Hiperuricemia asintomática y enfermedad arterial coronaria / Asymptomatic hyperuricaemia and coronary artery disease

Antecedentes: El ácido úrico se ha relacionado con la tendencia de precipitarse para formar cristales, que se presenta desde manera asintomática hasta con artritis, tofos o litiasis renal. Con anterioridad, se ha asociado la hiperuricemia asintomática a la presencia de enfermedad cardiovascular. Objetivos: Determinar la asociación de enfermedad arterial coronaria compleja en pacientes con hiperuricemia asintomática. Material y métodos: Se realizó estudio observacional, transversal, retrospectivo, unicéntrico. En un hospital de tercer nivel de México, en el periodo comprendido de junio del 2017 a marzo del 2019. Se incluyó a todos los pacientes que ingresaron para realizar angiografía coronaria; se excluyó a los pacientes con gota, uso de diuréticos y enfermedad renal crónica. Resultados: Durante el periodo del estudio se seleccionó a un total de 300 pacientes, de los cuales 40% presentaron hiperuricemia. Los pacientes con hiperuricemia eran de mayor edad (59 vs. 63; p = 0,002). El grupo de pacientes con hiperuricemia asintomática tuvo mayor proporción de lesiones coronarias complejas (64 vs. 35%; p ≤ 0,0001), así como también mayor puntuación del SYNTAX I score (27 vs. 17; p ≤ 0,001). Hubo mayor probabilidad de presentar lesiones coronarias complejas en este grupo de pacientes (OR 3,4; p ≤ 0,0001). Además, en la división por grupos de nivel de ácido úrico, se relacionaba con la presencia de lesiones coronarias complejas (Q1 = 0,5; p = 0,06); (Q2 = 2; p = 0,01) y (Q3 = 3; p ≤ 0,0001). Conclusión: Los pacientes con hiperuricemia asintomática tienen mayor riesgo de presentar lesiones coronarias complejas.(AU)

Background: Uric acid has been related to a tendency to precipitate to form crystals, presenting asymptomatically, until the formation of arthritis, tophi or renal lithiasis. Previously, the presence of asymptomatic hyperuricaemia has been associated with the presence of cardiovascular disease. Objectives: To determine the association of complex coronary artery disease in patients with asymptomatic hyperuricaemia. Material and methods: An observational retrospective, transversal, unicentric study was conducted in a tertiary hospital in Mexico, in the period from June 2017 to March 2019. All patients admitted for coronary angiography were included; patients with gout, use of diuretics and chronic kidney disease were excluded. Results: During the study period, a total of 300 patients were collected, of which 40% presented hyperuricaemia. The patients with hyperuricaemia were older (59 vs. 63, P = .002). The group of patients with asymptomatic hyperuricaemia had a higher proportion of complex coronary lesions (64 vs. 35%, P ≤ .0001) as well as a higher SYNTAX I score (27 vs. 17, P ≤ .001). There was a higher probability of presenting complex coronary lesions in this group of patients (OR 3.4, P ≤ .0001). In addition, in the group division of uric acid levels, it was related to the presence of complex coronary lesions (Q1 = .5, P = .06), (Q2 = 2, P = .01) and (Q3 = 3, P ≤ .0001). Conclusion: Asymptomatic hyperuricaemia has a higher prevalence and association of presenting complex coronary lesions.(AU)

Deformación miocárdica de la aurícula izquierda en pacientes con lupus eritematoso sistémico / Left Atrial Strain in Patients With Systemic Lupus Erythematosus

Antecedentes: En los pacientes con lupus eritematoso sistémico (LES) la disfunción diastólica del ventrículo izquierdo (DDVI) puede ser la única manifestación de involucro cardiaco anticipando una disfunción sistólica. Se ha visto que la deformación miocárdica de la aurícula izquierda (AI), mediante el strain longitudinal global de la AI (SLGAI), puede llegar a ser de utilidad en valorar la función diastólica. Objetivo: Evaluar la función de la AI mediante la deformación miocárdica en pacientes con LES. Comparar el strain de la AI en pacientes con LES activos, inactivos y controles. Métodos: Se incluyeron 50 pacientes con LES y se compararon con controles sanos pareados por edad y sexo. Se midió por ecocardiograma transtorácico la deformación miocárdica mediante el SLGAI, el strain de las 3 fases del ciclo de la AI y la tasa de strain. La diferencia entre los grupos se analizó de forma univariante. Resultados: El SLGAI en pacientes con LES fue menor que en los controles sanos (41,6% vs. 50,5%; p=0,02), así como también fue menor en las 3 fases del ciclo de la AI. No hubo diferencias en la tasa de strain en ambos grupos (LES 2,5s−1 vs. controles sanos 2,75s−1; p=0,1). También se encontró que el SLGAI fue menor en pacientes activos en comparación con controles e inactivos. Conclusiones: Los pacientes con LES tienen menor deformación miocárdica de la AI, lo que se expresa como una menor función diastólica correlacionando con daño miocárdico subclínico precoz.(AU)

Background: In patients with systemic lupus erythematosus (SLE), left ventricle diastolic dysfunction (LVDD) may be the only manifestation of cardiac involvement in anticipation of systolic dysfunction. It has been seen that myocardial deformation of the left atrium (LA), through the LA global longitudinal strain (LAGLS), may be useful in assessing diastolic function. Objective: To evaluate LA function through myocardial deformation in patients with LES, and compare the LA strain in patients with active, inactive and controls. Methods: Fifty patients with SLE were included and compared with 50 healthy controls paired by age and gender. Myocardial deformation was measured by transthoracic echocardiogram, to investigate the LAGLS, the strain of the three phases of the LA cycle and the strain rate. The differences between groups were compared in univariate analysis. Results: LAGLS in SLE patients was less than in the controls (41.6% vs. 50.5%; p=.02), and in the 3 phases of the LA cycle. There were no differences in the LA strain rate in both groups (SLE 2.5s−1 vs. controls 2.75s−1; p=.1). It was also found that the LAGLS was lesser in active patients than controls and inactive. Conclusions: SLE patients have lower myocardial deformation of the LA, which is expressed as a lower diastolic function correlating with early subclinical myocardial damage.(AU)

Left Atrial Strain in Patients With Systemic Lupus Erythematosus. / Deformación miocárdica de la aurícula izquierda en pacientes con lupus eritematoso sistémico.

BACKGROUND: In patients with systemic lupus erythematosus (SLE), left ventricle diastolic dysfunction (LVDD) may be the only manifestation of cardiac involvement in anticipation of systolic dysfunction. It has been seen that myocardial deformation of the left atrium (LA), through the LA global longitudinal strain (LAGLS), may be useful in assessing diastolic function. OBJECTIVE: To evaluate LA function through myocardial deformation in patients with LES, and compare the LA strain in patients with active, inactive and controls. METHODS: Fifty patients with SLE were included and compared with 50 healthy controls paired by age and gender. Myocardial deformation was measured by transthoracic echocardiogram, to investigate the LAGLS, the strain of the three phases of the LA cycle and the strain rate. The differences between groups were compared in univariate analysis. RESULTS: LAGLS in SLE patients was less than in the controls (41.6% vs. 50.5%; p=.02), and in the 3 phases of the LA cycle. There were no differences in the LA strain rate in both groups (SLE 2.5s-1 vs. controls 2.75s-1; p=.1). It was also found that the LAGLS was lesser in active patients than controls and inactive. CONCLUSIONS: SLE patients have lower myocardial deformation of the LA, which is expressed as a lower diastolic function correlating with early subclinical myocardial damage.

Asymptomatic hyperuricaemia and coronary artery disease. / Hiperuricemia asintomática y enfermedad arterial coronaria.

BACKGROUND: Uric acid has been related to a tendency to precipitate to form crystals, presenting asymptomatically, until the formation of arthritis, tophi or renal lithiasis. Previously, the presence of asymptomatic hyperuricaemia has been associated with the presence of cardiovascular disease. OBJECTIVES: To determine the association of complex coronary artery disease in patients with asymptomatic hyperuricaemia. MATERIAL AND METHODS: An observational retrospective, transversal, unicentric study was conducted in a tertiary hospital in Mexico, in the period from June 2017 to March 2019. All patients admitted for coronary angiography were included; patients with gout, use of diuretics and chronic kidney disease were excluded. RESULTS: During the study period, a total of 300 patients were collected, of which 40% presented hyperuricaemia. The patients with hyperuricaemia were older (59 vs. 63, P = .002). The group of patients with asymptomatic hyperuricaemia had a higher proportion of complex coronary lesions (64 vs. 35%, P ≤ .0001) as well as a higher SYNTAX I score (27 vs. 17, P ≤ .001). There was a higher probability of presenting complex coronary lesions in this group of patients (OR 3.4, P ≤ .0001). In addition, in the group division of uric acid levels, it was related to the presence of complex coronary lesions (Q1 = .5, P = .06), (Q2 = 2, P = .01) and (Q3 = 3, P ≤ .0001). CONCLUSION: Asymptomatic hyperuricaemia has a higher prevalence and association of presenting complex coronary lesions.

Expression patterns of CD28 and CTLA-4 in early, chronic, and untreated rheumatoid arthritis.

BACKGROUND: T-cell activation pathways have been proposed as trigger mechanisms in the pathogenesis of rheumatoid arthritis (RA). CD28 and CTLA-4 play major roles in regulating the stimulatory and inhibitory co-signals in T cells. OBJECTIVE: To analyze the association between soluble and surface expression of CD28 and CTLA-4 with the clinical parameters of RA patients. METHODS: A total of 35 RA patients classified as early RA (n = 14), chronic RA (n = 14), and untreated RA (n = 7), as well as 7 age- and sex-matched control subjects (CS) were included. Surface expression of CD28 and CTLA-4 on T cells was evaluated by flow cytometry. Soluble levels of CD28 (sCD28), CTLA-4 (sCTLA-4), and anti-CCP antibodies were measured by ELISA. RESULTS: A significant lower percentage of CD8 + T cells positive to CD28 (CS = 64.9% vs RA = 42.7%, P = .04), and diminished surface expression of CD28 (CS: MFI = 122.9 vs RA: MFI = 33.1, P = .006), were found in chronic RA patients compared to CS. Higher sCD28 were observed in early RA patients compared with chronic RA patients (P < .05). sCTLA-4 was found increased in untreated RA patients compared to early RA patients (P < .05). sCD28 concentration correlated with anti-CCP levels (rho = -0.12; P = .032). The soluble and surface expressions of CTLA-4 were not associated with RA clinical parameters. CONCLUSIONS: In RA, the percentage of CD8 + CD28+ T cells decreases and expresses fewer membrane CD28 than CS. sCD28 levels are lower in chronic RA and are associated negatively with anti-CCP levels. sCTLA 4 levels are lower in early RA patients than in untreated RA patients.

Polimorfismo -1123G mayor que C en el gen PTPN22 y anticuerpos antipéptido citrulinado cíclico en la artritis reumatoide / PTPN22 -1123G is greater than C polymorphism and anti-cyclic citrullinated protein antibodies in rheumatoid arthritis

Introducción y objetivos: El gen de la proteína tirosina fosfatasa no receptora de tipo 22 (PTPN22) codifica la proteína linfoide tirosina fosfatasa -Lyp-, un importante regulador negativo de la activación de células T, que se ha asociado a distintos trastornos autoinmunitarios. El polimorfismo -1123G>C en el gen PTPN22 parece afectar al control de la transcripción de este gen, pero hasta la fecha, la importancia biológica sobre su contribución al riesgo de desarrollar artritis reumatoide (AR) sigue siendo desconocida. En el presente estudio evaluamos la asociación del polimorfismo -1123G>C con anti-cyclic citrullinated protein antibodies (anti-CCP, «anticuerpos antipéptido citrulinado cíclico») y el riesgo de desarrollar AR en la población del occidente de México. Materiales y métodos: Se realizó un estudio transversal analítico, en el que participaron 300 pacientes con AR clasificados de acuerdo con los criterios del ACR-EULAR y 300 sujetos control (SC). El polimorfismo -1123 G>C se genotipificó mediante PCR-RFLP. Los niveles de anticuerpos anti-CCP fueron cuantificados mediante una prueba de ELISA. Resultados: Encontramos una mayor prevalencia de genotipos homocigotos CC en SC en comparación con los pacientes con AR (OR 0,41; intervalo de confianza del 95% 0,24-0,71; p=0,001), lo que demuestra un posible efecto protector contra la AR. En cuanto a los niveles de anti-CCP, los portadores del genotipo CC mostraron los niveles más bajos en el grupo de AR (p<0,05). Conclusión: El genotipo CC del polimorfismo -1123G>C en el gen PTPN22 es un factor protector para la AR en la población mestiza mexicana y se asocia con niveles bajos de anticuerpos anti-CCP (AU)

Background and objectives: The protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene encodes an important negative regulator of T-cell activation, lymphoid-specific phosphatase -Lyp- and has been associated with different autoimmune disorders. The PTPN22 -1123G>C polymorphism appears to affect the transcriptional control of this gene, but to date, the biological significance of this polymorphisms on rheumatoid arthritis (RA) risk remains unknown. We evaluate the association of PTPN22 -1123G>C polymorphism with anti-cyclic citrullinated protein antibodies (anti-CCP) and risk for RA in population from Western Mexico. Material and methods: A transversal analytic study, which enrolled 300 RA patients classified according to ACR-EULAR criteria and 300 control subjects (CS) was conducted. The -1123 G>C polymorphism was genotyped by PCR-RFLP. The anti-CCP antibodies levels were quantified by ELISA kit. Results: We found a higher prevalence of homozygous PTPN22 -1123CC genotype in CS than in RA patients (OR 0.41; 95% confidence interval 0.24-0.71; P=.001), suggesting a potential protective effect against RA. Concerning anti-CCP levels, the CC genotype carriers showed the lowest median levels in RA (P<.05).Conclusion: The PTPN22 -1123CC genotype is a protector factor to RA in a Mexican-mestizo population and is associated with low anti-CCP antibodies (AU)

PTPN22 -1123G>C polymorphism and anti-cyclic citrullinated protein antibodies in rheumatoid arthritis. / Polimorfismo −1123G>C en el gen PTPN22 y anticuerpos antipéptido citrulinado cíclico en la artritis reumatoide.

BACKGROUND AND OBJECTIVES: The protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene encodes an important negative regulator of T-cell activation, lymphoid-specific phosphatase -Lyp- and has been associated with different autoimmune disorders. The PTPN22 -1123G>C polymorphism appears to affect the transcriptional control of this gene, but to date, the biological significance of this polymorphisms on rheumatoid arthritis (RA) risk remains unknown. We evaluate the association of PTPN22 -1123G>C polymorphism with anti-cyclic citrullinated protein antibodies (anti-CCP) and risk for RA in population from Western Mexico. MATERIAL AND METHODS: A transversal analytic study, which enrolled 300 RA patients classified according to ACR-EULAR criteria and 300 control subjects (CS) was conducted. The -1123 G>C polymorphism was genotyped by PCR-RFLP. The anti-CCP antibodies levels were quantified by ELISA kit. RESULTS: We found a higher prevalence of homozygous PTPN22 -1123CC genotype in CS than in RA patients (OR 0.41; 95% confidence interval 0.24-0.71; P=.001), suggesting a potential protective effect against RA. Concerning anti-CCP levels, the CC genotype carriers showed the lowest median levels in RA (P<.05). CONCLUSION: The PTPN22 -1123CC genotype is a protector factor to RA in a Mexican-mestizo population and is associated with low anti-CCP antibodies.

The -319C/+49G/CT60G haplotype of CTLA-4 gene confers susceptibility to rheumatoid arthritis in Mexican population.

Several single nucleotide polymorphisms (SNPs) within the CTLA-4 gene and elevated serum levels of soluble CTLA-4 (sCTLA-4) have been associated with autoimmunity including rheumatoid arthritis (RA). In this case-control study, we evaluated the relationship between the -319C/T (rs5742909) and CT60 G/A (rs3087243) SNPs and sCTLA-4 levels in 200 RA patients and 200 control subjects (CS) from Western Mexico. Both SNPs were genotyped with the polymerase chain reaction-restriction fragment length polymorphism technique and the sCTLA-4 levels were quantified using an enzyme-linked immunosorbent assay kit. In addition, we performed a haplotype analysis, including our previous data of the +49A/G (rs231775) SNP. The G/A genotype of the rs3087243 SNP was associated with a decreased risk of RA [odd ratio (OR) 0.61, 95% confidence interval (CI) 0.38-0.96, p = 0.024]. This protection was also observed in the negative anti-cyclic citrullinated peptide group of RA carriers of the A allele (OR 0.48, 95% CI 0.22-1.05, p = 0.042). On the contrary, we identified the -319C/+49G/CT60G haplotype of CTLA-4 gene as a risk factor for RA (OR 1.69, 95% CI 1.13-2.52, p = 0.01). The sCTLA-4 levels were not associated with RA (p = 0.377), but were correlated with the functional disability of these patients (r = 0.282, p = 0.012). However, in CS the C/T genotype of the rs5742909 SNP, as well as the G/G and G/A genotypes of the rs3087243 SNP were associated with higher sCTLA-4 levels (p < 0.001). In conclusion, our results suggest that the -319C/+49G/CT60G haplotype of CTLA-4 gene is a genetic marker of susceptibility to RA in Western Mexico, whereas the rs3087243 SNP confers protection against this disease. Moreover, both SNPs showed an effect on the sCTLA-4 production in our control population. However, further studies are required to evaluate the role of sCTLA-4 in RA, as well as the molecular and functional basis of the association between both CTLA-4 gene SNPs and soluble levels of CTLA-4 in CS.