DR. RAMON ESTRUCH HOSPITAL CLINIC UNIVERSIDAD DE BARCELONA

Transcripción

1 ESTUDIO PREDIMED Dieta Mediterránea y prevención del síndrome metabólico y de las enfermedades crónicas DR. RAMON ESTRUCH HOSPITAL CLINIC UNIVERSIDAD DE BARCELONA

2 La enfermedad cardiovascular es la principal causa de muerte al inicio del siglo XXI IAM AVC AOEEII Aneurisma Aorta

3 Factores de Riesgo de Aterosclerosis No modificables Edad Género Genética Modifiable Lípidos cldl, chdl, TG Hipertensión Diabetes Obesidad Homocisteíana Hábitos - Tabaquismo - Dietas aterogénicas - Alto consumo de alcohol - Sedentarismo

4 El riesgo de enfermedad coronaria depende de las concentraciones de cldl y chdl (Framingham) Relative Risk for Coronary H D 3 2,5 2 1,5 1 0,5 0 chdl 20 mg/dl chdl 45 mg/dl chdl 65 mg/dl chdl 80 mg/dl 100 mg/dl 160 mg/dl 220 mg/dl Cholesterol LDL Kannel WB. Am Heart J 1985;110:

5 MORTALIDAD GLOBAL 2000: PRINCIPALES FACTORES RELACIONADOS Mortalidad atribuida (En miles; total 55,861,000) Ezzati, et al. Lancet. 2002;360:

6 CASOS DE DIABETES EN EL 2000 y PREVISIONES PARA EL 2030 NEJM 2007;356:214

7 LA EPIDEMIA DEL SIGLO XXI: OBESIDAD

8 INCLUIDOS LOS NIÑOS

9 La obesidad aumenta el riesgo de enfermedad cardiovascular Relative Risk of Death 3,0 2,6 2,2 1,8 1,4 1,0 0,6 Men (N=84.376) Women (N= ) No history of smoking or cardiovascular disease <18, Body Mass Index (BMI) Calle EE y cols. NEJM 1999; 341:

10 El sobrepeso aumenta el riesgo de enfermedad cardiovascular Adaptado de Adams KF. NEJM 2006

11 Abdominal fat and myocardial infarction INTERHEART Study Importance of the central distribution of fat Yusuf S et al. Lancet, 2005

12 Obesidad Abdominal: Diana terapeútica en el control del riesgo CV

13 Sobrepeso y enfermedad cardiovascular Síndrome Metabólico Factor independiente Alto LDL-C FRCV subyacentes Bajo HDL-C Alto Triglic. Alta PA Enfermedad Cardiovascular Edad Tabaco Género Hist. Famil.+ Diabetes

14 Suma de factores atherogénicos: Efecto multiplicador sobre riesgo CV Hipertensión (SP 195 mmhg) x3 X4.5 x9 x16 Tabaco X1.6 x4 x6 Colesterol (300 mg/dl)

15 El tratamiento de los factores de riesgo cardiovascular puede retrasar la progresión de la aterosclerosis y la aparición de sus principales manifestaciones clínicas: los eventos cardiovasculares

16 LAS MEJORES ARMAS CONTRA LA ENFERMEDAD CARDIOVASCULAR: DIETA Y EJERCICIO

17 EJERCICIO

18 Cumulative Mortality According to Year of Follow-up and Distance Walked per Day Total mortality (%) Ranges of distance walked (miles/day) Year of follow-up Hakim, AA. et al. N Engl J Med 1998; 338: 94-99

19 Effects of the Mediterranean-Style Diet on the Primary Prevention of Cardiovascular Disease (PREDIMED)

20 Otros objetivos Determinar los cambios en el metabolismo de la glucosa, presión arterial, perfil lipídico, peso corporal, marcadores de inflamación y otros marcadores intermedios de riesgo vascular para entender mejor como los cambios dietéticos pueden modificar el riesgo de sufrir complicaciones cardiovasculares Identificar los sujetos con determinadas características fenotípicas y genotípicas que pueden beneficiarse más de la dieta mediterránea

21 Sample size and Randomization 7,447 participants Control Low Fat Diet Mediterranean Diet + Mediterranean Diet + n= 2,450 n= 2,543 n= 2,454

22 PREDIMED TRIAL: 3-mo. changes p<0.001 p<0.001 p=0.017 p=0.039 p<0.001 p<0.001 Ann Intern Med 2006;145:1-11

23 Eligible subjects (n = 1125) n = 255 excluded n = 82 Not meeting inclusion criteria n = 127 Refused to participate n = 46 Others reasons Selected subjects (n = 870) n = 452 diabetic subjects MeDiet + VOO n = 139 MeDiet + tree nuts n = 145 Control n = 134 n = 1 acute myocardial infraction n = 1 death from other causes n = 1 stroke n = 1 death by cancer n = 1 death by other causes Year 1 Year 3 MeDiet + VOO n = 138 MeDiet + VOO n = 121 n = 2 death by cancer n = 1 death from other causes n = 1 stroke MeDiet + tree nuts n = 144 MeDiet + tree nuts n = 132 n = 1 death by cancer Control n = 131 Control n = 116 n = 1 death by cancer n = 1 death by other causes n = 1 stroke n = 1 loss of follow-up n = 1 acute myocardial infraction n = 1 death by other causes n = 1 stroke n = 1 death by cancer n = 2 acute myocardial infraction n = 1 stroke Year 6 MeDiet + VOO n = 29 MeDiet + tree nuts n = 30 Control n = 24

24 CUMULATIVE INCIDENCE OF DIABETES IN THE CONTROL GROUP AND THE INTERVENTION GROUPS DURING 5.5 YEARS 1.00 P a vs c = P b vs c = MedDiet + VOO Cumulative diabetes free-survival a b MedDiet +Nuts Control group c Years

25 HYPERTENSION ABPM: Better correlation with lesions of target organs, cardiovascular risk and prognosis

26 mmhg SYSTOLIC PRESSURE (Mean, CI 95%) Basal versus 3-month follow up Baseline 3-month. Baseline 3-month. Baseline 3-month OLIVE OIL (n=257) NUTS (n=258) LOW FAT (n=257)

27 mmhg DIASTOLIC PRESSURE (Mean, CI 95%) Basal versus 3-month follow up Baseline 3-month. Baseline 3-month. Baseline 3-month OLIVE OIL (n=257) NUTS (n=258) LOW FAT (n=257)

28 mg/dl TOTAL CHOLESTEROL (Mean, CI 95%) Basal versus 3-month follow up OLIVE OIL (n=257) NUTS (n=258) LOW FAT (n=257)

29 mg/dl HDL CHOLESTEROL (Mean, CI 95%) Basal versus 3-month follow up OLIVE OIL (n=257) NUTS (n=258) LOW FAT (n=257)

30 mg/dl LDL CHOLESTEROL (Mean, CI 95%) Basal versus 3-month follow up OLIVE OIL (n=257) NUTS (n=258) LOW FAT (n=257)

31 PREDIMED STUDY FLOW CHART Assessed for eligibility (n = 1487) Did not meet inclusion criteria (n=101) Declined to participate (n=72) Felt unable to change diet (n=21) Other reasons (n=29) Evaluable participants at baseline Med-diet with Virgin Olive Oil (n=419) Evaluable participants at baseline Med-diet with Mixed Nuts (n = 423) Evaluable participants at baseline Control Group (n = 422) Developed stroke (n=1) Died from cancer (n=1) Declined follow-up (n=7) Other reasons (n=1) Did not tolerate nuts (n=2) Died from cancer (n=1) Acute coronary event (n=1) Declined follow-up (n=6) Other reasons (n=2) Died from cancer (n=1) Died from acute coronary event (n=2) Developed stroke (n=1) Declined follow-up (n=12) Evaluable participants at 1 year (n=409) Evaluable participants at 1 year (n=411) Evaluable participants at 1 year (n=404) Arch Intern Med 2008;168:

32 METABOLIC SYNDROME STATUS AND ITS COMPONENTS AT BASELINE MedDiet+VOO MedDiet+Nuts Control Diet P (n=409) (n=411) (n=404) Metabolic syndrome 61.6 (252) 60.6 (249) 61.9 (250) 0.92 Waist circumference 65.3 (267) 64.5 (265) 69.8 (282) 0.22 Low level of HDL cholesterol 26.4 (108) 21.2 (87) 24.0 (97) 0.12 High triglyceride levels 29.8 (122) 29.0 (119) 31.4 (127) 0.74 High fasting serum glucose 67.5 (276) 66.7 (274) 66.6 (269) 0.96 High blood pressure 97.1 (397) 95.1 (391) 95.0 (384) 0.27 Percentage (number) P value for comparisons across groups with Pearson s chi-square test for categorical variables or oneway ANOVA for numerical variables. Arch Intern Med 2008

33 BASELINE AND 1-YEAR PREVALENCE OF METABOLIC SYNDROME BY DIET ASSIGNMENT P<0.05 vs Control diet MedDiet, Mediterranean diet; VOO, virgin olive oil. Arch Intern Med 2008

34 ODDS RATIOS AND 95% CONFIDENCE INTERVALS OF 1-YEAR RESOLUTION (TOP) AND INCIDENCE (BOTTOM) OF THE METS IN THE 2 MED-DIET GROUPS IN COMPARISON WITH THE CONTROL DIET Metabolic syndrome regression Metabolic syndrome development Odds ratio (95% confidence interval) Control group Med-Diet + VOO Med-Diet + Nuts The logistic regression model was adjusted for sex, age, and weight changes.

35 Mechanisms of effects of the Mediterranean diet

36 Fitó for the PREDIMED group. Arch Inter Med 2007;167: n = 372 Mediet+VOO=123 Mediet+nuts=128 control=121

37

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

39 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) Am J Clin Nutr 2009

40 PREDIMED TRIAL: 3-m changes Ann Intern Med 2006;145:1-11

41 PREDIMED TRIAL: 3-m changes Ann Intern Med 2006;145:1-11

42 PREDIMED TRIAL: 3-m changes

43 124 Eligible Participants 17 participants excluded: -9 did not meet criteria -4 declined to participate -2 unable to change diet -2 alcoholism -1 gastrointestinal disease Randomization n=107 Med-Diet+ VOO (n=35) Med-Diet+ Nuts n=36 Low Fat Diet n=36 1 did not tolerated 1-year Evaluation (n=35) 1-year Evaluation (n=35) 1-year Evaluation (n=36)

44 Analysis of Lymphocyte and Monocyte Adhesion Molecules and Chemokines MED + VOO MED + Nuts LFD Initial 1 year Initial 1 year Initial 1 year T Lymphocytes LFA 1 (MFI) VLA 4 (MFI) Monocytes LFA 1 (MFI) Mac 1 (MFI) VLA 4 (MFI) CD40 (MFI) P 0.05 P MED Mediterranean Diet; VOO: Virgin Olive Oil; LFD: Low Fat Diet

45 E-Sel P-Sel VCAM-1 ICAM-1 IL-6 CRP 100 Change % * * * * * * * * * -100 *

46 Urpi-Sarda et al. J Nutr 2012; Δ FOODS AND NUTRIENTS TERTILES 0,3 0,2 0,1 a a 0,3 0,2 0,1 a ab TNFR60, µg/l TNFR60, µg/l 0-0,1-0,2-0,3-0,4-0,5-0,6 0,3 0,2 0,1 0-0,1-0,2-0,3-0,4 0-0,1-0,2-0,3-0,4 1 (n=131) ( -0.3) 2 (n=125) (-0.3 to 24) 3 (n=128) ( 24) 1,5 a a -1 a -1,5 1 (n=132) ( -3.7) 2 (n=127) (-3.7 to 9.8) 3 (n=125) ( 9.8) b TNFR60, µg/l TNFR80, µg/l 1 0,5 0-0,5 b 1 (n=101) ( -24.5) 2 (n=112) (-24.5 to 62.7) 3 (n=121) ( 62.7) ab 1 (n=132) ( -3.7) 2 (n=127) (-3.7 to 9.8) 3 (n=125) ( 9.8) a 14 points score b

47 Conclusiones

48 CONCLUSIONES Parece que nunca es tarde para cambiar (mejorar) nuestros hábitos alimentarios y reducir nuestros factores de riesgo vascular. Una dieta mediterránea suplementada con alimentos ricos en grasa no saturada (AOVE y FS): No da lugar a un aumento de peso ni del perímetro abdominal. Se asocia a un menor riesgo de diabetes, mejora el perfil lipídico y disminuye la presión arterial. Reduce la prevalencia de síndrome metabólico Reduce los marcadores de estrés oxidativo, así como los biomarcadores de inflamación.

49 MUCHAS GRACIAS