patricio lópez-jaramillo, md. phd

Patricio López-Jaramillo, MD. PhD.Director de Investigaciones, Facultad de

Medicina, Universidad de Santander UDES.

Director de Investigaciones de la Fundación Oftalmológica de Santander FOSCAL,

Bucaramanga.

FACTORES DE RIESGO PARA FACTORES DE RIESGO PARA PREECLAMPSIA EN LA PREECLAMPSIA EN LA

POBLACION COLOMBIANAPOBLACION COLOMBIANA

ETIOLOGY ETIOLOGY We propose that the endothelial dysfuction

observed in pre-eclamptic women from developing countries seems to be mainly related to

nutritional deficiencies as calcium intake, subclinical infections and metabolic disorders, while in developed countries the genetic and

immunological alterations seem to be the most probable factors responsible for the development

of PE, and it is related with the quality of the prenatal care system.

Lopez-Jaramillo et al. J Hypertens 23 : 1121-1129,2005

NONO

ONOOONOO--

NONO PGIPGI 22

OO --22

22

SOCIOECONOMIC SITUATIÓNSOCIOECONOMIC SITUATIÓN

NUTRITIONALNUTRITIONALSERVICESSERVICES INFRASTRUCTUREINFRASTRUCTURE

SOCIALSOCIALINSECURITYINSECURITY

DEFICIENT CALCIUM AND DEFICIENT CALCIUM AND ANTIOXIDANT VITAMIN INTAKE ANTIOXIDANT VITAMIN INTAKE

AND HIGH FAT INTAKEAND HIGH FAT INTAKE

INADEQUATE INADEQUATE PRENATAL PRENATAL

CONTROL SYSTEM CONTROL SYSTEM AND DELIVERYAND DELIVERY

HIGH PREVALENCE OF HIGH PREVALENCE OF SUBCLINICAL CHRONIC SUBCLINICAL CHRONIC

INFECTIONSINFECTIONS

ANXIETYANXIETYPSYCHOSOCIALPSYCHOSOCIAL

STRESSSTRESS

DECREASED LEVELS OF SERUM IONIC CALCIUM DECREASED LEVELS OF SERUM IONIC CALCIUM AND INCREASED LEVELS OF CHOLESTEROL, AND INCREASED LEVELS OF CHOLESTEROL,

INSULINE, TRIGLYCERIDES, LDL, oxo-LDLINSULINE, TRIGLYCERIDES, LDL, oxo-LDL

HIGH LEVELS OF PROINFLAMMATORY CYTOKINES HIGH LEVELS OF PROINFLAMMATORY CYTOKINES TNF-TNF-, IL-6, CRPIL-6, CRP

NAD (P) H OXIDASENAD (P) H OXIDASE

XANTHINE OXIDASEXANTHINE OXIDASE

NO SYNTHASENO SYNTHASE

ENDOTHELIAL DYSFUNCTIÓNENDOTHELIAL DYSFUNCTIÓN

HYPERTENSIONHYPERTENSION PROTEINURIAPROTEINURIA EDEMAEDEMA PLATELET ACTIVATIONPLATELET ACTIVATION

PREECLAMPSIAPREECLAMPSIA

TXATXA

STATUSSTATUSHEALTHHEALTH SANITARYSANITARY

O -O -22

López-Jaramillo et al. Braz J Med Biol Res 2001;34:227-235

NUTRIENT INTAKE IN ECUADORIAN PREGNANT

TEENAGERS

López-Jaramillo et al. Obstet Gynecol, 1997;90:162-167

a) López-Jaramillo et al. Br J Obstet Gynaecol 1989,96:648-655; b) Lancet 1991,335:293 ; c) Obstet Gynecol, 1997;90:162-167

EFFECT OF CALCIUM SUPPLEMENTATION ON THE OUTCOMES OF ECUADORIAN PREGNANT WOMEN

Atallah et al. The Cochrane Library, Issue 1. Chichester; John Wiley;2004

Calcium supplementation

reduces the risk of PE in populations with low-dietary calcium intake

NO is the responsible for the hemodynamic changes

in normal pregnancy ?

It is altered in preeclampsia ?

López-Jaramillo P and Moncada S. Medical Hypotheses 1995;45:68-72.

BALANCE BETWEEN PRODUCTION AND

INACTIVATION OF NO

NO

O2

VasoconstrictorProatheroscleroticProthrombotic

-

NOO2

Production

Inactivation

VasodilatorAntiatherogenicAntithrombotic

-

López-Jaramillo and Casas. J Hum Hypertens 2002; 16 : S34- S37

López-Jaramillo and Casas. J Human Hypertension 2002; 16 : S100-S103

ORIGINS AND INTERACTIONS BETWEEN ROS AND RNS

ONOO-

NO2+ OH* *NO2

O2-

O2 /NADH

Respirationmythochondrial O2 /NADH

NADPHOxidase

XhantineoxidaseO2 /Xhantine

Oxidation ofEndogenousBiomolecules

Arg/O2 *NONO synthase

LOO*

LOONO

RSNO RSH

• Ang II

• LDL

• TNF alpha

Is an Inflammatory State secondary to infection the

responsible for the Oxidative stress observed in Preeclamptic women ?

Lopez-Jaramillo P. Seminars Perinatol 2000;24:33-36

C-REACTIVE PROTEIN C-REACTIVE PROTEIN CONCENTRATIONS CONCENTRATIONS

Teran et al. Int J Gynecol Obstet 2001;75:243-249

TUMOUR NECROSIS FACTOR TUMOUR NECROSIS FACTOR ALPHA CONCENTRATIONS ALPHA CONCENTRATIONS


INTERLEUKIN 6 CONCENTRATIONS INTERLEUKIN 6 CONCENTRATIONS


15.354 pregnant women, 15.354 pregnant women, low socioeconomic status, low socioeconomic status, 14-20 weeks of gestation, 14-20 weeks of gestation, 25 years old.25 years old.

IS INFECTION A MAYOR RISK FACTOR

FOR PREECLAMPSIA?

Herrera et al. Medical Hypotheses 2001;57:393-397

BacteriuriaBacteriuria 11.766 (11.5%)

Vaginal InfectionsVaginal Infections 22.150 (14%)

Bacterial Vaginosis Bacterial Vaginosis 449.4%

Chlamydia Trachomatis Chlamydia Trachomatis 2222.5%

Trichomona VaginalisTrichomona Vaginalis 14.6%

Group B StreptococciGroup B Streptococci 13.5%

BacteriuriaBacteriuria and Vaginal Infectionsand Vaginal Infections 783 ( 5.1%)

RESULTS


____________________________________________________________________________________________________

IncidenceIncidence Preceeding 5 yearsPreceeding 5 years % reduction % reduction____________________________________________________________________________________________________PreeclampsiaPreeclampsia 277 (1.8%) 5.1% 64.7

Preterm birthPreterm birth

476 (3.8%) 8.0% 52.5

Low birthweightLow birthweight

952 (6.2%) 13.2% 53__________________________________________________

RESULTS


FMD, CRP CONCENTRATIONS AND LEUKOCYTE COUNT

Garcia et al. Am J Hyperten. 2007;20:98-103.

Contreras A et al. J Periodontol. 2006;77: 182-188.

PERIODONTITIS IS ASSOCIATED WITH PREECLAMPSIA IN

PREGNANT WOMENIn our population we have

demostrated that after adjusting for other risk

factors, chronic periodontal disease was significantly

associated with preeclampsia

C-REACTIVE PROTEIN IN C-REACTIVE PROTEIN IN PREECLAMPSIA ACCORDING TO PREECLAMPSIA ACCORDING TO

PERIODONTAL CONDITIONPERIODONTAL CONDITION

Herrera et al. Journal of Hypertension 2007; 25: 1459-1464.

Herrera et al. Journal of Hypertension 2007; 25: 1459-1464.

Preeclamptic Preeclamptic WomenWomen

Non preeclampticNon preeclamptic

PPvalue*value*

MicroorganismMicroorganism CasesCases ControlsControls

(n=145)(n=145) (n=253)(n=253)

nn %% nn %%

Red ComplexRed Complex

Porphyromonas gingivalisPorphyromonas gingivalis 9090 62.162.1 127127 50.250.2 0.020.02

Tannerella forsythiaTannerella forsythia 4242 29.029.0 5252 20.620.6 NSNS

Green ComplexGreen Complex

A.actinomycetemcomitansA.actinomycetemcomitans 5353 36.636.6 7373 28.928.9 NSNS

Eikenella corrodensEikenella corrodens 7373 50.350.3 9494 37.237.2 0.010.01

FREQUENCY DETECTION OF PERIODONTOPATHIC

BACTERIA

HOMEOSTATIC MODEL HOMEOSTATIC MODEL ASSESSMENT (LOG- HOMA) ASSESSMENT (LOG- HOMA)

IN PREGNANCYIN PREGNANCY

Sierra-Laguado et al. Am J Hypertens. 2007; 20: 437-442.

These results support the proposal that in Andean women at high risk of PE, after the calcium deficit is

resolved and the subclinical infections are treated, the

metabolic syndrome can be, together with genetic and immunological factors, the

responsible cause for the remainder incidence of PE

METABOLIC SYNDROME

Lopez-Jaramillo et al. J Hypertens 23 (5) : 1121-1129,2005

12

23:1121-1129

23:1121-1129

FMD AND ADMA IN PREGNANT WOMEN WITH FMD AND ADMA IN PREGNANT WOMEN WITH BILATERAL NOTCHES WHO DEVELOPED BILATERAL NOTCHES WHO DEVELOPED

PREECLAMPSIAPREECLAMPSIA

Savvidou, Lancet 2003; 361:1511-1517

ADMA CONCENTRATIONS IN ECUADORIAN PREGNANT WOMEN

López-Jaramillo et al. Br J Obstet Gynaecol 1996,103,33-38

PLASMA CONCENTRATIONS OF ADMA, L-ARGININE, AND SDMA

Mass et al. JAMA, 2004; 291: 823- 824

Mass et al. JAMA, 2004; 291: 823-824

PLASMA CONCENTRATIONS OF ADMA, L-ARGININE, AND SDMA

L-ARGININE AND ADMAL-ARGININE AND ADMAPLASMA CONCENTRATIONS IN PLASMA CONCENTRATIONS IN

NORMAL PREGNANCY AND NORMAL PREGNANCY AND PREECLAMPSIAPREECLAMPSIA

López-Jaramillo et al. J Hypertens. 23:1121-1129, 2005

PREDICTED

PREECLAMPSIA INTERNATIONAL CASE -

CONTROL STUDY TO IDENTIFY RISK FACTORS

DIFFERENCES IN DEVELOPED AND

DEVELOPING COUNTRIES

patricio lópez-jaramillo, md. phd

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