Background: Cardiovascular (CV) morbidity, mortality and metabolic syndrome are associated with rheumatoid arthritis (RA). A recent trial has suggested increased risk of major CV events (MACE) upon the Janus kinase (JAK) inhibitor tofacitinib compared with anti-tumor necrosis factor α (TNF-α) therapy. In our study, we evaluated lipids and other metabolic markers in relation to vascular function and clinical markers in RA patients undergoing one-year tofacitinib therapy. Patients and methods: Thirty RA patients treated with either 5 mg or 10 mg bid tofacitinib were included in a 12-month follow-up study. Various lipids, paraoxonase (PON1), myeloperoxidase (MPO), thrombospondin-1 (TSP-1) and adipokine levels, such as adiponectin, leptin, resistin, adipsin and chemerin were determined. In order to assess flow-mediated vasodilation (FMD), common carotid intima-media thickness (IMT) and arterial pulse-wave velocity (PWV) ultrasonography were performed. Assessments were carried out at baseline, and 6 and 12 months after initiating treatment. Results: One-year tofacitinib therapy significantly increased TC, HDL, LDL, APOA, APOB, leptin, adipsin and TSP-1, while significantly decreasing Lp(a), chemerin, PON1 and MPO levels. TG, lipid indices (TC/HDL and LDL/HDL), adiponectin and resistin showed no significant changes. Numerous associations were found between lipids, adipokines, clinical markers and IMT, FMD and PWV (p < 0.05). Regression analysis suggested, among others, association of BMI with CRP and PWV (p < 0.05). Adipokines variably correlated with age, BMI, CRP, CCP, FMD, IMT and PWV, while MPO, PON1 and TSP-1 variably correlated with age, disease duration, BMI, RF and PWV (p < 0.05). Conclusions: JAK inhibition by tofacitinib exerts balanced effects on lipids and other metabolic markers in RA. Various correlations may exist between metabolic, clinical parameters and vascular pathophysiology during tofacitinib treatment. Complex assessment of lipids, metabolic factors together with clinical parameters and vascular pathophysiology may be utilized in clinical practice to determine and monitor the CV status of patients in relation with clinical response to JAK inhibition.

Background/Objectives: Rheumatoid arthritis (RA) has been associated with accelerated atherosclerosis and cerebrovascular alterations. Our 2017 study compared 60 RA patients to healthy controls, assessing vascular, neurological, and cognitive parameters. The present study is a follow-up of these RA patients to evaluate disease progression and vascular changes over time, using their 2017 results as baseline. Methods: In 2023, we reassessed 43 of the original 60 RA patients using laboratory testing, carotid ultrasound, functional transcranial Doppler (TCD) and brain magnetic resonance imaging (MRI) examinations. Changes over time were analyzed within the same individuals. Results: Inflammatory markers and lipid profiles showed a trend toward improvement, though changes were not statistically significant, except for a significant increase in vitamin D (p < 0.001) and a decrease in Disease Activity Score in 28 Joints (DAS28) scores (p < 0.001). Carotid ultrasound revealed a significant increase in plaque burden (p = 0.022 on the right side and p = 0.008 on the left), while carotid intima media thickness (cIMT) showed a non-significant rise. TCD measurements indicated significantly increased pulsatility (p < 0.001 on the right, p = 0.001 on the left side) and resistance (p = 0.001 on the right, p = 0.012 on the left side) indices and reduced flow velocities (p < 0.001 on the right and p = 0.001 on the left side) in bilateral middle cerebral arteries (MCAs). The cerebrovascular reserve capacity was significantly lower on the right side overall (p = 0.013), with further decline noted in the methotrexate (MTX)-treated subgroup on the left side (p = 0.043). MRI findings showed non-significant numerical trends toward worsening lacunar small-vessel disease (p = 0.405) and cerebral atrophy (p = 0.063), with higher but stable lacunar infarction scores among MTX users (p = 0.023). Conclusions: Despite improved inflammatory control, RA patients demonstrated progressive vascular and hemodynamic alterations over time, while MRI changes should be interpreted as trends. These findings support multimodal vascular monitoring in RA.

Percutaneous coronary intervention (PCI) is a frequently performed treatment option for recanalization in patients with chronic total occlusion (CTO). As CTO-PCIs are often complicated and challenging for interventionalists, the stressful and damaging nature of the procedure can be remarkable, thus platelets can be easily activated. Our aim was to investigate the effect of CTO-PCI on platelet activation and the expression of selected circulating microRNAs (miR) of platelet and endothelium origin after CTO-PCI. In this study, 50 subjects after CTO-PCI were enrolled. Blood samples were obtained before PCI, at 2 days and 3–6 months after the procedure to measure the degree of platelet activation and the level of plasma miR-223, miR-181b, and miR-126. Patients were divided based on the characteristics of the intervention. Patients with higher Japanese CTO scores and longer duration of PCI showed significantly elevated platelet P-selectin positivity (p = 0.004 and p = 0.013, respectively) 2 days after the procedure compared to pre-PCI and increased concentration of soluble P-selectin 3–6 months after the intervention (higher Japanese CTO score: p = 0.028 and longer duration of PCI: p = 0.023) compared to baseline values. Shorter total stent length caused a significantly lower miR-181b expression at 3–6 months after the intervention (p = 0.031), while no difference was observed in miR-223 and miR-126. One stent thrombosis occurred during the follow-up period. Although these technically challenging CTO-PCIs may cause enhanced platelet activation right after the intervention and long-term endothelial cell dysfunction, these interventions are not associated with more adverse clinical events.

Background/Objectives: Rheumatoid arthritis (RA) is associated with increased cerebrovascular risk and altered bone metabolism. Transcranial Doppler (TCD) and transcranial color-coded duplex sonography (TCCD) require an adequate transtemporal acoustic window (TAW), which may be limited by temporal bone thickness and structure. Our previous cross-sectional work showed a high frequency of temporal acoustic window failure (TAWF) in female RA patients. The present exploratory follow-up study evaluated whether binary TAW status showed detectable net progression over an 8-year interval. Methods: In 2017, 62 female RA patients and 60 age-matched female controls underwent standardized TCD/TCCD assessment and clinical/laboratory characterization. In 2023, 43 of the original RA patients were re-evaluated by the same experienced neurosonographer using standardized transtemporal insonation and TCCD verification when needed. TAW status was recorded bilaterally as existing TAW or TAWF and analyzed using paired transition counts and exact McNemar tests; treatment subgroup comparisons were exploratory. Results: Right-sided TAW was present in 27/43 patients and absent in 16/43 at both time points (TAWF prevalence 37.2%, 95% CI 24.4–52.1%). No right-sided discordant transition was observed (0/43; exact upper 95% bound 8.2%; exact McNemar p = 1.000). Left-sided TAW was present in 20/43 patients and absent in 23/43 at both time points (TAWF prevalence 53.5%, 95% CI 38.9–67.5%). Two left-sided discordant transitions were observed: one apparent gain and one apparent loss of TAW (2/43, 4.7%; exact 95% CI 0.6–15.8%; exact McNemar p = 1.000). Bilateral TAWF remained present in 15/43 patients at both time points. No statistically detectable differences in TAW status were observed among MTX, IFX, and TCZ groups, but these subgroup analyses were underpowered. Conclusions: In this treated female RA cohort, binary TAW status showed no detectable net progression over 8 years. These data do not prove true biological stability of skull sonographic permeability, and smaller changes cannot be excluded. Mechanistic links with disease control, vitamin D status, treatment exposure, or bone remodeling require larger studies with direct temporal bone imaging and semi-quantitative acoustic-window grading.