Autoimmune diseases and new-onset atrial fibrillation:a UK Biobank study

AimsThe underlying mechanisms of atrial fibrillation (AF) are largely unknown. Inflammation may underlie atrial remodelling. Autoimmune diseases, related to increased systemic inflammation, may therefore be associated with new-onset AF.Methods and resultsParticipants from the population-based UK Biobank were screened for rheumatic fever, gastrointestinal autoimmune diseases, autoimmune diseases targeting the musculoskeletal system and connective tissues, and neurological autoimmune diseases. Between 2006 and 2022, participants were followed for incident AF. Cox proportional hazards regression analyses were performed to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) to quantify associations. 494 072 participants free from AF were included (median age 58.0 years, 54.8% women). After a median of 12.8 years, 27 194 (5.5%) participants were diagnosed with new-onset AF. Rheumatic fever without heart involvement (HR, 95% CI: 1.47, 1.26–1.72), Crohn’s disease (1.23, 1.05–1.45), ulcerative colitis (1.17, 1.06–1.31), rheumatoid arthritis (1.39, 1.28–1.51), polyarteritis nodosa (1.82, 1.04–3.09), systemic lupus erythematosus (1.82, 1.41–2.35), and systemic sclerosis (2.32, 1.57–3.44) were associated with a larger AF risk. In sex-stratified analyses, rheumatic fever without heart involvement, multiple sclerosis, Crohn’s disease, seropositive rheumatoid arthritis, psoriatic and enteropathic arthropathies, systemic sclerosis and ankylosing spondylitis were associated with larger AF risk in women, whereas only men showed a larger AF risk associated with ulcerative colitis.ConclusionsVarious autoimmune diseases are associated with new-onset AF, more distinct in women. Our findings elaborate on the pathophysiological differences in autoimmunity and AF risk between men and women

The design of a learning environment based on the theory of multiple intelligence and the study its effectiveness on the achievements, attitudes and retention of students

AbstractMultiple intelligences theory (MIT) which takes into account students’ individual differences has an important role in the teaching and learning process. In this study a novel learning environment based on MIT which takes students’ interests and needs into an account has been developed. Many activities were carried out depending on students’ intelligence types. The effects of different activities on students’ achievements, attitudes toward chemistry and retention of knowledge in periodical features’ variety at the 10th class were measured and compared. The comparison between experimental group, which was instructed through MIT learning strategies and materials, and control group thought by traditional methods was observed. The research was applied in the first semester of 2009-2010 education years. The study carried out on 75 high school students in Izmir. The application of the study was lasted for 8 weeks containing methods and tests’ practices. Following MIT assessment survey, achievement test and attitude scales were used to analyze its effectiveness. Based on the theories and literature data, an instructional material included concept maps, puzzles, stories, classical music in background, group games, and photos about periodic features’ variety as an alternative to traditional written material. As a result of statistical analysis there were significant differences between achievement post-test and attitudes post-test towards chemistry course of control and experimental groups. Consequently, instructional methods needed to be varied so students could use their intellectual strengths to better understand topics, increase their intrinsic motivation, intervention and encourage active student engagement to improve learning at middle school level

Genome-wide association trans-ethnic meta-analyses identifies novel associations regulating coagulation Factor VIII and von Willebrand Factor plasma levels

BACKGROUND: Factor VIII (FVIII) and its carrier protein von Willebrand factor (VWF) are associated with risk of arterial and venous thrombosis and with hemorrhagic disorders. We aimed to identify and functionally test novel genetic associations regulating plasma FVIII and VWF. METHODS: We meta-analyzed genome-wide association results from 46 354 individuals of European, African, East Asian, and Hispanic ancestry. All studies performed linear regression analysis using an additive genetic model and associated ≈35 million imputed variants with natural log-transformed phenotype levels. In vitro gene silencing in cultured endothelial cells was performed for candidate genes to provide additional evidence on association and function. Two-sample Mendelian randomization analyses were applied to test the causal role of FVIII and VWF plasma levels on the risk of arterial and venous thrombotic events. RESULTS: We identified 13 novel genome-wide significant ( P≤2.5×10-8) associations, 7 with FVIII levels ( FCHO2/TMEM171/TNPO1, HLA, SOX17/RP1, LINC00583/NFIB, RAB5C-KAT2A, RPL3/TAB1/SYNGR1, and ARSA) and 11 with VWF levels ( PDHB/PXK/KCTD6, SLC39A8, FCHO2/TMEM171/TNPO1, HLA, GIMAP7/GIMAP4, OR13C5/NIPSNAP, DAB2IP, C2CD4B, RAB5C-KAT2A, TAB1/SYNGR1, and ARSA), beyond 10 previously reported associations with these phenotypes. Functional validation provided further evidence of association for all loci on VWF except ARSA and DAB2IP. Mendelian randomization suggested causal effects of plasma FVIII activity levels on venous thrombosis and coronary artery disease risk and plasma VWF levels on ischemic stroke risk. CONCLUSIONS: The meta-analysis identified 13 novel genetic loci regulating FVIII and VWF plasma levels, 10 of which we validated functionally. We provide some evidence for a causal role of these proteins in thrombotic events

Multi-phenotype analyses of hemostatic traits with cardiovascular events reveal novel genetic associations

Background: Multi-phenotype analysis of genetically correlated phenotypes can increase the statistical power to detect loci associated with multiple traits, leading to the discovery of novel loci. This is the first study to date to comprehensively analyze the shared genetic effects within different hemostatic traits, and between these and their associated disease outcomes. Objectives: To discover novel genetic associations by combining summary data of correlated hemostatic traits and disease events. Methods: Summary statistics from genome wide-association studies (GWAS) from seven hemostatic traits (factor VII [FVII], factor VIII [FVIII], von Willebrand factor [VWF] factor XI [FXI], fibrinogen, tissue plasminogen activator [tPA], plasminogen activator inhibitor 1 [PAI-1]) and three major cardiovascular (CV) events (venous thromboembolism [VTE], coronary artery disease [CAD], ischemic stroke [IS]), were combined in 27 multi-trait combinations using metaUSAT. Genetic correlations between phenotypes were calculated using Linkage Disequilibrium Score Regression (LDSC). Newly associated loci were investigated for colocalization. We considered a significance threshold of 1.85 × 10−9 obtained after applying Bonferroni correction for the number of multi-trait combinations performed (n = 27). Results: Across the 27 multi-trait analyses, we found 4 novel pleiotropic loci (XXYLT1, KNG1, SUGP1/MAU2, TBL2/MLXIPL) that were not significant in the original individual datasets, were not described in previous GWAS for the individual traits, and that presented a common associated variant between the studied phenotypes. Conclusions: The discovery of four novel loci contributes to the understanding of the relationship between hemostasis and CV events and elucidate common genetic factors between these traits

Effect of the stromelysin-1 promoter on efficacy of pravastatin in coronary atherosclerosis and restenosis

It has proved difficult to identify high-risk patients for atherosclerosis and to determine how they might respond to medication. Recently, a common promoter variant of the human stromelysin-1 gene has been reported, which has been shown to affect the transcription. We investigated whether this polymorphism had any impact on the risk of events, especially restenosis and progression of coronary artery disease and whether the effect was modulated by treatment with pravastatin. The stromelysin-1 genotype was determined for 496 men with coronary artery disease and cholesterol levels between 4.0 and 8.0 mmol/L, participating in the Regression Growth Evaluation Statin Study (REGRESS) study, a clinical trial assessing the effect of the lipid-lowering drug pravastatin on the progression of atherosclerosis. Patients in the placebo group with 5A6A or 6A6A genotypes had more clinical events than patients with the 5A5A genotype (26% and 12%, respectively, p = 0.03). In the pravastatin group, the risk of clinical events in patients with 5A6A or 6A6A genotypes was lower, compared with placebo, whereas it was unchanged in those with a 5A5A genotype (p value for interaction: 0.038). Also, the incidence of repeat angioplasty in the placebo group was greater in patients with the 6A6A or 5A6A genotypes, compared with 5A homozygotes (38% and 40%, respectively, vs 11%, p = 0.09). Again, treatment substantially reduced the incidence in heterozygotes and 6A homozygotes (0% and 15%, respectively), whereas it was unchanged in 5A homozygotes (28%, p for interaction: 0.002). These effects were independent of the effects of pravastatin on the lipid levels. Thus, this study suggests that the stomelysin-1 promoter polymorphism confers a genotype-specific response to medication in determining clinical event-free survival and the risk for symptom-driven repeat angioplasty. This variant may therefore act as a predictor, not only of disease progression, but also of response to therapy and risk of restenosi

Metabolic syndrome and risk of restenosis in patients undergoing percutaneous coronary intervention

OBJECTIVE - Patients with metabolic syndrome have increased risk of cardiovascular events. The number of patients With Metabolic syndrome is rapidly increasing, and these patients Often need revascularization. However, only limited data are available on the effect of metabolic syndrome on restenosis in patients undergoing percutaneous coronary intervention (PCI). RESEARCH DESIGN AND METHODS - To assess the role of trieLabolic syndrome in the development of restenosis, we performed an analysis in a population of patients from the GENetic DEterininants of Restenosis (GENDER) study. The GENDER project, a multicenter prospective study, included consecutive patients after successful PCI and was designed to study the predictive value of various genetic and other risk factors for subsequent clinical restenosis, defined as target vessel revascularization (TVR) or combined end point of death, myocardial infarction, and TVR. This subpopulation of GENDER consisted of 901 patients, 448 of whom (49.7%) had metabolic syndrome. RESULTS - on multivariable Cox regression analysis, Controlling for age, sex, previous myocardial infarction, stent length, current smoking, and Statin therapy, there was no association between increased risk of TVR (hazard ratio 1.03 [95% CI 0.68-1.57]) or the combined end point (1.05 [0.71-1.55]) and the presence of metabolic syndrome. CONCLUSIONS - This study demonstrates that metabolic syndrome is not associated with TVR or the combined end point after PCI. Furthermore, accumulating characteristics of metabolic syndrome were neither associated with increased risk of TVR nor with the combined end point. Therefore, PCI has equal beneficial results in patients with or Without Metabolic syndrome. This is important information in light of the pandemic proportion of Metabolic syndrome that the medical community will face

Effect of the stromelysin-1 promoter on efficacy of pravastatin in coronary atherosclerosis and restenosis

It has proved difficult to identify high-risk patients far atherosclerosis and to determine how they might respond ta medication. Recently, a common promoter variant of the human stromelysin-T gene has been reported, which has been shown to affect the transcription. We investigated whether this polymorphism had any impact on the risk of events, especially restenosis and progression of coronary artery disease and whether the effect was modulated by treatment with pravastatin. The stromelysin-1 genotype was determined for 496 men with coronary artery disease and cholesterol levels between 4.0 and 8.0 mmol/L, participating in the Regression Growth Evaluation Satin Study (REGRESS) study, a clinical trial assessing the effect of the lipid-lowering drug pravastatin on the progression of atherosclerosis. patients in the placebo group with 5A6A or 6A6A genotypes had more clinical events than patients with the 5A5A genotype (26% and 12%, respectively, p = 0.03). In the pravastatin group, the risk of clinical events in patients with 5A6A or 6A6A genotypes was lower, compared with placebo, whereas it was unchanged in chose with a 5A5A genotype (p value for interaction: 0.038). Also, the incidence of repeat angioplasty in the placebo group was greater in patients with the 6A6A or 5A6A genotypes, compared with 5A homozygotes (38% and 40%, respectively, vs 11%, p 0.09). Again, treatment substantially reduced the incidence in heterozygotes and 6A homozygotes (0% and 15%, respectively), whereas it was unchanged in 5A homozygotes (28%, p for interaction: 0.002). These effects were independent of the effects of pravastatin on the lipid levels. Thus, this study suggests that the stomelysin-1 promoter polymorphism confers a genotype-specific response to medication in determining clinical event-free survival and the risk for symptom-driven repeat angioplasty. This variant may therefore oct as a predictor, not only of disease progression, but also of response to therapy and risk of restenosis. (C) 1999 by Excerpta Medico, Inc