Utility of myeloperoxidase in the differential diagnosis of acute coronary syndrome.

OBJECTIVES: To determine the usefulness of myeloperoxidase in discriminating between patients with acute coronary syndrome and patients with chest pain by other causes. METHODS: The study included all patients over 18 years of age who come consecutively to the emergency department from September 2015 to December 2015 with chest pain of non-traumatic origin. The initial patient evaluation was performed according to the study protocol for patients with suspected acute coronary syndrome (ACS) in our Emergency Department. This included the serial measurement of troponin, and in this case myeloperoxidase, with serialization on admission and at 6h. For the determination of myeloperoxidase (MPO), a single step sandwich enzyme immunoassay by Siemens, automated on a Dimension analyser, was used. RESULTS: Statistically significant differences were observed in the concentration of myeloperoxidase at time 0 among patients diagnosed with ACS: 505 (413)pmol/L, and non-ACS patients: 388 (195)pmol/L (p<.001), as well as at 6h (p<.001). An area under the curve ROC of 0.824 was obtained at 6h for ACS patients, with a confidence interval of 95% from 0.715 to 0.933 and a level of significance of p<.001. Statistically significant differences were also found in the concentration of myeloperoxidase at time 0 and at 6h among patients with ACS and patients with heart disease other than coronary artery disease. CONCLUSIONS: The concentration of MPO helps to differentiate between ACS and non-ACS patients, as well as between ACS patients and patients with heart diseases other than coronary artery disease.

Utility of myeloperoxidase in the differential diagnosis of acute coronary syndrome / Utilidad de la determinación de mieloperoxidasa en el diagnóstico diferencial del síndrome coronario agudo

Abstract Objectives: To determine the usefulness of myeloperoxidase in discriminating between patients with acute coronary syndrome and patients with chest pain by other causes. Methods: The study included all patients over 18 years of age who come consecutively to the emergency department from September 2015 to December 2015 with chest pain of non- traumatic origin. The initial patient evaluation was performed according to the study protocol for patients with suspected acute coronary syndrome (ACS) in our Emergency Department. This included the serial measurement of troponin, and in this case myeloperoxidase, with serialization on admission and at 6 h. For the determination of myeloperoxidase (MPO), a single step sandwich enzyme immunoassay by Siemens, automated on a Dimension analyser, was used. Results: Statistically significant differences were observed in the concentration of myeloperoxidase at time 0 among patients diagnosed with ACS: 505 (413) pmol/L, and non-ACS patients: 388 (195) pmol/L (p < .001), as well as at 6 h (p < .001). An area under the curve ROC of 0.824 was obtained at 6 h for ACS patients, with a confidence interval of 95% from 0.715 to 0.933 and a level of significance of p <.001. Statistically significant differences were also found in the concentration of myeloperoxidase at time 0 and at 6 h among patients with ACS and patients with heart disease other than coronary artery disease. Conclusions: The concentration of MPO helps to differentiate between ACS and non-ACS patients, as well as between ACS patients and patients with heart diseases other than coronary artery disease.

Resumen Objetivos: Conocer la utilidad de mieloperoxidasa (MPO) para discriminar entre pacientes con síndrome coronario agudo y dolor torácico de otras causas. Métodos: De septiembre a diciembre de 2015 se incluyeron todos los pacientes mayores de 18 años que acudieron de forma consecutiva al servicio de urgencias con dolor torácico de origen no traumático. La evaluación inicial del paciente se realizó de acuerdo con el protocolo de estudio para pacientes con sospecha de síndrome coronario agudo (SCA) en nuestro servicio de urgencias, que incluye la medición de troponina y en este caso MPO, con serialización al ingreso y a las 6 h. Para la determinación de MPO se utilizó un inmunoensayo enzimático de tipo sándwich, de una sola etapa de Siemens, automatizado en un equipo Dimension . Resultados: Se obtuvieron diferencias estadísticamente significativas en la concentración de MPO a tiempo 0 entre los pacientes con diagnóstico de SCA: 505 (413) pmol/l y los pacientes no SCA: 388 (195 pmol/l (p < 0.001), así como a las 6 h (p < 0.001). Se obtuvo a las 6 h un área bajo la curva ROC para pacientes con SCA de 0.824 con un intervalo de confianza del 95% de 0.715 a 0.933 y un grado de significación p < 0.001. También se obtuvieron diferencias estadísticamente significativas en la concentración de MPO tanto a tiempo 0 como a las 6 h entre pacientes con SCA y pacientes con enfermedad cardiaca diferente de enfermedad coronaria. Conclusiones: La concentración de MPO sirve para diferenciar entre pacientes SCA y pacientes que no son SCA, así como entre pacientes SCA y pacientes con otras enfermedades cardiacas diferentes a la enfermedad coronaria.

Paraoxonase 1 gene polymorphisms and enzyme activities in coronary artery disease and its relationship to serum lipids and glycemia / Polimorfismos en el gen de la paraoxonasa 1 y sus actividades enzimáticas en la enfermedad coronaria. Su relación con el perfil lipídico y la glucemia

Abstract Objectives Oxidative stress and inflammation are important processes in development of atherosclerosis. Paraoxonase 1 (PON1) is a bioscavenger enzyme associated with inflammation and oxidative stress. We evaluate the association of two single nucleotide polymorphisms in PON1 gene, and enzyme activities with lipid profile and glycemia. Methods This case-control study consisted of 126 patients with coronary artery disease (CAD) and 203 healthy controls. PON Q192R and L55M polymorphisms were detected by real-time PCR. Paraoxonase and arylesterase activities were determined spectrophotometrically. Blood glucose, cholesterol, triglycerides, HDL, and LDL were measured. Results PON1 QR192 polymorphism had a major effect on paraoxonase but no effect on arylesterase serum activities. Paraoxonase activity was higher in RR genotype and lowest in QQ genotype. Paraoxonase and arylesterase activities were higher in LL and lower in MM genotypes of PON1 LM55 polymorphism. RQ and LM variants showed intermediate activities between respective homozygous. Elevated concentrations of triglycerides in cases correlate with QQ variant or the presence of M allele. Glucose levels were elevated in cases with QQ variant or with the presence of M allele. Cholesterol and LDL did not show variations in control and cases with any variant of both polymorphisms. HDL is lower in cases with respect to controls independently of genotypes. All differences were significant with p < 0.05. Conclusions Our results confirm the relationship between variations in PON1 activities and lipid metabolism, and showed that genetically programmed low PON1 activities would have certain responsibility in the increase in glycemia and concomitantly the aggravation of atherosclerotic disease.

Resumen Objetivos La enzima paraoxonasa 1 (PON1), está asociada con el estrés oxidativo y la inflamación, procesos importantes en el desarrollo de la aterosclerosis. Evaluamos la asociación de 2 polimorfismos de un solo nucleótido en el gen PON1 y sus actividades enzimáticas con el perfil lipídico y la glucemia. Métodos Estudio caso-control en 126 pacientes con enfermedad coronaria y 203 controles sanos. Los polimorfismos PON Q192R y L55M fueron detectados por PCR en tiempo real y las actividades de paraoxonasa y arilesterasa por espectrofotometría. Se midieron glucemia, colesterol, triglicéridos, HDL y LDL. Resultados El polimorfismo PON1 QR192 afectó la actividad de paraoxonasa pero no la de arilesterasa. La actividad de paraoxonasa fue mayor en el genotipo RR y menor en QQ. Ambas actividades fueron mayores en el genotipo LL y menores en MM del polimorfismo PON1 LM55. Las variantes RQ y LM mostraron actividades intermedias entre los respectivos homocigotos. Concentraciones elevadas de triglicéridos en los casos correlacionaron con la variante QQ o la presencia del alelo M. Los niveles de glucosa fueron elevados en los casos QQ o con la presencia del alelo M. El colesterol y el LDL no variaron ni en los casos ni en los controles con ambos polimorfismos. El HDL fue menor en los casos respecto de los controles, independientemente del genotipo. Conclusiones Los resultados confirman la relación entre las variaciones en las actividades de PON1 y el metabolismo lipídico y mostraron que las bajas actividades de PON1 genéticamente programadas tendrían cierta responsabilidad en el aumento de la glucemia y, concomitantemente, en la agravación de la enfermedad aterosclerótica.

Paraoxonase 1 gene polymorphisms and enzyme activities in coronary artery disease and its relationship to serum lipids and glycemia.

OBJECTIVES: Oxidative stress and inflammation are important processes in development of atherosclerosis. Paraoxonase 1 (PON1) is a bioscavenger enzyme associated with inflammation and oxidative stress. We evaluate the association of two single nucleotide polymorphisms in PON1 gene, and enzyme activities with lipid profile and glycemia. METHODS: This case-control study consisted of 126 patients with coronary artery disease (CAD) and 203 healthy controls. PON Q192R and L55M polymorphisms were detected by real-time PCR. Paraoxonase and arylesterase activities were determined spectrophotometrically. Blood glucose, cholesterol, triglycerides, HDL, and LDL were measured. RESULTS: PON1 QR192 polymorphism had a major effect on paraoxonase but no effect on arylesterase serum activities. Paraoxonase activity was higher in RR genotype and lowest in QQ genotype. Paraoxonase and arylesterase activities were higher in LL and lower in MM genotypes of PON1 LM55 polymorphism. RQ and LM variants showed intermediate activities between respective homozygous. Elevated concentrations of triglycerides in cases correlate with QQ variant or the presence of M allele. Glucose levels were elevated in cases with QQ variant or with the presence of M allele. Cholesterol and LDL did not show variations in control and cases with any variant of both polymorphisms. HDL is lower in cases with respect to controls independently of genotypes. All differences were significant with p<0.05. CONCLUSIONS: Our results confirm the relationship between variations in PON1 activities and lipid metabolism, and showed that genetically programmed low PON1 activities would have certain responsibility in the increase in glycemia and concomitantly the aggravation of atherosclerotic disease.

Lack of an association between matrix metalloproteinase polymorphisms and coronary heart disease in a Han Chinese population.

Coronary heart disease (CHD) has become a leading cause of human deaths worldwide. Recent studied showed that polymorphisms of the matrix metalloproteinase (MMP) genes played important roles in extracellular matrix remodeling and contribute to the pathogenesis of vascular diseases. Here, we investigated whether these MMP gene polymorphisms were associated with CHD in Han Chinese. Our case-control study was involved with 1509 unrelated individuals, including 777 CHD cases and 732 controls. We selected a total of five polymorphisms whose genotypes were determined using Sequenom iPLEX technology. Our results showed there were no significant associations between the five MMP gene polymorphisms and CHD risk at either genotype or allele levels (P > 0.05). Further subgroup analyses by sex were also unable to reveal any significant association (P > 0.05). In conclusion, no significant associations were found between the five MMP gene polymorphisms and the risk of CHD in Han Chinese.

Traditional risk factors and angiotensin-converting enzyme insertion/deletion gene polymorphism in coronary artery disease.

We investigated whether the insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene and serum ACE levels are associated with traditional risk factors of coronary artery disease (CAD). We enrolled 250 individuals without CAD and 750 individuals suffering from CAD who were angiographically diagnosed. Biochemical risk factors, the ACE (I/D) gene polymorphism, and ACE serum levels were compared. ACE genotypes were determined using real-time polymerase chain reaction. ACE serum levels were determined using an enzyme-linked immunosorbent assay. Lipid parameters were determined spectrophotometrically using an autoanalyzer. Compared to the control group, the CAD group showed significantly higher serum ACE levels (P < 0.001). The highest ACE levels were found in those with the DD genotype. Other genotypes also presented statistically significant differences. We observed a significant difference between the control and coronary patient groups regarding the levels of total cholesterol, triglyceride, high-density lipoprotein-cholesterol, and low-density lipoprotein-cholesterol (P < 0.05). ACE (I/D) genotypes and serum ACE levels may be associated with risk factors and the development of CAD.

Type-2 diabetes mellitus and the frequency of the G22A polymorphism of the adenosine deaminase gene in a mixed population in Brazil.

BACKGROUND: Most individuals diagnosed with diabetes mellitus (about 90%) have type 2 disease (T2DM). T2DM is associated with a high genetic predisposition and is characterized by changes in the secretion and action of insulin. There have been reports of increased activity of the adenosine deaminase enzyme in individuals with coronary heart disease and DM. METHODS: We evaluated 162 patients with T2DM and 160 individuals without the disease. Additionally, a subgroup of 81 individuals at higher risk of developing cardiovascular diseases was formed from the group of patients with diabetes on the basis of their serum levels of high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc) and triglycerides. PCR-RFLP was performed to analyze the TaqI polymorphism G428A of the ADA gene; this technique identifies the ADA*01 and ADA*02 alleles. RESULTS: Genotype frequencies were calculated for three patient groups, as follows. Patients with diabetes: ADA*01;*01 (142/159, 89.3%), ADA*01;*02 (16/159, 10.1%) and ADA*02;*02 (1/159, 0.6%); control group: ADA*01;*01 (146/160, 91.3%), ADA*01;*02 (12/160, 7.5%) and ADA*02;*02 (2/160, 1.3%); patients at risk of cardiovascular disease: ADA*01;*01 (71/78, 91.0%), ADA*01;*02 (7/78, 9.0%) and ADA*02;*02 (0/78, 0.0%). CONCLUSION: No statistically significant differences between the groups were observed in the genotype and allele frequencies. However, this fact does not rule out the need for further studies on the frequencies of this polymorphism in the Brazilian population, on any association with ADA enzyme activity, and on other risk factors that can affect the quality of life of Brazilian patients with T2DM.

Association of circulating levels of nicotinamide phosphoribosyltransferase (NAMPT/Visfatin) and of a frequent polymorphism in the promoter of the NAMPT gene with coronary artery disease in diabetic and non-diabetic subjects.

BACKGROUND: Nicotinamide phosphoribosyltransferase (NAMPT) is the limiting enzyme in one of pathways of synthesis of Nicotinamide Adenine Dinucleotide, a redox coenzyme. NAMPT is considered as an insulin-mimetic factor and a potential regulatory factor in inflammatory and immune processes. Associations of circulating NAMPT levels with cardiovascular disease (CVD) and insulin resistance have been reported. We investigated association of circulating NAMPT levels and the rs9770242 NAMPT gene polymorphism with coronary artery disease (CAD). METHODS: We studied 594 Brazilian subjects undergoing a coronary angiography (49% of whom had type 2 diabetes). CAD, defined as stenosis greater than 50% in one major coronary vessel or branch, was observed in 68% of subjects. Genetic studies were also performed in 858 North-American Non-Hispanic White subjects with type 2 diabetes (49% with CAD). RESULTS: We observed an interaction between glycemic and CAD status on the comparison of NAMPT levels by CAD status. NAMPT levels were higher in type 2 diabetic patients with CAD as compared to those without CAD: 5.27 ± 2.93 ng/ml vs. 4.43 ± 2.94 ng/ml, p = 0.006 (mean ± SD). NAMPT levels were not significantly different in non-diabetic subjects with or without CAD. The T-allele of rs9770242 was associated with CAD in the Brazilian cohort (OR 1.46, 95% CI 1.06 - 2.01, p = 0.02) while no association was observed in the North-American cohort. CONCLUSIONS: Our data suggest that circulating NAMPT levels are associated with CAD in type 2 diabetic patients. NAMPT rs9770242 polymorphism may be associated with CAD in some populations.

11ß-hydroxysteroid dehydrogenase type 1 gene expression is increased in ascending aorta tissue of metabolic syndrome patients with coronary artery disease.

11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD-1) activity and mRNA levels are increased in visceral and subcutaneous adipose tissues of metabolic syndrome subjects. We analyzed 11ß-HSD-1 expression in human epicardial adipose (EA) and ascending aorta (AA) tissues of metabolic syndrome patients and examined their contribution to the development of coronary atherosclerosis. The 11ß-HSD-1 expression was evaluated by qRT-PCR in EA and AA tissues of 20 metabolic syndrome patients with coronary artery disease (metabolic syndrome group) and 10 non-metabolic syndrome patients without coronary artery disease (controls). 11ß-HSD-1 expression was increased in EA and AA tissues of the metabolic syndrome group (4.1- and 5.5-fold, respectively). A significant positive correlation was found between 11ß-HSD-1 expression in EA tissue and waist hip ratio and 11ß-HSD-1 expression in AA tissue and body mass index, while a negative correlation was found between 11ß-HSD-1 expression in EA tissue and HDL. Expression of CD68, a macrophage marker, was significantly increased in both tissues of the metabolic syndrome group; it was 2-fold higher in AA tissue compared to EA tissue in the metabolic syndrome group. Our findings of increased expression of 11ß-HSD-1 and CD68 in AA tissue of the metabolic syndrome group lead us to suggest that they contribute to coronary atherosclerosis in metabolic syndrome. This positive correlation between obesity markers and 11ß-HSD-1 in AA and EA tissues strengthens the evidence that 11ß-HSD-1 has a role in metabolic syndrome. To the best of our knowledge, this is the first report showing 11ß-HSD-1 and CD68 expression in AA tissue of metabolic syndrome patients. We suggest that there is tissue-specific expression of 11ß-HSD-1 in metabolic syndrome and associated cardiovascular disorders.

Lack of association between plasma myeloperoxidase levels and angiographic severity of coronary artery disease in patients with acute coronary syndrome.

OBJECTIVE: To evaluate the association between plasma myeloperoxidase (MPO) levels and angiographic severity of coronary atherosclerotic lesions in patients with non-ST elevation acute coronary syndrome (ACS). DESIGN AND METHODS: This cross-sectional study examined high-risk ACS patients who underwent coronary angiography within 72 h of the onset of symptoms by measuring their plasma MPO levels after sheath insertion. Gensini score was used to evaluate angiographic severity of coronary artery disease. RESULTS: A total of 48 patients were included in the study. Median MPO levels and Gensini scores were 6.9 ng/mL (4.4-73.5 ng/mL) and 10 (0-87.5), respectively. Spearman's correlation coefficient did not show a significant association between MPO levels and Gensini scores (r (s) = 0.2; p = 0.177). There was no correlation between MPO and age, hypertension, diabetes, leukocyte count, troponin I, CK-MB ≥ 2 × ULN (upper limit of normal), TIMI risk score ≥ 4 and Gensini score in the multivariate analysis. CONCLUSION: Our findings indicate that MPO expression is not associated with anatomical severity of coronary lesions in ACS.

Prognostic value of myeloperoxidase in coronary artery disease: comparison of unstable and stable angina patients.

BACKGROUND: Atherosclerosis is a chronic inflammatory process, and myeloperoxidase (MPO) seems to contribute directly to the pathogenesis of acute coronary syndrome (ACS). OBJECTIVE: To compare MPO levels among the patients with stable and unstable ischemic heart disease and to evaluate their independent prognostic value for cardiovascular events. METHODS: MPO and C-reactive protein (CRP) were assessed in two cohorts of coronary artery disease patients, including 178 patients with stable angina and 130 patients with ACS evaluated at the emergency department. RESULTS: MPO and CRP levels were significantly higher among patients with ACS [MPO 93 (54-127) vs. 9.9 pmol/l (5-21) and high sensitivity-CRP 11 (3-27) vs. 2.6 mg/l (1-5)]. Among patients with stable angina, high sensitivity-CRP levels greater than 3 mg/l were associated with a three-fold risk of further cardiovascular events during a mean follow-up period of 13+/-4 months, although there was no significant association between MPO levels and outcomes. Among patients with ACS, baseline MPO level was an independent predictor of major adverse cardiac events during hospitalization, odds ratio of 3.8 (95% confidence interval: 1.2-12) for the combined endpoint (death, recurrent angina, heart failure, and arrhythmia). CRP levels were associated with hospital mortality in patients with ACS, but were not independently related to cardiovascular events. CONCLUSION: Elevated MPO levels among the ACS patients suggest that this marker may participate in plaque vulnerability and instability process, whereas higher CRP levels were predictive of cardiac events only among the stable angina patients. These findings suggest distinct role of the inflammatory markers studied in the pathophysiology of coronary artery disease.

Secretory phospholipase A2 in patients with coronary artery disease.

This study investigated the correlation of sPLA2 (secretory phospholipase A2) activity with the atheromatosis extent in subjects with coronary artery disease (CAD) undergoing coronary angiography. We analyzed 123 patients, including 35 subjects with angiographically normal coronary arteries (controls), 31 with mild/moderate atheromatosis (stenosis of 30-70% of the luminal diameter in one or more coronary arteries) and 57 with severe atheromatosis (>70% stenosis). Plasma sPLA2 activity was significantly higher in subjects with severe [127.7 U/ml (102.3-162.7); p < 0.0001] and mild/moderate [112.0 U/ml (100.6-146.9); p < 0.0001] atheromatosis than in controls [19.8 U/ml (15.1-32.1)]. In a multiple logistic regression model, adjusted for age, gender, body mass index, tabagism, hypertension, sedentarism, family history for coronary artery disease, diabetes mellitus, total cholesterol, HDLc, LDLc, triglycerides, high sensitivity C-reactive protein and phospholipase A2, only sPLA2 was observed to be independently associated with severe CAD (>70% of stenosis) (p < 0.0001).

Genetic polymorphisms involved in folate metabolism and concentrations of methylmalonic acid and folate on plasma homocysteine and risk of coronary artery disease.

OBJECTIVES: Alterations in the enzymes involved in homocysteine (Hcy) metabolism or vitamin deficiency could play a role in coronary artery disease (CAD) development. This study investigated the influence of MTHFR and MTR gene polymorphisms, plasma folate and MMA on Hcy concentrations and CAD development. MMA and folate concentrations were also investigated according to the polymorphisms. METHODS: Two hundred and eighty-three unrelated Caucasian individuals undergoing coronary angiography (175 with CAD and 108 non-CAD) were assessed in a case-control study. Plasma Hcy and MMA were measured by liquid chromatography/tandem mass spectrometry. Plasma folate was measured by competitive immunoassay. Dietary intake was evaluated using a nutritional questionnaire. Polymorphisms MTHFR and MTR were investigated by polymerase chain reaction (PCR) followed by enzyme digestion or allele-specific PCR. RESULTS: Hcy mean concentrations were higher in CAD patients compared to controls, but below statistical significance (P = 0.246). Increased MMA mean concentrations were frequently observed in the CAD group (P = 0.048). Individuals with MMA concentrations >0.5 micromol/l (vitamin B(12) deficiency) were found only in the CAD group (P = 0.004). A positive correlation between MMA and Hcy mean concentrations was observed in both groups, CAD (P = 0.001) and non-CAD (P = 0.020). MMA mean concentrations were significantly higher in patients with hyperhomocysteinemia in both groups, CAD and non-CAD (P = 0.0063 and P = 0.013, respectively). Folate mean concentration was significantly lower in carriers of the wild-type MTHFR 1298AA genotype (P = 0.010). CONCLUSION: Our results suggest a correlation between the MTHFR A1298C polymorphism and plasma folate concentration. Vitamin B(12) deficiency, reflected by increased MMA concentration, is an important risk factor for the development both of hyperhomocysteinemia and CAD.

Presencia del alelo T para el polimorfismo rs2781666 G>T del gen arginasa 1 constituye un factor protector contra enfermedad arterial coronaria / The presence of T allele for rs2781666 G>T common variant of arginase 1 gene constitutes a protector factor against coronary artery disease in Southern Chilean subjects

Introducción: Variaciones moleculares en el gen de la arginasa I, ARGl, podrían provocar un aumento de la expresión de la enzima o de su actividad, lo que puede llevar a una disfunción endotelial al disminuir la producción de óxido nítrico por parte de la eNOS. Así, el objetivo del presente estudio fue investigar la posible asociación del polimorfismo rs2781666 G>T y la presencia de enfermedad coronaria (confirmada con angiografía) en individuos de la región de La Araucanía. Material y Métodos: En el presente estudio, de tipo casos y controles, fueron evaluados 247 sujetos, con edades entre 30 y 74 años; 124 individuos pacientes con enfermedad arterial coronaria (casos) y 123 controles. La genotipificación del polimorfismo rs2781666 del gen ARGl fue realizada mediante PCR- RFLR Resultados: La frecuencia del genotipo homocigoto TT para el polimorfismo rs2781666 del gen ARGl fue de 6.5 por ciento en el grupo casos y 8 por ciento en el grupo control, difiriendo significativamente (p=0.032). La frecuencia relativa del alelo T también presentó diferencias significativas entre casos y controles (0.230 vs. 0.325, p=0.031). La OR relacionada al alelo mutado T fue de 0.63 (I.C. 95 por ciento, 0.43 - 0.94), confirmando la presencia de la asociación observada. Conclusión: Los resultados obtenidos sugieren que el polimorfismo rs2781666 G>T del gen ARGl confiere protección contra enfermedad coronaria en la población analizada. Sin embargo, este resultado debe ser replicado en otros grupos poblacionales de nuestro país.

Background: Recent data support a role for arginase 1 (ARG1) in the initiation, development, and complications of coronary artery disease. Thus, in the present study we investigated the possible association between the rs2781666 G>T variant of ARG1 and the presence of CAD confirmed by angiography in Chilean subjects. Methods: A total of 124 unrelated patients with diagnosis of CAD confirmed by angiography (stenosis > 70 percent) and 123 healthy controls (30 - 74 years old) were included in this study. The rs2781666 G>T variant of the ARG1 gene was evaluated by PCR-RFLR Results: The frequency of TT homozygous genotype in CAD patients was lower when compared to control group (6.5 percent vs. 8.0 percent, p=0.032). Similarly, the T allele frequency was different between CAD and control groups (0.230 vs. 0.325, p=0.031). The OR for CAD related to T allele was 0.64 (95 percent CI. = 0.43-0.94), con-firming the association founded. Conclusion: These findings suggest that the T allele for rs2781666 polymorphism of the ARG1 gene constitutes an inherited protective factor against CAD in Southern Chilean subjects.

In vitro simultaneous transfer of lipids to HDL in coronary artery disease and in statin treatment.

The exchange of lipids with cells and other lipoproteins is a crucial process in HDL metabolism and for HDL antiatherogenic function. Here, we tested a practical method to quantify the simultaneous transfer to HDL of phospholipids, free-cholesterol, esterified cholesterol and triacylglycerols and to verify the lipid transfer in patients with coronary artery disease (CAD) or undergoing statin treatment. Twenty-eight control subjects without CAD, 27 with CAD and 25 CAD patients under simvastatin treatment were studied. Plasma samples were incubated with a donor nanoemulsion prepared by ultrasonication of the constituent lipids and labeled with radioactive lipids; % lipids transferred to HDL were quantified in the HDL-containing supernatant after chemical precipitation of non-HDL fractions and the nanoemulsion. The assay was precise and reproducible. Increase of temperature (4-37 degrees C), of incubation period (5 min to 2 h), of HDL-cholesterol concentration (33-244 mg/dL) and of mass of nanoemulsion lipids (0.075-0.3 mg/microL) resulted in increased lipid transfer from the nanoemulsion to HDL. In contrast, increasing pH (6.5-8.5) and albumin concentration (3.5-7.0 g/dL) did not affect lipid transfer. There was no difference between CAD and control non-CAD with regard to the lipid transfer, but statin treatment reduced the transfer to HDL of all four lipids. The test herein described is a valid and practical tool for exploring an important aspect of HDL metabolism.

Actividades paraoxonasa y arilesterasa bajas en sujetos mexicanos con enfermedad arterial coronaria / Low paraoxonase and arylesterase plasma activities in mexican patients with coronary artery disease

PURPOSE: To determine the Paraoxonase-1 (PON1) activity as well as its pheno- and genotypes at position 192 in Mexican subjects with diagnosis of coronary heart disease (CHD). METHODS: We determined the PON1-192 polymorphism by PCR-RFLP, and serum PON1 activity, using either paraoxon (PONase activity) or phenylacetate (ARE activity) as substrates, in 155 clinically healthy individuals (control group), and 155 patients with at least one myocardial infarction (CHD group). The biochemical A/B phenotype was determined by the ratio of the NaCI 1 M-stimulated PONase activity divided by the ARE activity. RESULTS: We found significantly lower PONase and ARE activities in CHD patients as compared to controls (233.1 +/- 102.1 vs. 295.8 +/- 159.1 nmol/min/mL, and 103.1 +/- 33.7 vs 220.2 +/- 120.7 micromol/min/mL, respectively, p<0.05 for both). Allele and genotype frequencies for PON1-192 were similar in CHD patients and healthy controls. Moreover, in the control group, the PON1-192 Q/R genotype did not matched with the A/B phenotype as has been proposed by other studies. CONCLUSIONS: There were important differences in the ARE and PONase activities between Mexican CHD patients and controls, suggesting that PON1 activity could be a good marker of CHD risk, whereas PON1-192 lacks of value to assess such risk.

Myeloperoxidase and coronary arterial disease: from research to clinical practice.

Myeloperoxidase (MPO) is an enzyme derived of leukocytes that catalyze formation of numerous reactive oxidant species. Besides members of the innate host defense, evidences have been proving the contribution of these oxidants to tissue injury during inflammation. MPO participates in proatherogenic biological activities related to the evolution of cardiovascular disease, including initiation, propagation and acute complications of atherosclerotic process. Thereby, MPO and its inflammatory cascade represents an attractive target for prognostical investigation and therapeutics in atherosclerotic cardiovascular disease. In this review, we present the state of the art in the understanding of biological actions to clinical evidences of the relationship between MPO and coronary arterial disease. Several studies point to the independent effect of MPO levels in the evolution of disease and incidence of events in patients with acute coronary syndrome. However, the additional predictive value of MPO levels in the cardiovascular risk assessment, to incorporate it to the clinical practice as marker of plaque vulnerability, is still not consistent. Additional studies are necessary to confirm its role in the different forms of presentation of ischemic disease, besides the standardization of the assay, fundamental point for transition of this marker from research atmosphere to use in clinical routine: : from laboratory to clinical practice.

Mieloperoxidase e doença arterial coronariana: da pesquisa à prática clínica / Myeloperoxidase and coronary arterial disease: from research to clinical practice

A mieloperoxidase (MPO) é uma enzima derivada de leucócitos que catalisa a formação de numerosas espécies reativas oxidantes. Além de integrantes da resposta imune inata, evidências têm comprovado a contribuição desses oxidantes para o dano tecidual durante inflamação. A MPO participa de atividades biológicas pró-aterogênicas relacionadas à evolução da doença cardiovascular, incluindo iniciação, propagação e as fases de complicação aguda do processo aterosclerótico. Dessa forma, a MPO e sua cascata inflamatória representam um alvo atrativo para investigação prognóstica e terapêutica na doença aterosclerótica cardiovascular. Nesta revisão, apresentamos o estado da arte no entendimento das ações biológicas às evidências clínicas da relação entre MPO e doença arterial coronariana. Vários estudos apontam para o efeito independente dos níveis de MPO na evolução da doença e ocorrência de eventos em pacientes com síndrome coronariana aguda. Entretanto, ainda não é consistente o valor preditivo adicional dos níveis de MPO na estratificação de risco cardiovascular para incorporá-la à prática clínica como sinalizadora de vulnerabilidade de placa. Estudos adicionais são necessários para confirmar seu papel nas diferentes formas de apresentação da cardiopatia isquêmica, além da padronização do ensaio, ponto fundamental para a transição desse marcador do ambiente de pesquisa para uso na rotina clínica.

Myeloperoxidase (MPO) is an enzyme derived of leukocytes that catalyze formation of numerous reactive oxidant species. Besides members of the innate host defense, evidences have been proving the contribution of these oxidants to tissue injury during inflammation. MPO participates in proatherogenic biological activities related to the evolution of cardiovascular disease, including initiation, propagation and acute complications of atherosclerotic process. Thereby, MPO and its inflammatory cascade represents an attractive target for prognostical investigation and therapeutics in atherosclerotic cardiovascular disease. In this review, we present the state of the art in the understanding of biological actions to clinical evidences of the relationship between MPO and coronary arterial disease. Several studies point to the independent effect of MPO levels in the evolution of disease and incidence of events in patients with acute coronary syndrome. However, the additional predictive value of MPO levels in the cardiovascular risk assessment, to incorporate it to the clinical practice as marker of plaque vulnerability, is still not consistent. Additional studies are necessary to confirm its role in the different forms of presentation of ischemic disease, besides the standardization of the assay, fundamental point for transition of this marker from research atmosphere to use in clinical routine: : from laboratory to clinical practice.

-786T>C polymorphism of the endothelial nitric oxide synthase gene in Chilean subjects with coronary artery disease and controls.

BACKGROUND: The vascular endothelium plays an important role in the atherosclerotic process through the release of mediators such as nitric oxide. The NO relaxes vascular smooth muscle, inhibits platelet activation, and modulates migration and growth of vascular smooth muscle cells; consequently eNOS may have a significant atheroprotective function through this mechanism. The -786T>C polymorphism of the eNOS gene has been implicated in the development of coronary artery disease (CAD). We investigated the possible association between presence of CAD documented by angiography and the -786T>C polymorphism of the NOS3 gene in Chilean individuals. METHODS: A total of 112 unrelated patients with diagnosis of CAD and 109 controls were included in this study. The -786T>C gene polymorphism was analyzed by PCR-RFLP. RESULTS: The frequency of CC homozygous genotype for -786T>C polymorphism was 6% in CAD patients and 4% in the control group. However, the genotype distribution and allele frequencies were not significantly different between CAD and control subjects (P=NS). Moreover, the odds ratio for CAD associated with the C variant failed to reach statistical significance (OR=1.03; 95% CI: 0.60-1.76, P=NS). CONCLUSION: These findings suggest that the -786T>C polymorphism of the eNOS gene was not associated with CAD in study Chilean individuals.

[Low paraoxonase and arylesterase plasma activities in Mexican patients with coronary artery disease]. / Actividades paraoxonasa y arilesterasa bajas en sujetos mexicanos con enfermedad arterial coronaria.

PURPOSE: To determine the Paraoxonase-1 (PON1) activity as well as its pheno- and genotypes at position 192 in Mexican subjects with diagnosis of coronary heart disease (CHD). METHODS: We determined the PON1-192 polymorphism by PCR-RFLP, and serum PON1 activity, using either paraoxon (PONase activity) or phenylacetate (ARE activity) as substrates, in 155 clinically healthy individuals (control group), and 155 patients with at least one myocardial infarction (CHD group). The biochemical A/B phenotype was determined by the ratio of the NaCI 1 M-stimulated PONase activity divided by the ARE activity. RESULTS: We found significantly lower PONase and ARE activities in CHD patients as compared to controls (233.1 +/- 102.1 vs. 295.8 +/- 159.1 nmol/min/mL, and 103.1 +/- 33.7 vs 220.2 +/- 120.7 micromol/min/mL, respectively, p<0.05 for both). Allele and genotype frequencies for PON1-192 were similar in CHD patients and healthy controls. Moreover, in the control group, the PON1-192 Q/R genotype did not matched with the A/B phenotype as has been proposed by other studies. CONCLUSIONS: There were important differences in the ARE and PONase activities between Mexican CHD patients and controls, suggesting that PON1 activity could be a good marker of CHD risk, whereas PON1-192 lacks of value to assess such risk.