Patricio López-Jaramillo, MD. PhD.

1. 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.

2. 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

3. SOCIOECONOMIC SITUATIÓN SANITARY SOCIAL INSECURITY NUTRITIONAL HEALTH INFRASTRUCTURE STATUS SERVICES DEFICIENT CALCIUM AND ANTIOXIDANT VITAMIN INTAKE AND HIGH FAT INTAKE INADEQUATE PRENATAL CONTROL SYSTEM AND DELIVERY 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 2 NO NO SYNTHASE - ONOO PGI 2 NO ENDOTHELIAL DYSFUNCTIÓN - O TXA 2 2 HYPERTENSION PROTEINURIA EDEMA PLATELET ACTIVATION PREECLAMPSIA López-Jaramillo et al. Braz J Med Biol Res 2001;34:227-235

4. NUTRIENT INTAKE IN ECUADORIAN PREGNANT TEENAGERS López-Jaramillo et al. Obstet Gynecol, 1997;90:162-167

5. 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

6. Calcium supplementation reduces the risk of PE in populations with low-dietary calcium intake Atallah et al. The Cochrane Library, Issue 1. Chichester; John Wiley;2004

9. 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.

13. BALANCE BETWEEN PRODUCTION AND INACTIVATION OF NO Production Inactivation - O2 VasodilatorAntiatherogenicAntithrombotic NO NO VasoconstrictorProatheroscleroticProthrombotic - O2 López-Jaramillo and Casas. J Hum Hypertens 2002; 16 : S34- S37

14. O /NADH 2 NO2 OH* *NO2 + Respiration mythochondrial RSNO RSH O /NADH 2 - ONOO NADPH Oxidase - NO Arg /O2 * O Xhantine 2 oxidase NO synthase O /Xhantine 2 * Oxidation of Endogenous Biomolecules LOO LOONO ORIGINS AND INTERACTIONS BETWEEN ROS AND RNS • Ang II • LDL • TNF alpha López-Jaramillo and Casas. J Human Hypertension 2002; 16 : S100-S103

17. 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

18. C-REACTIVE PROTEIN CONCENTRATIONS Teran et al. Int J Gynecol Obstet 2001;75:243-249

19. TUMOUR NECROSIS FACTOR ALPHA CONCENTRATIONS Teran et al. Int J Gynecol Obstet 2001;75:243-249

20. INTERLEUKIN 6 CONCENTRATIONS Teran et al. Int J Gynecol Obstet 2001;75:243-249

22. 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

23. 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

24. RESULTS __________________________________________________ Incidence Preceeding 5 years % reduction __________________________________________________ Preeclampsia 277 (1.8%) 5.1% 64.7 Preterm birth 476 (3.8%) 8.0% 52.5 Low birthweight 952 (6.2%) 13.2% 53 __________________________________________________ Herrera et al. Medical Hypotheses 2001;57:393-397

25. FMD, CRP CONCENTRATIONS AND LEUKOCYTE COUNT Garcia et al. Am J Hyperten. 2007;20:98-103.

26. 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.

27. C-REACTIVE PROTEIN IN PREECLAMPSIA ACCORDING TO PERIODONTAL CONDITION Herrera et al. Journal of Hypertension 2007; 25: 1459-1464.

28. FREQUENCY DETECTION OF PERIODONTOPATHIC BACTERIA Herrera et al. Journal of Hypertension 2007; 25: 1459-1464.

29. HOMEOSTATIC MODEL ASSESSMENT (LOG- HOMA) IN PREGNANCY Sierra-Laguado et al. Am J Hypertens. 2007; 20: 437-442.

30. 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

31. 12 23:1121-1129 23:1121-1129

33. FMD AND ADMA IN PREGNANT WOMEN WITH BILATERAL NOTCHES WHO DEVELOPED PREECLAMPSIA Savvidou, Lancet 2003; 361:1511-1517

34. ADMA CONCENTRATIONS IN ECUADORIAN PREGNANT WOMEN López-Jaramillo et al. Br J Obstet Gynaecol 1996,103,33-38

35. PLASMA CONCENTRATIONS OF ADMA, L-ARGININE, AND SDMA Mass et al. JAMA, 2004; 291: 823- 824

36. PLASMA CONCENTRATIONS OF ADMA, L-ARGININE, AND SDMA Mass et al. JAMA, 2004; 291: 823-824

37. L-ARGININE AND ADMAPLASMA CONCENTRATIONS IN NORMAL PREGNANCY AND PREECLAMPSIA López-Jaramillo et al. J Hypertens. 23:1121-1129, 2005

39. PREDICTED PREECLAMPSIA INTERNATIONAL CASE -CONTROL STUDY TO IDENTIFY RISK FACTORS DIFFERENCES IN DEVELOPED AND DEVELOPING COUNTRIES