt0.05 plt0.01 plt0.05 plt0.01
Cirkulation 2001 103 651-7
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plt0.01, Kruskall-Wallis test
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plt0.01, Kruskall-Wallis test
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plt0.01, Kruskall-Wallis test
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Table 5. Linear Multiple Regression Analysis
(Backward) With HRV Indices as Dependent Factors
Modifiable Factors Modifiable Factors Modifiable Factors Modifiable Factors Nonmodifiable Factors
Medication Medication n-3 PUFA Related Lifestyle Nonmodifiable Factors
RR ?-Blocker DHA(g), n-3 PUFA(a) DHA(g), n-3 PUFA(a) Tobacco Age
SDNN ?-Blocker DHA(g) DHA(g) Tobacco MI
SDNNindex DHA(g), n-3 PUFA(g), EPA(g), EPA(a) DHA(g), n-3 PUFA(g), EPA(g), EPA(a) Tobacco
SCANNindex ?-Blocker DHA(g) DHA(g) Tobacco
RMSSD ?-Blocker EPA(a), n-3 PUFA(a), EPA(g) EPA(a), n-3 PUFA(a), EPA(g) Age
PNN50 ?-Blocker EPA(g), DHA(g), EPA(a), , n-3 PUFA(a) EPA(g), DHA(g), EPA(a), , n-3 PUFA(a)
Backward linear multiple regression analysis was conducted with the following independent modifiable factors (1) body mass index medical therapy with (2) ACE inhibitors, (3) ?-blockers, or (4) calcium inhibitors (5) wine intake (6) tobacco use (7) EPA in granulocytes EPA(g) (8) DHA in granulocytes DHA(g) (9) total n3 PUFAs in granulocytes PUFA(g) (10) EPA in adipose tissueEPA(a) (11) DHA in adipose tissue DHA(a) and (12) total n3 PUFAs in adipose tissue PUFA(a). Nonmodifiable factors included in the test were (13) age, (14) left ventricular ejection fraction, (15) previous MI, (16) sex, and (17) the extent of coronary artery disease. Significant independent factors are given. Backward linear multiple regression analysis was conducted with the following independent modifiable factors (1) body mass index medical therapy with (2) ACE inhibitors, (3) ?-blockers, or (4) calcium inhibitors (5) wine intake (6) tobacco use (7) EPA in granulocytes EPA(g) (8) DHA in granulocytes DHA(g) (9) total n3 PUFAs in granulocytes PUFA(g) (10) EPA in adipose tissueEPA(a) (11) DHA in adipose tissue DHA(a) and (12) total n3 PUFAs in adipose tissue PUFA(a). Nonmodifiable factors included in the test were (13) age, (14) left ventricular ejection fraction, (15) previous MI, (16) sex, and (17) the extent of coronary artery disease. Significant independent factors are given. Backward linear multiple regression analysis was conducted with the following independent modifiable factors (1) body mass index medical therapy with (2) ACE inhibitors, (3) ?-blockers, or (4) calcium inhibitors (5) wine intake (6) tobacco use (7) EPA in granulocytes EPA(g) (8) DHA in granulocytes DHA(g) (9) total n3 PUFAs in granulocytes PUFA(g) (10) EPA in adipose tissueEPA(a) (11) DHA in adipose tissue DHA(a) and (12) total n3 PUFAs in adipose tissue PUFA(a). Nonmodifiable factors included in the test were (13) age, (14) left ventricular ejection fraction, (15) previous MI, (16) sex, and (17) the extent of coronary artery disease. Significant independent factors are given. Backward linear multiple regression analysis was conducted with the following independent modifiable factors (1) body mass index medical therapy with (2) ACE inhibitors, (3) ?-blockers, or (4) calcium inhibitors (5) wine intake (6) tobacco use (7) EPA in granulocytes EPA(g) (8) DHA in granulocytes DHA(g) (9) total n3 PUFAs in granulocytes PUFA(g) (10) EPA in adipose tissueEPA(a) (11) DHA in adipose tissue DHA(a) and (12) total n3 PUFAs in adipose tissue PUFA(a). Nonmodifiable factors included in the test were (13) age, (14) left ventricular ejection fraction, (15) previous MI, (16) sex, and (17) the extent of coronary artery disease. Significant independent factors are given. Backward linear multiple regression analysis was conducted with the following independent modifiable factors (1) body mass index medical therapy with (2) ACE inhibitors, (3) ?-blockers, or (4) calcium inhibitors (5) wine intake (6) tobacco use (7) EPA in granulocytes EPA(g) (8) DHA in granulocytes DHA(g) (9) total n3 PUFAs in granulocytes PUFA(g) (10) EPA in adipose tissueEPA(a) (11) DHA in adipose tissue DHA(a) and (12) total n3 PUFAs in adipose tissue PUFA(a). Nonmodifiable factors included in the test were (13) age, (14) left ventricular ejection fraction, (15) previous MI, (16) sex, and (17) the extent of coronary artery disease. Significant independent factors are given. Backward linear multiple regression analysis was conducted with the following independent modifiable factors (1) body mass index medical therapy with (2) ACE inhibitors, (3) ?-blockers, or (4) calcium inhibitors (5) wine intake (6) tobacco use (7) EPA in granulocytes EPA(g) (8) DHA in granulocytes DHA(g) (9) total n3 PUFAs in granulocytes PUFA(g) (10) EPA in adipose tissueEPA(a) (11) DHA in adipose tissue DHA(a) and (12) total n3 PUFAs in adipose tissue PUFA(a). Nonmodifiable factors included in the test were (13) age, (14) left ventricular ejection fraction, (15) previous MI, (16) sex, and (17) the extent of coronary artery disease. Significant independent factors are given.
Cirkulation 2001 103 651-7
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Videnskabelige medarbejdere gennem godt 30 år

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