patricio lÓpez-jaramillo md phd facp director de investigacion y de la clinica de...
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PATRICIO LÓPEZ-JARAMILLO MD PhD FACP
DIRECTOR DE INVESTIGACION Y DE LA CLINICA DE SINDROMEMETABOLICO, PREDIABETES Y DIABETES. FOSCAL
DIRECTOR DE INVESTIGACIONES DE LA FACULTAD DE MEDICINA DE LA
UNIVERSIDAD DE SANTANDER UDES
BUCARAMANGA-COLOMBIA
LECCIONES APRENDIDAS DE LOS LECCIONES APRENDIDAS DE LOS ESTUDIOS INTERHEART, ESTUDIOS INTERHEART, INTERSTROKE Y PUREINTERSTROKE Y PURE
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DEATHS FROM CVD WORLDWIDE
Over 70% of the global
burden of heart
attack and stroke is in developing countries
0
5
10
15
20
25
30
Establishedeconomiesand formersocialistcountries
Developingcountries
1990 2020
9
5
6
19
CV
D D
eath
s (m
illi
on
s)
KS Reddy. NEJM 2004; 350:2438
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Epidemiological data indicates a continuous relationship between blood pressure level and CAD related mortality
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COMPARISON OF THE LA INTERHEART STUDY RISK FACTOR PROFILES WITH THE
OVERALL INTERHEART STUDY
Lanas, et al. Circulation. 2007;115:1067-1074
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ODDS RATIOS OF ACUTE MYOCARDIAL INFARCTION AND CORRESPONDING
POPULATION-ATTRIBUTABLE RISKS BY GENDER
Lanas, et al. Circulation. 2007;115:1067-1074
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Rueda-Clausen et al. International Journal of Cardiolology. 2008;125:111-112.Rueda-Clausen et al. International Journal of Cardiolology. 2008;125:111-112.
EPIDEMIC OF OVERWEIGHT AND OBESITY IN EPIDEMIC OF OVERWEIGHT AND OBESITY IN LATIN AMERICA AND THE CARIBBEANLATIN AMERICA AND THE CARIBBEAN
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LA TRIADA CARDIOMETABOLICA
DIABETES / ENFERMEDAD CARDIO-CEREBRO VASCULAR
HIPERINSULINISMO/ RESISTENCIA A LA
INSULINA
INFLAMACION DE BAJO GRADO
OBESIDAD ABDOMINAL
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.
RAS EXPRESSION IN HUMAN ADIPOSE TISSUE
Karlsson C, et al. J Clin Endocrinol Metab. 1998; 83: 3925-3929
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ANGIOTENSIN II ENHANCES ENDOTHELIAL TNF ΑLPHA PROTEIN PRODUCTION
Arenas et al, Am J Physiol. Cell Physiol. 2004 ; 286 : C779-C784
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Risk factor Overall Hypertensive Nonhypertensives P value mean% mean% mean%
(n=300) (n=138) (n=162)____________________________________________________________________________________
Age (years) 59.8 65.2 55.2 <0.001 BMI (kg/m2) 28.6 29.6 27.8 0.002 Waist circunf 103.2 104.8 101.9 0.008 Fasting glicemia (mg/dL, mean) 100.2 107.0 94.3 <0.001 ____________________________________________________________________________________BMI, body mass index
MEAN VALUES OF CONTINUOUS RISK FACTORS FOR HIGH BLOOD PRESSURE
BY HYPERTENSION STATUS
Bautista et al. J Hypertens 2001;19:857-861
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CRUDE AND SEX AND AGE ADJUSTED CRUDE AND SEX AND AGE ADJUSTED PREVALENCE FOR HYPERTENSION BY PREVALENCE FOR HYPERTENSION BY
C-REACTIVE PROTEIN QUARTILESC-REACTIVE PROTEIN QUARTILES
Bautista et al. J Hypertens Bautista et al. J Hypertens 2001;19:857-8612001;19:857-861
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TUMOR NECROSIS FACTOR ALPHA TUMOR NECROSIS FACTOR ALPHA AND FLOW MEDIATED AND FLOW MEDIATED
VASODILATATIONVASODILATATION
López-Jaramillo et al. Rev Esp Cardiol. 2007;60:168-178
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BLOOD PRESSURE AND C REACTIVE BLOOD PRESSURE AND C REACTIVE PROTEIN IN A HISPANIC PEDIATRIC PROTEIN IN A HISPANIC PEDIATRIC
POPULATIONPOPULATION
López-Jaramillo et al. Am J Hypertens 2008; 21: 527-532
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PLASMA ASYMMETRIC DIMETHYLARGININE AND C-REACTIVE PROTEIN
CONCENTRATIONS
Garcia et al. Int J Cardiol 2007;127:176-178Garcia et al. Int J Cardiol 2007;127:176-178
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INSULIN RESISTANCE: FOCUS ON INSULIN RESISTANCE: FOCUS ON SIGNALING PATHWAYSSIGNALING PATHWAYS
Adapted from Henriksen EJ, Jacob S. J Cell Physiol. 2003;196:171-9.
BK2 receptor
BKNO
NO Glucose transport
GLUT-4 trans-location
GLUT-4 biosynthesis
GLUT-4
Akt1
PI3-KIRS-1
AT1 receptor
Insulin receptor
Insulin
+ +
+
+
+
+
-
-
Ang II
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GLYCEMIA & CV EVENTS: META-GLYCEMIA & CV EVENTS: META-REGRESSIONREGRESSION
@ 2 hr G = 7.8 mM (140 mg%)… @ Fasting G = 6.1 mM (110 mg%)… RR=1.58 (1.19-2.10) RR=1.33 (1.06-1.67)
After removal of any DM: p=0.0006 for 2 h G p=0.06 for FPG
Coutinho M, Gerstein HC, et al. Diabetes Care. 1999;22:233-240.
Rel
ativ
e R
isk
4 6 8 10 11
2-hour glucose
72 108 144 180 198R
elat
ive
Ris
k
4 7 8 9
Fasting glucose
5 6
72 90 108 126 144 162
3
2.5
2
1.5
1
3
2.5
2
1.5
1
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DYSGLYCEMIA >> NORMOGLYCEMIA IN DYSGLYCEMIA >> NORMOGLYCEMIA IN ACUTE AND STABLE CV DISEASEACUTE AND STABLE CV DISEASE
• Consecutive pts: 2107 in-pts; 2854 out-pt elective CV consults in Europe (71% men; mean age 66)
• OGTT/old DM in 1587 (75%) acute & 1857 (66%) elective pts before discharge or within 2 mo.
Euro Heart SurveyEuro Heart SurveyBartnik et al; Eur Ht J 2004;1880Bartnik et al; Eur Ht J 2004;1880
NGT
IFG
IGT
Known DM
New DM
29%35%
22%22%
31% 30%
15%10%
3%3%
0
20
40
60
80
100%
Acute Elective
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DISGLICEMIA >> A NORMOGLICEMIA DISGLICEMIA >> A NORMOGLICEMIA EN PACIENTES CON PRIMER INFARTOEN PACIENTES CON PRIMER INFARTO
• Grupo de estudio: 458 pacientes
admitidos con un primer infarto agudo de miocardio en diferentes centros nacionales y 1 centro internacional (27.2 % mujeres, 72.8 hombres)
30,4 %
15.1 %
15,8%
17.7 %
9.49 %
0
20
40
60
80
100%
Pacientes IAM
Glicemia Normal
Glicemia alterada en ayunas
Intolerancia OG
Antedecente DM
DM de novo
Leyendas
11.3 % Glicemia Alterada en ayunas e intolerancia OG
Lopez-Jaramillo et al. Journal of Diabetes 2011; 3 (Suppl 1): 73
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HYPERINSULINEMIA IS A PREDICTOR OF NEW
CARDIOVASCULAR EVENTS
Garcia et al. Int J Cardiol. 2011; 145:85-90
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HYPERINSULINEMIA IS A PREDICTOR OF NEW
CARDIOVASCULAR EVENTS
Garcia et al. Int J Cardiol. 2011;145:85-90
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HYPERINSULINEMIA IS A PREDICTOR OF NEW
CARDIOVASCULAR EVENTS
Garcia et al. Int J Cardiol. 2011; 145: 85-90
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HYPERINSULINEMIA IS A PREDICTOR OF NEW
CARDIOVASCULAR EVENTS
Garcia et al. Int J Cardiol. 2011: 145: 85-90
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REACTIVIDAD VASCULARREACTIVIDAD VASCULAR
Anillos de Arteria mamaria interna (2 a 3 mm)
Curvas Dosis – Respuesta:
•Cloruro Potásico (KCl)
•Acetilcolina (ACh)
•Fenilefrina (PE)
•Nitropusiato Sódico (SNP)
•Angiotensina II (AII)Rueda-Clausen et al. Int J Cardiol 2010,139: 32-41
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REACTIVIDAD VASCULARREACTIVIDAD VASCULAR
Rueda-Clausen et al. Int J Cardiol 2010,139: 32-41
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PLASMA LEVELS OF LEPTIN AND PLASMA LEVELS OF LEPTIN AND ADIPONECTIN IN RELATION TO WAIST ADIPONECTIN IN RELATION TO WAIST
CIRCUNFERENCECIRCUNFERENCE
Rueda-Clausen et al. Int J Cardiol 2010,139: 32-41
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Epigenetic and Epigenomic
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http://www.springerlink.com/content/j3tj16543664/
Published online: 17 May 2006
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OBESITY AND OBESITY AND METABOLIC SYNDROME METABOLIC SYNDROME
ARE A NORMAL ARE A NORMAL BIOLOGICAL RESPONSE BIOLOGICAL RESPONSE
TO AN ABNORMAL TO AN ABNORMAL DEVELOPMENT OF DEVELOPMENT OF
SOCIETYSOCIETY
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MECHANISMS POSSIBLY PARTICIPATING IN THE GENESIS OF METABOLIC
SYNDROME AND CARDIOVASCULAR MORTALITY IN DEVELOPING COUNTRIES
López-Jaramillo et al. Rev Esp Cardiol. 2007;60:168-178
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MATERNAL MALNUTRITION AND FETAL MATERNAL MALNUTRITION AND FETAL PROGRAMMING ASSOCIATED WITH PROGRAMMING ASSOCIATED WITH GREATER CV RISK IN ADULT LIFEGREATER CV RISK IN ADULT LIFE
López-Jaramillo P. Rev Esp Cardiol. 2009; 62: 670-676
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POPULATION URBAN AND RURAL EPIDEMIOLOGY (PURE
STUDY)
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Country Urban Rural Overall
All HIC 21.9 19.8 20.8
All UMIC 17.8 15.4 16.5
All LMIC 16.3 8.7 12.0
All LIC 22.4 18.8 20.5
ALL countries 19.4 15.0 17.1
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The Polypill Concept – A Strategy to Reduce CV Risk by More than 80%
• For all people with established CVD
• For people > 55 years independent of cholesterol and BP levels
Wald NJ, Law MR. BMJ 2003;326:1419
Statin
Thiazide
BB
ACEI/ARA II
Metformin ?
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