LECCIONES APRENDIDAS DE LOS
ESTUDIOS INTERHEART,
INTERSTROKE Y PURE
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
DEATHS FROM CVD WORLDWIDE
30
CVD Deaths (millions)
Over 70%
of the global
burden of
heart attack
and stroke is
in
developing
countries
25
6
20
15
10
5
5
19
Established
economies
and former
socialist
countries
Developing
countries
9
0
1990
2020
KS Reddy. NEJM 2004; 350:2438
Epidemiological
data indicates a
continuous
relationship
between blood
pressure level and
CAD related
mortality
COMPARISON OF THE LA INTERHEART STUDY
RISK FACTOR PROFILES WITH THE OVERALL
INTERHEART STUDY
Lanas, et al. Circulation. 2007;115:1067-1074
ODDS RATIOS OF ACUTE MYOCARDIAL
INFARCTION AND CORRESPONDING
POPULATION-ATTRIBUTABLE RISKS BY GENDER
Lanas, et al. Circulation. 2007;115:1067-1074
EPIDEMIC OF OVERWEIGHT AND OBESITY IN
LATIN AMERICA AND THE CARIBBEAN
Rueda-Clausen et al. International Journal of Cardiolology. 2008;125:111-112.
LA TRIADA CARDIOMETABOLICA
OBESIDAD ABDOMINAL
HIPERINSULINISMO/
RESISTENCIA A LA
INSULINA
INFLAMACION DE
BAJO GRADO
DIABETES / ENFERMEDAD CARDIOCEREBRO VASCULAR
RAS EXPRESSION IN HUMAN
ADIPOSE TISSUE
.
Karlsson C, et al. J Clin Endocrinol Metab. 1998; 83: 3925-3929
ANGIOTENSIN II ENHANCES
ENDOTHELIAL TNF ΑLPHA
PROTEIN PRODUCTION
Arenas et al, Am J Physiol. Cell Physiol. 2004 ; 286 : C779-C784
MEAN VALUES OF CONTINUOUS RISK
FACTORS FOR HIGH BLOOD PRESSURE BY
HYPERTENSION STATUS
Risk factor
Overall
mean%
(n=300)
Hypertensive
mean%
(n=138)
Nonhypertensives P value
mean%
(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
Bautista et al. J Hypertens 2001;19:857-861
CRUDE AND SEX AND AGE ADJUSTED
PREVALENCE FOR HYPERTENSION BY CREACTIVE PROTEIN QUARTILES
Bautista et al. J Hypertens 2001;19:857-861
TUMOR NECROSIS FACTOR ALPHA AND
FLOW MEDIATED VASODILATATION
López-Jaramillo et al. Rev Esp Cardiol. 2007;60:168-178
BLOOD PRESSURE AND C REACTIVE
PROTEIN IN A HISPANIC PEDIATRIC
POPULATION
López-Jaramillo et al. Am J Hypertens 2008; 21: 527-532
PLASMA ASYMMETRIC DIMETHYLARGININE
AND C-REACTIVE PROTEIN CONCENTRATIONS
Garcia et al. Int J Cardiol 2007;127:176-178
INSULIN RESISTANCE: FOCUS ON
SIGNALING PATHWAYS
BK
NO
BK2
receptor
+
NO
Glucose
transport
Akt1
Insulin
receptor
Insulin
+
+
+
+
IRS-1
PI3-K
+
-
GLUT-4
translocation
GLUT-4
biosynthesis
GLUT-4
AT1
receptor
Ang II
Adapted from Henriksen EJ, Jacob S. J Cell Physiol. 2003;196:1719.
GLYCEMIA & CV EVENTS: METAREGRESSION
2.5
3
2-hour glucose
2
1.5
1
Relative Risk
Relative Risk
3
2.5
Fasting glucose
2
1.5
1
10
11
4
6
8
72
108
144
180
198
@ 2 hr G = 7.8 mM (140 mg%)…
RR=1.58 (1.19-2.10)
8
9
5
4
6
7
72
90
108 126 144 162
@ Fasting G = 6.1 mM (110 mg%)…
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.
DYSGLYCEMIA >> NORMOGLYCEMIA IN
ACUTE AND STABLE CV DISEASE
• Consecutive pts: 2107 in-pts; 2854 out-pt elective
CV consults in Europe (71% men; mean age 66)
%
100
• OGTT/old DM
in 1587 (75%)
acute & 1857
(66%) elective
pts before
discharge or
within 2 mo.
Known DM
31%
30%
New DM
80
60
40
15%
22%
10%
22%
3%
3%
20
0
Euro Heart Survey
Bartnik et al; Eur Ht J 2004;1880
29%
Acute
35%
Elective
IGT
IFG
NGT
DISGLICEMIA >> A NORMOGLICEMIA EN
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)
%
100
Leyendas
15,8%
80
17.7 %
60 11.3 %
40
20
15.1 %
Antedecente DM
DM de novo
Glicemia Alterada
en ayunas e
intolerancia OG
9.49 %
Intolerancia OG
30,4 %
Glicemia alterada
en ayunas
Glicemia Normal
0
Pacientes IAM
Lopez-Jaramillo et al. Journal of Diabetes 2011; 3 (Suppl 1): 73
HYPERINSULINEMIA IS A PREDICTOR
OF NEW CARDIOVASCULAR EVENTS
Garcia et al. Int J Cardiol. 2011; 145:85-90
HYPERINSULINEMIA IS A PREDICTOR
OF NEW CARDIOVASCULAR EVENTS
Garcia et al. Int J Cardiol. 2011;145:85-90
HYPERINSULINEMIA IS A PREDICTOR
OF NEW CARDIOVASCULAR EVENTS
Garcia et al. Int J Cardiol. 2011; 145: 85-90
HYPERINSULINEMIA IS A PREDICTOR
OF NEW CARDIOVASCULAR EVENTS
Garcia et al. Int J Cardiol. 2011: 145: 85-90
REACTIVIDAD 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
REACTIVIDAD VASCULAR
Rueda-Clausen et al. Int J Cardiol 2010,139: 32-41
PLASMA LEVELS OF LEPTIN AND
ADIPONECTIN IN RELATION TO WAIST
CIRCUNFERENCE
Rueda-Clausen et al. Int J Cardiol 2010,139: 32-41
Epigenetic and Epigenomic
Published online: 17 May 2006
http://www.springerlink.com/content/j3tj16543664/
OBESITY AND METABOLIC
SYNDROME ARE A
NORMAL BIOLOGICAL
RESPONSE TO AN
ABNORMAL
DEVELOPMENT OF
SOCIETY
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
MATERNAL MALNUTRITION AND FETAL
PROGRAMMING ASSOCIATED WITH GREATER
CV RISK IN ADULT LIFE
López-Jaramillo P. Rev Esp Cardiol. 2009; 62: 670-676
POPULATION URBAN AND RURAL
EPIDEMIOLOGY (PURE STUDY)
PURE: Prevalence of HTN by countries
within economic regions and by urban vs.
rural
Urban
Rural
70
60
50
40
30
20
10
0
HIC
UMIC
LMIC
LIC
HTN control amongst all PURE participants
with HTN urban vs. rural
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
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 ?
FOSCAL:
A VUESTRAS ORDENES
investigaciones@foscal.com.co
jplopezj@gmail.com
GRACIAS