Non-invasive evaluation of arterial wall properties in patients with Primary Antiphospholipid Syndrome

Objetivo: A aterosclerose prematura e acelerada tem sido recentemente reconhecida como um fator adicional de dano vascular nos pacientes com Síndrome Antifosfolípide Primária (SAFP). Esses pacientes podem ser beneficiados com o emprego de métodos para detecção precoce de aterosclerose como a Velocidade de Onda de Pulso (VOP) e o Echo-tracking (ET). Esses métodos têm sido reconhecidos pela capacidade de avaliar de forma não-invasiva a progressão da aterosclerose na parede vascular. Portanto, nosso principal objetivo foi avaliar a aterosclerose prematura nesses pacientes com SAFP. Pacientes e Métodos: 27 pacientes do sexo feminino com SAFP definida pelos critérios de Sapporo e 27 pacientes controles pareadas por sexo, idade e índice de massa corpórea foram selecionadas de forma consecutiva. Todas as pacientes sofreram trombose e foram subdivididas de acordo com o sítio vascular: arterial (n=12) e venoso (n=11). Os critérios de exclusão foram: idade > 55 anos, raça negra, hipertensão descontrolada, uso de corticosteróides e estatinas, diabetes, dislipidemia prévia, gravidez, menopausa, outras trombofilias, colagenoses, doenças vasculares de outras etiologias, obesidade definido por Índice de massa corpórea (IMC) >30 m/kg2 e tabagismo. Todas as pacientes foram submetidas à VOP no leito fêmoro-carotídeo (Complior) e echo-tracking pelo Wall Track System no leito carotídeo para avaliação das propriedades funcionais dos vasos. Resultados: Ambos os grupos SAFP e controles não mostraram diferença em relação à idade (41.5 ± 9.3 vs. 41.2 ± 10.2 anos; p=0.92) e IMC (22.7 ± 3.4 vs. 22.6 ± 3.7 kg/m2; p=0.91). Todas as pacientes apresentaram VOP semelhante às controles (p=0.34), o espessamento íntima-média (EIM) foi semelhante nos dois grupos (p=0.29) assim como os demais parâmetros do echo-tracking como o diâmetro carotídeo (p=0.26), a distensibilidade (p=0.92), os coeficientes de complacência (p=0.36) e o módulo elástico (p=0.78). A pressão sistólica (PS) das pacientes estava aumentada em relação às controles (p=0.02). De acordo com o sítio de trombose, as pacientes com eventos arteriais demonstraram um aumento na VOP em relação àquelas com eventos venosos (p=0.01) mesmo com mesmo EIM (p=0.52). Ambos resultados não foram influenciados pela idade ou duração de doença. Os níveis de colesterol total (p=0.002), LDL (p=0.02) e apolipoproteína B (p=0.03) foram mais altos nas pacientes com SAFP com eventos arteriais exclusivos. Na análise multivariada, observamos correlação da VOP com a idade (r=0.584; p=0.001) e com o diâmetro do vaso (DV) (r=0.407; p=0.04). Foi observada uma correlação positiva da VOP com o colesterol total (r=0.507, p=0.01), LDL (r=0.402, p=0.05), e triglicérides (r=0.583, p=0.003). O EIM apresentou correlação direta com o DV (r=0.393; p=0.04) e com a distensibilidade (r=0.373, p=0.05). Conclusão: A aterosclerose na SAFP apresenta curso peculiar e de forma precoce. A VOP foi um método mais adequado para detectar a disfunção vascular secundária à rigidez arterial, visto que, não foram detectadas alterações vasculares funcionais pelo ET.Objective: Premature and accelerated atherosclerosis has been recently recognized as an additional vascular damage in Primary Antiphospholipid Syndrome (PAPS). These patients could benefit from non-invasive diagnostic methods to detect atherosclerosis as the Pulse Wave Velocity (PWV) and the Echo-Tracking (ET) device. By precise measurement of arterial stiffness, these methods output an indirect way to evaluate the vascular wall lesion progression. Our main objective was to evaluate premature atherosclerosis in PAPS.PATIENTS AND METHODS: 27 female patients with PAPS (Sapporo criteria) and 27 age-, body mass index- and sex-matched controls were consecutively selected. All PAPS patients had previous thrombosis and were subdivided according to the type of vascular exclusive event: arterial (n=12) and venous (n=11). Exclusion criteria were: age >55 years, black race, uncontrolled hypertension, smoking, diabetes, previous dyslipidemia, other thrombophilias, vascular and collagen diseases, corticosteroids and statins use, pregnancy, menopause, and obesity defined as body mass index (BMI)>30 m/kg2. All subjects underwent the PWV in femoral-carotidal bed (Complior) and echo-tracking by a Wall Track System in carotidal bed to analyze vascular wall functional properties. RESULTS: Both groups PAPS and controls did not show any difference regarding age (41.5 ± 9.3 vs. 41.2 ± 10.2 years; p=0.92) and BMI (22.7 ± 3.4 vs. 22.6 ± 3.7 kg/m2; p=0.91). All PAPS patients had PWV values similar to controls (p=0.34). Intima-media thickness (IMT) was also similar between groups (p=0.29) as well as all the other echo tracking parameters such as carotideal diameter (p=0.26), distensibility (p=0.92), compliance coefficients (p=0.36), and elastic modulus (p=0.78) were similar among groups. A higher systolic blood pressure was observed was observed in PAPS patients than controls (p=0.02). According to the site of thrombosis, PAPS patients with exclusive arterial events showed a higher PWV compared to those with venous (p=0.01) but had similar IMT (p=0.52). Both results were not influenced by age or disease duration. Total cholesterol (p=0.002), LDL (p=0.02), and apolipoprotein B (p=0.03) levels were higher in PAPS with exclusive arterial events compared to those with exclusive venous events. Multivariate analysis in PAPS showed that PWV was related to age (r=0.584; p=0.001) and blood vessel diameter (VD) (r=0.407; p=0.04). Moreover, PWV did also positively correlated with total cholesterol (r=0.507, p=0.01), LDL (r=0.402, p=0.05), and triglycerides (r=0.583, p=0.003). IMT also had a positive correlation with VD (r=0.393; p=0.04) and distensibility (r=0.373; p= 0.05). CONCLUSION: Atherosclerosis in PAPS has a peculiar course with an early onset, remarkably in those patients with arterial events. PWV was a sensible method to detect impaired functional vessel related to stiffness since no significant changes were observed in functional vascular properties by Echo- Tracking (ET) device

A importância de reconhecer a síndrome antifosfolípide na medicina vascular

Resumo A síndrome antifosfolipíde (SAF) é uma doença autoimune sistêmica caracterizada por trombose arterial ou venosa recorrente e/ou morbidade gestacional e pela presença dos anticorpos antifosfolipídeos, podendo apresentar outras manifestações vasculares, como microangiopatia, arteriopatia crônica e SAF catastrófica. Determinados testes laboratoriais para a síndrome (por exemplo, o anticoagulante lúpico) podem sofrer interferência do uso de medicações anticoagulantes, dificultando o diagnóstico. A fisiopatologia da SAF é complexa, sendo enumerados no texto diversos mecanismos patogênicos relacionados à coagulação, ao endotélio e às plaquetas. Por fim, discutimos o tratamento da SAF de acordo com a presença e o tipo de manifestações clínicas, o uso dos anticoagulantes orais diretos e o manejo perioperatório de pacientes com SAF

Impact of switching between reference biologics and biosimilars of tumour necrosis factor inhibitors for rheumatoid arthritis: a systematic review and network meta-analysis

Abstract What is the impact of switching between biologics and biosimilars of adalimumab, etanercept, and infliximab on efficacy and safety for rheumatoid arthritis? A systematic review and network meta-analysis were performed to compare switching and non-switching groups of treatments. Pooled Risk Relative (RR) or standardised mean differences (SMD) with 95% credible intervals (95% CrIs) were obtained. Seventeen randomized trials with a switching phase involving 6,562 patients were included. Results showed that a single switch from biologics to biosimilars compared to continuing biologics had comparable effects for primary and co-primary outcomes, the American College of Rheumatology criteria with 20% response (ACR20) (7 trials, 1,926 patients, RR 0.98, 95% CrIs 0.93 to 1.03) and the Health Assessment Questionnaire—Disability Index (HAQ-DI) (5 trials, 1,609 patients, SMD − 0.07, 95% CrIs − 0.23 to 0.1), and within the equivalence margins: ACR20 [RR 0.94, 1.06] and HAQ-DI [SMD − 0.22, 0.22]. The risk of treatment-emergent adverse events, discontinuation, and positive anti-drug antibodies were comparable after switching. Safety results were imprecise, and the follow-up period might not be sufficient to evaluate long-term effects, especially malignancies. Overall, the practice of single switching between approved biologics and biosimilars of Tumour Necrosis Factor inhibitors is efficacious and safe for rheumatoid arthritis

Quantifying subclinical central nervous lesions in primary antiphospholipid syndrome: The role of magnetization transfer imaging

Purpose: To define the role of magnetization transfer imaging (MTI) in detecting subclinical central nervous system (CNS) lesions in primary antiphospholipid syndrome (PAPS). Materials and Methods: Ten non-CNS PAPS patients were compared to 10 CNS PAPS patients and 10 age- and sex-matched controls. All PAPS patients met Sapporo criteria. All Subjects underwent conventional MRI and complementary MTI analysis to compose histograms. CNS viability was determined according to the magnetization transfer ratio (MTR) by mean pixel intensity (MPI) and the mean peak height (MPH). Volumetric cerebral measurements were assessed by brain parenchyma factor (BPF) and total/cerebral volume. Results: MTR histograms analysis revealed that MPI was significantly different among groups (P < 0.0001). Non-CNS PAPS had a higher MPI than CNS PAPS, (30.5 +/- 1.01 vs. 25.1 +/- 3.17 percent unit (pu); P < 0.05) although lower than controls (30.5 +/- 1.01 vs. 31.20 < 0.50 pu; P < 0.05). MPH in non-CNS PAPS (5.57 +/- 0.20% (1/pu)} was similar to controls (5.63 +/- 0.20% (1/pu), P > 0.05) and higher than CNS PAPS (4.71 +/- 0.30% (1/pu), P < 0.05). A higher peak location (PL) was also observed in the CNS PAPS group in comparison with the other groups (P < 0.0001). In addition, a lower BPF was found in non-CNS PAPS compared to controls (0.80 +/- 0.03 vs. 0.84 +/- 0.02 units; P < 0.05) but similar to CNS PAPS (0.80 +/- 0.03 vs. 0.79 +/- 0.05 units; P > 0.05). Conclusion: Our findings suggest that non-CNS PAPS patients have subclinical cerebral damage. The long-term-clinical relevance of MTI analysis in these patients needs to be defined by prospective studies

High frequency of osteoporosis and fractures in women with dermatomyositis/polymyositis

Bone mass was only previously studied in juvenile dermatomyositis/polymyositis (DM/PM) patients. Therefore, the objective this study was to evaluate the prevalence of osteoporosis and fractures in adult DM/PM. Forty female DM/PM and 78 age-, gender-, and BMI-matched healthy controls were studied. Medical charts and clinical interviews of all patients were evaluated for demographic and clinical data, including disease activity, cumulative doses of glucocorticoid, menarche and menopause age, and fractures. Bone mineral density (BMD) using dual X-ray absorptiometry (DXA) were measured at lumbar spine (L1-L4) and hip. A decreased BMD in lumbar spine [0.902 (0.136) vs. 0.965 (0.141) g/cm(2), P = 0.022] and femoral neck [0.729 (0.12) vs. 0.784 (0.127) g/cm(2), P = 0.027] was observed in patients compared to controls. In addition, osteoporosis was more frequent in patients than in controls in both lumbar spine (20 vs. 3.8%, P = 0.007) and the femoral neck (27.5 vs. 10.3%, P = 0.016). Moreover, a high prevalence of fractures was found in patients in comparison to healthy subjects (17.9 vs. 5.1%, P = 0.040; OR = 3.92; CI 95%: 1.07-14.33). Comparing DM/PM patients with (n = 17) and without (n = 23) osteoporosis/fractures, significant differences were observed regarding age [56.8 (11.9) vs. 48.3 (13.2) years, P = 0.042], weight [62.05 (13.56) vs. 71.51 (11.46) kg, P = 0.022] and frequency of post menopausal women (94.1 vs. 65.2%, P = 0.0002). No differences were observed concerning height, lean mass, total fat mass, disease activity, mean value of creatine kinase, cumulative glucocorticoid dose, or bisphosphonate use. Logistic regression analysis revealed a negative association between the presence of osteoporosis/fractures and weight (OR: 0.92, 95% CI: 0.85-0.98; P = 0.016). This is the first study that analyzed bone mass in adult DM/PM patients and it demonstrated that about one quarter of these patients have osteoporosis/fracture.Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ) [300559/2009-7, 300665/2009-1]Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Wilhelm Agricola Federico Foundation GrantWilhelm Agricola Federico Foundation Gran

Omega-3 Fatty Acid Supplementation Improves Endothelial Function in Primary Antiphospholipid Syndrome: A Small-Scale Randomized Double-Blind Placebo-Controlled Trial

Endothelial cells are thought to play a central role in the pathogenesis of antiphospholipid syndrome (APS). Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation has been shown to improve endothelial function in a number of diseases; thus, it could be of high clinical relevance in APS. The aim of this study was to evaluate the efficacy of n-3 PUFA supplementation on endothelial function (primary outcome) of patients with primary APS (PAPS). A 16-week randomized clinical trial was conducted with 22 adult women with PAPS. Patients were randomly assigned (1:1) to receive placebo (PL, n = 11) or n-3 PUFA (ω-3, n = 11) supplementation. Before (pre) and after (post) 16 weeks of the intervention, patients were assessed for endothelial function (peripheral artery tonometry) (primary outcome). Patients were also assessed for systemic markers of endothelial cell activation, inflammatory markers, dietary intake, international normalized ratio (INR), and adverse effects. At post, ω-3 group presented significant increases in endothelial function estimates reactive hyperemia index (RHI) and logarithmic transformation of RHI (LnRHI) when compared with PL (+13 vs. −12%, p = 0.06, ES = 0.9; and +23 vs. −22%, p = 0.02, ES = 1.0). No changes were observed for e-selectin, vascular adhesion molecule-1, and fibrinogen levels (p &gt; 0.05). In addition, ω-3 group showed decreased circulating levels of interleukin-10 (−4 vs. +45%, p = 0.04, ES = −0.9) and tumor necrosis factor (−13 vs. +0.3%, p = 0.04, ES = −0.95) and a tendency toward a lower intercellular adhesion molecule-1 response (+3 vs. +48%, p = 0.1, ES = −0.7) at post when compared with PL. No changes in dietary intake, INR, or self-reported adverse effects were observed. In conclusion, 16 weeks of n-3 PUFA supplementation improved endothelial function in patients with well-controlled PAPS. These results support a role of n-3 PUFA supplementation as an adjuvant therapy in APS. Registered at http://ClinicalTrials.gov as NCT01956188

Post-acute COVID-19 in three doses vaccinated autoimmune rheumatic diseases patients: frequency and pattern of this condition

Abstract Background Data on post-acute COVID-19 in autoimmune rheumatic diseases (ARD) are scarce, focusing on a single disease, with variable definitions of this condition and time of vaccination. The aim of this study was to evaluate the frequency and pattern of post-acute COVID-19 in vaccinated patients with ARD using established diagnosis criteria. Methods Retrospective evaluation of a prospective cohort of 108 ARD patients and 32 non-ARD controls, diagnosed with SARS-CoV-2 infection (RT-PCR/antigen test) after the third dose of the CoronaVac vaccine. Post-acute COVID-19 (≥ 4 weeks and > 12 weeks of SARS-CoV-2 symptoms) were registered according to the established international criteria. Results ARD patients and non-ARD controls, balanced for age and sex, had high and comparable frequencies of ≥ 4 weeks post-acute COVID-19 (58.3% vs. 53.1%, p = 0.6854) and > 12 weeks post-acute COVID-19 (39.8% vs. 46.9%, p = 0.5419). Regarding ≥ 4 weeks post-acute COVID-19, frequencies of ≥ 3 symptoms were similar in ARD and non-ARD controls (54% vs. 41.2%, p = 0.7886), and this was also similar in > 12 weeks post-acute COVID-19 (68.3% vs. 88.2%, p = 0.1322). Further analysis of the risk factors for ≥ 4 weeks post-acute COVID-19 in ARD patients revealed that age, sex, clinical severity of COVID-19, reinfection, and autoimmune diseases were not associated with this condition (p > 0.05). The clinical manifestations of post-acute COVID-19 were similar in both groups (p > 0.05), with fatigue and memory loss being the most frequent manifestations. Conclusion We provide novel data demonstrating that immune/inflammatory ARD disturbances after third dose vaccination do not seem to be a major determinant of post-acute COVID-19 since its pattern is very similar to that of the general population. Clinical Trials platform (NCT04754698)