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Background: The complement system is involved in pathogenesis of cardiovascular disease, and might play a role in accelerated atherogenesis in spondylarthropathies (SpA). Hence, we examined complement activation in SpA, and its relationship to antirheumatic treatment, inflammatory and cardiovascular markers., Methods: From PSARA, a prospective observational study, we examined 51 SpA patients (31 psoriatic arthritis (PsA), and 20 ankylosing spondylitis (AS)), starting tumor necrosis factor (TNF) inhibitor alone (n = 25), combined with methotrexate (MTX) (n = 10), or MTX monotherapy (n = 16). Complement activation was determined by the soluble terminal complement complex (sC5b-9), inflammation by erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and endothelial function by finger plethysmography (Endopat) at baseline, after 6 weeks and 6 months of treatment., Results: SpA patients had sC5b-9 levels at (PsA) or above (AS) the upper limit of the estimated reference range. Median sC5b-9 levels decreased significantly from baseline to 6 weeks, with no significant difference between the AS and PsA group. Notably, a significant reduction in sC5b-9 was observed after administration of TNF inhibitor ± MTX, whereas no significant changes were observed in patients treated with MTX alone. Between 6 weeks and 6 months, sC5b-9 remained stable across all subgroups. Reduction in sC5b-9 was independently related to decreased ESR and CRP, and to increased high density cholesterol and total cholesterol. Reduction in sC5b-9 from baseline to 6 weeks was associated with improved EF in age and gender adjusted analyses., Conclusion: TNF-inhibition, but not MTX monotherapy, led to rapid and sustained reduction of complement activation in SpA. Thus, the observed decrease in cardiovascular morbidity in patients treated with TNF-inhibitors might be partly due to its beneficial effect on complement., Trial Registration: Clinical Trials (NCT00902005), retrospectively registered on the 14th of May 2009., Competing Interests: The authors have declared that no competing interests exist.

Background: Vitamin D has an important role in the immune system, and has been linked to rheumatoid arthritis (RA) and coronary artery disease (CAD). The exact mechanisms by which vitamin D is involved in these processes are still unclear. Therefore, we wanted to search for differences in expression of genes involved in the vitamin D receptor (VDR) activation pathway and genes that are known to alter upon vitamin D stimulation, in the aortic adventitia of CAD patients with and without RA., Methods: Affymetrix microarray was used to determine gene expression profile in surgical specimens from the adventitia of the ascending aorta of CAD patients with RA (n = 8) and without RA (n = 8) from the Feiring Heart Biopsy Study., Results: We identified three vitamin D associated genes that were differentially expressed between RA and non-RA patients: Growth arrest and DNA-damage-inducible protein 45 alpha (GADD45A) (FC = 1.47; p = 0.006), Nuclear Receptor Co-repressor 1 (NCOR1) (FC = 1,21; p = 0.005) and paraoxonases 2 (PON2) (FC = -1.37; p = 0.01). High expression of GADD45A in RA tissues was confirmed by real-time qRT-PCR. GADD45A expression correlated with plasma levels of 1,25(OH)2D3 (rs = 0.69; p = 0.003)., Conclusions: Microarray analyses revealed higher expression of GADD45A and NCOR1; and lower expression of PON2 in the aortic adventitia of RA than non-RA patients. Further studies are needed to elucidate if and how GADD45A, NCOR1 and PON2 are involved in the development of accelerated atherosclerosis in RA. In theory, some of these factors might have proatherogenic effects whereas others might reflect an underlying vascular pathology promoting atherogenesis (such as vascular stress)., Competing Interests: The authors have declared that no competing interests exist.

Background: Although statins are often discontinued when myalgia arises, a causal relationship may not always exist. How well-tolerated statins are when rechallenge is blinded and controlled is unclear. Methods and findings: We performed a systematic review and meta-analysis (PROSPERO CRD42023437648) to evaluate the success of statin rechallenge versus matched placebo in those who were previously statin intolerant. Our primary outcome was intolerance; our secondary outcome was the myalgia or global symptom score. Medline, Embase, CINAHL Plus, Scopus, and CENTRAL were searched from inception to May 1, 2023. Eligible trials were randomized controlled trials with parallel or crossover designs examining statin rechallenge in statin-intolerant adults. Two independent reviewers selected studies, extracted data, and assessed risk of bias (Cochrane Collaboration's risk-of-bias tool 1). Relative risk (RR) and mean difference (MD) were estimated using fixed effect Mantel-Haenszel statistics. Of 1,941 studies screened, 8 met our inclusion criteria (8 to 491 participants from Asia, Europe, North America, and Oceana). Compared to placebo, intolerance was more common in statin users [325/906 (36%) vs 233/911 (26%), RR 1.40, 95% CI, 1.23 to 1.60, I2 = 0%, 7 trials, number needed to harm 10] and there was no statistically significant difference in myalgia or global symptom score on a 100-point scale [MD 1.08, 95% CI, -1.51 to 3.67, I2 = 0%, 5 trials]. Limitations include only 1 trial asking participants about intolerable symptoms (vs inferring intolerance from discontinuation or trial withdrawal); the small number of trials; the possibility of attrition bias; and the potential for carryover effects in crossover/n-of-1 trial designs. Conclusions: Of those previously intolerant of statins who were rechallenged with a statin and compared to placebo recipients, medication intolerance was more common amongst statin recipients. However, there was no significant difference in mean myalgia or global symptom score between statin and placebo, and only one-third of those previously believed to be statin intolerant were unable to tolerate a statin on blinded rechallenge; one-quarter were intolerant of placebo. [ABSTRACT FROM AUTHOR]

Background: The precise impact of sex difference on in-hospital mortality in ST-elevation myocardial infarction (STEMI) patients are unclear, and the studies are no longer consistent. Therefore, we sought to evaluate the impact of sex differences in a cohort of STEMI patients. Methods: We analyzed the data of 2647 STEMI patients enrolled in the Kermanshah STEMI Cohort from July 2017 to May 2020. To accurately clarify the relationship between sex and hospital mortality, propensity score matching (PSM) and causal mediation analysis was applied to the selected confounder and identified intermediate variables, respectively. Results: Before matching, the two groups differed on almost every baseline variable and in-hospital death. After matching with 30 selected variables, 574 male and female matched pairs were significantly different only for five baseline variables and women were no longer at greater risk of in-hospital mortality (10.63% vs. 9.76%, p = 0.626). Among the suspected mediating variables, creatinine clearance (CLCR) alone accounts for 74% (0.665/0.895) of the total effect equal to 0.895(95% CI: 0.464–1.332). In this milieu, the relationship between sex and in-hospital death was no longer significant and reversed -0.233(95% CI: -0.623–0.068), which shows the full mediating role of CLCR. Conclusion: Our research could help address sex disparities in STEMI mortality and provide a consequence. Moreover, CLCR alone can fully explain this relationship, which can highlight the importance of CLCR in predicting the short-term outcomes of STEMI patients and provide a useful indicator for clinicians. [ABSTRACT FROM AUTHOR]

Background: In the context of the ageing of the French population, physical activity becomes a principal means for maintaining good health. International organisations are thus giving increasing importance to physical activity in programmes of disease-prevention. In parallel with these concerns, studies have shown the impact of sedentary activities (in particularly as a result of the seated position and screen time) on health. Objective: To show the links between physical activity, sedentarism and health indicators and to identify the socio-demographic variables by which they are influenced (particularly gender). Study design: This is a transversal epidemiological study conducted among the French population between 2014 and 2016 by Santé publique France, the national public health agency. Methods: The RPAQ (Recent Physical Activity Questionnaire) was used to measure the physical activity and sedentary lifestyle of individuals. The analyses focus on the behaviours among the population of older adults (55–74 years old, n = 1155). Results: A third of French older adults does not meet the WHO recommended physical activity levels, particularly so among women. The results of this survey point to significant links between health indicators (especially overweight and obesity) and the physical activity level and sedentarity of older adults. From the age of 60, energy expenditure linked to physical activity increases before decreasing from the age of 65. Older adults spend almost 6 hours per day in sedentary activities. The combinations between physical activity and sedentarism highlight four profiles of older adults. The most active profile is the one with the best health indicators. Conclusion: The links between health, sedentarity and physical activity are unequivocal: people who achieve the WHO recommendations for physical activity and spend less than 7 hours each day in sedentary activities are those who also have the best health indicators. These results vary with sociographic characteristics and reveal significant links with health indicators. [ABSTRACT FROM AUTHOR]

Background: The complement system plays an important role in pathophysiology of cardiovascular disease (CVD), and might be involved in accelerated atherogenesis in rheumatoid arthritis (RA). The role of complement activation in response to treatment, and in development of premature CVD in RA, is limited. Therefore, we examined the effects of methotrexate (MTX) and tumor necrosis factor inhibitors (TNFi) on complement activation using soluble terminal complement complex (TCC) levels in RA; and assessed associations between TCC and inflammatory and cardiovascular biomarkers. Methods: We assessed 64 RA patients starting with MTX monotherapy (n = 34) or TNFi with or without MTX co-medication (TNFi±MTX, n = 30). ELISA was used to measure TCC in EDTA plasma. The patients were examined at baseline, after 6 weeks and 6 months of treatment. Results: Median TCC was 1.10 CAU/mL, and 57 (89%) patients had TCC above the estimated upper reference limit (<0.70). Compared to baseline, TCC levels were significantly lower at 6-week visit (0.85 CAU/mL, p<0.0001), without significant differences between the two treatment regimens. Notably, sustained reduction in TCC was only achieved after 6 months on TNFi±MTX (0.80 CAU/mL, p = 0.006). Reductions in TCC after treatment were related to decreased C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and interleukin 6, and increased levels of total, high and low-density lipoprotein cholesterol. Similarly, baseline TCC was significantly related to baseline CRP, ESR and interleukin 6. Patients with endothelial dysfunction had higher baseline TCC than those without (median 1.4 versus 1.0 CAU/mL, p = 0.023). Conclusions: Patients with active RA had elevated TCC, indicating increased complement activation. TCC decreased with antirheumatic treatment already after 6 weeks. However, only treatment with TNFi±MTX led to sustained reduction in TCC during the 6-month follow-up period. RA patients with endothelial dysfunction had higher baseline TCC compared to those without, possibly reflecting involvement of complement in the atherosclerotic process in RA. [ABSTRACT FROM AUTHOR]

Introduction: Whether amount of time spent in sedentary activities influences on clustered metabolic risk in elderly, and to what extent such an influence is independent of physical activity behavior, remain unclear. Therefore, the aim of the study was to examine cross-sectional associations of objectively assessed physical activity and sedentary behavior on metabolic risk outcomes in a sample of elderly community-dwelling women. Methods: Metabolic risk outcomes including waist circumference, systolic and diastolic blood pressures, fasting levels of plasma glucose, HDL-cholesterol and triglycerides were assessed in 120 community-dwelling older women (65–70 yrs). Accelerometers were used to retrieve daily sedentary time, breaks in sedentary time, daily time in light (LPA) and moderate-to-vigorous physical activity (MVPA), and total amount of accelerometer counts. Multivariate regression models were used to examine influence of physical activity and sedentary behavior on metabolic risk outcomes including a clustered metabolic risk score. Results: When based on isotemporal substitution modeling, replacement of a 10-min time block of MVPA with a corresponding time block of either LPA or sedentary activities was associated with an increase in clustered metabolic risk score (β = 0.06 to 0.08, p < 0.05), and an increase in waist circumference (β = 1.78 to 2.19 p < 0.01). All associations indicated between sedentary time and metabolic risk outcomes were lost once variation in total accelerometer counts was adjusted for. Conclusions: Detrimental influence of a sedentary lifestyle on metabolic health is likely explained by variations in amounts of physical activity rather than amount of sedentary time per se. Given our findings, increased amounts of physical activity with an emphasis on increased time in MVPA should be recommended in order to promote a favorable metabolic health profile in older women. [ABSTRACT FROM AUTHOR]