Methylation status of LDLR, PCSK9 and LDLRAP1 is associated with cardiovascular events in familial hypercholesterolemia

Aim: Methylation of LDLR, PCSK9 and LDLRAP1 CpG sites was assessed in patients with familialhypercholesterolemia (FH). Methods: DNA methylation of was analyzed by pyrosequencing in 131FH patients and 23 normolipidemic (NL) subjects. Results: LDLR, PCSK9 and LDLRP1 methylationwas similar between FH patients positive (MD) and negative (non-MD) for pathogenic variantsin FH-related genes. LDLR and PCSK9 methylation was higher in MD and non-MD groups thanNL subjects (p < 0.05). LDLR, PCSK9 and LDLRAP1 methylation profiles were associated withclinical manifestations and cardiovascular events in FH patients (p < 0.05). Conclusion: Differentialmethylation of LDLR, PCSK9 and LDLRAP1 is associated with hypercholesterolemia and cardiovascularevents. This methylation profile maybe useful as a biomarker and contribute to the management ofFH.

Frecuencia de eventos cardiovasculares en pacientes con lupus eritematoso sistémico / Frequency of cardiovascular events in patients with systemic lupus erythematosus

Resumen Introducción: el progreso en los tratamientos para el lupus eritematoso sistémico (LES) resultó en una disminución de la mortalidad; sin embargo, la enfermedad cardiovascular y las complicaciones infecciosas aún son las principales causas de muerte. La evidencia apoya la participación del sistema inmunológico en la generación de la placa aterosclerótica, así como su conexión con las enfermedades autoinmunes. Objetivos: describir la frecuencia de eventos cardiovasculares (ECV) en el Registro de Lupus Eritematoso Sistémico de la Sociedad Argentina de Reumatología (RELESSAR) transversal, así como sus principales factores de riesgo asociados. Materiales y métodos: estudio descriptivo y transversal para el cual se tomaron los pacientes ingresados en el registro RELESSAR transversal. Se describieron las variables sociodemográficas y clínicas, las comorbilidades, score de actividad y daño. ECV se definió como la presencia de al menos una de las siguientes patologías: enfermedad arterial periférica, cardiopatía isquémica o accidente cerebrovascular. El evento clasificado para el análisis fue aquel posterior al diagnóstico del LES. Se conformaron dos grupos macheados por edad y sexo 1:2. Resultados: 1515 pacientes mayores de 18 años participaron del registro. Se describieron 80 pacientes con ECV (5,3%). En este análisis se incluyeron 240 pacientes conformando dos grupos. La edad media fue de 47,8 (14,4) y 47,6 (14,2) en el grupo con y sin ECV respectivamente. Los pacientes con ECV tuvieron mayor duración del LES en meses, mayor índice de Charlson, mayor SLICC (Systemic Lupus International Collaborating Clinics/American College of Rheumatology), mayor frecuencia de manifestaciones neurológicas, síndrome antifosfolípido, hospitalizaciones y uso de ciclofosfamida. Las únicas variables asociadas en el análisis multivariado fueron el índice de Charlson (p=0,004) y el SLICC (p<0,001). Conclusiones: los ECV influyen significativamente en nuestros pacientes, y se asocian a mayor posibilidad de daño irreversible y comorbilidades.

Abstract Introduction: progress in treatments for systemic lupus erythematosus (SLE) has resulted in a decrease in mortality; however, cardiovascular and infectious diseases remain the leading causes of death. Evidence supports the involvement of the immune system in the generation of atherosclerotic plaque, as well as its connection to autoimmune diseases. Objectives: to describe the frequency of cardiovascular disease (CVD) in the cross-sectional RELESSAR registry, as well as its associated variables. Materials and methods: a descriptive and cross-sectional study was performed using patients admitted to the cross-sectional RELESSAR registry. Sociodemographic variables, clinical variables, comorbidities, activity and damage scores were described. CVD was defined as at least one of the following: peripheral arterial disease, ischemic heart disease, or cerebrovascular accident. All patients with at least one CVD were included in our analysis (heart attack, central nervous system vascular disease, and peripheral arteries atherosclerotic disease). The event classified for the analysis was that after the diagnosis of SLE. SLE diagnosis was previous to CVD. Two groups matched by age and sex, 1:2 were formed. Results: a total of 1515 patients older than 18 years participated in the registry. Eighty patients with CVD (5.3%) were described in the registry. Two-hundred and forty patients were included, according to two groups. The mean age was 47.8 (SD 14.4) and 47.6 (SD 14.2) in patients with and without CVD, respectively. Patients with CVD had a longer duration of SLE in months, a higher Charlson index, a higher SLICC, increased frequency of neurological manifestations, antiphospholipid syndrome, hospitalizations, and use of cyclophosphamide. The associated variables in the multivariate were the Charlson Index (p=0.004) and the SLICC (p<0.001). Conclusions: CVDs have a significant influence on our patients, being associated with a greater possibility of damage and comorbidities.

Predictive values of bilirubin for in-hospital adverse events in patients with ST-segment elevation myocardial infarction after primary percutaneous coronary intervention

Abstract Purpose To investigate the association between serum bilirubin levels and in-hospital Major Adverse Cardiac Events (MACE) in patients with ST-segment Elevation Myocardial Infarction (STEMI) undergoing primary Percutaneous Coronary Intervention (PCI). Methods A total of 418 patients with STEMI who underwent primary PCI were enrolled from October 1st, 2021 to October 31st 2022. The average age of enrolled participants was 59.23 years, and 328 patients (78.50%) were male patients. Patients were divided into MACE (patients with angina pectoris after infarction, recurrent myocardial infarction, acute heart failure, cardiogenic shock, malignant arrhythmias, or death after primary PCI) (n = 98) and non-MACE (n = 320) groups. Univariate and multivariate logistic regression analyses were performed to estimate the association between different bilirubin levels including Total Bilirubin (TB), Direct Bilirubin (DB), Indirect Bilirubin (IDB), and risk of in-hospital MACE. The area under the Receiver Operating Characteristic (ROC) curve was used to determine the accuracy of bilirubin levels in predicting in-hospital MACE. Results The incidence of MACE in STEMI patients increased from the lowest to the highest bilirubin tertiles. Multivariate logistic regression analysis showed that increased total bilirubin level was an independent predictor of in-hospital MACE in patients with STEMI (p for trend = 0.02). Compared to the first TB group, the ORs for risk of MACE were 1.58 (95% CI 0.77‒3.26) and 2.28 (95% CI 1.13‒4.59) in the second and third TB groups, respectively. The ROC curve analysis showed that the areas under the curve for TB, DB and IDB in predicting in-hospital MACE were 0.642 (95% CI 0.578‒0.705, p < 0.001), 0.676 (95% CI 0.614‒0.738, p < 0.001), and 0.619 (95% CI 0.554‒0.683, p < 0.001), respectively. Conclusions The current study showed that elevated TB, DB, and IDB levels are independent predictors of in-hospital MACE in patients with STEMI after primary PCI, and that DB has a better predictive value than TB and IDB.

Endoprótesis coronaria y doble terapia antiplaquetaria prolongada. Un estudio longitudinal / Coronary stent and prolonged dual antiplatelet therapy. A longitudinal study

Resumen Introducción: En las guías actuales europeas para el manejo del infarto de miocardio posterior a la colocación de endoprótesis coronaria (stent), no existe consenso sobre la duración ideal de la terapia antiagregante plaquetaria dual (DAPT, dual antiplatelet therapy) para prevenir la trombosis-reestenosis del stent sin aumentar el riesgo significativo de sangrado. Objetivo: Reportar el porcentaje de sangrado mayor y de eventos cardiovasculares mayores asociados a la DAPT prolongada en pacientes atendidos en el Instituto Nacional de Cardiología y tratados con intervención coronaria percutánea primaria y stent. Métodos: Se realizó un estudio longitudinal, prospectivo observacional y descriptivo no experimental. Los pacientes fueron captados de noviembre de 2016 a diciembre de 2017. Resultados: Fueron seleccionados 135 pacientes con una media de edad de 57 ± 10 años, quienes cumplieron un seguimiento clínico por tres años. La obesidad y la hipertensión destacaron como principales factores de riesgo. Posterior al uso de DAPT durante tres años, se registró 3.7 % de mortalidad, 1.48 % de sangrado mayor y 4.4 % de trombosis-reestenosis. Conclusiones: El uso prolongado de DAPT estaría justificado por la alta incidencia de trombosis-reestenosis, sin incremento significativo en el riesgo de sangrado y con disminución de los eventos cardiovasculares mayores.

Abstract Introduction: In current European guidelines for the management of myocardial infarction after coronary stent placement, there is no consensus on dual antiplatelet therapy (DAPT) ideal duration to prevent stent thrombosis-restenosis without significantly increasing the bleeding risk. Objective: To report the percentage of major bleeding and presence of major cardiovascular events associated with prolonged DAPT in patients recruited at the National Institute of Cardiology, treated with primary percutaneous coronary intervention and stent. Methods: A longitudinal, prospective, observational, non-experimental, descriptive study was carried out. Patients were recruited from November 2016 to December 2017. Results: One-hundred and thirty-five patients with a mean age of 57 ± 10 years who completed the three-year follow-up were selected. Obesity and hypertension stood out as the main risk factors. After using DAPT for three years, 3.7% of mortality, 1.48% of major bleeding, and 4.4% of thrombosis-restenosis were recorded. Conclusions: Prolonged use of DAPT would be justified by the high incidence of thrombosis-restenosis, without a significant increase in bleeding risk, as well as a decrease in major cardiovascular events.

Is the variation in monocyte to high-density lipoprotein cholesterol ratio a predictor of major cardiovascular events after acute coronary syndrome?

In clinical practice, we need to develop new tools to identify the residual cardiovascular risk after acute coronary syndrome (ACS). This study aimed to evaluate whether the monocyte to high-density lipoprotein cholesterol ratio (MHR) variation (ΔMHR) obtained during hospital admission (MHR1) and repeated in the first outpatient evaluation (MHR2) is a predictor of major adverse cardiovascular events (MACE) after ACS. One hundred ninety-one patients admitted for ACS were prospectively included. The ΔMHR was calculated by subtracting MHR1 from MHR2. Patients were followed for 166±38 days in which the occurrence of MACE was observed. The best cutoff for ΔMHR was zero (0), and individuals were divided into two groups: ΔMHR<0 (n=113) and ΔMHR≥0 (n=78). The presence of MACE was higher in the ΔMHR≥0 (22%) than in the ΔMHR<0 (7%), with a hazard ratio (HR) of 3.96 (95% confidence interval [CI]: 1.74-8.99; P=0.0004). After adjusting for confounders, ΔMHR≥0 remained an independent MACE predictor with an adjusted HR of 3.13 (95%CI: 1.35-7.26, P=0.008). In conclusion, our study showed that ΔMHR was an independent MACE predictor after ACS. Thus, ΔMHR is a potential marker of residual cardiovascular risk after ACS.

Chronic inflammatory diseases, subclinical atherosclerosis, and cardiovascular diseases: Design, objectives, and baseline characteristics of a prospective case-cohort study ‒ ELSA-Brasil

Abstract Objectives This analysis describes the protocol of a study with a case-cohort to design to prospectively evaluate the incidence of subclinical atherosclerosis and Cardiovascular Disease (CVD) in Chronic Inflammatory Disease (CID) participants compared to non-diseased ones. Methods A high-risk group for CID was defined based on data collected in all visits on self-reported medical diagnosis, use of medicines, and levels of high-sensitivity C-Reactive Protein >10 mg/L. The comparison group is the Aleatory Cohort Sample (ACS): a group with 10% of participants selected at baseline who represent the entire cohort. In both groups, specific biomarkers for DIC, markers of subclinical atherosclerosis, and CVD morbimortality will be tested using weighted Cox. Results The high-risk group (n = 2,949; aged 53.6 ± 9.2; 65.5% women) and the ACS (n=1543; 52.2±8.8; 54.1% women) were identified. Beyond being older and mostly women, participants in the high-risk group present low average income (29.1% vs. 24.8%, p < 0.0001), higher BMI (Kg/m2) (28.1 vs. 26.9, p < 0.0001), higher waist circumference (cm) (93.3 vs. 91, p < 0.0001), higher frequencies of hypertension (40.2% vs. 34.5%, p < 0.0001), diabetes (20.7% vs. 17%, p = 0.003) depression (5.8% vs. 3.9%, p = 0.007) and higher levels of GlycA a new inflammatory marker (p < 0.0001) compared to the ACS. Conclusions The high-risk group selected mostly women, older, lower-income/education, higher BMI, waist circumference, and of hypertension, diabetes, depression, and higher levels of GlycA when compared to the ACS. The strategy chosen to define the high-risk group seems adequate given that multiple sociodemographic and clinical characteristics are compatible with CID.

Mesa 3: Efectos cardiovasculares de fármacos antidiabéticos / Table 3: Cardiovascular effects of anti-diabetic drugs

Los eventos cardiovasculares representan la mayor complicación de la diabetes. La evidencia sugiere que la metformina mejora los resultados cardiovasculares en pacientes con diabetes, especialmente en el United Kingdom Prospective Diabetes Study (UKPDS) y otros estudios posteriores, por distintos mecanismos. Hay pocos estudios de seguridad cardiovascular para sulfonilureas aunque no tendrían un perfil seguro a este nivel. La gliclazida parece ser la de mejor performance de las drogas de este grupo. Algo similar ocurre con las meglitinidas, para las cuales los datos indican que no aumentarían el riesgo pero tampoco mejorarían la incidencia de eventos cardiovasculares. Las tiazolidinedionas son las drogas más cuestionadas, aunque los estudios y metaanálisis son contradictorios no habría dudas que aumentan el riesgo de insuficiencia cardíaca. Los inhibidores de la DPPIV mostraron resultados neutros a excepción de saxagliptina que aumentaría el riesgo de internación por insuficiencia cardíaca. Existen datos convincentes que los inhibidores de los receptores SGLT-2 a nivel renal y los análogos del GLP-1 intestinal tienen efectos positivos a nivel cardiovascular, con algunas diferencias entre los integrantes de esta familia. En cuanto a las insulinas, los estudios sugieren que tanto los análogos lentos como rápidos tendrían un mejor perfil cardiovascular, ligado principalmente a la menor incidencia de hipoglucemias severas, que insulina NPH y regular respectivamente.

Cardiovascular events represent the greatest complication of diabetes. Evidence suggests that metformin improves CV outcomes in patients with diabetes, especially in the United Kingdom Prospective Diabetes Study (UKPDS) and other subsequent studies, by different mechanisms. There are few cardiovascular safety studies for sulfonylureas although they would not have a safe profile at this level. Gliclazide appears to be the best performing drug in this group. Something similar occurs with meglitinides for which the data indicates that they would not increase the risk but neither would they improve the incidence of cardiovascular events. Thiazolidinediones are the most questioned drugs, although the studies and meta-analyzes are contradictory, there would be no doubt that they increase the risk of heart failure. DPPIV inhibitors showed neutral results except for saxagliptin, which would increase the risk of hospitalization for heart failure. There is convincing data that SGLT-2 receptor inhibitors at the renal level and intestinal GLP-1 analogues have positive effects at the cardiovascular level with some differences between the members of these families. Regarding insulins, studies suggest that both slow and fast analogues would have a better cardiovascular profile, mainly linked to the lower incidence of severe hypoglycemia, than NPH and regular insulin, respectively

Eventos cardiovasculares y su relación con cambios tensionales / Cardiovascular events and their relation to tension changes

RESUMEN La tensión arterial no es constante, y cambia frecuentemente en respuesta a estímulos fisiológicos de la vida diaria. Se realizó una revisión sistemática en inglés y español de los principales artículos publicados en PubMed, Scielo y MEDLINE durante el periodo comprendido desde el año 2010 hasta 2018, acerca de la variabilidad de la tensión arterial y sus complicaciones. Esto se ha documentado por el uso de la medición ambulatoria de la tensión arterial, una técnica que cada vez está más disponible para medir la tensión arterial y sus variaciones durante el día y la noche, con una frecuencia regular cada 15- 30 minutos a lo largo de un periodo de 24 horas. Esta técnica ha demostrado la diferencia de la tensión arterial en las diferentes mediciones durante el día y la noche, estos cambios en tan corto tiempo son predictores de las complicaciones cardiovasculares independiente de los valores absolutos (AU).

SUMMARY Blood pressure is not constant, and changes frequently in response to the physiological stimuli of everyday living. Was carried out a systematic revision in English and Spanish of the main articles published in PubMed, Scielo and MEDLINE during the period from the year 2010 up to 2018, about the variability of the Blood pressure and his complication. This has been documented by the use of ambulatory Blood pressure monitoring, a technique becoming more widely available that measures Blood pressure at regular intervals-typically each 15-30 min-throughout a 24-h period. This technique has demonstrated that differences among the daylong multiple readings-labelled as short-term variability-are predictive of cardiovascular outcomes independent of absolute Blood pressure levels (AU).

Glucantime y prolongación del intervalo QTc: una combinación fatal / Glucantime and QTc interval prolongation: A fatal combination

Resumen La leishmaniosis cutánea es una enfermedad causada por un parásito pro tozoo intracelular; el glucantime es una opción terapéutica, aunque está asociado con alteraciones cardiovasculares, siendo la más frecuente la prolongación del intervalo QTc que se presenta entre el 17,8 % y 19 % de los pacientes. Si este efecto no es detectado a tiempo puede causar una arritmia fatal por torsade de pointes. Se presenta el caso de una paciente de 77 años quien se encontraba en tratamiento con glucantime intramus cular como tratamiento de leishmaniosis cutánea e ingresó por un cuadro clínico de hipocalemia severa refractaria y episodios de torsade de pointes; posteriormente, presentó fibrilación ventricular que no respondió a des fibrilación y reanimación. Las alteraciones en la repolarización cardiaca producidas por este medicamento se consideran secundarias a la acu mulación de compuestos pentavalentes y trivalentes en el miocardio. No existe tratamiento específico para esta situación, pero siempre se debe realizar manejo de soporte, evitar fármacos que prolonguen el intervalo QT, normalizar los niveles de potasio y de magnesio, elevar la frecuencia cardiaca con isoproterenol e implantar marcapaso transvenoso para lograr sobre-estimulación y reducción de los periodos refractarios.

Abstract Cutaneous leishmaniasis is a disease caused by an intracellular protozoan parasite; Glucantime is a therapeutic option, although it is associated with cardiovascular alterations, the most frequent being the prolongation of the QTc interval, that occurs between 17.8% and 19% of patients. If this effect is not early recognized, it can cause a fatal arrhythmia due to torsade de pointes. The case of a 77-year-old patient who was receiving intramuscu lar glucantime as treatment for cutaneous leishmaniasis is presented, the patient was admitted with severe refractory hypokalemia and episodes of torsade de pointes; subsequently, presented ventricular fibrillation that did not respond to defibrillation and resuscitation. The alterations in cardiac repolarization produced by this medicine are considered secondary to the accumulation of pentavalent and trivalent compounds in the myocardium. There is no specific treatment for this situation, but supportive manage ment should always be performed, avoid drugs that prolong the QT inter val, normalize potassium and magnesium levels, raise the heart rate with isoproterenol and implant transvenous pacemaker to achieve over-stimulation and reduction of refractory periods.

Efectos cardiovasculares de los nuevos fármacos no insulínicos en diabetes / Cardiovascular effects of new non-insulinic anti-diabetes drugs]

La diabetes mellitus constituye actualmente un grave problema de salud pública a nivel mundial, que incrementa el riesgo de presentar complicaciones tanto microvasculares como macrovasculares. Aunque lograr los objetivos de glucemia recomendados reduce el riesgo de complicaciones microvasculares, el efecto de los fármacos para tratar la hiperglucemia sobre las complicaciones macrovasculares y la muerte cardiovascular es motivo de preocupación. En este contexto, las agencias regulatorias han modificado la normativa para la aprobación de nuevos fármacos en diabetes, de forma que establecen la necesidad de demostrar que son capaces de disminuir la glucemia junto con una evaluación sólida de la seguridad cardiovascular. El objetivo de este trabajo es revisar los efectos cardiovasculares de las nuevas familias de fármacos no insulínicos, en especial en su efecto sobre el riesgo de eventos cardiovasculares mayores. En los últimos años, finalmente, se ha confirmado que algunos fármacos para tratar la diabetes no solo son seguros desde el punto de vista cardiovascular, sino que incluso han mostrado capacidad para reducir el riesgo de enfermedad cardiovascular en la diabetes mellitus tipo 2. La evidencia obtenida ha determinado la actualización de algunas guías terapéuticas vigentes cuando el riesgo cardiovascular debería considerarse una variable fundamental al momento de la elección terapéutica en pacientes con diabetes.

Diabetes mellitus is currently a serious public health problem worldwide, that increases the risk of presenting microvascular and macrovascular complications. Although achieving the recommended blood glucose goals reduces the risk of microvascular complications, the effect of the drugs used to treat hyperglycemia on macrovascular complications and cardiovascular death is a cause for concern. In this context, the regulatory agencies have modified the regulations for the approval of new drugs in diabetes, by adding the need to demonstrate that they are capable of lowering blood glucose levels together with a solid assessment of cardiovascular safety. The objective of this study is to review the cardiovascular effects of the new families of non-insulin drugs, with special emphasis on their effect on the risk of major cardiovascular events. In recent years, it has finally been confirmed that some of the drugs used to treat diabetes are not only safe from a cardiovascular point of view, but have even shown capacity to reduce the risk of cardiovascular disease in type 2 diabetes mellitus. The evidence obtained determined the updating of some current therapeutic guidelines when cardiovascular risk should be considered a fundamental variable at the time of therapeutic choice in patients with diabetes.

Incidencia de eventos cardiovasculares mayores asociada a la suspensión de doble terapia antiagregante en pacientes con enfermedad coronaria e implante de stent / Incidence of major adverse cardiovascular events associated to suspension of dual antiplatelet therapy in patients with coronary disease and stent implants

Resumen Objetivo: Determinar el riesgo de presentar eventos cardiovasculares mayores en pacientes con síndrome coronario agudo e implante de stent, que suspendieron la doble terapia antiagregante antes de un año de tratamiento. Métodos: Estudio analítico de pacientes con síndrome coronario agudo e implante de stent que recibieron doble terapia antiagregante al egreso hospitalario. Se describieron las características sociodemográficas, clínicas y paraclínicas. Se determinó la prevalencia de suspensión de doble terapia antiagregante antes de un año de tratamiento y el riesgo de eventos cardiovasculares mayores mediante un modelo de riesgos proporcionales Cox. Resultados: Se incluyeron 873 pacientes. La prevalencia de suspensión de doble terapia antiagregante fue 39,18%. El grupo que continuó la terapia por un año tuvo mayor frecuencia de enfermedad coronaria previa (19,13% p = 0,03). La principal indicación del procedimiento en los pacientes que suspendieron la terapia fue infarto sin ST elevado (36,8%). La suspensión de la doble terapia antiagregante antes del año estuvo asociada con mayor incidencia de MACE a un año (HR 1,31 95% IC 0,65-2,62 p = 0,45). La presencia de enfermedad arterial periférica, diabetes mellitus y más de un vaso enfermo se relacionó con eventos adversos cardiovasculares a un año. Conclusiones: La suspensión antes de los doce meses de la doble terapia antiagregante en pacientes con implante de stent posterior a un síndrome coronario agudo, es frecuente y parece no estar asociada con mayor incidencia de desenlaces cardiovasculares mayores; sin embargo, la causa de la interrupción puede influir en los desenlaces clínicos y debe tenerse en cuenta en la práctica clínica.

Abstract Objective: To determine the risk of developing major adverse cardiovascular events (MACEs) in patients with acute coronary syndrome and stent implant who suspended dual antiplatelet therapy before one year of treatment. Methods: Analytical study of patients with acute coronary syndrome and stent implant who received dual antiplatelet therapy upon hospital admission. Sociodemographic, clinical and paraclinical features were described. The prevalence of dual antiplatelet therapy suspensión before one year of treatment was determined, and for assessing the risk of major adverse cardiovascular events a Cox proportional hazard regression model was used. Results: 873 patients were included. Prevalence of dual antiplatelet therapy suspension was 39.18%. The group who continued the therapy during a year had a higher frequency of previous coronary disease (19.13%, p = 0.03). The main indication for the procedure in patients who interrupted their treatment was infarction without ST elevation (36.8%). Dual therapy suspensión before one year was not related to a higher incidence of MACEs after one year (HR1.31, CI 95% 0.65-2.62 p = 0.45). The presence of peripheral arterial disease, diabetes mellitus and more than one abnormal vessel was related to adverse cardiovascular effects within one year. Conclusions: The suspension of dual antiplatelet therapy before twelve months in patients with a stent implant posterior to an acute coronary syndrome is frequent and does not seem to be associated to a higher incidence of major adverse cardiovascular events; nevertheless, the reason for the interruption could influence the clinical outcome and must be taken into account for clinical practice.

Assessment of cardiovascular risk in patients with rheumatoid arthritis using the SCORE risk index / Avaliação do risco cardiovascular de pacientes com artrite reumatoide utilizando o índice SCORE

ABSTRACT Introduction: Rheumatoid arthritis is an autoimmune disease that causes systemic involvement and is associated with increased risk of cardiovascular disease. Objective: To analyze the prediction index of 10-year risk of a fatal cardiovascular disease event in female RA patients versus controls. Methods: Case-control study with analysis of 100 female patients matched for age and gender versus 100 patients in the control group. For the prediction of 10-year risk of a fatal cardiovascular disease event, the SCORE and modified SCORE (mSCORE) risk indexes were used, as suggested by EULAR, in the subgroup with two or more of the following: duration of disease ≥10 years, RF and/or anti-CCP positivity, and extra-articular manifestations. Results: The prevalence of analyzed comorbidities was similar in RA patients compared with the control group (p > 0.05). The means of the SCORE risk index in RA patients and in the control group were 1.99 (SD: 1.89) and 1.56 (SD: 1.87) (p = 0.06), respectively. The means of mSCORE index in RA patients and in the control group were 2.84 (SD = 2.86) and 1.56 (SD = 1.87) (p = 0.001), respectively. By using the SCORE risk index, 11% of RA patients were classified as of high risk, and with the use of mSCORE risk index, 36% were at high risk (p< 0.001). Conclusion: The SCORE risk index is similar in both groups, but with the application of the mSCORE index, we recognized that RA patients have a higher 10-year risk of a fatal cardiovascular disease event, and this reinforces the importance of factors inherent to the disease not measured in the SCORE risk index, but considered in mSCORE risk index.

RESUMO Introdução: Artrite reumatoide (AR) é uma doença autoimune que determina manifestações sistêmicas e está associada a aumento do risco de evento cardiovascular. Objetivo: Analisar o índice SCORE de predição de evento cardiovascular em pacientes do gênero feminino portadores de AR comparados com controles sem a doença. Métodos: Estudo de caso-controle com análise de 100 pacientes pareadas por gênero e idade versus 100 pacientes do grupo controle. Para a predição do risco de evento cardiovascular fatal em 10 anos, usamos os índices SCORE e SCORE modificado (mScore), conforme sugerido pela Eular, no subgrupo com 2 ou mais dos seguintes: duração da doença ≥ 10 anos, positividade para fator reumatoide e/ou anti-CCP e manifestações extra-articulares. Resultados: A prevalência das comorbidades analisadas foi similar nas pacientes com AR, em comparação com o grupo controle (p > 0,05). As médias do índice SCORE foram 1,99 (DP: 1,89) e 1,56 (DP: 1,87) nas portadoras de AR e nos controles (p = 0,06), respectivamente. Com o uso do índice mScore, nas pacientes com AR foi encontrada a média de 2,84 (DP: 2,86) versus 1,56 nos controles (DP: 1,87) (p = 0,001). Ao usar o índice SCORE, 11% dos portadores de AR foram classificados como de alto risco; com o índice mScores, 36% obtiveram essa classificação (p < 0,001). Conclusões: O índice SCORE é semelhante nos dois grupos, mas com a aplicação do índice mScore identificamos que os pacientes com AR têm maior risco de evento cardiovascular fatal em 10 anos, com ênfase na importância dos fatores inerentes à doença não mensurados no índice SCORE, mas considerados no índice mScore.

Factores de riesgo cardiovascular en síndrome metabólico / Cardiovascular risk factors in metabolic syndrome

El síndrome metabólico es un grupo de factores de riesgo para desarrollar evento coronario; alteración del metabolismo de la glucosa, diabetes, obesidad abdominal, dislipidemia e hipertensión forman parte de él. Seestima que una cuarta parte de la población adulta lo presenta, tienen dos veces de riesgo de morir y tresveces más riesgo de padecer algún evento coronario o evento Cerebrovascular comparado a quienes no lopresentan. También las personas tienen cinco veces más posibilidad de desarrollar diabetes tipo 2. Laspatologías que lo conforman, parecen tener una interrelación fisiopatológica, que las va uniendo. Laspoblaciones latinoamericanas presentan características que las hacen especialmente susceptibles a padecerestas patologías cardio-metabólicas. El reconocimiento de estas características en los pacientes tiene unaimportancia especial debido a que indica la necesidad de aplicar medidas activas para reducir el riesgo cardiovascular.

Metabolic syndrome is a group of the most dangerous risk factors for coronary event, alteration in glucosemetabolism; diabetes, abdominal obesity, dyslipidemia and hypertension are components of this. It isestimated that a quarter of the adult population has it, they have twice probabilities to die, three times as likelyto coronary event or Cerebrovascular event compared to those do not have it. Also people are five times morelikely at risk for type 2 Diabetes. The pathologies that comprise it seem to have a pathophysiologicalinterrelationship, which puts together. Latin American populations have characteristics that make themespecially susceptible to these cardiometabolic diseases. Recognition of these characteristics in patients isparticularly important because it indicates the need for active measures to reduce cardiovascular risk.

Análise de eficácia, eventos adversos e desfechos cardiovasculares em estudos relacionados às combinações de nifedipino GITS ou anlodipino com medicamentos que atuam no sistema renina angiotensina aldosterona / Efficacy analysis, adverse events and cardiovascular outcomes in studies related to combinations of nifedipine GITS or amlodipine with drugs acting on the renin angiotensin aldosterone system

Revisamos 17 estudos com o objetivo de avaliar a eficácia anti-hipertensiva da combinação de antagonistas de cálcio com bloqueadores dos receptores de angiotensina na redução da pressão arterial, de desfechos cardiovasculares e na incidência de efeitos adversos. A terapia combinada de bloqueador de canais de cálcio anlodipino ou nifedipino GITS, mais o bloqueador de receptor de angiotensina II valsartana, mostrou-se, na maioria dos estudos, mais eficaz que a monoterapia para redução de pressão arterial, além de mais benéfica quanto à diminuição de eventos cardiovasculares. O perfil de segurança e tolerabilidade das combinações também se revelou bastante aceitável, com o manejo de efeitos adversos favorecido pela maior possibilidade de ajustes de doses de substâncias com diferentes mecanismos de ação, sem comprometimento da eficácia anti-hipertensiva.

We reviewed 17 studies in order to evaluate the antihypertensive efficacy on the combination of calcium antagonists and angiotensin receptor blockers in lowering the blood pressure, cardiovascular outcomes and incidence of side effects. The combination therapy of amlodipine or nifedipine GITS calcium channel blockers, and angiotensin II receptor blocker valsartan showed, in most studies, more effective than monotherapy to lower blood pressure, as well as more beneficial to decrease cardiovascular events. The safety profile and tolerability of the combinations also proved quite acceptable, with side effects management benefited by higher possibility of adjustments on doses of substances with different mechanisms of actions, without affecting the antihypertensive efficacy.

Does calcium intake affect cardiovascular risk factors and/or events?

Dietary intervention is an important approach in the prevention of cardiovascular disease. Over the last decade, some studies have suggested that a calcium-rich diet could help to control body weight, with anti-obesity effects. The potential mechanism underlying the impact of calcium on body fat has been investigated, but it is not fully understood. Recent evidence has also suggested that a calcium-rich diet could have beneficial effects on other cardiovascular risk factors, such as insulin resistance, dyslipidemia, hypertension and inflammatory states. In a series of studies, it was observed that a high intake of milk and/or dairy products (the main sources of dietary calcium) is associated with a reduction in the relative risk of cardiovascular disease. However, a few studies suggest that supplemental calcium (mainly calcium carbonate or citrate) may be associated with an increased risk of cardiovascular events. This review will discuss the available evidence regarding the relationship between calcium intake (dietary and supplemental) and different cardiovascular risk factors and/or events.

C-reactive protein in acute coronary syndrome: association with 3-year outcomes

Inflammatory markers have been associated with clinical outcome in patients with acute coronary syndrome (ACS). The present study evaluated the role of high-sensitivity C-reactive protein (CRP) measurements as a predictor of late cardiovascular outcomes after ACS. One hundred and ninety-nine ACS patients in a Coronary Care Unit from March to November 2002 were included and were reassessed clinically after ~3 years. Clinical variables and CRP levels were evaluated as predictors of major cardiovascular events (MACE, defined as the occurrence of cardiac death, ischemic stroke or myocardial infarction) and mortality. Statistical analyses included Cox multivariable analysis and survival curves (Kaplan-Meier). Of the 199 patients, 11 died within 1 month (5.5 percent). Of the 188 remaining patients, 22 died after a mean follow-up of 2.9 ± 0.5 years. Baseline CRP levels for patients with MACE (N = 57) were significantly higher than those of patients with no events (median = 0.67 mg/L; 25th-75th percentiles = 0.32 and 1.99 mg/L vs median = 0.45 mg/L; 25th-75th percentiles = 0.24 and 0.83 mg/L; P < 0.001). Patients with CRP levels >3 mg/L had a significantly lower survival than the other two groups (1-3 and <1 mg/L; P = 0.001, log-rank test). The odds ratio for MACE was 7.41 (2.03-27.09) for patients with CRP >3 mg/L compared with those with CRP <1 mg/L. For death by any cause, the hazard ratio was 4.58 (1.93-10.86). High CRP levels predicted worse long-term outcomes (MACE and death by any cause) in patients with ACS.

Dor torácica na emergência de um hospital geral / Thoracic pain in a general hospital emergency

Introdução: Dentre as doenças cardiovasculares, a condição mais prevalente é a dor torácica aguda não traumática. Objetivo: Identificar a freqüência de dor torácica na emergência e a descrição dos eventos na internação em 6 meses. Métodos: O estudo apresenta duas etapas: estudo transversal e série de casos, em pacientes com dor torácica na emergência, onde foi avaliado o protocolo assistencial. A dor foi classificada nas categorias: infarto agudo do miocárdio (IAM), angina pectoris e dor não-anginosa, de acordo com a clínica, eletrocardiografia e marcadores de necrose miocárdica. O teste ergométrico foi realizado de acordo com protocolo de Bruce. Os eventos em 6 meses foram mensurados. Resultados: No período de novembro de 2004 a janeiro de 2005 foram atendidos 80.184 pacientes na emergência do Hospital Conceição (HNSC). Desses atendimentos, 1.564 (2%) apresentavam dor torácica. Foram avaliados 52 pacientes, 34 (65%) masculino, idade média de 59 anos (dp 14,74), 69% internaram (38% com infarto, 27% angina e 4% dor não-anginosa), 17% realizaram teste ergométrico. Conclusão: Constatou-se uma baixa freqüência (2%) dos atendimentos devido a dor torácica não-traumática, porém elevada incidência de infarto e angina instável (AU)

Introduction: Among the cardiovascular emergencies the most frequent cause is nontraumatic acute thoracic pain in the emergency room. Objective: To identify thoracic pain frequency in the emergency and cardiovascular events in 6 months. Methods: A crosssectional and a case series study were carried out to evaluate thoracic pain guideline. Myocardial infarct, angina pectoris, and non-angina pain were identified based on clinical features, ECG abnormality and myocardial necrosis indicators. The ergometric test was carried out according to the Bruce Protocol. The events in 6 months were measured. Results: Between November 2004 through January 2005, 80,184 patients received care in the emergency room of Hospital Conceição. Among them, 1564 (2%) had thoracic pain. We had investigated 52 of these patients, 34 (65%) of whom were males, with an average age of 59 years old (sd 14.74). Regarding to the diagnosis, 69% had been admitted (38% with the diagnosis of infarct, 27% with angina and 4% with non-angina pain), 17% performed the ergometric test. Conclusion: A low frequency (2%) of non-traumatic thoracic pain has been identified, although there was a high incidence of infarct and unstable angina in these patients. There was a high prevalence of cardiovascular events in 6 months in the three studied groups (AU)

Control de la hipertensión arterial con medicamentos: actualización 2005 / Pharmacologic control of high blood pressure: up to date 2005

El uso adecuado de los medicamentos antihipertensivos es fundamental para garantizar el cumplimiento de las metas de presión arterial y la adherencia de los pacientes al tratamiento de la hipertensión, elementos necesarios para cumplir con el objetivo fundamental de disminuir el riesgo absoluto cardiovascular de los pacientes. Esta es una revisión narrativa basada en una búsqueda sistemática de la literatura, en la cual se seleccionaron los estudios aleatorizados controlados de terapia antihipertensiva inicial y se compararon tratamientos entre fármacos de dos o más grupos, que tengan como desenlace la reducción de eventos cardiovasculares.

Adequate use of antihypertensive drugs is one of the key elements to guarantee the achievement of blood pressure goals and the adherence of patients to treatment, in order to diminish the absolute cardiovascular risk. This article is a narrative review based on a systematic literature search in which randomized, controlled studies of initial antihypertensive therapy were selected and treatments with drugs of two or more groups were compared having as outcome the reduction of cardiovascular events.