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.

Ventilación mecánica invasiva en pacientes con COVID-19 en un hospital privado de México. Una serie de casos: descripción y evolución de un protocolo de intubación temprana / Invasive mechanical ventilation in patients with COVID-19 in a private hospital in Mexico. A case series: description and evolution of an early intubation protocol / Ventilação mecânica invasiva em pacientes com COVID-19 em um hospital privado no México. Uma série de casos: descrição e evolução de um protocolo de intubação precoce

Resumen: La mortalidad de los pacientes de COVID-19 en ventilación mecánica y las estrategias empleadas varían en la literatura. El objetivo de esta serie de casos es describir el curso clínico de pacientes en ventilación mecánica invasiva con COVID-19 y su desenlace a 28 días. Se incluyeron 21 pacientes con un promedio de edad de 49 ± 13 años, 81% de sexo masculino y 38% con al menos una comorbilidad. Las variables ventilatorias iniciales fueron PaO2/FiO2 de 135 ± 53, PEEP 12 cmH2O, presión meseta 26 ± 4.8 cmH2O, distensibilidad estática 32 ± 8.5 mL/cmH2O, driving pressure 15 ± 3.9 cmH2O y poder mecánico 19.2 ± 4 J/min. El 67% de los pacientes estuvieron en posición prono y en 76% se empleó bloqueante neuromuscular. Los desenlaces a 28 días fueron 21 días libres de ventilación mecánica y 14% de mortalidad.

Abstract: The mortality and ventilation strategies of COVID-19 ARDS vary in the literature. The objective of this case series is to describe the clinical course of patients on invasive mechanical ventilation with COVID-19 and its outcome at 28 days. Twenty-one patients were included with an average age of 49 ± 13 years, 81% male and 38% with at least one comorbidity. The initial ventilatory variables were PaO2/FiO2 of 135 ± 53, PEEP 12 cmH2O, plateau pressure 26 ± 4.8 cmH2O, static compliance 32 ± 8.5 mL/cmH2O, driving pressure 15 ± 3.9 cmH2O, and mechanical power 19.2 ± 4 J/min. 67% of the patients received prone position and in 76% a neuromuscular blocker was used. The 28-day outcomes were 21 days of mechanical ventilation-free days and 14% mortality.

Resumo: A mortalidade de pacientes com COVID-19 em ventilação mecânica e as estratégias utilizadas variam na literatura. O objetivo desta série de casos é descrever a evolução clínica de pacientes em ventilação mecânica invasiva com COVID-19 e sua evolução em 28 dias. Incluíram-se 21 pacientes com média de idade de 49 ± 13 anos, 81% do sexo masculino e 38% com pelo menos uma comorbidade. As variáveis ventilatórias iniciais foram PaO2/FiO2 135 ± 53, PEEP 12 cmH2O, pressão de platô 26 ± 4.8 cmH2O, complacência estática 32 ± 8.5 mL/cmH2O, pressão motriz 15 ± 3.9 cmH2O e potência mecânica 19.2 ± 4 J/min. 67% dos pacientes estavam em decúbito ventral e em 76% foi utilizado bloqueador neuromuscular. Os resultados aos 28 dias foram 21 dias sem ventilação mecânica e 14% de mortalidade.

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.

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.

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.

Association of renin-angiotensin system genes polymorphisms and risk of premature ST elevation myocardial infarction in young Mexican population.

: The renin-angiotensin system plays an important role in the regulation of blood pressure and the development of coronary artery disease. The aim was to examine the association of the insertion deletion in the angiotensin-converting enzyme gene, M235T and T174M polymorphisms in the angiotensinogen gene with ST elevation acute myocardial infarction (STEAMI) in young Mexican population. We analyzed 242 unrelated patients with STEAMI 45 or less years of age, admitted to a cardiovascular intense care unit, and 242 individuals without STEAMI matched by age and sex, recruited from January 2006 and June 2013. The polymorphisms insertion deletion, M235T and T174M were determined in all participants by a polymerase chain-reaction-restriction fragment length polymorphism assay. There was a significant difference in the insertion deletion genotype distribution between two groups (P = 0.03) and a higher percentage of the T allele M235T polymorphism in the group of STEAMI patients (P = 0.02). The T174M polymorphism was not associated (P = 0.08). The insertion deletion and M235T polymorphisms, smoking, hypertension, familial history of cardiovascular disease and dyslipidemia were independent risk factors for STEAMI. Our results identified that the D allele from the insertion deletion and M235T but not T174M polymorphisms represent an independent risk factor for STEAMI in young Mexican population.

Reduced proliferation of endothelial colony-forming cells in unprovoked venous thromboembolic disease as a consequence of endothelial dysfunction.

BACKGROUND: Venous thromboembolic disease (VTD) is a public health problem. We recently reported that endothelial colony-forming cells (ECFCs) derived from endothelial cells (EC) (ECFC-ECs) from patients with VTD have a dysfunctional state. For this study, we proposed that a dysfunctional status of these cells generates a reduction of its proliferative ability, which is also associated with senescence and reactive oxygen species (ROS). METHODS AND RESULTS: Human mononuclear cells (MNCs) were obtained from peripheral blood from 40 healthy human volunteers (controls) and 50 patients with VTD matched by age (20-50 years) and sex to obtain ECFCs. We assayed their proliferative ability with plasma of patients and controls and supernatants of cultures from ECFC-ECs, senescence-associated ß-galactosidase (SA-ß-gal), ROS, and expression of ephrin-B2/Eph-B4 receptor. Compared with cells from controls, cells from VTD patients showed an 8-fold increase of ECFCs that emerged 1 week earlier, reduced proliferation at long term (39%) and, in passages 4 and 10, a highly senescent rate (30±1.05% vs. 91.3±15.07%, respectively) with an increase of ROS and impaired expression of ephrin-B2/Eph-4 genes. Proliferation potential of cells from VTD patients was reduced in endothelial medium [1.4±0.22 doubling population (DP)], control plasma (1.18±0.31 DP), or plasma from VTD patients (1.65±0.27 DP). CONCLUSIONS: As compared with controls, ECFC-ECs from individuals with VTD have higher oxidative stress, proliferation stress, cellular senescence, and low proliferative potential. These findings suggest that patients with a history of VTD are ECFC-ECs dysfunctional that could be associated to permanent risk for new thrombotic events.

Hypofibrinolytic State in Subjects with Type 2 Diabetes Mellitus Aggravated by the Metabolic Syndrome before Clinical Manifestations of Atherothrombotic Disease.

Background. Metabolic and genetic factors induce plasminogen activator inhibitor type-1 (PAI-1) overexpression; higher PAI-1 levels decrease fibrinolysis and promote atherothrombosis. Aim. To assess PAI-1 antigen levels among subjects with type 2 diabetes mellitus (T2DM) plus Metabolic Syndrome (MetS) before clinical manifestations of atherothrombosis and the contribution of metabolic factors and 4G/5G polymorphism of PAI-1 gene on the variability of PAI-1. Methods. We conducted an observational, cross-sectional assay in a hospital in Mexico City from May 2010 to September 2011. MetS was defined by the International Diabetes Federation criteria. PAI-1 levels and 4G/5G polymorphism were determined by ELISA and PCR-RFLP analysis. Results. We enrolled 215 subjects with T2DM plus MetS and 307 controls. Subjects with T2DM plus MetS had higher PAI-1 levels than the reference group (58.4 ± 21 versus 49.9 ± 16 ng/mL, p = 0.026). A model with components of MetS explained only 12% of variability on PAI-1 levels (R2 = 0.12; p = 0.001), with ß = 0.18 (p = 0.03) for hypertension, ß = -0.16 (p = 0.05) for NL HDL-c, and ß = 0.15 (p = 0.05) for NL triglycerides. Conclusion. Subjects with T2DM plus MetS have elevated PAI-1 levels before clinical manifestations of atherothrombotic disease. Metabolic factors have a more important contribution than 4G/5G polymorphism on PAI-1 plasma variability.

GLU298ASP and 4G/5G Polymorphisms and the Risk of Ischemic Stroke in Young Individuals.

BACKGROUND: Polymorphisms in the endothelial nitric oxide synthase (eNOS) and in the plasminogen activator inhibitor -1 (PAI-1) genes have been implicated in stroke pathogenesis but results are still controversial. The aim of this study was to examine the possible contribution of Glu298Asp in the eNOS and 4G/5G in the PAI-1polymorphisms with ischemic stroke in a young Mexican population. MATERIALS AND METHODS: In a case-control study, conducted between January 2006 and June 2010, 204 patients ≤45 years of age with ischemic stroke and 204 controls matched by age and gender, were recruited. The Glu298Asp and 4G/5G polymorphisms were determined in all participants by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: There was a significant difference in the Glu298Asp genotype distribution (P=0.001) and allele frequency between the two groups (P=0.001). The 4G/5G genotype distribution (P=0.40) and the allele frequency was similar between groups; (P=0.13). There were independent factors for ischemic stroke: Asp carriage (GluAsp+AspAsp) (P=0.02); smoking (P=0.01); hypertension (P=0.03), and familial history of atherothrombotic disease (P=0.04). CONCLUSIONS: The Asp allele from the Gu298Asp gene represents an independent risk factor for ischemic stroke in a young Mexican population. In contrast, the 4G/5G was not associated with an increased risk for this disease in the same group of patients, as previously has been demonstrated in other populations.

Proinflammatory and prothrombotic state in subjects with different glucose tolerance status before cardiovascular disease.

BACKGROUND: Inflammation has been associated with insulin resistance, type 2 diabetes mellitus (T2DM), and atherothrombosis. AIM: To determine differences in levels of proinflammatory and prothrombotic markers such as high sensitivity C-reactive protein (hs-CRP) and fibrinogen in subjects with normal glucose tolerance (NGT), prediabetes, and T2DM and to establish their relationship with other cardiovascular risk factors before clinical manifestations of cardiovascular disease. METHODS: We conducted a nonrandomized, cross-sectional assay in a hospital at México City. The levels of hs-CRP and fibrinogen were measured and compared according to glucose tolerance status. RESULTS: We enrolled 1047 individuals and they were distributed into NGT n = 473, pre-DM n = 250, and T2DM n = 216. There was a statistical difference between NGT and T2DM groups for fibrinogen (P = 0.01) and hs-CRP (P = 0.05). Fibrinogen and hs-CRP showed a significant positive correlation coefficient (r = 0.53, P<0.0001). In a multiple stepwise regression analysis, the variability in fibrinogen levels was explained by age, HbA1c, and hs-CRP (adjusted R² = 0.31, P<0.0001), and for hs-CRP it was explained by BMI and fibrinogen (adjusted R² = 0.33, P<0.0001). CONCLUSION: Inflammation and prothrombotic state are present in people with T2DM lacking cardiovascular disease. Fibrinogen and Hs-CRP are positively correlated. Fibrinogen and hs-CRP concentrations are predominantly determined by BMI rather than glucose levels.

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.

Platelet glycoprotein IIIA PIA2 polymorphism is associated with ST elevation acute myocardial infarction in young Mexican population.

Platelet membrane glycoprotein IIb/IIIa plays an important role in adhesion and platelet aggregation. Polymorphisms of genes in platelet activation and fibrinolysis have been associated with myocardial infarction (MI), however this has not been confirmed by others, and results are still controversial. The aim of this study was to determine the frequency distribution and association of polymorphism in the platelet glycoprotein GPIIIa PLA/A2 and the possible interaction with the 4G/5G in the plasminogen activator inhibitor genes with ST elevation acute myocardial infarction (STEAMI) in young Mexican subjects. A total of 254 unrelated patients with first STEAMI ≤45 years of age, who were admitted to a cardiovascular intense care unit and 254 healthy controls matched by age and gender were recruited from January 2006 and May 2011. The PIA1/A2 and 4G/5G polymorphism were determined in all participants by a PCR restriction based restriction endonuclease digestion. There was a difference in the PIA2 allele distribution between both groups (P = 0.001). Also, we found an increased percent of 4G allele in the group of patients compared to control group (P = 0.001). There was an increased risk for STEAMI in carries with the allele PIA2 and 4G (OR = 4.3, CI 95 % 1.7-6.5). The modifiable risk factors such: smoking, hypertension, family history of cardiovascular disease, and dyslipidemia were associated with myocardial infarction. This is the first study to evaluate the role of gene polymorphism in both the thrombotic and fibrinolytic pathways in young Mexican individuals with STEAMI and suggest a synergistic effect between PIA2 and 4G allele.

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.

C677T polymorphism of the 5,10 MTHFR gene in young Mexican subjects with ST-elevation myocardial infarction.

BACKGROUND AND AIMS: The C677T polymorphism of 5,10 methylenetetrahydrofolate reductase (MTHFR) gene has been associated with hypertension and coronary artery disease in several populations worldwide, but results are still controversial. The aim of this study was to examine the possible association of C677T polymorphism with ST-elevation myocardial infarction (STEMI) in young Mexican subjects. METHODS: In a case-control study, 167 unrelated patients < or = 45 years of age with diagnosis of STEMI who were admitted to a cardiovascular intense care unit and 167 unrelated controls subjects matched by age and gender were recruited from January 2006 and June 2009. The C677T polymorphism was determined in all participants by a polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP). RESULTS: There was no significant difference in the genotype distribution between groups (p = 0.69) or allele frequency (p = 0.40). There were independent factors for STEMI: smoking (OR 4.9, 95% CI 3.0-8.1, p = 0.001), hypertension (OR 1.8, 95% CI 1.0-3.3, p = 0.03), family history of atherothrombotic disease (OR 2.3, 95% CI 2.0-4.6, p = 0.02), and dyslipidemia (OR 3.2, 95% CI 1.8-5.6, p <0.001). Diabetes mellitus did not represent an independent risk factor for STEMI (OR 1.2, 95% CI 0.2-2.2, p = 0.82). CONCLUSIONS: The TT genotype from the C677T of 5,10 MTHFR gene is not an independent risk factor for STEMI in the Mexican population. However, more studies are needed to determine the possible "protective effect" of the C677T polymorphism in our population.