Embed Size (px)
Citation preview
Haemostatic cardiovascular risk factors: Haemostatic cardiovascular risk factors: complementary effects of red wine and complementary effects of red wine and mediterranean diet in young population.mediterranean diet in young population.
Diego Mezzano, M.D. Diego Mezzano, M.D. Department of Hematology-Oncology Department of Hematology-Oncology School of Medicine School of Medicine
P. Catholic P. Catholic University of ChileUniversity of Chile
Talca, Agosto 22, 2006
ObjectivesObjectives
1.1. To compare the effect of an alcohol-free To compare the effect of an alcohol-free Mediterranean-type diet and a High-fat diet on Mediterranean-type diet and a High-fat diet on haemostatic variables.haemostatic variables.
2.2. To test whether red wine supplementation To test whether red wine supplementation modifies these variables, independently of diet.modifies these variables, independently of diet.
Composition of DietsComposition of DietsMDMD HFDHFD
Total calories (kcal/day)Total calories (kcal/day) 25652565 25652565
Calories in protein (%)Calories in protein (%) 17.617.6 17.617.6
Calories in fat (%)Calories in fat (%) 27.327.3 39.939.9
Saturated fats (g/day)Saturated fats (g/day) 22.722.7 35.835.8
MUFA (g/day)MUFA (g/day) 37.937.9 35.535.5
PUFA (g/day)PUFA (g/day) 9.69.6 32.032.0
-3 FA (g/day)-3 FA (g/day) 1.641.64 0.960.96
Olive oil (mL/day)Olive oil (mL/day) 3232 00
Fruits, vegetables (g/day)Fruits, vegetables (g/day) 675675 246246
MD
MD + RED WINE MD
HFD HFD + RED WINE
HFD
0 30 60 90
GROUP MD
GROUP HFD
N = 21
N = 21
Diet Intervention Design
Comparison between MD and HFD Comparison between MD and HFD groups at T0groups at T0
Variable:Variable: MDMD HFDHFD p =p =
Age (years)Age (years) 21.2 21.2 1.7 1.7 22.6 22.6 4.5 4.5 0.210.21
Body mass index (kg/mBody mass index (kg/m22)) 23.4 23.4 2.0 2.0 23.7 23.7 2.5 2.5 0.570.57
Serum albumin (g/L)Serum albumin (g/L) 5.1 5.1 0.24 0.24 5.1 5.1 0.17 0.17 0.820.82
Blood hemoglobin (g/L)Blood hemoglobin (g/L) 151 151 7.5 7.5 152 152 8.7 8.7 0.600.60
Plasma cholesterol (mmol/L)Plasma cholesterol (mmol/L) 4.42 4.42 0.720.72
4.57 4.57 0.670.67
0.440.44
Triacylglycerides (mmol/L)Triacylglycerides (mmol/L) 1.13 1.13 0.570.57
1.05 1.05 0.560.56
0.590.59
Comparison between MD and HFD Comparison between MD and HFD groups at T0groups at T0
Variable:Variable: MDMD HFDHFD p =p =
Plasma Plasma -carotene (-carotene (mol/L)mol/L) 0.26 0.26 0.150.15
0.37 0.37 0.250.25
0.080.08
Plasma ascorbate (Plasma ascorbate (mol/L)mol/L) 54.7 54.7 15.015.0
53.5 53.5 10.910.9
0.780.78
Serum folate (nmol/L)Serum folate (nmol/L) 13.8 13.8 3.1 3.1 11.7 11.7 2.8 2.8 0.190.19
Eicosapentaenoic acid (%)Eicosapentaenoic acid (%) 1.20 1.20 0.560.56
0.93 0.93 0.440.44
0.190.19
Comparison between MD and HFD Comparison between MD and HFD groups after 30 daysgroups after 30 days
Variable:Variable: MDMD HFDHFD p =p =
Plasma Plasma -carotene (-carotene (mol/L)mol/L) 0.49 0.49 0.190.19
0.23 0.23 0.140.14
0.00010.0001
Plasma ascorbate (Plasma ascorbate (mol/L)mol/L) 55.9 55.9 11.211.2
29.7 29.7 8.9 8.9 0.00010.0001
Serum folate (nmol/L)Serum folate (nmol/L) 14.2 14.2 4.3 4.3 10.5 10.5 2.6 2.6 0.0020.002
Eicosapentaenoic acid (%)Eicosapentaenoic acid (%) 1.50 1.50 0.7 0.7 0.85 0.85 0.300.30
0.0010.001
Time [Days]
0 30 60 90
To
tal
ch
ole
ste
rol
(mg
/dL
)
0
50
100
150
200
HFDMD
Differential effects of diet and red Differential effects of diet and red wine on haemostatic CVRFwine on haemostatic CVRF
• Several haemostasis proteins which participate Several haemostasis proteins which participate in the generation, inhibition or removal of in the generation, inhibition or removal of fibrin, are either established or potential fibrin, are either established or potential CVRF.CVRF.
• Among them, plasma levels of fibrinogen, Among them, plasma levels of fibrinogen, factors VIIc and VIIIc, tPA and PAI-1.factors VIIc and VIIIc, tPA and PAI-1.
Days
0 30 60 90
Fib
rino
gen
(mg/
dL)
0
200
210
220
230
240
250
260
270
280
HFDMD
Days
0 30 60 90
Fac
tor
VIIc
(%
)
0
65
70
75
80
85
90
Days
0 30 60 90
Fac
tor
VIII
(%
)
0
50
55
60
65
70
75
80
85
90
Days
0 30 60 90
AT
III (
%)
0
120
125
130
135
140
145
150
155
P=0.03
P=0.001
P=0.034
P=0.05
P=0.006 P=0.01
Days0 30 60 90
Pro
tein
S (
%)
0
70
75
80
85
90
HFDMD
p = 0.013
Days0 30 60 90
tPA
-Ag
(n
g/d
L)
0
2
3
4
5
6
7
HFDMD
p = 0.01
Days
0 30 60 90
PA
I-A
g (
ng
/dL
)
0
20
25
30
35
40
45
HFDMD
p = 0.0003
Differential effects of diet and red wine Differential effects of diet and red wine on primary hemostasis variableson primary hemostasis variables
• Primary hemostasis: processes that mediate Primary hemostasis: processes that mediate interaction of interaction of plateletsplatelets with the with the vessel wallvessel wall..
• Platelet function is an essential phenomenon in the Platelet function is an essential phenomenon in the pathogenesis of arterial cardiovascular events, and pathogenesis of arterial cardiovascular events, and pharmacological agents that decrease platelet-vessel pharmacological agents that decrease platelet-vessel wall interaction are pivotal in preventing and/or wall interaction are pivotal in preventing and/or treating these accidents.treating these accidents.
• Some important variables of primary hemostasis Some important variables of primary hemostasis include bleeding time, plasma vWF levels and include bleeding time, plasma vWF levels and platelet aggregation and secretion.platelet aggregation and secretion.
Time [days]
0 30 60 90
Ble
ed
ing
tim
e [m
in]
0
2
4
6
8
10
MDHFD
p = 0.017
Time [days]
0 30 60 90
Pla
sma
von
Will
ebra
nd fa
ctor
[%]
0
60
70
80
90
100
110
120
130
HFDMD
Days
0 30 60 90
Pla
tele
t agg
rega
tion/
secr
etio
n (%
)4
M A
DP
0
10
20
30
40
50
60
Aggreg HFDAggreg MDSecret HFDSecret MD
ADP 4M
p = 0.07
Days
0 30 60 90 Pla
tele
t a
gg
reg
atio
n/s
ecr
etio
n (
%)
8
M A
DP
0
10
20
30
40
50
60
70
80
Aggreg HFDAggreg MDSecret HFDSecret MD
ADP 8M
Days
0 30 60 90 Pla
tele
t agg
rega
tion/
secr
etio
n (%
)1
g/m
L co
llage
n
10
20
30
40
50
60
70
80Aggreg HFDAggreg MDSecret HFDSecret MD
p = 0.003
Collagen, 1g/mL
Days
0 30 60 90 Pla
tele
t agg
rega
tion/
secr
etio
n (%
)2
g/m
L co
llage
n
20
30
40
50
60
70
80
Aggreg HFDAggreg MDSecret HFDSecret MD
p = 0.005
p = 0.013
Collagen, 2g/mL
Conclusions. 1.Conclusions. 1.
1.1. Intake of a MD, compared with a HFD, was associated Intake of a MD, compared with a HFD, was associated with an overall improvement in haemostatic CV risk with an overall improvement in haemostatic CV risk factors: lower plasma fibrinogen and factors VIIc and factors: lower plasma fibrinogen and factors VIIc and VIIIc, and higher levels of protein S. Red wine VIIIc, and higher levels of protein S. Red wine supplementation in both diets resulted in further decrease supplementation in both diets resulted in further decrease in plasma fibrinogen and factor VIIc, but in increases in in plasma fibrinogen and factor VIIc, but in increases in PAI-1 and t-PAAg.PAI-1 and t-PAAg.
2.2. The longer BT in individuals on MD, independently of red The longer BT in individuals on MD, independently of red wine, denotes less interaction of platelets with the wine, denotes less interaction of platelets with the vascular wall, which could be beneficial from the point of vascular wall, which could be beneficial from the point of view of cardiovascular (CV) risk.view of cardiovascular (CV) risk.
Conclusions. 2.Conclusions. 2.
3.3. Moderate consumption of red wine results in a Moderate consumption of red wine results in a significant increase in significant increase in ex vivo ex vivo platelet aggregation platelet aggregation and secretion after stimulation with collagen, and secretion after stimulation with collagen, whereas no significant changes were observed whereas no significant changes were observed when platelets were challenged with other when platelets were challenged with other agonists.agonists.
4.4. Our observations denote that some of the Our observations denote that some of the beneficial effects of moderate red wine beneficial effects of moderate red wine consumption would be mediated by its favourable consumption would be mediated by its favourable influence on hemostatic CV risk factors and not on influence on hemostatic CV risk factors and not on inhibition of platelet responses. inhibition of platelet responses.
Complementary effects of Mediterranean diet and moderate Complementary effects of Mediterranean diet and moderate red wine intake on haemostatic cardiovascular risk factors.red wine intake on haemostatic cardiovascular risk factors. Mezzano D, Leighton F, Martínez C, Marshall G, Cuevas A, Castillo O, D, Leighton F, Martínez C, Marshall G, Cuevas A, Castillo O, Panes O, Muñoz B, Pérez DD, Mizón C, Rozowski J, San Martín A, Panes O, Muñoz B, Pérez DD, Mizón C, Rozowski J, San Martín A, Pereira J. Pereira J. Eur J Clin Nutr 2001; 55: 444-451.Eur J Clin Nutr 2001; 55: 444-451.
Mediterranean diet, but not red wine, is associated with beneficial changes on primary haemostasis.
Mezzano D, Leighton F, Strobel P, Martínez C, Marshall G, Cuevas A, Castillo O, Panes O, Muñoz B, Rozowski J, Pereira J.
Eur J Clin Nutr 2003; 57: 439-446.
Days
0 30 60 90
Fib
rin
og
en
(m
g/d
L)
0
200
210
220
230
240
250
260
270
280
HFDMD
p = 0.03
p = 0.001
Days
0 30 60 90
Fa
cto
r V
IIc
(%
)
0
65
70
75
80
85
90
HFDMD
p = 0.034
p = 0.05
Days
0 30 60 90
Fa
cto
r V
IIIc
(%
)
0
50
55
60
65
70
75
80
85
90
HFDMD
p = 0.006
Days
0 30 60 90
AT
III (
%)
0
120
125
130
135
140
145
150
155
HFDMD
p = 0.01
Days
0 30 60 90
Pro
tein
C (
%)
0
80
85
90
95
100
105
110
115HFDMD
Days
0 30 60 90
Pla
tele
t agg
rega
tion/
secr
etio
n (%
)8
M e
pine
phrin
0
10
20
30
40
50
60Aggreg HFDAggreg MDSecret HFDSecret MD
p = 0.02
Epinephrin 8M
