Proprotein convertase subtilisin/kexin type 9 is related to disease activity and damage in patients with systemic erythematosus lupus

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that regulates cholesterol metabolism through low-density lipoprotein receptor degradation and that has been linked to cardiovascular (CV) disease. The purpose of the present study was to examine whether PCSK9 levels are disrupted compared with controls in patients with systemic lupus erythematosus (SLE). We additionally sought to establish whether PCSK9 is related to both the abnormalities in the lipid profile and to the disease activity or damage of patients with SLE. Methods: We performed a cross-sectional study that encompassed 366 individuals: 195 SLE patients and 171 age-, sex-, and statin intake-matched controls. PCSK9, lipoproteins serum concentrations, and lipid profiles were assessed in patients and controls. A multivariable analysis, adjusted for standard CV risk factors, was performed to evaluate the role of PCSK9 in SLE-related dyslipidemia. Results: Most lipid related-molecules were decreased in patients with SLE compared with controls. This downregulation included PCSK9, with PCSK9 levels being lower in patients than controls in the full multivariable analysis, including the modifications in lipid profiles that the disease itself produces {beta coefficient ?73 [95% confidence interval (CI) ?91 to ?54] ng/ml, p???0.001}. Both SLICC and SLEDAI scores were independently and positively related to PCSK9. Patients currently on hydroxychloroquine exhibited decreased levels of PCSK9 compared with those that were not taking hydroxychloroquine [beta coefficient ?30 (95% CI ?54 to ?6) ng/ml, p?=?0.015]. Conclusion: PCSK9 is downregulated in SLE compared with controls, but SLE patients with higher disease activity and damage exhibited higher PSCK9 serum levels.The authors disclosed receipt of the following financial support for the research, authorship, and/ or publication of this article: this work was supported by a grant to IF-A from the Spanish Ministry of Health, Subdirección General de Evaluación y Fomento de la Investigación, Plan Estatal de Investigación Científica y Técnica y de Innovación 2013–2016 and by Fondo Europeo de Desarrollo Regional - FEDER - (Fondo de Investigaciones Sanitarias, FIS PI14/00394, PI17/00083). The research of MAG-G is supported by the Instituto de Salud Carlos III (ISCIII) (Fondo de Investigación Sanitaria grants PI06/0024, PI09/00748, PI12/00060, PI15/00525, PI18/00043) and the ISCIII RETICS program (RD12/0009 and RD16/0012)

HDL cholesterol efflux capacity in rheumatoid arthritis patients: contributing factors and relationship with subclinical atherosclerosis

Background: Lipid profiles appear to be altered in rheumatoid arthritis (RA) patients because of disease activity and inflammation. Cholesterol efflux capacity (CEC), which is the ability of high-density lipoprotein cholesterol to accept cholesterol from macrophages, has been linked not only to cardiovascular events in the general population but also to being impaired in patients with RA. The aim of this study was to establish whether CEC is related to subclinical carotid atherosclerosis in patients with RA. Methods: We conducted a cross-sectional study that encompassed 401 individuals, including 178 patients with RA and 223 sex-matched control subjects. CEC, using an in vitro assay, lipoprotein serum concentrations, and standard lipid profile, was assessed in patients and control subjects. Carotid intima-media thickness (CIMT) and carotid plaques were assessed in patients with RA. A multivariable analysis was performed to evaluate the relationship of CEC with RA-related data, lipid profile, and subclinical carotid atherosclerosis. Results: Mean (SD) CEC was not significantly different between patients with RA (18.9 ± 9.0%) and control subjects (16.9 ± 10.4%) (p = 0.11). Patients with RA with low (? coefficient ?5.2 [?10.0 to 0.3]%, p = 0.039) and moderate disease activity (? coefficient ?4.6 [?8.5 to 0.7]%, p = 0.020) were associated with lower levels of CEC than patients in remission. Although no association with CIMT was found, higher CEC was independently associated with a lower risk for the presence of carotid plaque in patients with RA (odds ratio 0.94 [95% CI 0.89?0.98], p = 0.015). Conclusions: CEC is independently associated with carotid plaque in patients with RA

Incretins in patients with rheumatoid arthritis

Background: The precise mechanism linking systemic inflammation with insulin resistance (IR) in rheumatoid arthritis (RA) remains elusive. In the present study, we determined whether the incretin-insulin axis and incretin effect are disrupted in patients with RA and if they are related to the IR found in these patients. Methods: We conducted a cross-sectional study that encompassed 361 subjects without diabetes, 151 patients with RA, and 210 sex-matched control subjects. Insulin, C-peptide, glucagon-like peptide-1 (GLP-1), gastric inhibitory polypeptide (GIP), dipeptidyl peptidase 4 (DPP-4) soluble form, and IR indexes by homeostatic model assessment (HOMA2) were assessed. A multivariable analysis adjusted for IR-related factors was performed. Additionally, ten patients and ten control subjects underwent a 566-kcal meal test so that we could further study the postprandial differences of these molecules between patients and control subjects. Results: Insulin, C-peptide, and HOMA2-IR indexes were higher in patients than in control subjects. This was also the case for GLP-1 (0.49 ± 1.28 vs. 0.71 ± 0.22 ng/ml, p = 0.000) and GIP (0.37 ± 0.40 vs. 1.78 ± 0.51 ng/ml, p = 0.000). These differences remained significant after multivariable adjustment including glucocorticoid intake. Disease Activity Score in 28 joints with erythrocyte sedimentation rate (? coefficient 46, 95% CI 6?87, p = 0.026) and Clinical Disease Activity Index (? coefficient 7.74, 95% CI 1.29?14.20, p = 0.019) were associated with DPP-4 serum levels. GLP-1 positively correlated with ?-cell function (HOMA2 of ?-cell production calculated with C-peptide) in patients but not in control subjects (interaction p = 0.003). The meal test in patients with RA revealed a higher total and late response AUC for glucose response, a later maximal response of C-peptide, and a flatter curve in GIP response. Conclusions: The incretin-insulin axis, both during fasting and postprandial, is impaired in patients with RA.This work was supported by grants from the Spanish Ministry of Health, Subdirección General de Evaluación y Fomento de la Investigación, Plan Estatal de Investigación Científica y Técnica y de Innovación 2013–2016 Instituto de Salud Carlos III [ISCIII] PI14/00394) and by the Fondo Europeo de Desarrollo Regional (FEDER) (to IFA). The research of MAGG was supported by European Union FEDER funds and by the “Fondo de Investigación Sanitaria” (grants PI06/0024, PS09/00748, PI12/00060, and PI15/00525) of the Instituto de Salud Carlos III (ISCIII; Spanish Health Ministry). The research of MAGG was also partially supported by RETICS Programs RD12/0009 (RIER) and RD12/0009/0013 from the ISCIII (Spanish Health Ministry)

Protective Role of the Interleukin 33 rs3939286 Gene Polymorphism in the Development of Subclinical Atherosclerosis in Rheumatoid Arthritis Patients

OBJECTIVES: 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). METHODS: 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). RESULTS: 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. CONCLUSIONS: 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

Relevance of gastrointestinal manifestations in a large Spanish cohort of patients with systemic lupus erythematosus: what do we know?

SLE can affect any part of the gastrointestinal (GI) tract. GI symptoms are reported to occur in >50% of SLE patients. To describe the GI manifestations of SLE in the RELESSER (Registry of SLE Patients of the Spanish Society of Rheumatology) cohort and to determine whether these are associated with a more severe disease, damage accrual and a worse prognosis. METHODS: We conducted a nationwide, retrospective, multicentre, cross-sectional cohort study of 3658 SLE patients who fulfil =4 ACR-97 criteria. Data on demographics, disease characteristics, activity (SLEDAI-2K or BILAG), damage (SLICC/ACR/DI) and therapies were collected. Demographic and clinical characteristics were compared between lupus patients with and without GI damage to establish whether GI damage is associated with a more severe disease. RESULTS: From 3654 lupus patients, 3.7% developed GI damage. Patients in this group (group 1) were older, they had longer disease duration, and were more likely to have vasculitis, renal disease and serositis than patients without GI damage (group 2). Hospitalizations and mortality were significantly higher in group 1. Patients in group 1 had higher modified SDI (SLICC Damage Index). The presence of oral ulcers reduced the risk of developing damage in 33% of patients. CONCLUSION: Having GI damage is associated with a worse prognosis. Patients on a high dose of glucocorticoids are at higher risk of developing GI damage which reinforces the strategy of minimizing glucocorticoids. Oral ulcers appear to decrease the risk of GI damage. © The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology

HDL-Colesterol y su capacidad aceptora de colesterol procedente de macrófagos en artritis reumatoide: relación con la ateromatosis subclínica

En els pacients amb artritis reumatoide, la inflamació pròpia de la malaltia així com l’activitat de la mateixa, s’han relacionat amb un perfil lipídic anòmal. La capitat acceptora del colesterol HDL, coneguda como flux revers de colesterol, és la capacitat del HDL per acceptar el colesterol dels macròfags. Aquesta funció principal del HDL no només s’ha vinculat a esdeveniments cardiovasculars en població general, sinó també, sembla estar alterada en els pacients amb artritis reumatoide. En aquesta tesis doctoral es realitzen diferents anàlisis en una població de pacients amb artritis reumatoide amb l’objectiu de discernir si existeix una relació entre la capacitat acceptora del colesterol HDL i diversos paràmetres predictors de la aterosclerosis subclínica així com característiques de la pròpia malaltia articular. De la mateixa manera, s’estudia la possible associació entre les concentracions sèriques de les diferents lipoproteïnes i el perfil lipídic estàndard en els pacients i el grup control. La tesi inclou una revisió de la literatura sobre el risc cardiovascular en pacients amb artritis reumatoide, així com una revisió dels principals mecanismes fisiopatogènics implicats en l’augment del risc cardiovascular en aquests pacients. La investigació d’aquesta tesi es divideix en tres apartats. Un primer apartat en el que es descriuen les variables clíniques dels pacients amb artritis reumatoide i del grup control, i en el que es fa èmfasi en les diferències pertinents. Un segon apartat que reflexa les diverses associacions entre el perfil lipídic i la capacitat acceptora del colesterol en els pacients amb artritis reumatoide i els controls. Finalment, un tercer apartat en el que s’investiga la relació entre els paràmetres predictors d’aterosclerosi subclínica i la capacitat acceptora del colesterol. No hi ha dubte que caldran altres anàlisis per poder entendre profundament els mecanismes del risc cardiovascular a l’artritis, no obstant, els nostres resultats podrien ser un pas previ i tenir la seva aplicació a pràctica clínica.En los pacientes con artritis reumatoide, la inflamación propia de la enfermedad así como la actividad de la misma, se han relacionado con un perfil lipídico anómalo. La capacidad aceptora de colesterol HDL, conocida como flujo reverso de colesterol, es la capacidad del HDL para aceptar el colesterol de los macrófagos. Esta función principal del colesterol HDL no sólo se ha vinculado a eventos cardiovasculares en población general, sino también, parece estar alterada en los pacientes con artritis reumatoide. En esta tesis doctoral se realizan diferentes análisis en una población de pacientes con artritis reumatoide con el objetivo de discernir si existe una relación entre la capacidad aceptora del colesterol HDL y distintos parámetros predictores de la ateroesclerosis subclínica así como características de la propia enfermedad articular. Del mismo modo, se estudia la posible asociación entre las concentraciones séricas de las diferentes lipoproteínas y el perfil lipídico estándar en pacientes y grupo control. La tesis incluye una revisión de la literatura sobre riesgo cardiovascular en pacientes con artritis reumatoide así como una revisión de los principales mecanismos fisiopatogénicos implicados en el aumento de riesgo cardiovascular en estos pacientes. La investigación de la presente tesis se divide en tres apartados. Un primer apartado en el que se describen las variables clínicas de los pacientes con artritis reumatoide y el grupo control, y en el cual se establecen las diferencias pertinentes. Un segundo apartado que refleja las distintas asociaciones entre el perfil lipídico y la capacidad aceptora de colesterol en los pacientes y los controles. Finalmente, un tercer apartado en el que se investiga la relación entre los parámetros predictores de ateroesclerosis subclínica y la capacidad aceptora de colesterol. No cabe la menor duda que serán necesarios otros análisis para poder entender profundamente los mecanismos del riesgo cardiovascular en la artritis, sin embargo, nuestros resultados podrían ser un paso previo y tener su aplicación en práctica clínica.Lipid profiles appear to be altered in rheumatoid arthritis patients because of disease activity and inflammation. Cholesterol efflux capacity which is the ability of high-density lipoprotein cholesterol to accept cholesterol from macrophages, has been linked not only to cardiovascular events in the general population but also, to be impaired in patients with rheumatoid arthritis. In the present work, we performed different analyses in a rheumatoid arthritis population in order to investigate whether there is a relationship between the acceptance capacity of HDL cholesterol and different predictive parameters of subclinical atherosclerosis as well as characteristics of the joint disease itself. Similarly, the possible association between the serum concentrations of the different lipoproteins and the standard lipid profile in patients and control group is studied. Furthermore, the present work includes a review of the literature on cardiovascular risk in patients with rheumatoid arthritis as well as a review of the main pathophysiological mechanisms that may be involved in the increased cardiovascular risk in these patients. The thesis research is divided into three sections. The first section describes the clinical variables of patients with rheumatoid arthritis and the control group, and emphasizes the relevant differences. A second section reflecting the different associations between lipid profile and cholesterol acceptance capacity in patients with rheumatoid arthritis and controls. Finally, a third section investigating the relationship between predictive parameters of subclinical atherosclerosis and cholesterol acceptance capacity. Although other analyses will undoubtedly be necessary to understand in depth the mechanisms of cardiovascular risk in rheumatoid arthritis, some of our results might be a preliminary step and have applicability in clinical practice.Universitat Autònoma de Barcelona. Programa de Doctorat en Medicin

Sarcoidosis, a propósito de 68 casos

La sarcoidosis es una enfermedad sistémica, granulomatosa de etiología desconocida que afecta al adulto joven. Puede interesar a cualquier órgano aunque también existen formas asintomáticas. En este trabajo se describen las características clínicas, el tratamiento y la evolución de una serie de pacientes diagnosticados de sarcoidosis. Es un estudio retrospectivo en un hospital universitario con un área de referencia de 700.000 habitantes. La manifestación de inicio más frecuente fue el síndrome de Löfgren. La mayoría de los pacientes recibieron tratamiento con antiinflamatorios esteroideos y no esteroideos y presentaron una buena evolución, con resolución de la enfermedad.La sarcoïdosi és una malaltia sistèmica, granulomatosa d’etiologia desconeguda que afecta a l'adult jove. Pot afectar qualsevol òrgan encara que també hi ha formes asimptomàtiques. En aquest treball es descriuen les característiques clíniques, el tractament i l'evolució d'una sèrie de pacients diagnosticats de sarcoïdosi. És un estudi retrospectiu en un hospital universitari amb una àrea de referència de 700.000 habitants. La manifestació d'inici més freqüent va ser la síndrome de Löfgren. La majoria dels pacients van rebre tractament amb antiinflamatoris esteroïdals i no esteroïdals i varen evolucionar bé , cap a la curació de la malaltia

Sarcoidosis, a propósito de 68 casos

La sarcoidosis es una enfermedad sistémica, granulomatosa de etiología desconocida que afecta al adulto joven. Puede interesar a cualquier órgano aunque también existen formas asintomáticas. En este trabajo se describen las características clínicas, el tratamiento y la evolución de una serie de pacientes diagnosticados de sarcoidosis. Es un estudio retrospectivo en un hospital universitario con un área de referencia de 700.000 habitantes. La manifestación de inicio más frecuente fue el síndrome de Löfgren. La mayoría de los pacientes recibieron tratamiento con antiinflamatorios esteroideos y no esteroideos y presentaron una buena evolución, con resolución de la enfermedad.La sarcoïdosi és una malaltia sistèmica, granulomatosa d'etiologia desconeguda que afecta a l'adult jove. Pot afectar qualsevol òrgan encara que també hi ha formes asimptomàtiques. En aquest treball es descriuen les característiques clíniques, el tractament i l'evolució d'una sèrie de pacients diagnosticats de sarcoïdosi. És un estudi retrospectiu en un hospital universitari amb una àrea de referència de 700.000 habitants. La manifestació d'inici més freqüent va ser la síndrome de Löfgren. La majoria dels pacients van rebre tractament amb antiinflamatoris esteroïdals i no esteroïdals i varen evolucionar bé , cap a la curació de la malaltia

Sarcoidosis, a propósito de 68 casos

La sarcoidosis es una enfermedad sistémica, granulomatosa de etiología desconocida que afecta al adulto joven. Puede interesar a cualquier órgano aunque también existen formas asintomáticas. En este trabajo se describen las características clínicas, el tratamiento y la evolución de una serie de pacientes diagnosticados de sarcoidosis. Es un estudio retrospectivo en un hospital universitario con un área de referencia de 700.000 habitantes. La manifestación de inicio más frecuente fue el síndrome de Löfgren. La mayoría de los pacientes recibieron tratamiento con antiinflamatorios esteroideos y no esteroideos y presentaron una buena evolución, con resolución de la enfermedad.La sarcoïdosi és una malaltia sistèmica, granulomatosa d'etiologia desconeguda que afecta a l'adult jove. Pot afectar qualsevol òrgan encara que també hi ha formes asimptomàtiques. En aquest treball es descriuen les característiques clíniques, el tractament i l'evolució d'una sèrie de pacients diagnosticats de sarcoïdosi. És un estudi retrospectiu en un hospital universitari amb una àrea de referència de 700.000 habitants. La manifestació d'inici més freqüent va ser la síndrome de Löfgren. La majoria dels pacients van rebre tractament amb antiinflamatoris esteroïdals i no esteroïdals i varen evolucionar bé , cap a la curació de la malaltia