FACTORES DE RIESGO PARA
PREECLAMPSIA EN LA POBLACION
COLOMBIANA
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.
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
SOCIOECONOMIC SITUATIÓN
NUTRITIONAL
STATUS
DEFICIENT CALCIUM AND
ANTIOXIDANT VITAMIN INTAKE
AND HIGH FAT INTAKE
SANITARY
INFRASTRUCTURE
HEALTH
SERVICES
INADEQUATE
PRENATAL
CONTROL SYSTEM
AND DELIVERY
SOCIAL
INSECURITY
ANXIETY
PSYCHOSOCIAL
STRESS
HIGH PREVALENCE OF
SUBCLINICAL CHRONIC
INFECTIONS
DECREASED LEVELS OF SERUM IONIC CALCIUM
AND INCREASED LEVELS OF CHOLESTEROL,
INSULINE, TRIGLYCERIDES, LDL, oxo-LDL
HIGH LEVELS OF PROINFLAMMATORY CYTOKINES
TNF-, IL-6, CRP
NAD (P) H OXIDASE
O-
XANTHINE OXIDASE
NO
2
NO SYNTHASE
ONOO
NO
-
ENDOTHELIAL DYSFUNCTIÓN
O -2
HYPERTENSION
PGI 2
TXA 2
PROTEINURIA
EDEMA
PLATELET ACTIVATION
PREECLAMPSIA
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
EFFECT OF CALCIUM SUPPLEMENTATION ON THE
OUTCOMES OF ECUADORIAN PREGNANT WOMEN
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
Calcium
supplementation
reduces the risk of PE
in populations with lowdietary calcium intake
Atallah et al. The Cochrane Library, Issue 1. Chichester; John Wiley;2004
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
Production
Inactivation
-
NO
O2
NO
-
O2
Vasodilator
Antiatherogenic
Antithrombotic
Vasoconstrictor
Proatherosclerotic
Prothrombotic
López-Jaramillo and Casas. J Hum Hypertens 2002; 16 : S34- S37
ORIGINS AND INTERACTIONS
BETWEEN ROS AND RNS
NO2+
RSNO
OH*
*NO2
RSH
-
ONOO
Arg/O2
* NO
NO synthase
O
2
LOO *
LOONO
O2 /NADH
Respiration
mythochondrial
O2 /NADH
NADPH
• Ang II
Oxidase
• LDL
Xhantine
oxidase
O2 /Xhantine • TNF
alpha
Oxidation of
Endogenous
Biomolecules
López-Jaramillo and Casas. J Human Hypertension 2002; 16 : S100-S103
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
CONCENTRATIONS
Teran et al. Int J Gynecol Obstet 2001;75:243-249
TUMOUR NECROSIS FACTOR ALPHA
CONCENTRATIONS
Teran et al. Int J Gynecol Obstet 2001;75:243-249
INTERLEUKIN 6 CONCENTRATIONS
Teran et al. Int J Gynecol Obstet 2001;75:243-249
IS INFECTION A MAYOR RISK FACTOR
FOR PREECLAMPSIA?
15.354 pregnant women,
low socioeconomic status,
14-20 weeks of gestation,
25 years old.
Herrera et al. Medical Hypotheses 2001;57:393-397
RESULTS
Bacteriuria
1.766 (11.5%)
Vaginal Infections
2.150 (14%)
Bacterial Vaginosis
49.4%
Chlamydia Trachomatis
22.5%
Trichomona Vaginalis
14.6%
Group B Streptococci
13.5%
Bacteriuria
and Vaginal Infections
783 ( 5.1%)
Herrera et al. Medical Hypotheses 2001;57:393-397
RESULTS
__________________________________________________
Incidence
Preceeding 5 years
% reduction
__________________________________________________
Preeclampsia
277 (1.8%)
5.1%
64.7
8.0%
52.5
Preterm birth
476 (3.8%)
Low birthweight
952 (6.2%)
13.2%
53
__________________________________________________
Herrera et al. Medical Hypotheses 2001;57:393-397
FMD, CRP CONCENTRATIONS AND
LEUKOCYTE COUNT
Garcia et al. Am J Hyperten. 2007;20:98-103.
PERIODONTITIS IS ASSOCIATED WITH
PREECLAMPSIA IN PREGNANT WOMEN
In our population we have
demostrated that after adjusting
for other risk factors, chronic
periodontal disease was
significantly associated with
preeclampsia
Contreras A et al. J Periodontol. 2006;77: 182-188.
C-REACTIVE PROTEIN IN PREECLAMPSIA
ACCORDING TO PERIODONTAL CONDITION
Herrera et al. Journal of Hypertension 2007; 25: 1459-1464.
FREQUENCY DETECTION OF
PERIODONTOPATHIC BACTERIA
Preeclamptic
Women
Non preeclamptic
Cases
Controls
(n=145)
(n=253)
Microorganism
P
value*
n
%
n
%
Porphyromonas gingivalis
90
62.1
127
50.2
0.02
Tannerella forsythia
42
29.0
52
20.6
NS
A.actinomycetemcomitans
53
36.6
73
28.9
NS
Eikenella corrodens
73
50.3
94
37.2
0.01
Red Complex
Green Complex
Herrera et al. Journal of Hypertension 2007; 25: 1459-1464.
HOMEOSTATIC MODEL
ASSESSMENT (LOG- HOMA) IN
PREGNANCY
Sierra-Laguado et al. Am J Hypertens. 2007; 20: 437-442.
METABOLIC SYNDROME
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
Lopez-Jaramillo et al. J Hypertens 23 (5) : 1121-1129,2005
23:1121-1129
1
2
23:1121-1129
FMD AND ADMA IN PREGNANT WOMEN WITH BILATERAL
NOTCHES WHO DEVELOPED PREECLAMPSIA
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
PLASMA CONCENTRATIONS OF
ADMA, L-ARGININE, AND SDMA
Mass et al. JAMA, 2004; 291: 823-824
L-ARGININE AND ADMA
PLASMA CONCENTRATIONS IN NORMAL
PREGNANCY AND PREECLAMPSIA
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