frequency of lipid abnormalities in male chd patients rubins hb et al. am j cardiol...
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Frequency of lipid abnormalities in male CHD patients
Rubins HB et al. Am J Cardiol 1995;75:1196-1201
Occu
rren
ce o
f ab
norm
aliti
es (
%)
62
87
33
64
0
20
40
60
80
100
Elevatedtotal-C
ElevatedLDL-C
Elevatedtriglycerides
LowHDL-C
Comparative efficacy in raising low HDL-C
HD
L-C
(m
g/d
L)
Simva 20 vs Feno 200MType IIb Steinmetz1
Prava 20/40 vs Feno 200MDucobu2
Atorva 10 vs Feno 300SHeinonen3
45
40
35
30
25
Baseline Statin Fenofibrate
1Steinmetz, J Cardiovasc Pharmacol 1996;27:563–70 2Ducobu, Drugs 1997;54:615–333Heinonen, Abstract 66th Congress of the European Atherosclerosis Society, Florence 1996
A-IA-I
A-IIA-II
LPLLPL
C-IIIC-III
Fibrates
PPAR
Fibrates: Regulation of lipoproteinFibrates: Regulation of lipoproteinmetabolism by PPARmetabolism by PPAR
HDL particlesHDL particles TG rich particlesTG rich particles
PPRE
PPAR
RXR
PPRE
PPAR
RXR
PPRE
PPAR
RXR
PPRE
PPAR
RXR
Staels B et al. Circulation 1998;98:2088–93.
ABCA-1 gene
expression
Apo A-I
PPAR activator
Activated PPAR
Intracellularcholesterol
Human macrophages were cholesterol loaded
with AcLDL in the presence of PPAR
activator and incubated for 24 hourswith apo A-I
0
1
2
3
4
Relative decrease in cellular cholesterol after Apo A-I efflux
TC CE FC
Cholesterolefflux
PPAR activators induce cholesterol efflux from human macrophages
VA-HIT Study: Diabète type 2& traitement par fibrate (1)
(1) Bloomfield Rubins H et al.Arch Intern Med 2002; 162: 2597-2604
Facteurs de risque cardio-vasculaire• Sexe• Antécédents familiaux• Antécédents personnels • Lipides et lipoprotéines• Hypertension artérielle• Diabète• Insuffisance rénale chronique• Inflammations chroniques• Tabagisme• Mauvaises habitudes alimentaires• Sédentarité et activité physique insuffisante
Lipides plasmatiquesPression artérielle
Tendance aux thrombosesRésistance à insuline
OxydationHomocystéineInflammation
Fonction endothélialeIrritabilité ventriculaire
NUTRITION MCV
Nutrition et Pathologies Cardio-vasculaires
Effects of a dietary portfolio of cholesterol-lowering foods vs lovastatin on serum lipids and C-Reactive Protein
46 sujets adultes, sains mais hyperlipidémie25 H; 21 F; 59 1 ans; BMI 27.6 0.5
Intervention : distribution aléatoire A : apports pauvres en graisses sat & riches en céréales ent.B : mêmes apports + Lovastatin 20 mgC : apports riches en phytostérols (1.0 g / 1000 kcal)
protéines de soja (21.4 g / 1000 kcal) fibres visqueuses (9.8 g / 1000 kcal) amandes (14 g / 1000 kcal)
D.J.A. Jenkins et al, JAMA, 2003
Effects of a dietary portfolio of cholesterol-lowering foods vs lovastatin on serum lipids and C-Reactive Protein
D.J.A. Jenkins et al, JAMA, 2003
Adherence to a Mediterranean diet and survival in a Greek population
Etude prospective sur 22.043 adultes (20-86 ans)
Evaluation des apports alimentaires
Classification selon un «score méditerranéen»
Suivi sur 44 mois :
Adhésion au régime méditerranéen associée à
mortalité par maladies cardio-vasculaires et cancer
Trichopoulou A et al, N Engl J Med, 2003
Trichopoulou A et al, N Engl J Med, 2003
Mediterranean Diet, Traditional Risk Factors, and the Rate of Cardiovascular Complications After Myocardial Infarction
Final Report of the Lyon Diet Heart Study, de Lorgeril et al, 1999
Survie sans I.M. non mortel Survie sans complication
ALL: 1-week Food Records, Wt, BP & Metabolic ProfilesALL: 1-week Food Records, Wt, BP & Metabolic Profiles
All participants: Step 1 Prudent DietAll participants: Step 1 Prudent DietNational Cholesterol Education ProgramNational Cholesterol Education Program
+ Regular physical activity+ Regular physical activity
+ + Fruits: 250-300g per dayFruits: 250-300g per day+ Vegetables: 125-150g+ Vegetables: 125-150g+ Nuts: 25-50g walnuts/almonds+ Nuts: 25-50g walnuts/almonds+ + 400-500g/day of whole grains: 400-500g/day of whole grains:
legumes, rice, maize, wheatlegumes, rice, maize, wheat+ 3-4 servings mustard / soy bean oil+ 3-4 servings mustard / soy bean oil
Control Group BControl Group B501501
Intervention AIntervention A499499
Follow up: weekly, monthly, 3-monthly to 2 yearsFollow up: weekly, monthly, 3-monthly to 2 yearsEnd Points:End Points:1 Myocardial Infarction - fatal /nonfatal1 Myocardial Infarction - fatal /nonfatal2 Sudden Cardiac Death, 2 Sudden Cardiac Death, 3 Composite total of cardiac events3 Composite total of cardiac events
The Indo-Mediterranean diet heart study, R. Singh et al, Lancet, 2002
Change in Risk factors during study:Change in Risk factors during study:Both groups improved significantlyBoth groups improved significantly, but , but more so in Gp A, p<0.001 for all parametersmore so in Gp A, p<0.001 for all parameters
-35-30
-25-20-15
-10-505
We
igh
t
Sy
stB
P
LD
L
HD
L
TG
FB
S
Gp A
Gp B
RelevantRelevant““UnitsUnits””
-35-30
-25-20-15
-10-505
We
igh
t
Sy
stB
P
LD
L
HD
L
TG
FB
S
Gp A
Gp B
RelevantRelevant““UnitsUnits””
The Indo-Mediterranean diet heart study, R. Singh et al, Lancet, 2002
Numbers & rate ratios for cardiac endpoints, Numbers & rate ratios for cardiac endpoints, adjusted for age, gender, BMI, cholesterol and BPadjusted for age, gender, BMI, cholesterol and BP
Group AGroup A BB RateRate499499 501 501 Ratios Ratios
Non Fatal MI 21Non Fatal MI 21 4343 0.47 [0.280.47 [0.28--0.79]0.79]
Fatal MIFatal MI 1212 1717 0.67 [0.310.67 [0.31--1.42]1.42]
Sudden cardiac 6 Sudden cardiac 6 1616 0.33 [0.130.33 [0.13--0.86]0.86]deathdeath
Total CardiacTotal CardiacEndpointsEndpoints 3939 76 76 0.48 [0.330.48 [0.33--0.71]0.71]
The Indo-Mediterranean diet heart study, R. Singh et al, Lancet, 2002
Conclusions
The Indo-Mediterranean diet heart study, R. Singh et al, Lancet, 2002
• The Indo Mediterranean diet is a safe and The Indo Mediterranean diet is a safe and
economical means for improving the health economical means for improving the health
of poorer populationsof poorer populations
• The whole grains, fruits, vegetables and oils The whole grains, fruits, vegetables and oils
used in this study were traditional fare, used in this study were traditional fare,
grown by farmers at the present market cost grown by farmers at the present market cost
of aboutof about 1 US$1 US$ per day per day
Lancet Lancet
20022002
GISSI-Prevenzione Investigators. Lancet 1999;354:447-455; Marchioli R et al. Eur Heart J Suppl 2001;3(Suppl D):D85-D97.
GISSI-Prevenzione Trial: Design
11,323 patients randomized
4 lost to follow-up687 discontinued
vitamin E11 received omega-3 PUFAs
3 lost to follow-up768 discontinued omega-3 PUFAs
4 lost to follow-up848 discontinued omega-3 PUFAs808 discontinued
vitamin E
2 lost to follow-up15 received omega-3 PUFAs
2 received vitamin E
2835 given omega-3 PUFAs
2830 given vitamin E
2830 given omega-3 PUFAs & vitamin E
2828 controls
2835 analysed for outcomes
2830 analysed for outcomes
2830 analysed for outcomes
2828 analysed for outcomes
GISSI-Prevenzione Trial:Secondary Endpoint Results
Control Omega-3 Risk P-value PUFAs reduction
All-cause mortality 10.6% 8.4% 21% 0.0064
CV death 7.2% 5.1% 30% <0.001
Cardiac death 6.1% 4.0% 35% <0.001
Coronary death 5.2% 3.6% 32% <0.01
Sudden death 3.3% 1.8% 44% 0.0006
Non-fatal CV events 4.9% 4.9% 2% n.s.
Marchioli R et al. Eur Heart J Suppl 2001;3(Suppl D):D85-D97; Marchioli R et al. Circulation 2002;105:1897-1903.
GISSI-Prevenzione Trial: Early Effect of Omega-3 PUFAs on All-Cause Mortality
1.00
0.99
0.98
0.97
0.96
0.95
Pro
bab
ility
330210150600 90 180 270
Days
30 120 240 300 360
0.59 (95% CI 0.36-0.97)
P = 0.037
Omega-3 PUFAs
Control
Marchioli R et al. Circulation 2002;105:1897-1903.
Calculated adjusting for treatment interaction and major confounding variables
Modifications des recommandations • Réduire apports en graisses saturées (animales)• Remplacement par graisses mono-insaturées (olive, …)• Inclusion et augmentation des acides gras oméga-3
• Réduction des sucres simples• Remplacement par sucres lents (féculents, pâtes, pain
entier, …) • Retour aux céréales entières (fibres)
notion de mauvaises & bonnes graisses
mauvais et bons sucres
Modes de nutrition protecteurs
• Régime(s) méditerranéen(s)
• Adaptation possible à goûts/cultures différents graisses saturées sucres simples légumes et/ou fruits (y compris fruits secs)
• Apports caloriques raisonnables
• Apports protéiques raisonnables
• Vin en quantité modérée (sauf si contre-indications)
font partie d’un mode de vie (« lifestyle »)
Nutrition et Maladies c.v. : les messages
• Lésions d’athéroslérose souvent réversibles• Réduction du risque par mode de vie (-50% à –80%)• Suppléments alimentaires : NON, sauf si indications:
stérols végétaux
acides gras oméga-3
acide folique
(sélénium)
Modifications du mode de vie
• Arrêt cigarette
• Alimentation « santé »
sélection aliments / nutriments plaisants & sains activité physique (régulière) risque cardio-vasculaire ( - 80%)
• Effet additif à celui des médicaments ( lipides, tension artérielle)
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