Flavonóides Da Dieta Vs Mortalidade Por DAC (N 805 H) Zutphen Elderly Study-Seguim.: 5 Anos

Flavonides da Dieta vs Mortalidade por DAC (n=805 h) Zutphen Elderly Study-seguim.
: 5 anos
1 0,9 0,8
Risco Relativo
0,7 0,6 0,5 0,4 0,3 0,2 0,1 0

0 - 19
p < 0,003
19,1 - 29,9
> 29,9
Ingesto de Flavonides (mg/dia) RR ajustado para idade, dieta e FR

Hertog MCL et al. Lancet 1993;342:1007-11
Zutphen Elderly Study

805 homens; seguimento: 5 a.
Flavonides:resveratrol, quercetina, Kempferol, apigenina, luteolina e mirecitina Fontes: Ch Cebola Ma
61% 13% 10%

Hertog MCL et al. Lancet 1993;342:1007-11
Wine Consumption and CHD

1000
Finland
CHD = -4.99W + 652.4 r = -0.580
800
Ireland
U.S.
Mortality rate
U.K. Canada 600 Norway Denmark Sweden
Australia New Zealand
400
W. Germany
Netherlands Belgium
Austria Italy France
200
Japan
Switzerland
20
40
60
80
100
Wine, liter/capita-year
Hegsted DM, Ausman LM. J Nutr. 1988;118:1184-1189.
Alcohol and Stroke Risk

OR LOG 7.4 4.5 2.7 1.6 1.0 0.6 0.4 2.0 1.5 1.0 0.5 0.0 - 0.5 -1.0
Drinks per Day

OKeefe JH et al. JACC 2007;50:1009-14
FRUTIVAR- 2009
VINHO TINTO, UVA E ATEROSCLEROSE: PERSPECTIVAS

Dr. Protsio L. da Luz
Professor de Cardiologia, INCOR- HC,FMUSP
No h conflitos de interesse
Wine, alcohol, platelets, and the French paradox for coronary heart disease
300
CHD Mortality (1987) (men + women)

U.K. Denmark
Finland Ireland
Sweden
200
Norway Australia Germany Austria Netherlands Yugoslavia Belgium Switzerland Italy Spain FRANCE
100 Portugal
0 0 200 400 600
r = 0.73 p < 0.001

800 1000
Dairy fat (Calories) (1980-85)

Renaud S and Lorgeril M. Lancet 1992;339:1523-26
Wine, alcohol, platelets, and the French paradox for coronary heart disease
300
CHD Mortality (1987) (men + women)

U.K. Australia
Finland Ireland Denmark Sweden
200 Austria
Germany
Norway
Switzerland Italy 100 Portugal Spain Yugoslavia FRANCE
Netherlands Belgium
r = 0.87 p < 0.0001

200 300
0 0 200
145 + 0.138 dairy fat -0.917 wine

Renaud S and Lorgeril M. Lancet 1992;339:1523-26
Meta-Analysis of Wine Intake and Vascular Risk

Kozararevic, 1980 (17) Friedman, 1986 (18) Rimm, 1991 (19) Klatsky, 1990 (20) Wannamethee, 1999 (21)
Prospective studies
Rosenberg, 1981 (22) Kaufman, 1985 (23) Marques-Vidal, 1996 (28) Sacco, 1999 (24) Gaziano, 1999 (25) Triff, 1999 (26) Cleophas, 1996 (29) Brenner, 2001 (27)
Case-Control studies Overall

0.3 0.4 0.5 0.6 0.7 0.8 Prospective effect 0.9 1.0 1.1 Risk effect
Di Castelnuovo A et al. Circulation 2002;105:2836-2844
Alcohol and All-Cause Mortality

1.4 Relative Risk of Total Mortality 1.3 1.2 1.1 1.0 0.9 0.8 0.7 0.6 0 1 2 3 4 5 6 7 Men Women Confidence Intervals
Drinks per Day Alcohol Consumption
The Effect of Red Wine on Experimental Atherosclerosis: Lipid-Independent Protection
Protsio L. da Luz, Carlos V. Serrano Jr., Ana P. Chacra et al.

Exp Mol Pathology 1999;65:150-159
The Effect of Red Wine on Experimental Atherosclerosis: Lipid-Independent Protection. Da Luz P et al.1999;65:150-9
Avaliao da reatividade vascular endotlio dependente e independente com vinho tinto ( 250 ml/dia, por 14 dias)
P < 0,01
% Dilatao da artria braquial
20
P < 0,01
HR NT
10
0 Basal Vinho Tinto Basal Vinho Tinto
Coimbra S, Da Luz PL. BJMBR
Avaliao da reatividade vascular endotlio dependente e independente com suco de uva ( 500 ml/dia, por 14 dias)
% Dilatao da artria braquial
20
P < 0,01
P = ns
HR NT
10
0 Basal Suco de Uva Basal Suco de Uva
Coimbra S, Da Luz PL. BJMBR
Grape Juice and Coronary Artery Disease
15.0
10.0
% FMD
5.0
0.0
-5.0
Baseline
Grape Juice
Stein JH et al. Circulation 1999:100;1050-5
Mediterranean Diet and Coronary Heart Disease

100
90
Percent without event
80
Experimental
70
60
Control
50 p = 0.0002 40 1 2 3 4 5
Year
Lorgeril M et al. Circulation 1999;99:779-785
Reduo de Mortalidade por Aumento de Dois pontos no Escore de Dieta Mediterrnea EPIC - Grcia
N= 22.043 adultos; seguimento 44 meses
Hazard Ratio ajustado
1,0 0,8 0,6
Geral
DAC
Cncer
0,75 0,67
0,76
P<0.001
Trichopolou et al. N Eng J Med 2003; 348: 2599-608
Contribuio dos Alimentos na Reduo de Morte Estudo EPIC

25,00%
23,50%
20,00%
16,20% 16,60%
15,00%
10,60% 11,20%
10,00%
9,70%
5,00%
0,00%
Legumes Mono/Sat. Frutas/noz Vegetais Carne alta alta alta alta baixa Ingesto de Alimentos
lcool moderada
Trichopoulou et al. BMJ 2009;338:b2337
Alcohol and Age-related Macular Degeneration

10 9
AMD
Percent with AMD (%)
8 7 6 5 4 3 2 1 0 No alcohol Beer Wine Liquor
Types of alcohol
Obisesan TO el al. J Am Geriatr Soc 1998;46:1-7
AES NO CARDIACAS DO VINHO

- Degenerao macular senil 1 - Doena de Alzheimer 2 - Demncia 3 - Diabetes Mellitus 4,5 - Estrgeno 6 - lcera Duodenal 7 - Hiperplasia Prosttica Benigna 8
1 Obsisesan 2 Orgajazo 3 4 5
TO e col. J Am Geriatr Soc 1998;16:1-7
6 7
Ghem BD e col. Proc Natl Acad Sci USA 1997;94:1438-43 Aldoorl WH e col. Epidemiology 1997;8:420-4 EA e col. Am J Epidemiol 1999:149:106-15
JM e col. Rev Neurol 1997;153:185-92
Truelsen T e col. Neurology 2002;12:1300-11 Wei M e col. Diabetes Care 2000;23:18-22
8 Paltz
De Vegt F e col. Diabetes Research and Clinical Practice 2002;57:53-60
Reduo de Mortalidade Total Estudos HALE, SENECA e FINE

1507 H; 832 M; 70-90 a; segui: 1988-2000; 935 mortes
Dieta Alcool moderado Atividade Fisica Abstinencia Fumo Todos
Hazard ratio (%)
-10 -20 -30 -40 -50 -60 -70

Knoops et al. JAMA 2004; 292: 1433-9
www.nationalgeographicbr.com.br
Anlise de Prevalncia de Fatores de Risco Cardiovascular em Idoso do Projeto Veranpolis

Ivana da Cruz, A Manica, C Frentzel, G Flores, J Siviero, M Taufer, N Bruscato, R Ehlers, EH Moriguchi Instituto de Geriatria - PUCRS
SUBJECTS
Veranpolis, RS: - 16,910 hab. (1996) - 203 > 80 y.o. - last 5 years: 1 AMI death among > 80 Study Sample: - 100 > 80 y.o. - Age: 84.4 3.3 y. - 66 female: 34 male BRAZIL
* Veranpolis (Italian
Immigration)
Smoking Among Very Elderly Smoking Among Very Elderly

100% 80% 60% 40% 20% 0%
* * *
Never Former Smoker
Male Female
p<0,000 p<0,000
Distribution of Plasma Distribution of Plasma Lipid/Lipoproteins Lipid/Lipoproteins

250 200
* *
Male Female
mg/dl
150 100 50 0
*p<0,01
CT CT
TG TG
LDL-c LDL-c
HDL-c HDL-c
Como Eles Conseguem Viver Tanto

SARDOS Bebem vinho tinto (com moderao) Compartilham com o cnjuge o trabalho Comem queijo pecorino (e outros alimentos ricos em mega-3)
ADVENTISTAS Comem nozes e feijes Guardam o sbado Tm f
TODOS No fumam Priorizam a famlia Fazem atividades fsicas Tm vida social Comem frutas, verduras e gros integrais
OKINAWANOS Mantm amigos para toda a vida Comem pores pequenas Encontram sentido na vida
A Tale of Two Monkeys

Rhesus Monkeys at Wisconsin Primate Research Center, both 24, show effects of two regimens. ULTRA-LEAN DIET This handsome fellow has lower glucose and insulin levels-and looks younger, too. NORMAL FARE This monkey has higher triglycerides and more oxidative damage to his cells.
PROJETO SOBREVIDA
Efeito do tratamento crnico com resveratrol na sobrevida e em biomarcadores de envelhecimento em ratos idosos
da Luz PL, Krieger JK, Pereira AC, Myakawa AA, Tanaka LY, Brum PC
Restrio calrica
PNC1
Resveratrol
Sir/SIRT
atividade deacetilase NAD+ nicotinamida + -acetil-ADP-ribose
-estabilidade do DNA -reparo no DNA -silenciamento transcricional -regulao da p53
sobrevida
Howitz KT et al. Nature, 2003
Protocolo Sobrevida
Da Luz et al, 2008
-ratos Wistar - n=20/grupo -controle: rao e gua controle -vinho tinto (25%) na gua de beber -resveratrol (rao): 0,0015g/kg e 4g/kg - encurtamento do telmero
Tratamento com resveratrol
Modulao de mecanismos envolvidos na senescncia
- atividade da telomerase - p53 (supressora de tumor), p16 - inibidoras de cdk (cdki) - p21 - estresse oxidativo
-sobrevida
Anlise funcional
-tolerncia ao esforo fsico -consumo mximo de oxignio -funo endotelial
Projeto Confrarias
Pergunta : bebedores habituais de vinho tinto so biologicamente mais jovens que abstmios ? Tm menos aterosclerose ? Populao : 100 indviduos sadios, que bebam pelo menos 1 taa de vinho tinto/dia, pelo menos 4- 5 vezes/ semana, nos ltimos 5 anos 100 controles sadios, abstmios Comparveis em idade, e do sexo masculino O n= 200 foi calculado baseado no escore de clcio coronrio
da Luz et al-2008
Projeto Confrarias
Mtodos Avaliao clnica : FR, dados antropomtricos Registro alimentar - 3 dias Funo endotelial braquial e EIM carotdea por US Tomografia Computadorizada MD (64 ) coronria para escore de clcio e leses Perfil lipdico e PCRus ndices de envelhecimento em leuccitos circulantes: comprimento de telmero, telomerase, p53, p16, p21, bgalactosidase da Luz et al-2008
Contra-Indicaes ao uso de Vinho e/ou Bebidas Alcolicas

Arritmias cardacas Disfuno ventricular - ICC; Miocardiopatias Diabetes descompensada Doenas hepticas Alcoolismo Adolescentes Hipertrigliceridemia
O whisky o melhor amigo do homem. O whisky o cachorro engarrafado

Vincius de Moraes
Who was at greater risk for the development of heart disease?
Jim Fixx - marathon runner,

exercise advocate, author dead at 53 of a heart attack
Sir Winston Churchill broke

every tenet of healthy life style dead at age 91
JAMES MUELLER
Obrigado!
Contribuio dos Alimentos na Reduo de Morte Estudo EPIC

25,00%
23,50%
20,00%
16,60% 16,20%
15,00%
11,20% 10,60%
10,00%
9,70%
5,00%
0,00%
lcool moderada
Carne baixa
Vegetais alta
Frutas/noz Mono/Sat. Legumes alta alta alta
Ingesto de Alimentos Trichopoulou et al. BMJ 2009;338:b2337
Projeto Sobrevida; dados preliminares

ctr
p53 p16 -actina Western Blotting em homogenato de aorta
Da Luz et al.
alto baixo resv. vinho resv.
Relaxamento mximo ACh

65
Relaxamento mximo ao NPS
% Relaxamento
% relaxamento
*
60 55
100
75
50
CTR
baixo resv
vinho
alto resv
50
CTR
baixo resv
vinho
alto resv
*p<0,05 vs. CTR
Resveratrol e sobrevida em diferentes espcies

70% - Wood JG et al. Nature, 2003 18% -Viswanathan M et al. Dev Cell, 2005 16 - 20% - Wood LG et al. Nature, 2004
59% - Valenzano DR et al. Curr. Biol, 2006
Restrio calrica
PNC1
Resveratrol
Sir/SIRT
sobrevida
OBJETIVOS Analisar os efeitos do tratamento crnico com resveratrol sobre: a sobrevida de ratos normais; biomarcadores de envelhecimento. METODOLOGIA ratos Wistar machos - 8 meses idade - Cemib/Unicamp - gua - n=20 - veculo (etanol) - n=20 - resveratrol 1mg/kg/dia - n=20 Sobrevida: curva de Kaplan-Meier.
Biomarcadores de envelhecimento (n=5)

Tecidos coletados:
sangue (eritrcito, plasma e leuccito) corao, aorta, rim, fgado, pulmo e orelha SA--Galactosidase: deteco histoqumica aps incubao overnight c/ soluo X-Gal. Western Blot: p16 (Santa Cruz) , Arf (Upstate), p53 (Santa Cruz) e p21 (Calbiochem). Atividade da telomerase: TeloTAGGG Telomerase PCR ELISA (Roche). Comprimento do telmero: Telo TTAGGG Telomere Length (Roche): ddhibridizao com probe do telmero e deteco por reao luminescente GSH/GSSG: deteco eletroqumica em HPLC.
Resveratrol improves health and survival of mice on a highcalorie diet

100 Proporo sobreviventes (%) 80
60 40 20
Dieta padro Dieta hipercalrica Dieta hipercalrica + Resveratrol
0 50
60 70 80 90 100 Tempo sobrevivncia (semanas)
110
Baur et al. Nature 2006; 404: 337- 42
Alcohol and Coronary Calcium

Odds ratio For Severe Coronary Calcification
1.4 1.2 1.0 0.8 0.6 0.4 0.2 0
Non-drinkers
1 Drink/d
2 Drinks/d
> 2 Drinks/d
Effects of Moderate Alcohol Consumption on Cognitive Function in Women

TICS score < 31
15.0 - 30.0 g of alcohol/day 1.0 - 14.9 g of alcohol/day
Worst 10% for verbal memory score
Worst 10% for global cognitive score
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0
Multivariate Relative Risk of Cognitive Impairment

TICS = denotes the Telephone Interview for Cognitive Status
Stampfer MJ et al. NEJM 2005;352:245-53
Relative Risk of a Substantial Decline in Cognitive Function over a Two-Year Period, According to Alcohol Intake
Measure of Substantial Cognitive Decline* No. Who Completed Test None** Alcohol Intake
1.0-14.9 g/day 15.0-30.0 g/day relative risk (95 percent confidence interval)
TICS score for worst 10% of distribution of decline Multivariate-adjusted Verbal memory score for worst 10% of distribution of decline Multivariate-adjusted Global cognitive score for worst 10% of distribution of decline Multivariate-adjusted
11,102 1.00 0.85 (0.74-0.98) 1.04 (0.77-1.41) 9,670 1.00 0.83 (0.72-0.97) 0.76 (0.54-1.09) 9,661 1.00 0.89 (0.77-1.03) 0.82 (0.58-1.16)
* TICS denotes the Telephne Interview for Cognitive Status ** Nondrinkers (51%) served as the reference group
eNOS Induction by Red Wine

nt 450 *** p<0.001 ***
eNOS mRNA level (% of control)
417
400 350 300 250 200 150 100 50 0
eNOS
311 249 200
151 140 118
GAPDH EtOH-Co L.Chev. 10% TNGM
100
EtOH-Co L.Chev. 10%

Wallerath T et al. J Am Coll Cardiol 2003;41:471-8

250 ** p<0.05 *** p<0.001 200 *** ** ***
150
100
EtOHCo
1%
3% 10%
1%
3% 10%
1%
3% 10%
Dornfelder
Ch.Bonnet
L.Chevaliers
MACROSCOPIC PLANIMETRY OF AORTAS

Atherosclerotic Area/Total Area Ratio
Stained Area/Total Area (%)
80 60 40 20 0 Diet (n=10) Wine (n=11) NAPW (n=10)
Da Luz PL et al. Exp. Mol. Pathol. 1999;65:150-9 Exp. Pathol. 1999;65:150-
*
p = NS
*p<0.01: Diet vs Wine and NAPW
AORTA HISTOLOGIC EVALUATION

Intima/Media Thickness Ratio
Intima/Media Ratio (%)
80 60 40 20 0 Diet (n=9) Wine (n=8) NAPW (n=9)
Da Luz PL et al. Exp. Mol. Pathol. 1999;65:150-9 Exp. Pathol. 1999;65:150-
p = NS
*p<0.01: Diet vs Wine and NAPW Tukeys Studentized Range (HSD) Test

500
German red wines Bordeaux Rhone Burgundy French red wines *** *** *** ***
450 400 350 300 250 200 150 100 50 0
***
***
Kr Et Do Ch Ch L.C Sp Ch Ch Ch OH ieg tb .B .M .R rn .B .C he fel ou ell on ab are -C sh ur va eg de ier ss o ne eim gu lie ch rav r ea t es nd rs au er u e er de Ro se *** p<0.001 ng art Wallerath T et al. J Am Coll Cardiol 2003;41:471-8 en
Co

Ch. Bonnet L. Chevaliers
eNOS
-Tub.
EtOHCo
1%
3%
10%
EtOHCo
1%
3%
10%

450
* * p < 0.05 ** p < 0.01 ** *
**
NO production (% of control)
400 350 300 250 200 150 100 50 0
EtOHCo
1%
3%
10%
1%
3%
10%
Ch. Bonnet
L. Chevaliers

eNOS promoter activity (% of control)
400 350 300 250 200 150 100 50 0
** p < 0.01 *** p < 0.001
*** ***
***
**
EtOHCo
1%
3%
10%
1%
3%
10%
Ch. Bonnet
L. Chevaliers

eNOS promoter activity (% of each control)
0 50 100 150 200 250 300 350
pGI3basic
Luc -1600 +1 Luc -1111 +1 Luc -633 +1 Luc -326 +1
EtOH-Co L. Chevaliers 10%

120
*** **
100
** p < 0.01 *** p < 0.001
80
***
60
40
Ch. Bonnet 10% EtOH-Co
20
0 0 12 24 36
Time (h) after actinomycin D treatment

Flavonoid-rich Diets and Nitric Oxide in Rat Aorta

0
-20
Relaxation (%)
-40 -60
-80 -100
Control Dealcoholated red wine -9 -8 -7 -6 -5 -4 -3
Ach (-log M)
Benito S et al. British J Pharmcol 2002:135;910-6
Flavonoid-rich Diets and Nitric Oxide in Rat Aorta

1200
[NOS activity] (pmol citrulline (mg protein h)-1
150
* P<0.05 ** P<0.01
[-NO] (intensity units mg tissue)
200
** ** *
*
* P<0.01
* *
800
100
400
50
Diet
Control Dealcoholated red wine Quercetin Catechin
Diet
Benito S et al. British J Pharmcol 2002:135;910-6
Alcohol Consumption and Carotid Atherosclerosis: Evidence of DoseDependent Atherogenic Effects

Results From the Bruneck Study
Kiechl S et al. Stroke 1994;25:1593-1598
a
Current Alcohol Consumption
6.0 Odds ratio 3.0 2.0
age adjusted multivariate continuous alcohol variable
b
Type of Beverage
Odds ratio 3.0
Wine Other sources
2.0 1.0
1.0
0.5
0.5
1-50
51-99 51-
100100-
Alcohol consumption
g/day g/day
1-50
51-99 51-
100100-
Alcohol consumption
g/day g/day
Kiechl S et al. Stroke 1994;25:1593-1598 1994;25:1593-
a
Current Alcohol Consumption
6.0 Odds ratio 3.0 2.0
age adjusted multivariate continuous alcohol variable
b
Type of Beverage
Odds ratio 3.0
Wine Other sources
2.0 1.0
1.0
0.5
0.5
1-50
51-99 51-
100100-
Alcohol consumption
g/day g/day
1-50
51-99 51-
100100-
Alcohol consumption
g/day g/day
c
Current Alcohol Consumption Ex-Drinkers Excluded
Odds ratio 3.0
age adjusted multivariate
d
Gamma-Glutamyl Transferase
Odds ratio 3.0
age adjusted multivariate
2.0
2.0
1.0
1.0
0.5 0 1-50 51-99 51100100g/day g/day
0.5
-20
21-25 21-
26-30 26-
3131-
Alcohol consumption
Gamma-glutamyl transferase Gamma-
U/L
Flavonoid rich diet increases NO production in rat aorta

. Increases FMD . Increases eNOS production
Benito et al Brit J Pharmacol 135:910-6, 2002
Dieta Mediterrnea e Doena Isqumica do Corao Lyon Diet Heart Study 5 anos
Calorias* 2088; Lipidios* 34% (12% saturados e 6% polinsaturados); colesterol*- 312 mg; fibras*- 16 g; lcool - 6 g; protenas - 17 g Calorias* 1947; Lipidios* 30% ( 8% saturados e 5% polinsaturados); colesterol*- 203 mg; fibras* - 19 g; lcool - 6 g; protenas - 16 g
3
Eventos/ 100 pacientes-ano
2,7
2,5 2 1,5 1 0,5 0 Morte Cardaca IAM no Fatal 0,41 1,37 0,83
Controles n = 303 Experimental n = 302
0,36
0,54
Morte no Cardaca
Logeril et al. Circulation 1999; 99: 779
Lyon Diet Heart Study Perfil Lipdico - 5 anos

Controles n = 303
Nvel sangneo (mg/dl)
250 200 150 100 50 0
238,6
239,3
Experimental n = 302
175,5
174,4
49,5
49,9
67,6
74,9
Col Tot
HDL
LDL
TG
Logeril et al. Circulation 1999; 99: 779
Mortalily in Relation to Consumption of Alcohol: 13 Years Observations on Male British Doctors
De Lorgeril M et al. Lancet 1994;343:1454-1459
11,102 1.00 0.85 (0.74-0.98) 1.04 (0.77-1.41) 9,670 1.00 0.83 (0.72-0.97) 0.76 (0.54-1.09) 9,661 1.00 0.89 (0.77-1.03) 0.82 (0.58-1.16)
Proteo da Funo Cognitiva em Bebedores Moderados, idosos Mecanismos

Mukamal et al, The Cardiovascular Health
Study, Stroke 2001;32:1939-46
de anormalidade da substncia branca e infartos cerebrais em bebedores moderados vs abstmios Mukamal et al, JAMA 2003;289:1405-13 pronunciada reduo de demncia vascular e Alzheimer entre pessoas que consumiam 1 a 6 drinks/semana
Effects of Red Wine upon SNS and Endothelial Function in Humans

7 normal controls 9 hypertensives 10 hypercholesterolemics Methods : Brachial artery reactivity by US. Sympathetic activity in the peroneal nerve
Magalhes A,Consolim-Colombo F,Krieger EM, Da Luz PL- Thesis, 2006
Basal
Ice test
A HYPERTENSIVE man, 40 y.
PRE RW
Muscular contraction
29 burst/min
POST RW
46 burst/min
26 burst/min
43 burst/min
60 burst/min
37 burst/min
B HYPERCHOLESTEROLEMIC man, 46 y.
PRE RW
27 burst/min
36 burst/min
27 burst/min
POST RW
49 burst/min
63 burst/min
34 burst/min
RED WINE & VASCULAR REACTIVITY IN HUMANS

Brachial Artery FMD
20.0 18.0 16.0 14.0 12.0 10.0 8.0 6.0 4.0 2.0 0.0
Flow Independent Dilation

P=NS
* P<0.05
*
% Dilation
35.0 30.0 25.0 20.0 15.0 10.0 5.0
% Dilation
Pre RW
Post RW
0.0
Pre RW
Post RW
BP was not altered

Magalhes A,Consolim-Colombo F, Krieger EM, Da Luz PL- Thesis, 2006
Dyslipidemia (10) Arterial Hypertension (9) Controls (7)
WCC 2006 6 Sep 2006
Green Tea Catechin Improves Endothelial Dysfunction by Increases Circulation Endothelial Progenitor Cells in Chronic Smokers
W Kim, MD, MH Jeong, MD, YK Ahn, MD, SH Cho, BS, JH Yun, BS, T Kondo, MD, T Murohara, MD Heart Center, Chonnam National University Hospital Cardiovascular Department, Gwangju Veterans Hospital, Gwangju, Republic of Korea
Tea Green Tea Consumption improves FMD
Green tea is a free radical scavenger and has abundant catechin which exerts powerful antioxidant action. Short- and long-term black tea consumption reverses endothelial dysfunction in patients with coronary artery disease. Duffy, S. J. et al. Circulation 2001;104:151-156 Green tea reverses endothelial dysfunction in healty smokers. Nagaya, et al. Heart
2004;90:1485-6 Green
tea consumption was associated with low incidence of coronary artery disease in Japanese patients. Sano et al. Circ J. 2004;68:665-70
FMD Change Before and After Tx

P<0.0001 9.342.4(%) 9.34
14 13 12 11 10 9 8 7 6 5 4 3 2 1 0
7.25 7.252.8(%)
FMD
Before T x
After Tx
The Effect of EPCs Count of Green Tea

a
Dil AcylLDL/FITC lectin double positive attaching cells(mean/10 field)
b
P<0.001
200 150 100 50 0
Before
After
C
Before
D
After
After two weeks consumption, EPCs number (Dil AcLDL/FITC-lectin double positive attaching cells) was significantly increased from 118.235.7 baseline to 169.153.3
Quantification of EPCs by FACS

a a
Before CD45lowCD34+VEGFR2+ cells(/200ul)
After
b b
200 150 100 50 0
c
P<0.001
Before
After
Dil-AcLDL/FITC-lectin double positive cells derived from CD45lowCD34+VEGFR2+ cells

Arritmias cardacas Disfuno ventricular - ICC - Miocardiopatias Diabetes Doenas hepticas Alcoolismo
Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan

19 ger 37,8 ger 39,9 ger
21 ger 35,7 ger 29,4 ger 29,3 ger
Howitz et al. Nature 2003; 425: 191-6
Reduo Mortalidade Estudos HALE, SENECA e FINE

Dieta Alcool Atividade Fisica Abs. Fumo
DAC
DCV
Cancer
Outras causas
Hazard ratio (%)
0 -10 -20 -30 -40 -50 -60

Knoops et al. JAMA 2004; 292: 1433-9
modulo gnica Aumento do tempo de vida outras intervenes (caloric restriction)
Bartke A et al. Nature, 2001
Satyanarayana e Rudolph - J Clin Invest, 2004
gramas 420 440 460 480 500 520 540

ve c in i cia l
ve c fin al 1 m g/ kg in ici al
1 m g/ kg fin g 15 al g/ k in m
Progresso do peso aps 35 dias
15 m
ici g/ k
al g
f in
al
Hidroperxidos lipdicos no plasma

80 pmol/mg prot 60 40 20 0
veculo veic
*
1 mg/kg 1 mg/kg grupos
15 mg/kg mg/kg
*p<0,05 15 mg/kg vs. veculo
Grape Juice and Coronary Artery Disease
140 120
Mean Lag Time (min)
100 80 60 40 20 0
Baseline
Grape Juice
Stein JH et al. Circulation 1999:100;1050-5
GSH/GSSG
30 25 20 15 10 5 0 veculo 1 mg/kg grupos
*p=0,02 - 15 mg/kg vs. Veculo *p=0,03 - 15 mg/kg vs. 1 mg/kg
15 mg/kg
Red Wine Intake Prevents NF-B Activation

350 300 250
* *
% vs Basal
200
150 100 50
* * *
No Wine Low Dose Full Dose Vodka
0
ho ur s ho ur s ho ur s ho ur s 9
Blanco-Colio LM et al. Circulation 2000;102:1020-1026
RED WINE & VASCULAR REACTIVITY IN HUMANS

Brachial Artery FMD
20.0 18.0 16.0 14.0 12.0 10.0 8.0 6.0 4.0 2.0 0.0
Flow Independent Dilation

P=NS
* P<0.05
*
% Dilation
35.0 30.0 25.0 20.0 15.0 10.0 5.0
% Dilation
Pre RW
Post RW
0.0
Pre RW
Post RW
BP was not altered

Magalhes A,Consolim-Colombo F, Krieger EM, Da Luz PL- Thesis, 2006
Dyslipidemia (10) Arterial Hypertension (9) Controls (7)

6 7
8 Paltz
11,102 1.00 0.85 (0.74-0.98) 1.04 (0.77-1.41) 9,670 1.00 0.83 (0.72-0.97) 0.76 (0.54-1.09) 9,661 1.00 0.89 (0.77-1.03) 0.82 (0.58-1.16)

TICS score < 31
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0


Study, Stroke 2001;32:1939-46
Proteo da Funo Cognitiva em Bebedores Moderados, Idosos Mecanismos

eventos cardiovasculares ( HDL; fibrinognio e outros fatores trombticos) preservao da vasculatura cerebral AVCs subclnicos
(Mukamal et al. The Cardiovascular Health Study, Stroke 2001;32:1939-46. Mukamal et al, JAMA 2003;289:1405-13)
Red Wine Intake Prevents NF-B Activation in Peripheral Blood Mononuclear Cells of Healthy Volunteers During Postprandial Lipemia
16 voluntrios normais Caf da manh enriquecido com gordura: 602 kcal/m, com 342 kcal/m (56,8% como gordura) 140 kcal/m de vinho (dose moderada) 84 kcal/m de vinho (dose baixa)

200 10% 3% Ch. Bonnet Ch.
*** *** *** **
180
1%
160
*** ** * * *
* *
140
120
* P<0.05 ** p<0.01 *** p<0.001
100 0 12 24 36 48 60 10 d
Incubation time (h)

Wine With Meal Reduced Postprandial Glucose

0.8 0.6 0.4 0.2 0 -0.2 -60 0 60 120 180 240 300 360
glucose (mmol/L)
wine
Drinks per Day

Alcohol and CRP Levels

3.00 2.50
CRP, mg/L
2.00 1.50 1.00

All Subjects
0.5 0.0
Primary Prevention Secondary Prevention
No alcohol/ < 1/mo
1.3/mo
1-4/wk
5-7/wk
>2/d
Numbers of Drinks
VINHO TINTO E RESVERATROL CLULAS PROGENITORAS ENDOTELIAIS
Balestrieri et al. J Biochem. 2008;143:179-186
Xenohormesis: Sensing the Chemical Cues of Other Species

Howitz KT and Sinclair DA. Cell 2008;133:387-91
Direct Modulation of Key Mammalian Enzymes by Plant Metabolites
Howitz KT and Sinclair DA. Cell 2008;133:387-91
Alcohol Consumption, CRP and Fibrinogen

* P = 0.02
* P 0.001
Sierksma A et al. European J Clin Nutr 2002;56:1130-6
63Congresso Brasileiro de Cardiologia Curitiba, 9.9.2008
Controvrsia- Agonista USO MODERADO DE VINHO TINTO BENFICO NA PREVENO DA ATEROSCLEROSE Dr. Protsio L. da Luz
Diretor, Diviso de Cardiologia Clnica INCOR- HC,FMUSP
* No
h conflitos de interesse ( no sou abstmio, nem alcolatra !)

Arritmias cardacas Disfuno ventricular - ICC; Miocardiopatias Diabetes descompensada Doenas hepticas Alcoolismo Adolescentes Hipertrigliceridemia
Alcohol and Stroke Risk

OR LOG 7.4 4.5 2.7 1.6 1.0 0.6 0.4 2.0 1.5 1.0 0.5 0.0 - 0.5 -1.0
Drinks per Day

Alcohol and Coronary Calcium

Odds ratio For Severe Coronary Calcification
1.4 1.2 1.0 0.8 0.6 0.4 0.2 0
Non-drinkers
1 Drink/d
2 Drinks/d
> 2 Drinks/d
Mecanismos de Ao do Vinho Tinto

HDL agregao plaquetria expresso de NF-B e sntese de ET1 vasodilatao art. endotlio dependente (eNOS) anti-oxidante (?!) anti-inflamatrio cels. progenitoras endoteliais sensibilidade insulina
Obs.: flavonides (quercetina, apigenina, resveratrol e outros) parecem ser os elementos qumicos fundamentais

6 7
8 Paltz
11,102 1.00 0.85 (0.74-0.98) 1.04 (0.77-1.41) 9,670 1.00 0.83 (0.72-0.97) 0.76 (0.54-1.09) 9,661 1.00 0.89 (0.77-1.03) 0.82 (0.58-1.16)

TICS score < 31
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0


Study, Stroke 2001;32:1939-46
Proteo da Funo Cognitiva em Bebedores Moderados, Idosos Mecanismos

eventos cardiovasculares ( HDL; fibrinognio e outros fatores trombticos) preservao da vasculatura cerebral AVCs subclnicos
(Mukamal et al. The Cardiovascular Health Study, Stroke 2001;32:1939-46. Mukamal et al, JAMA 2003;289:1405-13)
Mecanismos de Ao do Vinho Tinto

HDL agregao plaquetria expresso de NF-B e sntese de ET1 vasodilatao art. endotlio dependente (eNOS) anti-oxidante (?!) anti-inflamatrio cels. progenitoras endoteliais sensibilidade insulina
Obs.: flavonides (quercetina, apigenina, resveratrol e outros) parecem ser os elementos qumicos fundamentais
Cardioprotective Alcohol Intake is:
1-2 drinks / day - men 1 drink / day - women 1 drink = 15g alcohol
Como Eles Conseguem Viver Tanto

SARDOS Bebem vinho tinto (com moderao) Compartilham com o cnjuge o trabalho Comem queijo pecorino (e outros alimentos ricos em mega-3)
ADVENTISTAS Comem nozes e feijes Guardam o sbado Tm f
TODOS No fumam Priorizam a famlia Fazem atividades fsicas Tm vida social Comem frutas, verduras e gros integrais
OKINAWANOS Mantm amigos para toda a vida Comem pores pequenas Encontram sentido na vida
A Tale of Two Monkeys

Rhesus Monkeys at Wisconsin Primate Research Center, both 24, show effects of two regimens. ULTRA-LEAN DIET This handsome fellow has lower glucose and insulin levels-and looks younger, too. NORMAL FARE This monkey has higher triglycerides and more oxidative damage to his cells.
Restrio calrica
PNC1 Sir/SIRT
Resveratrol
sobrevida
Resveratrol e sobrevida em diferentes espcies

70% - Wood JG et al. Nature, 2003 18% -Viswanathan M et al. Dev Cell, 2005 16 - 20% - Wood LG et al. Nature, 2004 59% - Valenzano DR et al. Curr. Biol, 2006
Baur JA et al Nature, 2006
HITLER ERA ABSTMIO !
Red Wine Intake Prevents NF-B Activation in Peripheral Blood Mononuclear Cells of Healthy Volunteers During Postprandial Lipemia
16 voluntrios normais Caf da manh enriquecido com gordura: 602 kcal/m, com 342 kcal/m (56,8% como gordura) 140 kcal/m de vinho (dose moderada) 84 kcal/m de vinho (dose baixa)

200 10% 3% Ch. Bonnet Ch.
*** *** *** **
180
1%
160
*** ** * * *
* *
140
120
* P<0.05 ** p<0.01 *** p<0.001
100 0 12 24 36 48 60 10 d
Incubation time (h)

Wine With Meal Reduced Postprandial Glucose

0.8 0.6 0.4 0.2 0 -0.2 -60 0 60 120 180 240 300 360
glucose (mmol/L)
wine
Drinks per Day

Alcohol and CRP Levels

3.00 2.50
CRP, mg/L
2.00 1.50 1.00

All Subjects
0.5 0.0
Primary Prevention Secondary Prevention
No alcohol/ < 1/mo
1.3/mo
1-4/wk
5-7/wk
>2/d
Numbers of Drinks
Red Wine Increases the Expression of Human Endothelial Nitric Oxide Synthase
A Mechanism That May Contribute to its Beneficial Cardiovascular Effects

Flavonóides Da Dieta Vs Mortalidade Por DAC (N 805 H) Zutphen Elderly Study-Seguim.: 5 Anos

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Flavonides da Dieta vs Mortalidade por DAC (n=805 h) Zutphen Elderly Study-seguim.

0,7 0,6 0,5 0,4 0,3 0,2 0,1 0

Ingesto de Flavonides (mg/dia) RR ajustado para idade, dieta e FR

Zutphen Elderly Study

Flavonides:resveratrol, quercetina, Kempferol, apigenina, luteolina e mirecitina Fontes: Ch Cebola Ma

61% 13% 10%

Wine Consumption and CHD

CHD = -4.99W + 652.4 r = -0.580

U.K. Canada 600 Norway Denmark Sweden

Australia New Zealand

Austria Italy France

Alcohol and Stroke Risk

Drinks per Day

VINHO TINTO, UVA E ATEROSCLEROSE: PERSPECTIVAS

CHD Mortality (1987) (men + women)

0 0 200 400 600

r = 0.73 p < 0.001

Dairy fat (Calories) (1980-85)

CHD Mortality (1987) (men + women)

Finland Ireland Denmark Sweden

Switzerland Italy 100 Portugal Spain Yugoslavia FRANCE

r = 0.87 p < 0.0001

145 + 0.138 dairy fat -0.917 wine

Meta-Analysis of Wine Intake and Vascular Risk

Case-Control studies Overall

Di Castelnuovo A et al. Circulation 2002;105:2836-2844

Alcohol and All-Cause Mortality

Drinks per Day Alcohol Consumption

OKeefe JH et al. JACC 2007;50:1009-14

The Effect of Red Wine on Experimental Atherosclerosis: Lipid-Independent Protection

Protsio L. da Luz, Carlos V. Serrano Jr., Ana P. Chacra et al.

% Dilatao da artria braquial

0 Basal Vinho Tinto Basal Vinho Tinto

Coimbra S, Da Luz PL. BJMBR

0 Basal Suco de Uva Basal Suco de Uva

Coimbra S, Da Luz PL. BJMBR

Grape Juice and Coronary Artery Disease

Stein JH et al. Circulation 1999:100;1050-5

Mediterranean Diet and Coronary Heart Disease

Percent without event

Lorgeril M et al. Circulation 1999;99:779-785

Hazard Ratio ajustado

1,0 0,8 0,6

Trichopolou et al. N Eng J Med 2003; 348: 2599-608

Contribuio dos Alimentos na Reduo de Morte Estudo EPIC

Trichopoulou et al. BMJ 2009;338:b2337

Alcohol and Age-related Macular Degeneration

Percent with AMD (%)

8 7 6 5 4 3 2 1 0 No alcohol Beer Wine Liquor

AES NO CARDIACAS DO VINHO

TO e col. J Am Geriatr Soc 1998;16:1-7

JM e col. Rev Neurol 1997;153:185-92

Truelsen T e col. Neurology 2002;12:1300-11 Wei M e col. Diabetes Care 2000;23:18-22

De Vegt F e col. Diabetes Research and Clinical Practice 2002;57:53-60

Reduo de Mortalidade Total Estudos HALE, SENECA e FINE

Hazard ratio (%)

-10 -20 -30 -40 -50 -60 -70

* * p < 0.05 p < 0.01 *

p < 0.01 * p < 0.001

p < 0.01 * p < 0.001