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

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

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

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

LA TRIADA CARDIOMETABOLICA

DIABETES / ENFERMEDAD CARDIO-CEREBRO VASCULAR

HIPERINSULINISMO/ RESISTENCIA A LA

INSULINA

INFLAMACION DE BAJO GRADO

OBESIDAD ABDOMINAL

.

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

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

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

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

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

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

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

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

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

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

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 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

REACTIVIDAD VASCULARREACTIVIDAD VASCULAR

Rueda-Clausen et al. Int J Cardiol 2010,139: 32-41

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

Epigenetic and Epigenomic

http://www.springerlink.com/content/j3tj16543664/

Published online: 17 May 2006 

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

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 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

POPULATION URBAN AND RURAL EPIDEMIOLOGY (PURE

STUDY)

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.cojplopezj@gmail.com

GRACIAS