Comparative Analysis of Coagulation Activation in Rheumatoid Arthritis Patients Treated With TNF Inhibitors Versus JAK Inhibitors: A Prospective Study.

OBJECTIVES: This study aims to investigate the activation of the coagulation system of RA patients and assess changes during anti-inflammatory treatment with tumor necrosis factor blockers (anti-TNF) and Janus kinase inhibitors (JAKi). METHODS: Biomarkers for the coagulation system, including D-dimer, fibrinogen, prothrombin time, activated partial thrombin time, prothrombin fragment 1 + 2, thrombin-antithrombin complex (TAT), activated factor IX, antithrombin complex, and von Willebrand factor (vWF), were longitudinally measured in 83 RA patients treated with anti-TNF and 38 RA patients with JAKi. Data were collected at baseline, after 1, 3, and 6 months. RESULTS: The mean age was 57 (±14) years; 76% was female. The mean DAS28-CRP was 3.6 (±1.3) for anti-TNF users and 4.1 (±1.4) for JAKi users at baseline and declined in both groups. Baseline coagulation markers levels were comparable between groups. In anti-TNF users, D-dimer and fibrinogen levels significantly declined (-0.31 mg/L, p = 0.01 and -0.71 g/L, p < 0.001, respectively), whereas TAT significantly increased after 6 months follow-up (1.46 µg/L, p = 0.03) and no effect on vWF (p = 0.98). In JAKi users, vWF declined significantly during the 6 months follow-up (-37.41%, p < 0.001); additionally, there were reductions of D-dimer, fibrinogen, and TAT that did not reach significance (-0.17 mg/L, p = 0.59; -0.49 g/L, p = 0.12; and 0.68 µg/L, p = 0.27, respectively). CONCLUSIONS: The prothrombotic tendency in active RA declined during effective treatment with both anti-TNF and JAKi. Altogether, the biomarkers used in this study suggest that an increased VTE risk in the first 6 months due to either treatment with anti-TNF or JAKi is unlikely.

Effect of anti-inflammatory therapy on vascular biomarkers for subclinical cardiovascular disease in rheumatoid arthritis patients.

OBJECTIVE: To assess the effect of 4 years of anti-inflammatory therapy on markers of subclinical vascular disease in rheumatoid arthritis patients. METHODS: Carotid intima media thickness (IMT), augmentation index (AIx@75) and pulse wave velocity (PWV) measurements were performed repeatedly in 61 RA patients (30 early RA starting with csDMARDs and 31 established RA starting with adalimumab) for 4 years. These markers were also measured in 29 controls with osteoarthritis at baseline (BL). RESULTS: IMT and AIx@75 at BL were higher in RA compared to OA, while PWV was higher in OA. In RA patients, AIx@75 and PWV decreased in the first 6 months after starting anti-inflammatory therapy. At 48 M, the level of AIx@75 remained lower than before therapy, while PWV at 48 M was comparable to BL (AIx@75: BL 28% (95% confidence interval 25-30%), 6 M 23% (20-26%), 48 M 25% (22-28%); PWV: BL 8.5 (7.8-9.2), 6 M 8.0 (7.1-8.9), 48 M 8.6 (7.6-9.6) m/s). IMT remained stable. There was an effect of disease activity (longitudinally, adjusted for changes over time) on IMT, AIx@75 and PWV. CONCLUSION: This study suggests modest beneficial changes in some surrogate markers of subclinical vascular disease after anti-inflammatory therapy. These changes were associated with improvement in disease activity markers. Whether or not these beneficial changes ultimately predict a reduction in clinicalcardiovascular endpoints remains to be established in prospective studies.

Bedside ultrasound to detect central venous catheter misplacement and associated iatrogenic complications: a systematic review and meta-analysis.

BACKGROUND: Insertion of a central venous catheter (CVC) is common practice in critical care medicine. Complications arising from CVC placement are mostly due to a pneumothorax or malposition. Correct position is currently confirmed by chest x-ray, while ultrasonography might be a more suitable option. We performed a meta-analysis of the available studies with the primary aim of synthesizing information regarding detection of CVC-related complications and misplacement using ultrasound (US). METHODS: This is a systematic review and meta-analysis registered at PROSPERO (CRD42016050698). PubMed, EMBASE, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials were searched. Articles which reported the diagnostic accuracy of US in detecting the position of CVCs and the mechanical complications associated with insertion were included. Primary outcomes were specificity and sensitivity of US. Secondary outcomes included prevalence of malposition and pneumothorax, feasibility of US examination, and time to perform and interpret both US and chest x-ray. A qualitative assessment was performed using the QUADAS-2 tool. RESULTS: We included 25 studies with a total of 2548 patients and 2602 CVC placements. Analysis yielded a pooled specificity of 98.9 (95% confidence interval (CI): 97.8-99.5) and sensitivity of 68.2 (95% CI: 54.4-79.4). US examination was feasible in 96.8% of the cases. The prevalence of CVC malposition and pneumothorax was 6.8% and 1.1%, respectively. The mean time for US performance was 2.83 min (95% CI: 2.77-2.89 min) min, while chest x-ray performance took 34.7 min (95% CI: 32.6-36.7 min). US was feasible in 97%. Further analyses were performed by defining subgroups based on the different utilized US protocols and on intra-atrial and extra-atrial misplacement. Vascular US combined with transthoracic echocardiography was most accurate. CONCLUSIONS: US is an accurate and feasible diagnostic modality to detect CVC malposition and iatrogenic pneumothorax. Advantages of US over chest x-ray are that it can be performed faster and does not subject patients to radiation. Vascular US combined with transthoracic echocardiography is advised. However, the results need to be interpreted with caution since included studies were often underpowered and had methodological limitations. A large multicenter study investigating optimal US protocol, among other things, is needed.

Lipid profile and NT-proBNP changes from pre-clinical to established rheumatoid arthritis: A 12 years follow-up explorative study.

OBJECTIVES: The aim of the current study was to explore the changes in lipid and NT-proBNP levels in rheumatoid arthritis (RA) patients through different phases of the disease: from the pre-clinical stage and RA onset up to the treatment phase with biological disease-modifying anti-rheumatic drugs (bDMARDS). METHODS: Thirty-eight consecutive patients, initially with arthralgia and rheumatoid factor and/or anti-citrullinated protein antibodies without arthritis, who later developed RA and eventually started treatment with bDMARDs, were included. Lipid spectrum and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were measured longitudinally from several months before diagnosis through treatment with bDMARDs. RESULTS: From baseline, C-reactive protein (CPR) initially increased sharply, decreasing with the start of biological treatment. Low-density lipoprotein-cholesterol (LDL-c) remained stable, high-density lipoprotein-cholesterol (HDL-c) increased, apolipoprotein A1 (ApoA1 and lipoprotein (a) (Lp(a)), and total cholesterol (TC)/HDL-c ratio and apolipoprotein B (ApoB) decreased during follow-up. NT-proBNP closely followed progression of CRP. TC, LDL-c, TC/HDL-c ratio, ApoA and ApoB inverse correlated with CRP, while Lp(a) positively correlated. HDL-c and triglycerides showed no correlation. CONCLUSION: Changes in the lipid profile and NT-proBNP in RA patients seem to be related to inflammation, with changes reflecting an increase in CVD risk occurring along with rises in CRP levels. These changes seem to already be present at diagnosis, indicating the need for timely control of inflammation.

Cardiovascular disease risk in patients with inflammatory arthritis nowadays still substantially elevated.

OBJECTIVES: This study aims to assess current cardiovascular disease risk and prevalence of risk factors in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (SpA). METHODS: 2050 consecutive patients with inflammatory arthritis (IA) and 939 controls were included, with 1308 patients with RA, 356 patients with PsA and 386 patients with SpA. In a prospective cohort setting, questionnaires regarding previous cardiovascular events and risk factors were used to assess cardiovascular risk and prevalence in patients with IA by calculating ORs using logistic regression models. RESULTS: 'Traditional' cardiovascular (CV) risk factors were significantly elevated in patients with IA compared with controls. Cardiovascular disease (CVD) ORs were increased in patients with RA and PsA compared with controls, 1.61 (95% CI: 1.04 to 2.48) and 2.12 (95% CI: 1.23 to 3.66), respectively, and a trend towards increased odds was observed in patients with SpA (OR 1.43; 95% CI: 0.79 to 2.59). After adjusting for traditional risk factors, CV risk was not increased in patients with RA (OR; 0.95, 95% CI: 0.58 to 1.55), PsA (OR 1.19; 95% CI: 0.64 to 2.22) and SpA (OR; 0.91, 95% CI: 0.47 to 1.77). CONCLUSION: CVD is currently still more prevalent in patients with IA compared with healthy controls and, more importantly, this elevated risk is highly influenced by an increased prevalence of 'traditional' CV risk factors. More attention to, as well as improvements in, identification and treatment of 'traditional' risk factors, need to be made for not only RA, but other IA conditions as well.

Cardiovascular Disease Risk in Rheumatoid Arthritis Anno 2022.

The risk for developing cardiovascular diseases (CVD) in rheumatoid arthritis (RA) patients is 1.5 times higher compared to the general population. This risk is partly due to the contribution of systemic inflammation in increased atherogenesis, while an increased prevalence of "traditional" cardiovascular risk factors, such as hypertension and dyslipidemia, is also attributed to nearly 50% of the total CVD risk. Most anti-rheumatic medication partly reduces this CVD risk, primarily by reducing inflammation. The increased risk is recognized by most guidelines, which advise consequent screening and multiplying calculated risk scores by 1.5. However, screening in daily clinical practice is poorly done, and RA patients often have undiagnosed and untreated risk factors. In conclusion, even nowadays, RA patients still have an increased risk of developing CVD. Advances in anti-inflammatory treatment partly mitigate this risk, but RA patients need mandatory screening for CV risk factors to turn their CVD risk towards that of the general population.