The LiVicordia study

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1 CARDIOVASCULAR HEALTH AND LIFESTYLE: NORDIC-BALTIC COMPARISON The LiVicordia study Zita Kučinskienė On behalf of the LiVicordia group

2

3

4 Mortality among men / from Ischemic heart diseases ( ). Age years Lithuania 250 Sweden Year

5 Mortality among men / from Ischemic heart diseases ( ). Age years Lithuania Sweden

6 Mirtingumas nuo kraujotakos sistemos ligų Lietuvoje

7 Mirtingumas nuo kraujotakos sistemos ligų Švedijoje

8 % γ tocopherol/chol+tg Lithuania Sweden 5 0 P< ,3,6,9 µmol/mmol

9 % Lycopene Lithuania Sw eden P< nm ol/l

10 24 h dietary recall Sweden Lithuania p Carbohydrates % <0.001 Total fat % < Protein % < Energy intake KJ NS Means

11 1 Long chain PUFA in adipose tissue 0,9 0,8 0,7 Vilnius men Linköping men 0,6 0,5 0,4 0,3 0,2 *** *** **** **** 0,1 0 20:4n6 20:5n3 22:5n3 22:6n3 ***P<0,001; ****P<0,0001

12 Oxysterols ng/ml 200 Linköping (n=50) Vilnius (n=50) NS NS NS NS 50 0 ** NS NS NS 7α-OH 7β-OH 5α,6a-ep5β,6 β-ep24-oh 25-OH 7-oxo 26-OH *= p<0.05, ***= p<0.01, ***= p<0.001

13 Urine levels of the oxidative DNA adduct 8-hydroxydeoxyguanosine (8-0HdG) (nmol/l), means±sem All Smokers Non-Smokers Vilnius 20,9±9,4(107) 23,0±10,5(38) 19,4±8,5(68) Linköping 14,9±7,4(99) 16,2±7,4(27) 14,5±7,5(72) p<0,001 p<0,01 p<0,001

14 Conclusion Lithuanian LDL is more susceptible to oxidation Fatty acid composition: 1) may contribute to lower LDL cholesterol in Lithuanians 2) do not explain the shorter LDL lag time The susceptibility to oxidation in Lithuanian men is probably due to lower intakes of antioxidants

15 Laboratory stress test BP HR Plasma Cortisol Catechol Lab stress Minutes Anger recall 6 min Arithmetic 4 min Cold pressor 90 sek BP= blood pressure HR=heart rate

16 Serum Cortisol response to stress test Mean values ± SEM nmol/l 500 B Linköping J Vilnius B 450 B P<0.01 B J J B J J P< B J Laboratory stress test min

17 Quality of life / Perceived health Sweden Lithuania p Quality of life; this year <0.001 Quality of life; last year <0.001 Quality of life; next year <0.001 Perceived health: Excellent of good 66% 24% <0.001 Not so good or not good at al 10% 43% <0.001

18 Conclusions The Vilnius men are more exposed and / or more susceptible to oxidative stress, possibly due to differences in diet and enviromental stress.

19 The new LiVicordia hypothesis Socioeconomic background Social environment, Personality characteristics Physiological reactivity to stress High baseline cortisol and attenuated cortisol response Oxidative stress Atherosclerosis Coronary Heart Disease Death

20 Conclusions 1. Vilnius men have more atherosclerosis, in line with vital statistics. 2. Conventional risk factors cannot explain neither the mortality difference nor the atherosclerosis difference. 3. One possible cause may be a relative deficiency in antioxidant vitamins in Vilnius men.

21 Conclusions The high and increasing mortality in CAD in Eastern Europe seems to be more due to deficiency states than to conventional risk factors.

22 The Lipid Unit, Faculty of Health Sciences, Linköping University Sweden 2003

23

24 Welcome to Vilnius, the European Capital of Culture in 2009!

25 Summary of results Vilnius men have; shorter LDL lag time less % saturated FA and more total PUFA in AT less saturated FA and less 18:2 of total FA in LDL less % 18:2 in LDL-cholesterol esters and LDL-phospholipids higher plasma 7b-OH cholesterol

26 Livicordia 1 Variable Vilnius n=109 Linköping n=103 LDL-cholesterol 3,29 ± 0,90 3,68 ± 0,99 ** (mm) γ-tocopherol/lipids 0,25 ±0,13 0,46 ±0,15*** (µm/mm) Lycopene (nm) 327 ± ±321*** β-carotene (nm) 377 ± ±321** Lag time (minutes) 67,6 ±12,7 79,4 ±12,9 ***

27 Traditional risk factors in the two study groups of men in Vilnius and Linköping, means (SEM) Vilnius n = 159 Linköping n = 151 Height, cm 175 (0.5) 178 (0.6) <0.001 BMI 27.0 (0.3) 25.3 (0.3) <0.001 SBP, mm Hg 139 (2) 133 (2) % (n) of current smokers 35 (55) 30 (44) LDL cholesterol, mmol/l 3.40 (0.07) 3.69 (0.08) p

28 VILNIAUS UNIVERSITETAS Vilniaus universiteto ligoninės Santariškių klinikos

29 FACULTY OF MEDICINE

30 VILNIUS UNIVERSITY

31 LDL oxidation method LDL preparation: A) Ultracentrifugation (UC); 1) 4 h gradient UC 2) 20 h steady state UC B) Dialysis: 20 h against PBS with EDTA (10 µm) + chloroamphenicol (0.1 g/l) continuously purged with N 2 C) Oxidation: (final concentrations) LDL 25 µg/ml + CuSO4 5 µm + EDTA 1 µm; temp C, absorbance reading (234 nm) every 2 minutes for 3-4 hours. Reference: H Kleinveld et al Clin. Chem 38:

32 Stress test Blood pressure Puls rate Blood sampling Catech Cortisol Psychical stress Mental stress Minutes

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