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Objective To assess the predictive value of four cardiovascular (CV) risk algorithms for identifying high-risk psoriatic arthritis (PsA) patients.Methods Evaluation of patients with PsA enrolled in the Spanish prospective project CARdiovascular in RheuMAtology. Baseline data of 669 PsA patients with no history of CV events at the baseline visit, who were followed in rheumatology outpatient clinics at tertiary centres for 7.5 years, were retrospectively analysed to test the performance of the Systematic Coronary Risk Assessment (SCORE), the modified version (mSCORE) European Alliance of Rheumatology Associations (EULAR) 2015/2016, the SCORE2 algorithm (the updated and improved version of SCORE) and the QRESEARCH risk estimator version 3 (QRISK3).Results Over 4790 years of follow-up, there were 34 CV events, resulting in a linearised rate of 7.10 per 1000 person-years (95% CI 4.92 to 9.92). The four CV risk scales showed strong correlations and all showed significant associations with CV events (p

Los criterios diagnósticos, los tratamientos en el momento de la admisión y los fármacos utilizados en pacientes con síndrome coronario agudo están bien definidos en innumerables guías. Sin embargo, existe incertidumbre acerca de las medidas para recomendar durante la planificación del egreso de los pacientes. Este documento reúne las evidencias más recientes y el tratamiento estandarizado y óptimo para los pacientes al momento del egreso de una hospitalización por un síndrome coronario agudo, para un cuidado integral y seguro en la transición del paciente entre la atención del evento agudo y el cuidado ambulatorio, con el objetivo de optimizar la recuperación de miocardio viable, garantizar la prevención secundaria más adecuada, reducir el riesgo de un nuevo evento coronario y la mortalidad, así como la adecuada reinserción de los pacientes en la vida cotidiana.

Patients with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) without myocardial infarction (MI) or stroke are at high risk for major cardiovascular events (MACEs). We aimed to provide real-world data on age-related clinical characteristics, treatment management, and incidence of major cardiovascular outcomes in T2DM-CAD patients in Spain from 2014 to 2018. We used EHRead® technology, which is based on natural language processing and machine learning, to extract unstructured clinical information from electronic health records (EHRs) from 12 hospitals. Of the 4072 included patients, 30.9% were younger than 65 years (66.3% male), 34.2% were aged 65–75 years (66.4% male), and 34.8% were older than 75 years (54.3% male). These older patients were more likely to have hypertension (OR 2.85), angina (OR 1.64), heart valve disease (OR 2.13), or peripheral vascular disease (OR 2.38) than those aged p < 0.001 for all comparisons). In general, they were also more likely to receive pharmacological and interventional treatments. Moreover, these patients had a significantly higher risk of MACEs (HR 1.29; p = 0.003) and ischemic stroke (HR 2.39; p < 0.001). In summary, patients with T2DM-CAD in routine clinical practice tend to be older, have more comorbidities, are more heavily treated, and have a higher risk of developing MACE than is commonly assumed from clinical trial data.

RESUMEN Introducción y objetivos: Los resultados del Magmaris en el síndrome coronario agudo son controvertidos y se necesitan más estudios para evaluar su seguridad a largo plazo. El objetivo del trabajo fue analizar mediante un estudio observacional la seguridad clínica más allá de 12 meses de los Magmaris implantados en un único centro hospitalario en pacientes con síndrome coronario agudo. Métodos: Se registraron de manera consecutiva 36 pacientes con Magmaris implantados entre noviembre de 2016 y noviembre de 2018 con diagnóstico de síndrome coronario agudo. Para el objetivo primario se consideró el combinado orientado al dispositivo de infarto de miocardio del vaso diana, fracaso de la lesión diana y muerte de causa cardiovascular. Como objetivo secundario se incluyó la trombosis del dispositivo. Resultados: En cuanto al combinado orientado al dispositivo no se observó infarto de miocardio del vaso diana (0%), en 2 casos (5,6%) se observó fracaso de la lesión diana y se constató 1 caso de muerte cardiaca (2,8%) a los 36 meses del implante del Magmaris, sin poder conocer la causa por no disponer de autopsia. Con respecto a los objetivos secundarios, no hubo casos de trombosis del Magmaris durante el seguimiento. Conclusiones: Nuestros resultados, con un seguimiento a largo plazo, apoyan...

ABSTRACT Introduction and objectives: The results of Magmaris implantation in the acute coronary syndrome setting is uncertain and more studies will be needed to assess the long-term safety profile of these devices. The objective of this work was to conduct an observational study to analyze the clinical safety profile of Magmaris implanted in a single hospital center in the acute coronary syndrome setting beyond 12 months. Methods: Registry of 36 patients with Magmaris devices implanted between November 2016 through November 2018 with a diagnosis of acute coronary syndrome included consecutively. The primary endpoint was considered the device-oriented composite endpoint of target vessel myocardial infarction, target lesion failure, and cardiac death. Secondary endpoints included Magmaris related thrombosis. Results: Regarding the device-oriented combination, no target vessel myocardial infarction was observed, 0 cases (0%), while target lesion failure was seen in 2 cases (5.6%). There were no cases of Magmaris thrombosis at the follow-up and only 1 case of cardiac death (2.8%) was found 36 months after Magmaris implantation. The cause of death could not be determined since no autopsy was performed. Conclusions: Our results with long-term follow-up confirm that Magmaris has a favorable clinical profile in the acute coronary syndrome complex setting.

(1) Background: Hyperkalemia is a common finding in patients with heart failure and reduced ejection fraction (HFrEF), though its prognostic significance is controversial. There is no consensus on optimal potassium levels in these patients. The primary endpoint of this study was to determine the 5-year incidence of hyperkalemia in a cohort of patients with HFrEF. Secondary endpoints were to determine predictors of hyperkalemia and its impact on overall 5-year mortality; (2) Methods: retrospective, longitudinal, single-center observational study of patients with HFrEF followed-up in a specialized unit between 2011 and 2019. Hyperkalemia was considered as potassium concentration > 5.5 mEq/L; (3) Results: Hyperkalemia was observed in 170 (16.8%) of the 1013 patients. The 5-year hyperkalemia-free survival rate was 82.1%. Hyperkalemia was more frequent at the beginning of follow-up. Factors associated with hyperkalemia in the multivariate analysis were baseline potassium (HR 3.13, 95%CI 2.15–4.60; p < 0.001), creatinine clearance (HR 0.99, 95%CI 0.98–0.99; p = 0.013), right ventricular function (HR 0.95, 95%CI 0.91–0.99; p = 0.016) and diabetes mellitus (HR 1.40, 95%CI 1.01–1.96; p = 0.047). The overall survival rate at 5 years was 76.4%. Normal–high potassium levels (5–5.5 mEq/L) were inversely associated with mortality (HR 0.60, 95%CI 0.38–0.94; p = 0.025); (4) Conclusions: Hyperkalemia is a common finding in patients with HFrEF with an impact on the optimization of neurohormonal treatment. In our retrospective study, potassium levels in the normal–high range seem to be safe and are not associated with increased mortality.

Objetivo: Este estudio tiene como objetivo investigar los cambios en los niveles séricos de CypC y su relación con eventos cardiovasculares a los 12 meses de seguimiento en pacientes con EAC. Método: El estudio incluyó un total de 125 sujetos (40 pacientes con EAC aguda, 40 pacientes con EAC crónica y 45 voluntarios de control) y se analizaron los niveles plasmáticos de CypC desde el inicio hasta los 6 y 12 meses para comprender mejor su comportamiento en la aterosclerosis. Resultados: Se demostró que los niveles séricos de CypC aumentaron gradualmente en pacientes con CAD [(30.63 pg/ml ± 3.77 al inicio del estudio, 38.70 pg/ml ± 6.41 a los 6 meses (p = 0.25) y 47.27 pg/ml ± 5.65 a los 12 meses (p = 0,007)]. Además, los niveles séricos de CypC durante el seguimiento fueron un predictor significativo de EAC (estadístico c 0.76 a los 6 meses y 0.89 a los 12 meses; p < 0.001). A pesar de ello, no hubo asociación significativa entre CypC y eventos cardiovasculares, pero los niveles séricos de CypC tendieron a ser más altos en los pacientes que sufrieron eventos cardiovasculares durante el seguimiento (29.02 pg/mL ± 6.39 vs. 79.96 pg/mL ± 22.18; p = 0.029). En este sentido, los niveles plasmáticos de hsCRP > 2.3 mg/L más NT-proBNP> 300 pg/ml juntos fueron predictores significativos de eventos cardiovasculares durante el seguimiento en pacientes con EAC con niveles de CypC > 17.5 pg/ml (p = 0.048). Conclusiones: Tomados en conjunto, nuestros resultados sugieren que los niveles séricos de CypC aumentan durante el seguimiento en pacientes con EAC y podría ser un nuevo biomarcador con un posible valor pronóstico en combinación con hsCRP y NT-proBNP.

Background: Determining the mechanism of supraventricular tachycardias with prolongedP ventriculoatrial (VA) intervals is sometimes a challenge. Our objective is to analyse the determinants, time course and diagnostic accuracy (atypical atrioventricular nodal reentrant tachycardias [AVNRT] versus orthodromic reentrant tachycardias through an accessory pathway [ORT]) of spontaneous VA intervals variation in patients with narrow QRS tachycardias and prolonged VA. Methods: A total of 156 induced tachycardias were studied (44 with atypical AVNRT and 112 with ORT). Two sets of 10 measurements were performed for each patient—after tachycardia induction and one minute later. VA and VV intervals were determined. Results: The difference between the longest and the shortest VA interval (Dif-VA) correlates significantly with the diagnosis of atypical AVNRT (C coefficient = 0.95 and 0.85 after induction and at one minute, respectively; p < 0.001). A Dif-VA ≥ 15 ms presents a sensitivity and specificity for atypical AVNRT of 50% and 99%, respectively after induction, and of 27% and 100% one minute later. We found a robust and significant correlation between the fluctuations of VV and VA intervals in atypical AVNRTs (Coefficient Rho: 0.56 and 0.76, after induction and at one minute, respectively; p < 0.001 for both) but not in ORTs. Conclusions: The analysis of VA interval variability after induction and one minute later correctly discriminates atypical AVNRT from ORT in almost all cases.

Introduction and objectivesPatients with type 2 diabetes (T2D) and stable coronary artery disease (CAD) previously revascularized with percutaneous coronary intervention (PCI) are at high risk of recurrent ischemic events. We aimed to provide real-world insights into the clinical characteristics and management of this clinical population, excluding patients with a history of myocardial infarction (MI) or stroke, using Natural Language Processing (NLP) technology.MethodsThis is a multicenter, retrospective study based on the secondary use of 2014-2018 real-world data captured in the Electronic Health Records (EHRs) of 1,579 patients (0.72% of the T2D population analyzed; n = 217,632 patients) from 12 representative hospitals in Spain. To access the unstructured clinical information in EHRs, we used the EHRead® technology, based on NLP and machine learning. Major adverse cardiovascular events (MACE) were considered: MI, ischemic stroke, urgent coronary revascularization, and hospitalization due to unstable angina. The association between MACE rates and the variables included in this study was evaluated following univariate and multivariate approaches.ResultsMost patients were male (72.13%), with a mean age of 70.5±10 years. Regarding T2D, most patients were non-insulin-dependent T2D (61.75%) with high prevalence of comorbidities. The median (Q1-Q3) duration of follow-up was 1.2 (0.3-4.5) years. Overall, 35.66% of patients suffered from at least one MACE during follow up. Using a Cox Proportional Hazards regression model analysis, several independent factors were associated with MACE during follow up: CAD duration (p < 0.001), COPD/Asthma (p = 0.021), heart valve disease (p = 0.031), multivessel disease (p = 0.005), insulin treatment (p < 0.001), statins treatment (p < 0.001), and clopidogrel treatment (p = 0.039).ConclusionsOur results showed high rates of MACE in a large real-world series of PCI-revascularized patients with T2D and CAD with no history of MI or stroke. These data represent a potential opportunity to improve the clinical management of these patients.

Patients with Type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) are at high risk of developing major adverse cardiovascular events (MACE). This is a multicenter, retrospective, and observational study performed in Spain aimed to characterize these patients in a real-world setting. Unstructured data from the Electronic Health Records were extracted by EHRead®, a technology based on Natural Language Processing and machine learning. The association between new MACE and the variables of interest were investigated by univariable and multivariable analyses. From a source population of 2,184,662 patients, we identified 4072 adults diagnosed with T2DM and CAD (62.2% male, mean age 70 ± 11). The main comorbidities observed included arterial hypertension, hyperlipidemia, and obesity, with metformin and statins being the treatments most frequently prescribed. MACE development was associated with multivessel (Hazard Ratio (HR) = 2.49) and single coronary vessel disease (HR = 1.71), transient ischemic attack (HR = 2.01), heart failure (HR = 1.32), insulin treatment (HR = 1.40), and percutaneous coronary intervention (PCI) (HR = 2.27), whilst statins (HR = 0.73) were associated with a lower risk of MACE occurrence. In conclusion, we found six risk factors associated with the development of MACE which were related with cardiovascular diseases and T2DM severity, and treatment with statins was identified as a protective factor for new MACE in this study.

Abstract Background Relationship between carotid and coronary artery disease (CAD) in patients undergoing invasive and non-invasive test is unclear. The aim of the study is to evaluate whether carotid disease is associated with CAD in patients submitted to exercise echocardiography (EE) and if it improves the EE ability to predict CAD. Methods We retrospectively studied 156 subjects without previous vascular disease who underwent EE, carotid ultrasonography and coronary angiography between 2002 and 2013. Positive EE was defined as exercise induced wall motion abnormalities, carotid disease according to Manheim and American Society of Echocardiography Consensus and significant CAD as stenosis ≥50%. Results Eighty-nine (57.1%) subjects had significant CAD. Factors associated with CAD in multivariate analysis were fasting plasma glucose (odds ratio [OR] 1.02, p = 0.031), pre-test probability of CAD > 65% (OR 3.71, p

OBJECTIVE:To evaluate the level of agreement between cardiologists regarding the management of oral anticoagulation (OAC) in patients with non-valvular atrial fibrillation (NVAF) in Spain. MATERIALS AND METHODS:A two-round Delphi study was performed using an online survey. In round 1, panel members rated their level of agreement with the questionnaire items on a 9-point Likert scale. Item selection was based on acceptance by ≥66.6% of panellists and the agreement of the scientific committee. In round 2, the same panellists evaluated those items that did not meet consensus in round 1. RESULTS:A total of 238 experts participated in round 1; of these, 217 completed the round 2 survey. In round 1, 111 items from 4 dimensions (Thromboembolic and bleeding risk evaluation for treatment decision-making: 18 items; Choice of OAC: 39 items; OAC in specific cardiology situations: 12 items; Patient participation and education: 42 items) were evaluated. Consensus was reached for 92 items (83%). Over 80% of the experts agreed with the use of DOACs as the initial anticoagulant treatment when OAC is indicated. Panellists recommended the use of DOACs in patients at high risk of thromboembolic complications (CHA2DS2-VASc ≥3) (83%), haemorrhages (HAS-BLED ≥3) (89%) and poor quality of anticoagulation control (SAMe-TT2R2 >2) (76%), patients who fail to achieve an optimal therapeutic range after 3 months on VKA treatment (93%), and those who are to undergo cardioversion (80%). Panellists agreed that the efficacy and safety profile of each DOAC (98%), the availability of a specific reversal agent (72%) and patient's preference (85%) should be considered when prescribing a DOAC. A total of 97 items were ultimately accepted after round 2. CONCLUSIONS:This Delphi panel study provides expert-based recommendations that may offer guidance on clinical decision-making for the management of OAC in NVAF. The importance of patient education and involvement has been highlighted.

Abstract Background This study aimed to determine whether, besides carotid ultrasound (US), a lateral lumbar spine radiography may also help identify ankylosing spondylitis (AS) patients at high risk of cardiovascular (CV) disease. Methods A set of 125 AS patients older than 35 years without a history of CV events, diabetes mellitus, or chronic kidney disease was recruited. Carotid US and lateral lumbar spine radiography were performed in all of them. The CV risk was calculated according to the total cholesterol systematic coronary risk evaluation (TC-SCORE) algorithm. Presence of carotid plaques was defined following the Mannheim Carotid Intima-media Thickness and Plaque Consensus. Abdominal aortic calcium (AAC) in a plain radiography was defined as calcific densities visible in an area parallel and anterior to the lumbar spine. Results Carotid US showed higher sensitivity than lateral lumbar spine radiography to detect high CV risk in the 54 patients with moderate TC-SCORE (61% versus 38.9%). Using carotid plaques as the gold standard test, a predictive model that included a TC-SCORE ≥ 5% or the presence of AAC in the lateral lumbar spine radiography in patients with both moderate and low CV risk (

We present the case of a patient with Takotsubo syndrome assessed by intracoronary flow and pressure guidewire, showing elevation of intracoronary pressures at the level of the anterior descending artery, and thus demonstrating a new therapeutic target in a still little understood etiopathogenic entity. The results of this test have never been previously reported in Takotsubo patients. Resumo: Apresentamos um caso dum paciente com síndrome de Takotsubo e a avaliação por fluxo intracoronário/fio de pressão, mostrando elevação das pressões intracoronárias ao nível da artéria descendente anterior, podendo demonstrar um novo alvo terapêutico numa entidade etiopatogénica ainda desconhecida. Os resultados deste teste nunca foram relatados previamente em pacientes de Takotsubo. Keywords: Coronary disease, Intracoronary pressure and flow guidewire, Takotsubo syndrome, Palavras-chave: Doença coronária, Guia de pressão/fluxo intracoronária, Síndrome de Takotsubo

We present first-in-human treatment with bioabsorbable magnesium scaffolds for percutaneous coronary intervention in a patient with nickel allergy. We present images from angiography and optical coherence tomography at three months. We also review the current status of these novel devices. Resumo: Apresentamos pela primeira vez o tratamento com suportes bioabsorbíveis de magnésio na intervenção coronária percutânea complexa de doentes com alergia ao níquel. Incluímos a angiografia e as imagens da tomografia de coerência óptica efetuadas durante um período de três meses. Analisamos também o estado atual deste equipamento inovador. Keywords: Bioabsorbable magnesium scaffolds, Nickel allergy, Complex percutaneous coronary intervention, Palavras-chave: Suportes bioabsorbíveis de magnésio, Alergia ao níquel, Intervenção coronária percutânea complexa

Objective: Since obesity has been associated with a higher inflammatory burden and worse response to therapy in patients with chronic inflammatory rheumatic diseases (CIRD), we aimed to confirm the potential association between body mass index (BMI) and disease activity in a large series of patients with CIRDs included in the Spanish CARdiovascular in rheuMAtology (CARMA) registry. Methods: Baseline data analysis of patients included from the CARMA project, a 10-year prospective study of patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) attending outpatient rheumatology clinics from 67 Spanish hospitals. Obesity was defined when BMI (kg/m2) was >30 according to the WHO criteria. Scores used to evaluate disease activity were Disease Activity Score of 28 joints (DAS28) in RA, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in AS, and modified DAS for PsA. Results: Data from 2234 patients (775 RA, 738 AS, and 721 PsA) were assessed. The mean ± SD BMI at the baseline visit were: 26.9 ± 4.8 in RA, 27.4 ± 4.4 in AS, and 28.2 ± 4.7 in PsA. A positive association between BMI and disease activity in patients with RA (β = 0.029; 95%CI (0.01–0.05); p = 0.007) and PsA (β = 0.036; 95%CI (0.015–0.058); p = 0.001) but not in those with AS (β = 0.001; 95%CI (−0.03–0.03); p = 0.926) was found. Disease activity was associated with female sex and rheumatoid factor in RA and with Psoriasis Area Severity Index and enthesitis in PsA. Conclusions: BMI is associated with disease activity in RA and PsA, but not in AS. Given that obesity is a potentially modifiable factor, adequate control of body weight can improve the outcome of patients with CIRD and, therefore, weight control should be included in the management strategy of these patients.

Objective. To determine if the use of the relative risk (RR) chart score may help to identify young ankylosing spondylitis (AS) patients at high risk of cardiovascular (CV) disease. Methods. 73 AS patients younger than 50 years were assessed. CV risk was calculated according to the total cholesterol systematic coronary risk evaluation (TC-SCORE) and the RR chart score. C-reactive protein (CRP) value at disease diagnosis and carotid ultrasound data were also analyzed. Results. Twenty (27.4%) patients exhibited carotid plaques being classified into the category of very high CV risk. None of them was found to have a high/very high TC-SCORE. CRP > 3 mg/L at disease diagnosis was associated with the presence of carotid plaques (odds ratio 5.66, p=0.03). Whereas only 5 (14.2%) of the 35 patients with RR = 1 had carotid plaques, 15 (39.5%) of 38 with RR > 1 showed plaques. A model that included the performance of carotid US in patients with RR > 1 who had CRP > 3 mg/L allowed us to identify 60% of very high risk patients, with a specificity of 77.4%. Conclusions. RR chart score assessment may help to identify young AS patients at high risk of CV disease.

Several studies suggest that there is a pathogenic link between chronic obstructive pulmonary disease (COPD) and cardiovascular diseases. On the other hand, increased sympathetic tone has been described in several respiratory diseases. Our objective was to determine whether hypertension mediated by sympathetic overactivity is a mechanism that explains the association between COPD and cardiovascular diseases.Prospective nested case-control observational study; 67 COPD patients were matched 1:1 by sex and age to controls with smoking history. 24 hour-blood pressure monitoring, urinary catecholamines and their metabolites measurement, echocardiography, carotid ultrasound examination, nocturnal oximetry and retinography were performed.classic cardiovascular risk factors and comorbidities were similarly distributed between cases and controls. No significant differences for blood pressure variables (difference for mean systolic blood pressure: -0·13 mmHg; 95% CI: -4·48,4·20; p = 0·94; similar results for all blood presssure variables) or catecholamines values were found between both groups. There was a tendency for lower left ventricle ejection fraction in the COPD cases, that approached statistical significance (64·8 ± 7·4 vs 67·1 ± 6·2, p = 0·05). There were no differences in the retinal arteriovenous ratio, the carotid intima-media thickness, or the number of carotid plaques, between cases and controls. Fibrinogen values were higher in the COPD group (378·4 ± 69·6 vs 352·2 ± 45·6 mg/dL, p = 0·01) and mean nocturnal oxygen saturation values were lower for COPD patients (89·0 ± 4·07 vs 92·3 ± 2·2%, p < 0·0001).Hypertension induced by sympathetic overactivity does not seem to be a mechanism that could explain the association between COPD and cardiovascular disease.

To determine whether the interleukin-33 (IL-33)-interleukin-1 receptor like 1 (IL-1RL1) signaling pathway is implicated in the risk of subclinical atherosclerosis in patients with rheumatoid arthritis (RA).A total of 576 Spanish RA patients from Northern Spain were genotyped for 6 well-known IL33-IL1RL1 polymorphisms (IL33 rs3939286, IL33 rs7025417, IL33 rs7044343, IL1RL1 rs2058660, IL1RL1 rs2310173 and IL1RL1 rs13015714) by TaqMan genotyping assay. The presence of subclinical atherosclerosis was determined by the assessment of carotid intima-media thickness (cIMT) by carotid ultrasound (US).RA patients carrying the TT genotype of the IL33 rs3939286 polymorphism had lower cIMT values than those homozygous for the CC genotype (mean ± standard deviation (SD): 0.71 ± 0.14 mm versus 0.76 ± 0.16 mm, respectively) while patients carrying the CT genotype had intermediate cIMT values (mean ± SD: 0.73 ± 0.17 mm). Moreover, RA patients carrying the mutant allele T of the IL33 rs3939286 polymorphism exhibited significantly lower cIMT values than those carrying the wild allele C (mean ± SD: 0.72 ± 0.16 mm versus 0.75 ± 0.18 mm respectively; p = 0.04). The association of both genotype and allele frequencies of IL33 rs3939286 and cIMT levels remained statistically significant after adjustment for sex, age at the time of US study, follow-up and center (p = 0.006 and p = 0.0023, respectively), evidencing that the potential effect conferred by IL33 rs3939286 may be independent of confounder factors. No association with other IL33-IL1RL1 genetic variants was observed.In conclusion, our results may suggest a potential protective effect of the IL33 rs3939286 allele T in the risk of subclinical atherosclerosis in patients with RA.

Objective. TRAIL is a potential biomarker of cardiovascular (CV) disease. Ankylosing spondylitis (AS) is a chronic inflammatory disease associated with metabolic syndrome (MeS) and accelerated atherosclerosis. We assessed whether disease activity, systemic inflammation, and MeS features were associated with circulating TRAIL levels in AS patients undergoing TNF-α antagonist infliximab therapy and if infliximab infusion modified TRAIL levels. Methods. We measured TRAIL serum levels in 30 nondiabetic AS patients without CV disease undergoing anti-TNF-α therapy, immediately before and after an infliximab infusion, and in 48 matched controls. Correlations of TRAIL levels with disease activity, systemic inflammation and MeS features, adipokines, and biomarkers of endothelial activation were evaluated. Changes in TRAIL levels following anti-TNF-α infusion were analyzed. Results. TRAIL levels were higher in AS patients than controls. TRAIL levels displayed an inverse correlation with total and LDL cholesterol. We observed an inverse correlation with QUICKI and a marginal association with HOMA-IR. We also found an inverse correlation with resistin and a marginal association with apelin and OPN. Anti-TNF-α infusion did not change TRAIL levels after 120′. Conclusion. Elevated TRAIL levels in AS patients may be the result of a compensatory mechanism to reduce CV risk in these patients.

Introduction. Rheumatoid arthritis (RA) is a polygenic disease associated with accelerated atherosclerosis and increased cardiovascular (CV) mortality. Recent studies have identified the ABO rs579459, PPAP2B rs17114036, and ADAMTS7 rs3825807 polymorphisms as genetic variants associated with coronary artery disease and the PIK3CG rs17398575 and EDNRA rs1878406 polymorphisms as the most significant signals related to the presence of carotid plaque in nonrheumatic Caucasian individuals. Accordingly, we evaluated the potential relationship between these 5 polymorphisms and subclinical atherosclerosis (assessed by carotid intima-media thickness (cIMT) and presence/absence of carotid plaques) and CV disease in RA. Material and Methods. 2140 Spanish RA patients were genotyped for the 5 polymorphisms by TaqMan assays. Subclinical atherosclerosis was evaluated in 620 of these patients by carotid ultrasonography technology. Results. No statistically significant differences were found when each polymorphism was assessed according to cIMT values and presence/absence of carotid plaques in RA, after adjusting the results for potential confounders. Moreover, no significant differences were obtained when RA patients were stratified according to the presence/absence of CV disease after adjusting for potential confounders. Conclusion. Our results do not confirm association between ABO rs579459, PPAP2B rs17114036, ADAMTS7 rs3825807, PIK3CG rs17398575, and EDNRA rs1878406 and subclinical atherosclerosis and CV disease in RA.

Rheumatoid arthritis is an inflammatory disease with high incidence of cardiovascular disease due to accelerated atherosclerosis. Osteoprotegerin (OPG) has been associated with increased risk of atherosclerotic disease in the general population. Several polymorphisms in the OPG gene with functional effects on cardiovascular disease in non-rheumatic individuals have been described. Therefore, we aimed to analyze the effect of three of these functional OPG polymorphisms on the risk of cardiovascular disease in a large and well-characterized cohort of Spanish patients with rheumatoid arthritis.Three OPG gene variants (rs3134063, rs2073618 and rs3134069) were genotyped by TaqMan assays in 2027 Spanish patients with rheumatoid arthritis. Anti-cyclic citrullinated peptide (anti-CCP) antibody testing was positive in 997 of 1714 tested. Also, 18.3% of the whole series had experienced cardiovascular events, including 5.4% with cerebrovascular accidents. The relationship between OPG variants and cardiovascular events was assessed using Cox regression.No association between OPG gene variants and cardiovascular disease was observed in the whole group of rheumatoid arthritis patients or in anti-CCP positive patients. Nevertheless, a protective effect of CGA haplotype on the risk of cardiovascular disease in general, and specifically in the risk of cerebrovascular complications after adjusting for sex, age at disease diagnosis and traditional cardiovascular risk factors was disclosed in anti-CCP negative patients (HR = 0.54; 95%CI: 0.31-0.95; p = 0.032 and HR = 0.17; 95%CI: 0.04-0.78; p = 0.022, respectively).Our results indicate a protective effect of the OPG CGA haplotype on cardiovascular risk, mainly due to a protective effect against cerebrovascular events in anti-CCP negative rheumatoid arthritis patients.

Insulin resistance is an essential feature of the metabolic syndrome that has been linked to rheumatoid arthritis (RA). Understanding how inflammation arising in one tissue affects the physiology and pathology of other organs remains an unanswered question with therapeutic implications for chronic conditions including obesity, diabetes mellitus, atherosclerosis, and RA. Adipokines may play a role in the development of atherogenesis in patients with RA. Biologic therapies, such as TNF-α antagonists, that block proinflammatory cytokines have beneficial effects on the insulin resistance that is often observed in patients with RA.

UNLABELLED:Rheumatoid arthritis (RA) is a complex polygenic inflammatory disease associated with accelerated atherosclerosis and increased risk of cardiovascular (CV) disease. Previous genome-wide association studies have described SMAD3 rs17228212 polymorphism as an important signal associated with CV events. The aim of the present study was to evaluate for the first time the relationship between this gene polymorphism and the susceptibility to CV manifestations and its potential association with the presence of subclinical atherosclerosis assessed by the evaluation of carotid intima-media thickness (cIMT) in patients with RA. METHODS:One thousand eight hundred and ninety-seven patients fulfilling classification criteria for RA were genotyped for SMAD3 rs17228212 gene polymorphism through TaqMan genotyping assay. Also, subclinical atherosclerosis determined by the assessment of cIMT was analyzed in a subgroup of these patients by carotid ultrasonography. RESULTS:No statistically significant differences were observed when allele frequencies of RA patients with or without CV events were compared. Nevertheless, when RA patients were stratified according to anti-cyclic citrullinated peptide (anti-CCP) status, we found that in RA patients who were negative for anti-CCP antibodies, the presence of C allele of SMAD3 rs17228212 polymorphism conferred a protective effect against the risk of cerebrovascular accident (CVA) after adjustment for demographic and classic CV risk factors (HR [95%CI]=0.36 [0.14-0.94], p=0.038) in a Cox regression model. Additionally, correlation between the presence of C allele of SMAD3 rs17228212 polymorphism and lower values of cIMT was found after adjustment for demographic and classic CV risk factors (p-value=0.0094) in the anti-CCP negative RA patients. CONCLUSIONS:Our results revealed that SMAD3 rs17228212 gene variant is associated with lower risk of CVA and less severe subclinical atherosclerosis in RA patients negative for anti-CCP antibodies. These findings may have importance to establish predictive models of CV disease in RA patients according to anti-CCP status.

ObjectiveRheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased cardiovascular (CV) mortality. Since CD40-CD154 binding has direct consequences on inflammation process initiation, we aimed to replicate previous findings related to disease susceptibility in Spanish RA population. Furthermore, as the major complication in RA disease patients is the development of CV events due to accelerated atherosclerosis, and elevated levels of CD40L/CD154 are present in patients with acute myocardial infarction, we assessed the potential association of CD40 and CD154/CD40L gene variants with CV risk in Spanish RA patients.MethodsOne thousand five hundred and seventy-five patients fulfilling the 1987 ACR classification criteria for RA and 1600 matched controls were genotyped for the CD40 rs1883832, rs4810485 and rs1535045 and CD154 rs3092952 and rs3092920 gene polymorphisms, using predesigned TaqMan single nucleotide polymorphism genotyping assays. Afterwards, we investigated the influence of CD40-CD154 gene variants in the development of CV events. Also, in a subgroup of 273 patients without history of CV events, we assessed the influence of these polymorphisms in the risk of subclinical atherosclerosis determined by carotid ultrasonography.ResultsNominally significant differences in the allele frequencies for the rs1883832 CD40 gene polymorphism between RA patients and controls were found (p=0.038). Although we did not observe a significant association of CD40-CD154 gene variants with the development of CV events, an ANCOVA model adjusted for sex, age at the time of the ultrasonography assessment, follow-up time, traditional CV risk factors and anti-cyclic citrullinated peptide antibodies disclosed a significant association (p=0.0047) between CD40 rs1535045 polymorphism and carotid intima media thickness, a surrogate marker of atherosclerosis.ConclusionData from our pilot study indicate a potential association of rs1883832 CD40 gene polymorphism with susceptibility to RA. Also, the CD40 rs1535045 gene variant may influence development of subclinical atherosclerosis in RA patients.

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased cardiovascular (CV) morbidity and mortality. Since interferon-gamma (IFN-γ) has a direct effect on inflammation, in this study we assessed the potential association of the IFNG functional gene variant rs2430561 with CV disease in patients with RA. METHODS: One thousand six hundred and thirty-five patients fulfilling the 1987 American College of Rheumatology classification criteria for RA were genotyped for the IFNG (rs2430561, +874T/A) gene polymorphism using TaqMan genotyping assay. Patients were stratified according to the presence of CV events or not. Logistic regression models to explain the presence of CV disease according to the IFNG rs2430561 allele distribution were performed. The potential influence of this variant in the development of subclinical atherosclerosis was also analyzed in a subgroup of patients with no history of CV events to determine carotid artery intima-media thickness (IMT) (n = 286) and presence of carotid plaques. Levels of the cytokine were determined in a subgroup of patients by ELISA. RESULTS: Adjusted logistic regression model disclosed that presence of the minor allele A was not associated with increased risk of suffering CV events in RA patients. Besides, differences did not achieve statistical significance regarding carotid IMT and presence of carotid plaques in RA patients carrying IFNG rs2430561 variant allele. Levels of IFN-γ were higher in patients who had suffered CV events compared to patients who did not. CONCLUSION: Our results do not support a role of IFNG rs2430561 (+874T/A) functional gene variant in the development of CV disease in RA patients.

Cardiovascular (CV) disease is the most common cause of premature mortality in patients with rheumatoid arthritis (RA). It is the result of an accelerated atherosclerotic process. Both RA and atherosclerosis are complex polygenic diseases. Besides traditional CV risk factors and chronic inflammation, a number of studies have confirmed the role of genetic factors in the development of the atherogenesis observed in RA. In this regard, besides a strong association between the HLA-DRB1*04 shared epitope alleles and both endothelial dysfunction, an early step in the atherosclerotic process, and clinically evident CV disease, other polymorphisms belonging to genes implicated in inflammatory and metabolic pathways, located inside and outside the HLA region, such as the 308 variant (G>A, rs1800629) of the TNFA locus, the rs1801131 polymorphism (A>C; position + 1298) of the MTHFR locus, or a deletion of 32 base pairs on the CCR5 gene, seem to be associated with the risk of CV disease in patients with RA. Despite considerable effort to decipher the genetic basis of CV disease in RA, further studies are required to better establish the genetic influence in the increased risk of CV events observed in patients with RA.