ATR1 A1166C (rs5186), FII G20210A (rs1799963), FV G1691A (rs6025), FXIII 97G > T (rs11466016) and MTHFR A1298C (rs1801131) polymorphisms and the risk of ST-elevation myocardial infarction in young Mexican individuals.

BACKGROUND: Previous studies had identified genetic variants associated with Myocardial Infarction, but results are inconclusive. We examined the association between FII G20210A (rs1799963), FV G1691A (rs6025), FXIII 97G > T (rs11466016), ATR1 A1166C (rs5186) and MTHFR A1298C (rs1801131) polymorphisms and ST elevation Myocardial Infarction in young Mexican individuals. METHODS: We included a total of 350 patients with Myocardial Infarction <45 years old and 350 controls matched by age and gender. The polymorphisms were analyzed by PCR-RFLP using specific restriction enzymes. DNA fragments were separated by electrophoresis in 2% gel of agarose and visualized using SYBR green. RESULTS: The A1166C (p = 0.004) but not FXIII 97G > T (p = 0.19), G20210A (p = 0.32), G1691A (p = No significant) and A1298C (p = 0.21) polymorphisms were associated with increased risk for ST elevation Myocardial Infarction. Moreover, dyslipidemia, hypertension, smoking and family history of atherothrombotic disease were associated. CONCLUSIONS: We found that A1166C represented increased risk for ST elevation Myocardial Infarction. However, G20210A, G1691A, 97G > T, and A1298C were not associated. In addition, we had determined that Glu298Asp, PLA1/A2, TAFI Thr325Ile, ACE I/D, AGT M235T and PAI-1 4G/5G polymorphisms represented increased risk in the same group of patients. However, MTHFR C677T, AGT T174M, FV G1691A, TSP-1 N700S, MTHFR C677T and TAFI 174 M polymorphisms were no associated. Our results suggest that in young patients with ST Myocardial Infarction, those polymorphisms could contribute to premature endothelial dysfunction, atherothrombosis, vasoconstriction, increased platelet aggregation, muscle cell migration and proliferation. Further studies are required to try to better assess gene-gene and gene-modifiable factors interaction.

Genetic Variants Associated with High Susceptibility of Premature Ischemic Stroke.

Background: Several polymorphisms had been associated with an increased risk of ischemic stroke, but results are inconclusive. The aim of this study was to examine the association between AGTR1 A1166C and TSP-1 N700S polymorphisms and ischemic stroke in a young Mexican population. Methods: In a case-control study, 250 patients ≤ 45 years of age with ischemic stroke and 250 controls matched by age and gender were included. The polymorphisms were determined in all participants by polymerase chain reaction. Results: There were statistical differences in genotype distribution (p = 0.01) and allele frequency (p = 0.001) of AGTR1 A1166C polymorphism. In contrast, there was a similar genotype distribution (p = 0.96) and allele frequency (p = 0.76) of the TSP1 N700S genetic variant between groups. Hypertension (p = 0.03), smoking (p = 0.02), and family history of atherothrombotic disease (p = 0.04) were associated with stroke, but not diabetes (p = 0.30) and dyslipidemia (p = 0.08). Conclusions: This is the first study in Mexican population to explore several genetic variants in young patients with ischemic stroke. Our results suggest that polymorphisms in the renin-angiotensin-aldosterone system could contribute to premature hypertension, endothelial dysfunction, atherothrombosis, vasoconstriction, smooth muscle cell migration, and proliferation. In contrast, polymorphisms in the coagulation factors are not associated with ischemic stroke. Environmental factors such as diabetes and dyslipidemia could be less important in the pathogenesis of ischemic stroke at a young age. We suggest that those polymorphisms should be determined in individuals with a family history of thrombosis to avoid the stroke development. Therefore, genotype-environmental combination could determine several possible phenotypes at different moments in life.

Polymorphisms in the Renin-Angiotensin System and eNOS Glu298Asp Genes Are Associated with Increased Risk for Essential Hypertension in a Mexican Population.

Background: Essential hypertension is the result of modifiable and genetic factors, and it is associated with increased risk for atherothrombosis. Some polymorphisms are associated with hypertensive disease. The objective was to analyze the association between eNOS Glu298Asp, MTHR C677T, AGT M235T, AGT T174M, and A1166C and ACE I/D polymorphisms with essential hypertension in the Mexican population. Materials and Methods: In the present study, 224 patients with essential hypertension and 208 subjects without hypertension were included. The Glu298Asp, C677T, M235T, T174M, A1166C, and I/D polymorphisms were determined by the PCR-RFLP technique. Results: We found statistical differences in age, gender, BMI, systolic and diastolic blood pressure, and total cholesterol between control and cases. However, we found no significant differences in HbA1c and triglycerides between both groups. We observed statistical significant differences in the genotype distribution of Glu298Asp (P = 0.001), I/D (P = 0.02), and M235T (P = 0.004) polymorphisms between both groups. In contrast, there were no differences related to distribution of genotypes of MTHFR C677T (P = 0.12), M174T (P = 0.46), and A1166C (P = 0.85) between cases and control groups. Conclusions: We identified that Glu298Asp, I/D, and M234T polymorphisms represented an increased risk for essential hypertension and those genetic variants could contribute to the presence of endothelial dysfunction and vasopressor effect, hyperplasia, and hypertrophy of smooth muscle cells, which had an impact for hypertension. In contrast, we found no association between C677C, M174T, and A1166C polymorphisms and hypertensive disease. We suggested that those genetic variants could be identified in individuals with high risk to avoid hypertension and thrombotic disease.

Self-regulation of TNF-α Induces Dysfunction of Endothelial Colony-forming Cells from Patients with Venous Thromboembolic Disease.

BACKGROUND: Endothelial colony-forming cells (ECFCs) contribute to postnatal vasculogenesis. In venous thromboembolic disease (VTD), they are functionally abnormal and produce high concentrations of TNF-α. OBJECTIVE: To analyze the TNF-α signaling pathway and its relationship with the expression of cell-cycle regulators. METHODS: Mononuclear cells (MNCs) were collected from the peripheral blood of 20 healthy human volunteers (controls) and 30 patients with VTD matched by age (20-50 years) and sex to obtain ECFCs. We analyzed the relative quantification of the gene transcripts of TNF, NFkB1, PLAU, HMOX1, GSS, eNOS, CDKN1A, and CDKN1B through quantitative RT-PCR (qRT-PCR assays). Identification of NF-κB and activated targets of each pathway: NF-κB (Ser536); IκBα (Ser32/Ser36); p38 (Thr180/Tyr182) JNK (Thr183/Tyr185), p53 and cell-cycle regulators: p16, p18, p21, p27, p57, Cyclin D, Cyclin E, Cyclin A, Cyclin B, CDK2, CDK4; cell-cycle status was determined by KI-67 and 7-AAD. Cells were analyzed with flow cytometry and the FlowJo vX software. RESULTS: In ECFCs from VTD patients, TNF-α receptor and NFkB were overexpressed and hyper-phosphorylated; eNOS and HMOX1 were down-regulated; cell-cycle regulators (p53, p18, p21) were elevated. In addition, the cell cycle was locked in the G2 phase. CONCLUSIONS: Our results strongly suggest that these molecular alterations in the pathway of TNF-α and cell cycle regulation induce endothelial dysfunction, reduced proliferation potential and vascular regeneration, and consequently, the occurrence of new thrombotic events.

Analysis of the quality of anticoagulation with vitamin K antagonists in three clinical scenarios in Mexico.

INTRODUCTION: Vitamin K antagonists (VKA) are a therapeutic alternative in patients with venous thromboembolic disease; however, numerous factors affect their pharmacology. OBJECTIVE: To evaluate the quality of VKA anticoagulation at three different time periods in Mexico. METHODS: Prospective study, nested in patient cohorts at three different clinical scenarios between 2013 and 2019. Outpatients with indication for treatment with VKAs for at least 12 months were included. Patients were managed according to the criteria of the treating physician. RESULTS: Patient general characteristics were similar between groups, except for the VKA indication. The results of 4,148 patients and 38,548 INR assessments were analyzed. The times in therapeutic range during the three phases of the study and pooled data were significantly higher for the anticoagulation clinic. Only the number of patient visits was significantly associated with the results, unlike age, gender, and type of VKA. CONCLUSIONS: VKAs are widely used, but it is difficult for therapeutic goals to be achieved, especially in non-specialized clinical services. Creation of anticoagulation clinics is an urgent need for the Mexican health system.

INTRODUCCIÓN: Los antagonista de la vitamina K (AVK) son una alternativa terapéutica en los pacientes con enfermedad tromboembólica venosa; sin embargo, numerosos factores afectan su farmacología. OBJETIVO: Evaluar la calidad de la anticoagulación AVK durante tres diferentes periodos en México. MÉTODOS: Estudio prospectivo, anidado en cohortes de pacientes en tres escenarios clínicos entre los años 2013-2019. Se incluyeron pacientes no hospitalizados con indicación para recibir AVK por al menos 12 meses, quienes fueron manejados de acuerdo con el criterio del médico tratante. RESULTADOS: Las características generales de los pacientes fueron similares entre los grupos, excepto por la indicación para usar los AVK. Se analizaron los resultados de 4148 pacientes y 38 548 evaluaciones de INR. Los tiempos en rango terapéutico durante las tres fases del estudio y los datos acumulados fueron significativamente mayores en la clínica de anticoagulación. Solo el número de visitas de control de los pacientes se asoció significativamente con los resultados, a diferencia de la edad, el sexo y el tipo de AVK. CONCLUSIONES: Los AVK se utilizan ampliamente, pero es difícil alcanzar la meta terapéutica, sobre todo en servicios clínicos no especializados. La creación de clínicas de anticoagulación es una necesidad urgente en el sistema mexicano de salud.

Soluble Endoglin and Uterine Artery Flow Doppler Ultrasonography as Markers of Progression to Preeclampsia in Women with Gestational Hypertension.

INTRODUCTION: Gestational hypertension (GH) pregnancies are at a high risk of developing adverse outcomes, including progression to preeclampsia. Prediction of GH-related adverse outcomes is challenging because there are no available clinical tests that may predict their occurrence. OBJECTIVE: The aim of the study was to determine the clinical usefulness of the soluble endoglin (sEng) and parameters of uterine artery flow (UtAF) measured by Doppler ultrasonography as markers of progression to preeclampsia in women with GH. SETTING: Mexico City, Mexico. MATERIAL AND METHODS: We included 77 singleton pregnant women with GH in a nested case-control study. Cases were women who progressed to preeclampsia (n = 36), and controls were those who did not (n = 41). Serum sEng and UtAF measurements were performed at enrollment. The main outcomes measured were progression to preeclampsia and occurrence of preterm delivery (PD) <37 and <34 weeks of gestation, small for gestational age infant (SGA), and fetal growth restriction (FGR). RESULTS: Women with sEng values in the highest tertile had higher risk of progression to preeclampsia, preterm delivery <34 weeks of gestation, and fetal growth restriction, odds ratios (ORs) ≥3.7. Patients with abnormal UtAF Dopp-ler-pulsatility index had higher risk of progression to preeclampsia, preterm delivery <34 weeks of gestation, small for gestational age infant, and fetal growth restriction (ORs ≥3.3). The presence of notch was associated with higher risk of progression to preeclampsia, preterm delivery <37 and <34 weeks of gestation, SGA infant, and fetal growth restriction (ORs ≥2.9). However, logistic regression analysis revealed that only serum sEng was a significant and independent risk factor for progression of GH to preeclampsia, preterm delivery <34 weeks of gestation, and fetal growth restriction (ORs ≥3.1). CONCLUSIONS: In GH pregnancies, UtAF Doppler ultrasonography is associated with increased risk of adverse outcomes and progression to preeclampsia. However, serum sEng concentration appears to be a better predictor to assess the risk of adverse maternal and perinatal outcomes and progression to preeclampsia.

Análisis de la calidad de la anticoagulación con antagonistas de la vitamina K en tres escenarios clínicos en México / Analysis of the quality of anticoagulation with vitamin K antagonists in three clinical scenarios in Mexico

Resumen Introducción: Los antagonista de la vitamina K (AVK) son una alternativa terapéutica en los pacientes con enfermedad tromboembólica venosa; sin embargo, numerosos factores afectan su farmacología. Objetivo: Evaluar la calidad de la anticoagulación AVK durante tres diferentes periodos en México. Métodos: Estudio prospectivo, anidado en cohortes de pacientes en tres escenarios clínicos entre los años 2013-2019. Se incluyeron pacientes no hospitalizados con indicación para recibir AVK por al menos 12 meses, quienes fueron manejados de acuerdo con el criterio del médico tratante. Resultados: Las características generales de los pacientes fueron similares entre los grupos, excepto por la indicación para usar los AVK. Se analizaron los resultados de 4148 pacientes y 38 548 evaluaciones de INR. Los tiempos en rango terapéutico durante las tres fases del estudio y los datos acumulados fueron significativamente mayores en la clínica de anticoagulación. Solo el número de visitas de control de los pacientes se asoció significativamente con los resultados, a diferencia de la edad, el sexo y el tipo de AVK. Conclusiones: Los AVK se utilizan ampliamente, pero es difícil alcanzar la meta terapéutica, sobre todo en servicios clínicos no especializados. La creación de clínicas de anticoagulación es una necesidad urgente en el sistema mexicano de salud.

Abstract Introduction: Vitamin K antagonists (VKA) are a therapeutic alternative in patients with venous thromboembolic disease; however, numerous factors affect their pharmacology. Objective: To evaluate the quality of VKA anticoagulation at three different time periods in Mexico. Methods: Prospective study, nested in patient cohorts at three different clinical scenarios between 2013 and 2019. Outpatients with indication for treatment with VKAs for at least 12 months were included. Patients were managed according to the criteria of the treating physician. Results: Patient general characteristics were similar between groups, except for the VKA indication. The results of 4,148 patients and 38,548 INR assessments were analyzed. The times in therapeutic range during the three phases of the study and pooled data were significantly higher for the anticoagulation clinic. Only the number of patient visits was significantly associated with the results, unlike age, gender, and type of VKA. Conclusions: VKAs are widely used, but it is difficult for therapeutic goals to be achieved, especially in non-specialized clinical services. Creation of anticoagulation clinics is an urgent need for the Mexican health system.

Interleukin-6 in Amniotic Fluid: A Reliable Marker for Adverse Outcomes in Women in Preterm Labor and Intact Membranes.

INTRODUCTION: Amniotic fluid (AF) interleukin-6 (IL-6) concentration has been associated to preterm delivery and perinatal morbidity and mortality in women with preterm labor and intact membranes. Nevertheless, the clinical significance of this biomarker of intra-amniotic inflammation (IAI) is still unclear due in part to the paucity of large studies. METHODS: AF IL-6 concentrations were determined in 452 consecutive women with preterm labor and intact membranes, categorized into 3 groups: 302 without IAI (IL-6 of <2.6 ng/mL), 64 with mild IAI (IL-6 of 2.6-11.2 ng/mL), and 86 with severe IAI (IL-6 of ≥11.3 ng/mL). RESULTS: The severe IAI group had a short pregnancy duration from amniocentesis to delivery (median 3 days) than in without IAI group (median 45 days); meanwhile, the mild IAI group had a latency that was intermediate to the severe and without IAI groups (median 9.5 days). As compared to women without IAI, women with mild and severe IAI had higher rates of preterm delivery at both <34 and <37 weeks of gestation and perinatal morbidity and mortality. Furthermore, the risk of various individual adverse outcomes (short latency from amniocentesis to delivery [at ≤3 days, ≤7 days, and ≤14 days], preterm delivery at both <34 and <37 weeks of gestation, histologic chorioamnionitis, respiratory distress syndrome, and congenital sepsis) was higher in women with severe IAI (OR ≥ 2.8), compared with women without IAI. CONCLUSIONS: AF IL-6 concentrations appear to be suitable marker to assess the degree of IAI and are associated with increased risk of adverse outcomes.

Circulating angiogenic factors are associated with progression to preeclampsia and the occurrence of adverse outcomes in women with gestational hypertension.

OBJECTIVE: Gestational hypertension is characterized by an imbalance in angiogenic factors. The goal of the current study was to evaluate whether circulating concentrations of proangiogenic and antiangiogenic factors are associated with the risk of progression to preeclampsia and development of adverse outcomes in women with gestational hypertension. METHODS: We studied 496 women with gestational hypertension. Patients were divided into three groups based on their degree of angiogenic imbalance, evaluated by the soluble fms-like tyrosine kinase-1/placental growth factor ratio: no angiogenic imbalance (≤38), mild angiogenic imbalance (>38-<85), and severe angiogenic imbalance (≥85) or stratified into tertiles according to soluble endoglin (sEng) levels. RESULTS: The concentrations of all angiogenic factors were significantly different in patients with gestational hypertension than in healthy pregnancy. A significant trend towards higher serum sEng levels was observed as the degree of angiogenic imbalance increased. Patients with severe angiogenic imbalance had higher rates of adverse maternal and perinatal outcomes and progression to preeclampsia (P < 0.001) when compared with patients with no or mild angiogenic imbalance. The risk of combined adverse maternal outcomes and specific adverse outcomes (hemolysis, elevated liver enzymes, low platelet count syndrome, preterm delivery, small-for-gestational-age infant, perinatal death, and progression to preeclampsia within 7, 14, 28, and 56 days) was higher in patients with severe angiogenic imbalance or sEng values in the highest tertile (odds ratio ≥5.6 and ≥2.0, respectively), compared with no angiogenic imbalance or the lowest tertile. CONCLUSION: In women with gestational hypertension at the time of initial evaluation, circulating concentrations of the soluble fms-like tyrosine kinase-1/placental growth factor ratio and sEng appear to be suitable markers to assess the risk of adverse maternal and perinatal outcomes and progression to preeclampsia.

Cystathionine ß-synthase and methylenetetrahydrofolate reductase mutations in Mexican individuals with hyperhomocysteinemia.

BACKGROUND: Hyperhomocysteinemia, a thrombotic risk factor, may have several causes. Among the genetic causes of hyperhomocysteinemia, there are polymorphisms in the enzymes methylenetetrahydrofolate reductase (C677T) and cystathionine ß-synthase (C699T, C1080T, and 844ins68). Although the frequency of hyperhomocysteinemia in our country is high, there is no evidence about the frequencies of these polymorphisms. METHODS: We analyzed 80 healthy individuals from several regions in our country. We evaluated the fasting and post-oral methionine load plasma Hcy and the genotypes in order to obtain the allele frequencies of the polymorphisms C677T of methylenetetrahydrofolate reductase and C699T, C1080T, and 844ins68 of the cystathionine ß-synthase. RESULTS: No individual had deficiency of folic acid, vitamins B12, or B6, but 80% had post-oral methionine load hyperhomocysteinemia. We found a significant increase in the Hcy plasma concentration associated with age and gender. Only the polymorphism C1080T was significantly associated with hyperhomocysteinemia. CONCLUSION: There is an association between fasting and post-oral methionine load plasma Hcy concentrations with the allelic frequencies of the polymorphisms C669T, 844ins68, and C1080T of the cystathionine ß-synthase and C667T of the methylenetetrahydrofolate reductase in healthy Mexican individuals. As compared with individuals with normal fasting or post-oral methionine load Hcy plasma levels, only C1080T was significantly associated with hyperhomocysteinemia.

Usefulness of the sFlt-1/PlGF (Soluble fms-Like Tyrosine Kinase-1/Placental Growth Factor) Ratio in Diagnosis or Misdiagnosis in Women With Clinical Diagnosis of Preeclampsia.

Preeclampsia is characterized by angiogenic imbalance (AI), sFlt-1 (soluble fms-like tyrosine kinase-1)/PlGF (placental growth factor) is useful for its diagnosis and prediction of adverse outcomes, but the relationship among the degrees of AI as assessed by this ratio with the correct diagnosis, clinical characteristics, and outcomes in women with clinical diagnosis of preeclampsia are unclear. We studied 810 women with clinical diagnosis of preeclampsia. Patients were divided into 3 groups based on their degree of AI, evaluated by the sFlt-1/PlGF ratio: no AI (≤38), mild AI (>38-<85), and severe AI (≥85). Patients with no AI were more likely to have comorbidities and false significant proteinuria compared with patients with mild and severe AI (P<0.001). The rates of preterm delivery, delivery within 14 days, and small-for-gestational-age infant were higher among patients with severe AI than in patients with no and mild AI (P<0.001) and in patients with mild AI that in those with no AI (P≤0.01). The occurrence of any adverse maternal outcome (HELLP syndrome, elevated liver enzymes, thrombocytopenia, placental abruption, acute kidney injury) was only present in patients with severe AI. Interestingly, the frequency of misdiagnosis of preeclampsia was progressively lower as the degrees of AI increased (no AI: 100%, mild AI: 88.2%, and severe AI: 15.6%). We concluded that in women with clinical diagnosis of preeclampsia, severe AI is characterized by high frequency of true preeclampsia and preeclampsia-related adverse outcomes, in contrast, no and mild AI, are characterized by unnecessary early deliveries, often due to misdiagnosis.

D-dimer as A Biomarker of Severity and Adverse Outcomes in Patients with Community Acquired Pneumonia.

BACKGROUND: Community-acquired pneumonia (CAP) stands as a main cause of hospitalization and mortality worldwide. Because of their limitation scoring systems such as CURB-65 and Pneumonia Severity Index (PSI) may underestimate the severity of the disease. Intravascular and intra-alveolar activation of coagulation factors may lead to fibrin deposition in alveoli and lung interstitium. The clinical utility of D-dimer measurement in patients with CAP is still unclear. The aim of this study was to evaluate the association of D-dimer levels with severity of CAP, need for invasive mechanical ventilation, vasopressor support, and 7 d in-hospital mortality. METHODS: Prospective observational study from August 2016-November 2017 in a secondary care level hospital at Mexico City. CURB-65 and PSI scores were calculated on admission. D-dimer levels were measured by a fluorescence immunoassay. RESULTS: A total of 61 adult patients with CAP were analyzed and categorized into low or high-risk groups using CURB 65 and PSI score. The average age was 71.6 ± 15 years, predominantly men (52%). Statistically significant higher D-dimer levels, vasopressor support, and mechanical ventilation were observed in high-risk groups. The AUC to predict 7 d in-hospital mortality was 0.93 (p <0.0001) for PSI, 0.853 (p = 0.01) for CURB 65, and 0.789 (p = 0.001) for D-dimer. A D-dimer cut-off point of 2400 mcg/L showed a sensitivity = 1 and a specificity = 0.614, as well as a positive predictive value = 0.154 and a negative predictive value = 1. CONCLUSION: D-dimer plasma levels are associated with the severity of CAP. Patients with D-dimer below 2400 mcg/L have low probability of mortality at 7 d after admission to the emergency department.

Effects of Rivaroxaban on Platelet Aggregation.

Rivaroxaban is a direct oral anti-factor Xa anticoagulant. It has recently been suggested that rivaroxaban may affect platelet function in vitro; however, little is known about the clinical impact of this likely antiplatelet effect and whether this probable phenomenon is dose-dependent. Our aim was to determine whether rivaroxaban at 4 different doses inhibits direct platelet aggregation. We included adult patients of both sexes and who were allocated to one of the following groups depending on the prescribed daily dose of rivaroxaban: 5, 10, 15, and 20 mg. In 80 patients (20 patients/group), the percentage of platelet aggregation was determined by means of platelet aggregometry tests before and after rivaroxaban use. Basal samples were obtained before starting rivaroxaban and 1 month after treatment, both 2 and 24 hours after the last dose of the drug (12 hours after in the case of rivaroxaban 5 mg). We used 5 platelet agonists: adenosine diphosphate, epinephrine, arachidonic acid, collagen, and thrombin. There were no significant changes in the percentage of platelet aggregation before and after rivaroxaban use independently of the dose administered and the agonist used. Our results have clearly shown that rivaroxaban, even at a high dose, does not directly affect platelet aggregation.

von Willebrand Disease and other hereditary haemostatic factor deficiencies in women with a history of postpartum haemorrhage.

INTRODUCTION: Postpartum haemorrhage (PPH) is the main cause of maternal morbidity and mortality globally, but it is far more important in non-developed countries. PPH represents 25% of all maternal deaths worldwide. Women with von Willebrand disease (VWD) and other inherited haemorrhagic disorders are at increased risk of PPH. Our aim was to establish a probable association of severe PPH in women with a history of haemostatic abnormalities. METHODS: An observational, controlled study of adult women with a one or more episodes of severe PPH requiring treatment in an intensive care unit or >10 units of blood products during the 24-hour period after diagnosis and their controls. The tests performed were blood cell count, blood group, renal, viral, liver function and haemostatic tests, fibrinogen, activity of the plasma factors and specific test to diagnose and classify VWD. RESULTS: We included 124 women with 133 PPH events and their controls. The median age at the first event was 25.5 years old. Results were significantly different between the groups in terms of fibrinogen concentration, VWF:Ag, VWF:RCo and FVIII. A specific diagnosis was established in 69 (55.6) and 4 (3.2%) patients in the PPH group and controls, respectively. Of 61 patients with VWD, 57 had type 1, two had type 2A, and another two had type 2B. CONCLUSION: Our results show a relationship between PPH and inherited haemostatic disorders. VWD was the most frequent diagnosis. Appropriate and opportune diagnosis before pregnancy of inherited haemostatic disorders may be important to effectively prevent and treat PPH.

Genetic Polymorphisms Associated with Thrombotic Disease Comparison of Two Territories: Myocardial Infarction and Ischemic Stroke.

BACKGROUND AND PURPOSE: The thrombin-activatable fibrinolysis inhibitor (TAFI) is an important inhibitor of fibrinolysis and plays a critical role in the pathogenesis of arterial thrombosis; genetic polymorphisms of the TAFI gene affect its activity and increase the risk of thrombosis. Moreover, studies in young patients are still scarce. The aim was to examine the contribution of the Thr325Ile and Ala147Thr polymorphisms with ST acute myocardial infarction (STEMI) or idiopathic ischemic stroke (IIS) in the young Mexican population. METHODS: A total of 244 patients with STEMI ≤45 years of age and 244 controls. In a second study, 250 patients with IIS ≤45 years of age were recruited, including 250 controls. In both studies, cases and controls were matched by age and sex. The polymorphisms were determined in all participants by PCR-RFLP. RESULTS: There was significant difference in the Thr325Ile genotype distribution (P = 0.001) and allele frequency (P = 0.001) between STEMI and control groups, but no difference in the Ala147Thr genotype distribution (P = 0.24) and allele frequency (P = 0.46), neither in the Thr325Ile genotype distribution (P = 0.25) nor in the Ala147Thr genotype distribution (P = 0.46) or their allele frequencies; there was significant difference between IIS and the control group. There were independent factors for STEMI: the Ile allele (P = 0.01), type 2 diabetes mellitus (P = 0.001), hypertension (P = 0.001), smoking (P = 0.001), dyslipidemia (P = 0.001), and family history of atherothrombotic disease (P = 0.001). The independent factors for IIS were hypertension (P = 0.001), smoking (P < 0.01), and family history of atherothrombotic disease (P < 0.01). CONCLUSIONS: The Thr325Ile polymorphism, but no Ala147Thr polymorphism, represents an independent risk factor for STEMI in the young Mexican population.

Soluble Endoglin As a Marker for Preeclampsia, Its Severity, and the Occurrence of Adverse Outcomes.

Preeclampsia is characterized by an imbalance in angiogenic factors, including sEng (soluble endoglin). However, the relationship of sEng with the severity of preeclampsia, clinical, and laboratory parameters, and the occurrence of adverse outcomes are not fully elucidated. We studied 1002 women with preeclampsia. Serum concentrations of sEng were measured by ELISA. Serum sEng levels were significantly different (P<0.001) in patients with preeclampsia than in healthy pregnancy. In addition, these factors were markedly different in patients with hemolysis, elevated liver enzymes, low platelet count syndrome and eclampsia than in patients with preeclampsia with or without severe features (P<0.001) and in patients with preeclampsia with severe features than in those without severe features (P<0.001). sEng correlated positively with blood pressure, proteinuria, and levels of creatinine, uric acid, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase; and inversely with gestational age, infant's birth weight, and platelets counts (P<0.001 for all). The risk of combined and specific adverse outcomes (pulmonary edema, acute renal failure, placental abruption, hepatic hematoma or rupture, maternal death, cerebral hemorrhage, thrombocytopenia, elevated liver enzymes, preterm delivery, small for gestational age infant, and need for endotracheal intubation, positive inotropic drug support, and hemodialysis) was higher in patients with sEng values in the highest quartile (odds ratio ≥3.1) compared with the lowest quartile. Patients in the highest quartile of sEng were more likely to deliver early compared with those in the lowest quartile (HR, 2.33; 95% CI, 1.91-2.84). We concluded that circulating concentrations of sEng seem to be a suitable marker to assess the severity of preeclampsia and are associated with increased risk of adverse outcomes.

Urinary IgM excretion: a reliable marker for adverse pregnancy outcomes in women with chronic kidney disease.

OBJECTIVE: Chronic kidney disease (CKD) pregnancies are at high risk of developing adverse outcomes. In non-pregnant subjects with CKD, higher urinary IgM levels are associated with poor renal survival and higher rates of cardiovascular deaths. In this study, we assessed whether urinary IgM levels are associated with an increased risk of adverse pregnancy outcomes (APO) in CKD pregnancies. METHODS: We performed a nested case-control study within a cohort of CKD patients with singleton pregnancies attended at a tertiary care hospital. The study included 90 CKD patients who eventually developed one or more APO and 77 CKD patients who did not. Urinary IgM excretion was determined from the 24-h urine samples at enrollment by an ultrasensitive enzyme immunoassay. RESULTS: The risk for combined APO and for preeclampsia (PE) was higher among women with urinary IgM and proteinuria levels values in the highest quartile or with CKD stages 4-5 (odds ratios, OR ≥ 2.9), compared with the lowest quartile or with CKD stage 1. Urinary IgM levels were more closely associated with the risk of either combined or specific APO (PE, preterm birth, and for having a small-for-gestational-age infant; OR ≥ 5.9) than either the degree of total proteinuria or CKD stages. Among patients with CKD stage 1, the risk of combined APO, PE, and preterm birth was higher in women with urinary IgM levels values in the highest quartile (OR ≥ 4.8), compared with the three lower quartiles, independently of proteinuria. CONCLUSION: In CKD pregnancies, at the time of initial evaluation, proteinuria and CKD stage are associated with increased risk of combined APO. However, urinary IgM concentrations appear to be better predictors of an adverse outcome and may be useful for risk stratification in CKD pregnancies.

Gene polymorphisms of angiotensin-converting enzyme and angiotensinogen and risk of idiopathic ischemic stroke.

OBJECTIVE: The renin-angiotensin system (RAS) is a hormonal signaling mechanism implicated in the atherosclerosis and regulation of blood pressure. Angiotensin-converting enzyme (ACE) a key enzyme in the RAS, plays important roles in vascular remodeling atherosclerosis, and ischemic stroke. The aim of this study was to examine the possible contribution of the I/D in the ACE gene, M235T and T174M in the angiotensinogen (AGT) gene polymorphisms with ischemic stroke in young Mexican population. MATERIALS AND METHODS: A total of 224 patients with diagnosis of idiopathic ischemic stroke ≤45 years of age, and 224 controls matched by age and gender, were recruited from 2006 and 2016. The I/D, M235T and T174M polymorphisms were determined in all participants by PCR-RFLP. RESULTS: There was a significant difference in the M235T genotype distribution (p = 0.01) and allele frequency between two groups (p = 0.01). Also, we found a significant difference in the T174M genotype distribution (p = 0.01) and the allele frequency between groups; (p = 0.02). In contrast, in I/D polymorphism, there was a similar genotype distribution; (p = 0.20) and allele distribution (p = 0.20). There were independent factors for ischemic stroke: M235T and T174M polymorphisms, smoking, hypertension, and familial history of atherothrombotic disease. The AGT levels were increased in the group of patients with stroke compared with the control group, but the AGT levels were not influenced by the allele or genotype in each polymorphism. CONCLUSIONS: The M235T and T174M polymorphisms represented an increased risk for stroke in young Mexican individuals. In contrast, the I/D was not associated with in the same group of patients. The AGT levels were higher in the acute phase of stroke, but it was not determined by the polymorphisms.

[Polimorfismos asociados a disfunción endotelial y a un estado protrombótico en jóvenes mexicanos con infarto cerebral].

OBJECTIVE: To examine the contribution the polymorphisms G20210A, G1691A and G10976A in the coagulation factors FII, FV, FVII, respectively; Glu298Asp and C677T in eNOS and 5,10 MTHFR in young Mexican population with cerebral infarction (CI). METHODS: 224 patients ≤ 45 years of age with CI and 224 controls matched by age and gender were recruited from 2006 and 2014. The polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: We identified a significant difference in the genotype distribution of Glu298Asp (p = 0.001) and C677T (p = 0.01) polymorphisms between CI patients and control groups. The genotype distribution in the FII G20210A, FV G1691A and FVII G10976A polymorphisms were similar. There were independent factors for ischemic stroke: Glu298Asp and C677T polymorphisms, smoking; hypertension, and familial history of thrombotic disease. CONCLUSIONS: The Glu298Asp and C677T, but not FII G20210A, FV G1691A and FVII G10976A polymorphisms were associated with CI. Our results suggest that endothelial dysfunction and the synergist interaction with other factors such as smoking and hypertension contribute to CI in young individuals.

OBJETIVO: Examinar la contribución de los polimorfismos G20210A, G1691A y G10976A en los factores de coagulación FII, FV y FVII respectivamente; Glu298Asp y C677T en la óxido nítrico sintasa endotelial y 5,10 metilentetrahidrofolato reductasa, en población joven mexicana con infarto cerebral (IC). MÉTODO: Se incluyeron 224 pacientes ≤ 45 años de edad con diagnóstico de IC y 224 controles pareados por edad y sexo, de 2006 a 2014. Los polimorfismos fueron determinados por la técnica de reacción en cadena de la polimerasa-polimorfismos de longitud de fragmentos de restricción. RESULTADOS: Identificamos una diferencia significativa en la distribución genotípica de los polimorfismos Glu298Asp (p = 0.001) y C677T (p = 0.01) entre el grupo de pacientes con IC y el control. La distribución genotípica de los polimorfismos FII G20210A, FV G1691A y FVII G10976A fue similar entre ambos grupos. Se identificaron como factores independientes de IC los polimorfismos Glu298Asp y C677T, el tabaquismo, la hipertensión y el antecedente de familiar de enfermedad trombótica. CONCLUSIONES: Los polimorfismos Glu298Asp y C677T, pero no FII G20210A, FV G1691A y FVII G10976A, se asociaron con IC. Nuestros resultados sugieren que la disfunción endotelial en interacción sinérgica con otros factores de riesgo, como tabaquismo e hipertensión, contribuye al IC en individuos jóvenes.