1. Nytta och risk med konsumtion av fet fisk Uppsala, okt.2002 Jørn Dyerberg Hjärta/kärlaspekter,omega-3-fettsyror

2. Age standardised death rates in per cent of all deaths from IHD in males aged 45-64 years Figures in Greenland based on the years 1974-76. IHD deaths U.S.40,4 Denmark34,7 Greenland5,3

3. Lancet 1971; 1:1143-6

5. 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 1975;28:958-66) GED 8:0 – 15:0 4.20.3 16:032.230.0 16:14.30.8 16:2 – 17:1 -0.7 18:017.014.6 18:114.912.4 18:25.422.3 18:30.10.2 18:4 – 20:3 3.30.7 20:43.87.4 20:57.41.8 22:0 – 22:5 2.22.2 22:63.62.2 24:0 – 24:1 2.54.2 Saturated54.547.3 Monoenes24.415.3 Polyenes21.134.2 20:5/20:41.950.24

6. Lancet 1978; 2:1179

7. 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 1979;2:433-5

8. The effect of n-3 PUFA supplementation on bleeding time (BT) in normals and different patient groups n-3 PUFA Duration Median BT (min) Patient group ng/day(weeks)beforeafter p value Angina pectoris 1 364.51255½N.S. IDDM 2 IDDM 2104655½0.05<p<0.10 Hyperlipemia 3 176656<0.05 Hypertension 4 104666½N.S. Normals 5 104656½<0.05 Normal 6 204455½<0.05 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.

17. Gissi-Prevenzione trial 2830 given n-3 PUFA plus vitamin E 11324 patients randomised 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 2828 controls 2830 given vitamin E2830 given n-3 PUFA Lancet 1999; 354: 447-55 Figure 1: Trial profile

18. GISSI – Preventione Trial Results (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;2544475-5 Lancet 1999; 254 : 4475-5

20. 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 n “Because 24-hour HRV indices appear to be stable and free of placebo effect, they may be ideal variables to assess intervention therapies” n “A powerful predictor of SCD” Circulation 1996;93:1043 Special Report

22. Omega-3 fedtsyrer og pludselig hjertedød DHA i trombocytter lav mellem høj (Am J Cardiol 1997;79:1670) Patienter med AMI og EF < 0.40 SDNN (ms) 1. kvartil 2.-3. kvartil 4. kvartil

24. HRV and DHA in healthy men r = 0.50, p<0.01 ---------Lowess regression ______linear regression r = 0.68, p<0.001 in the interval 1.3<DHA<2.1 Content of DHA in granulocytes Am J Clin Nutr 1999;70:333-7

25. Am J Clin Nutr 1999;70:331-7

27. Marine n-3 Fatty Acids, Wine Intake, and Heart Rate Variability in Patients Referred for Coronary Angiography Circulation 2001;103:651 n 295 patients referred for elective coronary angiography n Food questionnaire and drinking habits n Adipose tissue biopsy (n-3 fatty acids) n Granulocytes and platelets (n-3 fatty acids) n 24-hour HRV

28. Table 2. Fish Consumption (Fish Score) Related to n-3 PUFA Levels Fish Score 2-4(n=29)5-6(n=49)7-8(n=91)9-10(n-113)11-12(n=19) Granulocytes EPA, % EPA, % 0.63 (0.3) 0.68 (0.3) 0.77 (0.4) 1.02 (0.5) 1.12 (0.5)* DHA, % DHA, % 1.34 (0.4) 1.52 (0.4) 1.59 (0.4) 1.88 (0.5) 1.81 (0.5)* Total n-3 Total n-3 PUFA % PUFA % 3.30 (0.8) 3.56 (1.0) 3.82 (1.0) 4.56 (1.3) 4.41 (1.2)* Adipose tissue EPA, % EPA, % 0.09 (0.04) 0.11 (0.04) 0.12 (0.05) 0.14 (0.05) 0.16 (0.05)* DHA, % DHA, % 0.23 (0.09) 0.30 (0.12) 0.34 (0.14) 0.40 (0.16) 0.46 (0.18)* Total n-3 Total n-3 PUFA % 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 *p<0.001 (Kruskal-Wallis test) Cirkulation 2001; 103: 651-7

29. 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 Granulocyte Membranes EPADHA Total n-3 PUFA EPADHA RR0.0870.121*0.124*0.130* 0.166† 1.150* SDNN-0.0020.0440.0280.0880.150*0.132* SDNN index 0.048 0.0480.122*0.101 0.167 † 0.214 † 0.191 † SDANN index -0.0120.0100.0000.0630.124*0.113 RMSSD0.0330.138*0.1150.0830.152*0.101 PNN500.0350.1340.1140.0710.137*0.084 *p<0.05; †p<0.01 Cirkulation 2001; 103: 651-7

30. **: p<0.01, Kruskall-Wallis test

33. Table 5. Linear Multiple Regression Analysis (Backward) With HRV Indices as Dependent Factors Modifiable Factors NonmodifiableFactors Medication n-3 PUFA Related Lifestyle RR  -Blocker† DHA(g), † n-3 PUFA(a)* Tobacco † Age † SDNN  -Blocker* DHA(g)* Tobacco † MI* SDNNindex DHA(g), † n-3 PUFA(g),* EPA(g),* EPA(a)* Tobacco † SCANNindex  -Blocker † DHA(g)* Tobacco † RMSSD  -Blocker* EPA(a), † n-3 PUFA(a), † EPA(g)* Age* PNN50  -Blocker* 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 n=3 PUFAs in granulocytes [PUFA(g)]; (10) EPA in adipose tissue[EPA(a)]; (11) DHA in adipose tissue [DHA(a)]; and (12) total n=3 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

34. Videnskabelige medarbejdere gennem godt 30 år H.O. Bang Aase Brøndum Ruth Edgar Niels Hjørne Jens Zobbe Mortensen Terkild Arnfred Poul Madsen Gunnar Lauge Nielsen Niels Svaneborg Kim Varming Jørn Munkhof Møller Erik Stoffersen Kaj Anker Jørgensen Steen Dalby Kristensen Troels Ring Torben Mourits-Andersen Niels Grunnet Casper Jersild Peter Bjerregaard Eva Korup Jens Aarøe Arne Høj Nielsen Sir John Vane Salvador Moncada Hugh M. Sinclair Gerard Hornstra Arne Nordøy Egon Toft Erik Ernst Erik Berg Schmidt Jeppe Hagstrup Christensen