Irma Isordia-Salas

Association of the Plasminogen Activator Inhibitor-1 Gene 4G/5G Polymorphism With ST Elevation Acute Myocardial Infarction in Young Patients

INTRODUCTION AND OBJECTIVES To investigate the role of the 4G/5G polymorphism in the plasminogen activator inhibitor-1 (PAI-1) gene in patients with ST-elevation myocardial infarction (STEMI) aged < or =45 years and its influence on regulation of the plasma PAI-1 concentration. METHODS This case-control study included 127 consecutive patients aged < or =45 years with a diagnosis of STEMI who were admitted to a cardiovascular intensive care unit and 127 controls recruited between January 2006 and March 2007. Participants were genotyped for the 4G/5G polymorphism using the polymerase chain reaction and restriction fragment length polymorphism analysis, and their plasma PAI-1 concentrations were measured. Informed consent was obtained from all participants. RESULTS There was a significant difference in genotype distribution between the two groups (P< .002). The 4G allele occurred more frequently in the patient group (P=.032). In addition, there were significant independent associations between STEMI and the 4G allele (i.e., 4G/4G plus 4G/5G; odds ratio [OR]=2.29; 95% confidence interval [CI], 1.12-4.68; P=.022), smoking (OR=23.23; 95% CI, 8.92-60.47; P< .001), a family history of cardiovascular disease (OR=4.66; 95% CI, 2.06-10.52; P=.001) and hypertension (OR=5.42; 95% CI, 1.67-17.56; P=.005). The plasma PAI-1 concentration was higher in individuals who were homozygous for the 4G allele (P< .001). CONCLUSIONS The study findings indicate that the 4G allele is an independent risk factor for acute myocardial infarction in young patients, as are smoking, hypertension and a family history of inherited cardiovascular disease.

Changes in circulating concentrations of soluble fms-like tyrosine kinase-1 and placental growth factor measured by automated electrochemiluminescence immunoassays methods are predictors of preeclampsia.

Objective: Preeclampsia is characterized by an imbalance in angiogenic factors such as soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF). We herein assessed whether these factors measured by a newly developed automated electrochemiluminescence immunoassay are associated with risk to develop preeclampsia. Methods: We performed a nested case–control study within a cohort of 230 women with singleton pregnancies. The study included all 37 women who eventually developed preeclampsia and 29 normotensive controls. Serum samples were collected at 4-week intervals (from weeks 20th to 36th). sFlt-1 and PlGF were measured using a commercial automated immunoassay (Elecsys). Results: Women destined to develop preeclampsia had lower PlGF levels and higher sFlt-1 levels and sFlt-1/PlGF ratio than women with normal pregnancies. These changes became significant at 20 weeks in women destined to develop early preeclampsia (<34 weeks, P ⩽ 0.003), and at 24–28 weeks in women who later developed preeclampsia (P ⩽ 0.024). The risk for developing preeclampsia was higher among women with PlGF concentration values in the lowest quartile or with sFlt-1 levels and sFlt-1/PlGF ratio in the highest quartile of the control distribution. The odds ratios were higher and appeared earlier in women destined to develop early preeclampsia than in women who presented preeclampsia later. The sFlt-1/PlGF ratio was more tightly associated with risk of preterm or term preeclampsia than either angiogenic factor alone. Conclusion: Changes in circulating concentrations of PlGF, sFlt-1, and in the sFlt-1/PlGF ratio precede the onset of preeclampsia. The risk profile of circulating angiogenic factors for developing preeclampsia distinctly evolves depending on whether this condition is manifested at preterm or term.

Circulating Angiogenic Factors and Urinary Prolactin as Predictors of Adverse Outcomes in Women With Preeclampsia

Preeclampsia is characterized by an imbalance in angiogenic factors. Urinary prolactin (PRL) levels and its antiangiogenic PRL fragments have been associated with disease severity. In this study, we assessed whether these biomarkers are associated with an increased risk of adverse maternal and perinatal outcomes in preeclamptic women. We studied 501 women with preeclampsia attended at a tertiary care hospital. Serum concentrations of soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and soluble endoglin (sEng), as well as urinary PRL levels, were measured by enzymed-linked immunosorbent assay. Antiangiogenic PRL fragments were determined by immunoblotting. The risk for any adverse maternal outcome and for having a small-for-gestational-age infant was higher among women with sFlt-1/PlGF ratios, sEng, and urinary PRL level values in the highest quartile (odds ratios ≥2.7), compared with the lowest quartile. Both urinary PRL levels and the presence of antiangiogenic PRL fragments were more closely associated with the risk of specific adverse maternal outcomes (placental abruption, hepatic hematoma or rupture, acute renal failure, pulmonary edema, maternal death, and need for endotracheal intubation, positive inotropic drug support, and hemodialysis; odds ratios ≥5.7 and ≥4.7, respectively) than either sFlt-1/PlGF ratio or sEng alone. We concluded that in preeclamptic women at the time of initial evaluation, sFlt-1/PlGF ratio and sEng are associated with increased risk of combined adverse maternal outcomes. However, urinary PRL concentrations and its antiangiogenic fragments appear to be better predictors of an adverse maternal outcome and may be useful for risk stratification in preeclampsia.

The Glu298ASP polymorphism of the endothelial nitric oxide synthase gene is associated with premature ST elevation myocardial infarction in Mexican population

BACKGROUND The polymorphism Glu298Asp of endothelial nitric oxide (eNOS) gene has been associated with hypertension and coronary artery disease in several populations worldwide, but results are still controversial. We examined the possible association of the Glu298Asp with premature ST elevation myocardial infarction (STEAMI) in young Mexican population. METHODS In a case-control study 180 unrelated patients with STEAMI < or =45years who were admitted to a cardiovascular intense care unit and 180 apparently healthy controls matched by age and gender were recruited from January 2006 to June 2009. The polymorphism Glu298Asp was determined in all participants by a polymerase chain-reaction-restriction fragment length polymorphism assay (PCR-RFLP). RESULTS There was a significant difference in the genotype distribution between 2 groups (P=0.001). The allele Asp occurred more frequently in the patients group (P=0.001). There were independent factors for STEAMI: the Asp allele (OR 2.2, 95% CI 1.1-3.5, P=0.03), smoking (OR 5.0, 95% CI 3.1-8.2, P<0.001), hypertension (OR 2.0, 95% CI 1.0-3.5, P=0.03), family history of cardiovascular disease, (OR 3.7, 95% CI 2.0-4.6, P=0.02), and dyslipidemia (OR 3.4, 95% CI 2.0-6.3, P=0.02). CONCLUSIONS The Asp allele from the Gu298Asp polymorphism represents an independent risk factor for premature STEAMI in Mexican Mestizo population.

The C677T Polymorphism of the Methylenetetrahydrofolate Reductase Gene Is Associated with Idiopathic Ischemic Stroke in the Young Mexican-Mestizo Population

Background and Purpose: Previous studies have demonstrated that a common polymorphism in the gene encoding 5,10-methylenetetrahydrofolate reductase (MTHFR) is associated with an increased risk for stroke. However, this relation remains controversial. Our aim was to investigate the possible association between the C677T polymorphism in the MTHFR gene and idiopathic ischemic stroke in the young Mexican-Mestizo population. Methods: One hundred seventy-eight patients <45 years with idiopathic ischemic stroke and 183 controls were tested for the C677T polymorphism in the MTHFR gene. Causes of primary thrombophilia as well as classical risk factors for atherothrombotic disease were also evaluated. Results: There was a significant difference in the genotype distribution between patients and controls (p = 0.01), but the allele frequency was similar in both groups (p = 0.09). The univariate analysis identified the T allele as a risk factor for ischemic stroke (TT and CT carriers), as compared with homozygous for C allele (p = 0.01). Hypertension and smoking prevalences were significantly higher in the group of patients. Also the T allele was significantly associated with large-vessel ischemic stroke. The postoral methionine load homocysteine levels were higher in patients with ischemic stroke versus controls (p < 0.001). There was a low prevalence of primary thrombophilia markers. Conclusions: The T allele from the C677T polymorphism of the MTHFR gene represents an independent risk factor for idiopathic ischemic stroke at young age in the Mexican-Mestizo population. Also, hypertension and smoking were independent risk factors in our study population. Primary thrombophilic risk factors were not associated with ischemic stroke in our population.

Prevalence of Metabolic Syndrome Components in an Urban Mexican Sample: Comparison between Two Classifications

Background. The aim of this study was to examine the prevalence of metabolic syndrome (MS) components in an urban Mexican sample. Methods. A total of 854 subjects were included. Anthropometric, blood pressure measurements, clinical data, and overnight fasting blood samples were obtained from all subjects. Results. In accordance with definitions by the American Heart Association/ National Heart, Lung, and Blood Institute (AHA/NHLBI) and the International Diabetes Federation (IDF), the prevalence of MS among participants was 59.7 and 68.7%, respectively. The prevalence of MS was higher in women and in individuals older than 45 years of age. More than 40% of the subjects fulfilled four criterions of MS according to both definitions. Conclusions. There was a high prevalence of MS components in an urban Mexican sample. Therefore, strong strategies had to be developed for early detection of MS and its components to prevent DMT2 and atherothrombotic complications in these patients.

Activated protein C resistance and factor V Leiden in Mexico.

A common cause of hereditary thrombophilia is activated protein C resistance (APCR), and most cases result from factor V Leiden mutation. An APCR phenotype without association with factor V Leiden has been described. This transversal, observational, nonrandomized study evaluated these 2 phenomena in healthy indigenous and mestizo Mexican subjects (n = 4345), including 600 Mexican natives. No indigenous subjects had APCR, but 82 mestizo subjects did. After retesting, 50 subjects had a negative test. The remaining 32 subjects had factor V Leiden, giving a 0.85% prevalence of factor V Leiden in the mestizo Mexican population. Only 31% of APCR carriers had factor V Leiden. These results show a very low prevalence of APCR and factor V Leiden in Mexico. Except for factor V Leiden, there are no other mutations in the factor V gene responsible for the APCR phenotype. Acquired APCR is nearly twice as prevalent as the inherited variant.

The impact of CYP3A5*1/*3, PIA1/A2 and T744C polymorphisms on clopidogrel and acetylsalicylic acid response variability in Mexican population.

INTRODUCTION Clopidogrel is recommended in addition to aspirin to prevent atherothrombotic events in patients with acute coronary syndromes (ACS) and in those undergoing percutaneous coronary intervention (PCI). However, an interindividual variability in platelet inhibition response to clopidogrel has been demonstrated, and is associated with recurrent cardiovascular events. Multiple mechanisms have been associated with no response including genetics factors. MATERIALS AND METHODS The present study enrolled 60 patients with ACS undergoing emergent PCI. Platelet aggregation to adenosine diphosphate and arachidonic acid was assessed by turbidimetric method at 24 hours after dual administration of 300 mg of clopidogrel and 300 mg of acetylsalicylic acid loading dose. Clopidogrel or acetylsalicylic acid resistance was defined by persistence of Platelet Reactivity (PR=ADP-Ag >70% or PR=Arachidonic Acid-Ag>20%) respectively. The CYP3A51*/5*, PIA1/A2, and T744C polymorphisms were determined in all participants by PCR-RFLP. RESULTS The allelic frequencies were: CYP3A5*3 (71.65%), PIA2 (10.8%), and 744 C (15.0%). We founded high percent of clopidogrel resistance (60.0%), compared with 8.3% of acetylsalicylic acid in those patients. The genotype frequencies of those polymorphisms were similar between responders and non responders defined by PR. There was a high percent of coronary adverse events. CONCLUSIONS We identified a high percent of clopidogrel resistance in Mexican patients with ACS undergoing PCI. However, a normal platelet response to acetylsalicylic acid was observed in most of them. There was no association between CYP3A5*1/*3, PIA1/A2, and T744C polymorphisms and clopidogrel resistance. More studies are needed to determine the possible interaction between genetics factors, platelet response to clopidogrel and cardiovascular adverse events.

Serum erythropoietin levels in kidney donors after renal transplantation.

BACKGROUND Renal transplantation is the treatment of choice for many patients with end-stage renal disease. In the donor, renal excretory function is not affected after nephrectomy; however, little is known about other functions such as erythropoietin production. We studied the erythropoietin production in renal donors after nephrectomy. METHODS We included healthy individuals fulfilling the criteria for kidney donation. Blood samples were collected before and monthly from 1 to 6 months after nephrectomy. Complete blood cell counts and erythropoietin were assayed. RESULTS Eight kidney donors were studied. A significant increase in erythropoietin levels was observed during the first 3 months, but no difference was observed by the 4th month as compared with basal values. CONCLUSIONS Erythropoietin production rose during the first 3 months after nephrectomy. However, erythropoietin was normal by the 4th month. Unchanged hemoglobin levels may suggest that the compensatory production of erythropoietin could participate in the preservation of an adequate physiological status of the donor after nephrectomy.

Endothelial colony-forming cells: Biological and functional abnormalities in patients with recurrent, unprovoked venous thromboembolic disease

INTRODUCTION Endothelial cells (ECs) are an important component of the blood coagulation system because it maintains blood fluid. Because in patients with venous thromboembolic disease (VTD) a thrombophilic condition is not found sometimes, we investigated if endothelial colony-forming cells (ECFCs) from these patients have biological and functional abnormalities. PATIENTS AND METHODS Human mononuclear cells (MNCs) were obtained from peripheral blood from patients with VTD and controls to obtain ECFCs. These cells were assayed for their immunophenotype and electron microscopy characteristics and their ability to form capillary-like structures and to produce pro-inflammatory and pro-angiogenic cytokines and reactive oxygen species (ROS). RESULTS ECFCs appeared at 7 and 21 days of culture in VTD patients and controls, respectively. ECFCs increased 8-fold in patients and emerged 1 week earlier. No differences in the size of the colonies of ECFCs were found. Numbers and time of appearance of ECFCs was different between groups. ECFC-derived ECs (ECFC-ECs) of both groups expressed CD31, CD34, CD146, and CD-309 but none expressed CD45, CD14, or CD90. Interest CD34 was highly expressed in ECFC-ECs from patients. In both groups, ECFC-ECs showed similar capacity to form capillary-like structures but ECFC-ECs from patients had significant abnormalities in the mitochondrial membrane. We found a significant increase in ROS production in ECFC-ECs from patients. There were significant differences in cytokine profiles between VTD patients and controls. CONCLUSIONS We found a dysfunctional state in ECFC from VTD patients resembling some characteristics of dysfunctional ECs. These findings may help to understand some pathophysiological aspects of VTD.