Excess free iron is a substrate for the formation of reactive oxygen species (ROS), thereby augmenting oxidative stress. Oxidative stress is a well-established cause of organ damage in the liver, the main site of iron storage. Ferroptosis, an iron-dependent mechanism of regulated cell death, has recently been gaining attention in the development of organ damage and the progression of liver disease. We therefore summarize the main mechanisms of iron metabolism, its close connection to oxidative stress and ferroptosis, and its particular relevance to disease mechanisms in metabolic-dysfunction-associated fatty liver disease and potential targets for therapy from a clinical perspective.

Rheumatoid arthritis (RA) is a chronic autoimmune disease marked by systemic inflammation. While RA primarily affects the joints, its systemic effects may lead to an increased cerebro- and cardiovascular risk. Atherosclerosis of the carotid arteries is a significant risk factor for cerebrovascular events and serves as a surrogate marker for cardiovascular risk. This study explores the link between RA and carotid artery atherosclerosis with data from the Paracelsus 10,000 Study. Baseline assessments were conducted on individuals randomly selected from Salzburg and its surrounding regions. Participants diagnosed with RA based on ACR-EULAR classification criteria and who underwent carotid artery ultrasound were included. Data were gathered from a total of 9729 participants, among whom 299 were diagnosed with RA. Carotid arteries were examined using ultrasound imaging. The primary endpoint was the difference in the prevalence of plaque presence between the RA and non-RA groups. One univariate (Model I) and three multivariate analyses were conducted, with adjustments in Model II incorporating SCORE 2, while Model III accounted for metabolic syndrome, age and sex. Additionally, Model IV included further adjustments for high-sensitivity C-reactive protein (hs-CRP). Plaque presence was defined as the ultrasound detection of plaque formation larger than 0 mm², regardless of whether it was unilateral or bilateral. Additional assessments included carotid stenosis, intima-media thickness (IMT) and total plaque area (TPA). RA patients had a higher prevalence of plaque (50%) compared to non-RA individuals (38%). The odds ratio (OR) for plaque presence in RA patients versus non-RA individuals was 1.64 (95% CI 1.30–2.06). This association persisted after adjusting for SCORE2, with an adjusted odds ratio (aOR) of 1.65 (95% CI 1.26–2.15). The association remained significant when adjusting for metabolic syndrome, age and sex (aOR = 1.32, 95% CI 1.02–1.72) and also in Model IV, which included further adjustment for hs-CRP (OR = 1.33, 95% CI 1.02–1.74). The findings underscore an increased risk of cerebrovascular disease associated with RA. This study highlights the importance of thorough cerebrovascular and cardiovascular risk assessments, along with proactive management, for RA patients to reduce this risk. Recognizing the substantial impact of RA on stroke and cerebrovascular disease is important for enhancing patient care strategies. Carotid ultrasound appears to be an effective method for atherosclerosis screening in RA patients.

Background: Hyperferritinemia (HF) is a common finding and can be considered as metabolic HF (MHF) in combination with metabolic diseases. The definition of MHF was heterogenous until a consensus statement was published recently. Our aim was to apply the definition of MHF to provide data on the prevalence and characteristics of MHF in a Central-European cohort. Methods: This study was a retrospective analysis of the Paracelsus 10,000 study, a population-based cohort study from the region of Salzburg, Austria. We included 8408 participants, aged 40–77. Participants with HF were divided into three categories according to their level of HF and evaluated for metabolic co-morbidities defined by the proposed criteria for MHF. Results: HF was present in 13% (n = 1111) with a clear male preponderance (n = 771, 69% of HF). Within the HF group, 81% (n = 901) of subjects fulfilled the metabolic criteria and were defined as MHF, of which 75% (n = 674) were characterized by a major criterion. In the remaining HF cohort, 52% (n = 227 of 437) of subjects were classified as MHF after application of the minor criteria. Conclusion: HF is a common finding in the general middle-aged population and the majority of cases are classified as MHF. The new classification provides useful criteria for defining MHF.

Background: Rheumatoid arthritis (RA) is associated with systemic inflammation and increased risk of cardiovascular and metabolic comorbidities. The relationship between RA and metabolic dysfunction-associated steatotic liver disease (MASLD) has not been established in population-based studies. Methods: We conducted a cross-sectional analysis of 6638 participants from the population-based Paracelsus 10,000 cohort in Austria, including 187 individuals with physician-diagnosed RA meeting ACR/EULAR classification criteria. MASLD was defined using the Fatty Liver Index (≥ 60) combined with cardiometabolic risk factors according to 2024 EASL guidelines. We used Poisson regression models with sequential adjustment for demographic factors, metabolic syndrome, lifestyle factors, NSAID use, and cardiovascular risk (SCORE2). Liver fibrosis risk was assessed using the Fibrosis-4 Index (FIB-4). Results: MASLD prevalence was higher in RA patients than controls (41.2% vs. 28.5%, P < 0.001). In sequential regression models, the association between RA and MASLD persisted after adjustment for demographics (IRR, 1.55; 95% CI 1.33–1.82), metabolic and lifestyle factors (IRR, 1.20; 95% CI 1.03–1.40), and cardiovascular risk factors (IRR, 1.35; 95% CI 1.14–1.60; P < 0.001). In addition, RA patients showed elevated liver fibrosis markers (median FIB-4: 1.21 vs. 1.08; P < 0.001). Conclusions: In this population-based cohort, RA was independently associated with a 35% increased risk of MASLD and elevated liver fibrosis markers. These findings suggest that systematic liver assessment should be considered in the routine care of RA patients.

Austria, a country with a high standard of living and a well-developed healthcare system, still experiences socioeconomic status (SES) disparities that impact health outcomes. Rheumatoid arthritis (RA) is a chronic autoimmune disease associated with significant disability and comorbidities. While SES has been linked to RA prevalence and disease severity, its role in a high-income country like Austria remains underexplored. This study investigates the association between SES factors-education, income, employment status and migration background-and RA prevalence and outcomes. This population-based study used data from the Paracelsus 10,000 cohort in Salzburg, Austria and a cross-sectional design. A total of 9,256 participants aged 40-77 years were analyzed, including 289 individuals diagnosed with RA based on the ACR/EULAR classification criteria. SES was assessed through self-reported education, income, employment status and country of birth. Logistic regression models were used to evaluate the association between SES and RA, adjusting for age, sex, metabolic syndrome, smoking and alcohol consumption. RA prevalence was significantly lower among individuals with higher education (OR = 0.55, 95% CI: 0.37-0.82 for medium education; OR = 0.41, 95% CI: 0.25-0.68 for high education). Lower household income correlated with higher RA prevalence. Employment disparities were evident, with RA patients exhibiting higher rates of unemployment and work disability. Despite Austria's high standard of living, SES remains a key determinant of RA prevalence. Lower levels of education, income and employment are associated with higher rates of RA, highlighting the need for targeted public health interventions. Strengthening healthcare access, promoting early screening and offering economic support to vulnerable groups could be important steps toward reducing these disparities. Further research should explore the underlying mechanisms of this association and examine whether socioeconomic disparities also influence disease progression and patient outcomes.

Background: Rheumatoid arthritis (RA) has been linked to an increased risk of chronic kidney disease (CKD), but the predominant renal phenotype and its independence from established risk factors remain unclear. We examined the RA–CKD association in a large, population-based cohort. Methods: RA and CKD were defined using American College of Rheumatology/European Alliance of Associations for Rheumatology and KDIGO criteria. Logistic regression models were employed with stepwise adjustment: first for cardiovascular risk [Systematic COronary Risk Evaluation 2 (SCORE2)], followed by a model including age, sex, metabolic syndrome, smoking status, non-steroidal anti-inflammatory drug (NSAID) use and high-sensitivity C-reactive protein. Interaction terms were tested to evaluate effect modification. Results: Among 9665 participants from the Paracelsus 10,000 cohort, 296 (3.1%) had RA. CKD prevalence was higher in the RA group compared with controls (11.8% vs 6.7%, P < .001). Albuminuria at preserved estimated glomerular filtration rate was the dominant renal manifestation in RA (6.8% vs 4.2%, P = .027). In unadjusted analyses, RA was associated with higher odds of CKD [odds ratio (OR) 1.86, 95% confidence interval (CI) 1.30–2.68], an association that persisted after cardiovascular risk adjustment. However, the association was attenuated and no longer statistically significant in the fully adjusted model (OR 1.43, 95% CI 0.96–2.13). A significant interaction was observed with NSAID use (P = .042), whereby the association was largely confined to RA patients not using NSAIDs. Conclusions: RA is associated with a higher prevalence of CKD, primarily driven by albuminuria at preserved kidney function. This distinct renal phenotype appears largely mediated by metabolic comorbidities rather than inflammation alone. Our findings highlight the need for systematic albuminuria screening in RA patients to enable earlier detection and intervention.