Overview of effects of alcohol intake on cardiovascular disease

Transcription

1 Beverage specific effects Overview of effects of alcohol intake on cardiovascular disease Dr. Ramon Estruch Department of Internal Medicine, Barcelona University, Spain. CIBER OBN Institute of Health Carlos III,

2 THE DOBLE SIDE OF ALCOHOL

3 EFFECTS OF HIGH ETHANOL INTAKE ON CARDIOVASCULAR SYSTEM

4 TOXIC EFFECTS ON CARDIOVASCULAR SYSTEM ACUTE EFFECTS CHRONIC EFFECTS Heart Arrhythmias Holyday Heart syndrome Ventricular Dysfunction Hypertension Sudden Death Systolic Dysfunction Diastolic Dysfunction Subclinical cardiomyopathy Clinical cardiomyopathy

5 Arrhythmia in Alcoholics Controls (n= 10) Alcoholics w/out CMP (n= 30) Alcoholics with CMP (n= 20) Age (years) 42±9 42±8 44±8 Daily dose of ethanol (g) NA 243±75 206±59 Supraventricular Extra systoles (n) 2 (20%) 11 (36%) 5 (25%) Ventricular Extra systoles (n) 3 (30%) 10 (33%) 10 (50%) Occasional 2 (20%) 7 (23%) 3 (15%) Frequent 1 (10%) 3 (10%) 7 (35%) Simples 3 (30%) 2 (7%) 2 (10%) Complexes 0 (0%) 3 (10%) 8 (40%)

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7 N Engl J Med 1989

8 Ejection fraction (%) Lifetime dose of ethanol (Kg/Kg) N Engl J Med 1989

9 Ejection fraction (%) INFLUENCE OF ETHANOL ON LV-EF CHANGES Abstinent g/day g/day > 80 g/day Baseline 1 year 10 Baseline 1 year Baseline 1 year Baseline 1 year Ann Intern Med 2002

10 SURVIVAL ANALYSIS ALCOHOLICS WITH CARDIOMYOPATHY Cumulative survival (%) < 80 g ethanol/day p = > 80 g ethanol/day Follow-up (months) Ann Intern Med 2002

11 Ejection Fraction of Left Ventricular, % Toxic effects on Cardiovascular System 72 Asymptomatic men (n= 100) Asymptomatic women (n= 50) r = r = p< r = slope = p< Total Cumulative Dose of Alcohol, Kg/kg weight JAMA 1995

12 ACE Polymorphism in Alcoholics Group I (LVEF < 50%) Group II (LVEF > 60%) P= DD group I vs DD group II II ID DD Ann Intern Med 2002

13 EFFECTS OF HIGH ETHANOL INTAKE ON CENTRAL NERVOUS SYSTEM (STROKE)

14 Alcohol Consumption and Risk of Stroke: A Meta-analysis JAMA. 2003;289(5):

15 Romelsjö A, et al., Alcohol Alcohol. 2012; 47(3):322-7

16 Romelsjö A, et al., Alcohol Alcohol. 2012; 47(3):322-7

17 EFFECTS OF BINGE DRINKING

18 Meta-regression of dose response relation between weekly alcohol intake and relative risk (and the corresponding 95% confidence bands) of coronary heart disease in regular and irregular drinkers. Bagnardi V et al. J Epidemiol Community Health 2008;62:

19 Forest plots of drinking pattern and coronary heart disease. Bagnardi V et al. J Epidemiol Community Health 2008;62:

20 EFFECTS OF MODERATE ALCOHOL INTAKE ON CARDIOVASCULAR SYSTEM

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23 ALCOHOL CONSUMPTION AND MORTALITY FOR ANY CAUSE Reversion Point Maximum Protection Thirty-four studies provided 56 independent dose-response curves for a total of 1,015,835 subjects and 94,533 deaths from any cause. The association with a lower mortality was apparent up to 42 g/d and the lowest mortality was seen at 6 g/d, (RR, 0.81 [CI, ]).

24 Risk for Ischemic Stroke in 38,156 Male Health Professionals * * 0 0 <30 >30 <30 >30 <30 >30 0 d/w 1-2 drink/w 3-4 drink/w 3-4 > 5 drink/w g/day Mukamal KJ, et al., Ann Intern Med 2005

25 ALCOHOL CONSUMPTION AND RISK FOR CORONARY HEART DISEASE * * * * * > 50.0 g/day 11,711 men with hypertension. Follow-up 4 years Mukamal KJ, et al., Ann Intern Med 2007

26 Overall Mortality with Moderate Alc. Alc. drinkers vs Non-drinkers Metanalysis: 84 studies Mortality from all causes: RR 0.87 CI J- curve effect: Elevated risk >60g/d RR 1.30 CI Ronksley P, Brien S, Turner B, Mukamal K, Ghali W. BMJ 2011

27 Relative Risk of Myocardial Infarction in 38,077 health workers in the United States *** ** *** * *p<0.14; **p<0.04; ***p<0.001 compared with control New Engl J Med 2003

28 Relative Risk for Death from All Causes in Relation to Total Alcohol Intake 1.4 Non-wine drinkers Wine-drinkers Drinkers (1-30% win Drinkers (>30% wine Relative risk is set at a 1.0 among non drinkers (<1 drinks/week) >35 Alcohol Consumption, drinks/week Ann Intern Med 2000

29 Meta-analysis: Consumption of different alcoholic beverages and vascular risk Reduction of vascular risk Wine: 32% Beer: 22% Circulation 2002

30 Wine, beer or spirit drinking in relation to fatal and non-fatal cardiovascular events: a meta-analysis. Eur J Epidemiol. 2011

31 MECHANISMS OF ETHANOL CONSUMPTION ON CORONARY DISEASE The beneficial effects on surrogate markers of cardiovascular risk add biological plausibility to the epidemiological evidences of a protective effect of alcoholic beverages

32 Ross R. N Eng J Med 1999; 340:

33 Possible Mechanisms of Beneficial Effects of Moderate Consumption of Alcohol Prevention of arterial lesions Increase in HDL-cholesterol Reduction in the oxidation of LDL- cholesterol particles Changes in the endothelium of arterial wall Improving insulin sensitivity or others Prevention of arterial thrombosis Reduction of platelet aggregation Inhibition of clot formation Activation of fibrinolytic system

34 WINE - BEER Ethanol Phenolic compounds

35 COHORT STUDIES

36 PREDIMED STUDY 7,447 participants Control Low Fat Diet Mediterranean Diet + Mediterranean Diet + n= 2,450 n= 2,543 n= 2,454

37 PRIMARY END-POINTS Cardiovascular death Non-fatal myocardial infarction Non-fatal stroke SECONDARY END-POINTS Death from any cause Angina leading to revascularization procedure Heart failure, Peripheral artery disease Diabetes Cancer

38 POLYPHENOL INTAKE AND MORTALITY

39 RANDOMIZED CLINICAL TRIALS

40 Methodology Design: Randomized prospective cross-over clinical trials trialorizado Blood analysis Wash-out 1 Alcohol Intake Wash-out 2 Alcohol Intake Consumption of 20 (women) - 30 (men) g/day of alcohol Comparations: Polyphenol-rich alcoholic beverage vs polyphenol-poor alcoholic beverage.

41 LYMPHOCYTE AND MONOCYTE ADHESION MOLECULES AND CHEMOKINES LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN 1 (LFA-1) MAC 1 VERY LATE ACTIVATION ANTIGEN 4 (VLA-4) CD40, CD45 SYALIL-LEWIS MONOCYTE CHEMOTACTIC PEPTIDE -1 (MCP-1)

42 Alcohol and Arteriosclerosis Interaction leukocyte-endothelium Leukocyte Endothelium Quimioatractants of the endotheial surface

43 Alcohol and Arteriosclerosis Interaction leukocyte-endothelium Leukocyte Endothelium Selectines Quimioatractants of the endotheial surface

44 Alcohol and Arteriosclerosis Interaction leukocyte-endothelium Leukocyte Recruitment Slow Rolling Endothelium Selectines Quimioatractants of the endotheial surface Integrines Other molecules

45 Alcohol and Arteriosclerosis Interaction leukocyte-endothelium Leukocyte Endothelium Recruitment Slow Rolling Progresive activation of Igs Firm Adhesion Selectines Quimioatractants of the endotheial surface Integrines Other molecules

46 Alcohol and Arteriosclerosis Interaction leukocyte-endothelium Leukocyte Progresive activation of Igs Recruitment Endothelium Slow Rolling Firm Adhesion Transmigration Selectines Quimioatractants of the endotheial surface Integrines Other molecules

47 T lymphocytes Alcohol - PP Alcohol + PP Before After Before After LFA 1 (MFI) VLA 4 (MFI) Monocytes Adhesion Molecules Analysis in Lymphocytes and Monocytes LFA 1 (MFI) Mac 1 (MFI) VLA 4 (MFI) MCP 1 (MFI) P 0.05 P ATHEROSCLEROSIS 2004; 175:117-23

48 ICAM-1 (%) MCP-1 (%) TNFα (%) IL- 6 (%) P-selectina (%) E-selectina (%) CD40L (%) VCAM-1 (%) hspcr (%) Changes in adhesion molecules and other inflammatory markers * # ** * * *P < 0.05 **P < 0.01 # P < ** ** * 40 * * * Alcohol - PP Alcohol + PP * -10 # -20 ** # -20 Vázquez-Agell, et al; J Nutr, 2007

49 Monocyte-endothelium adhesion (DO) Alcohol and Arteriosclerosis Values of monocytary adhesion to an endothelial line in basal conditions and following stimulation with TNF-a - 39% - 96% * P<0.001 * * * +27% +12% +20% +0% Phase1 Phase 2 Phase 3 Phase 4 GIN WINE Am J Clin Nutr 2004; 80:225-30

50 ASSAY OF MONOCYTE- ENDOTHELIAL ADHESION (endothelial line Ea.Hy926) WASH-OUT TNF-a GIN BASELINE RED WINE

51 STUDY DESIGN Open 1 st INTERVENTION 2 nd INTERVENTION 3 rd INTERVENTION Crossover Randomized Volunteers WASH OUT 15 days Interventions: RW: 272mL red wine (30g OH) DRW: 272mL dealcoholized red wine G: 100mL gin (30g OH) Baseline Samples 28 days 28 days 28 days 1 st Intervention 2 nd Intervention 3 rd Intervention Samples Samples Samples

52 pg/ml RESULTS (Soluble Cytokines) Moderate alcohol consumption (RW and G interventions): Increased serum IL-10 Decreased serum MDC (Monocyte Derived Chemoquine) Antiinflammatory Interleukin-10 (IL-10) b b a a a b a b B RW DRW G P=0.033 P=0.001

53 RESULTS (Soluble Cytokines II) Red Wine Phenolic Compounds (RW and DRW interventions): decreased serum concentrations of: a b b a a b b a P=0.021 P=0.01 a b b a P=0.029

54 mmol/l pmol/l Changes in glucose control and lipid profile after three interventions in 67 subjects. Insulin HOMA-Insulin resistance A* A* B RW DRW G 1,8 1,6 1,4 1,2 1 0,8 0,6 0,4 0,2 0 B A* A* B RW DRW G 1,6 1,4 1,2 1 0,8 0,6 0,4 0,2 0 HDL-cholesterol A* A* B B RW DRW G 3,3 3,2 3,1 3 2,9 2,8 2,7 2,6 2,5 LDL/HDL ratio B A A* B RW DRW G Chiva-Blanch G et al. Clin Nutr. 2013, 32 (2):

55 g/l μmol/l μg/l Changes in glucose control and lipid profile after three interventions in 67 subjects. 3 2,5 2 1,5 1 0,5 0 Lipoprotein(a) B B A* B RW DRW G Apolipoprotein A-II A* A* B B RW DRW G 8,5 8 7,5 7 6,5 Apolipoprotein A-I A* B A* 6 B RW DRW G Chiva-Blanch G et al. Clin Nutr. 2013, 32 (2):

56 EFFECTS OF WINE POLYIFENOL ON BLOOD PRESSURE (I) Circulation Res 2012

57 EFFECTS OF WINE POLYIFENOL ON BLOOD PRESSURE (Ii) Circulation Res 2012

58 Design of the study DISEÑO O DEL ESTUDIO Prospectivo Cruzado Aleatorizado Controlado 1a INTERVENCIÓN CON 2a INTERVENCIÓN CON 3a INTERVENCIÓN CON Voluntarios LAVADO 14 días SIN SIN SIN Intervenciones: 660mL cerveza (30g OH) 990mL cerveza sin alcohol 92mL ginebra (30g OH) 28 días 28 días 28 días Estudio Clínico y Analítico Basal Estudio Clínico y Analítico 1a intervención Estudio Clínico y Analítico 2a intervención Estudio Clínico y Analítico 3a intervención

59 INCLUSION CRITERIA Men y. with: Diabetes mellitus (treated or repeated glycemia > 126 mg/dl, random glycemia > 200 mg/dl with symptoms or OGT Test > 200 mg/dl) and/or with THREE or more risk factors: CURRENT Smoking Hypertension (> 140/90 mm Hg) LDL-cholesterol > 160 mg/dl HDL-cholesterol < 40 mg/dl Overweight or Obesity (BMI > 25 Kg/m 2 ) Familiar history of early coronary heart disease

60 Monocyte Adhesion Molecules n = 33

61 Soluble Biomarkers of Inflammation n = 33

62 Changes in circulating EPC after the three interventions (expressed in terms of differences between before and after each intervention). Chiva-Blanch G. et al., Atherosclerosis. 2014; 233(2):

63 Changes in systolic and diastolic blood pressure in the 33 subjects studied after the three interventions. Chiva-Blanch G. et al., Nutrition, Metabolism & Cardiovascular Diseases, 2014

64 Other Cardiovascular Parameters n = 33

65 Conclusions

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67 THE DOUBLE SIDE OF ALCOHOL THANK YOU VERY MUCH

68 THANK YOU VERY