Association between chronic immune-mediated inflammatory diseases and cardiovascular risk

Objective To examine the association between chronic immune-mediated diseases (rheumatoid arthritis, systemic lupus erythematosus, or the following chronic immune-mediated inflammatory diagnoses groups: inflammatory bowel diseases, inflammatory polyarthropathies, systemic connective tissue disorders and spondylopathies) and the 6-year coronary artery disease, stroke, cardiovascular disease incidence and overall mortality; and to estimate the population attributable fractions for all four end-points for each chronic immune-mediated inflammatory disease. Methods Cohort study of individuals aged 35-85 years, with no history of cardiovascular disease from Catalonia (Spain). The coded diagnoses of chronic immune-mediated diseases and cardiovascular diseases were ascertained and registered using validated codes, and date of death was obtained from administrative data. Cox regression models for each outcome according to exposure were fitted to estimate hazard ratios (HR) in two models: (1) after adjustment for sex, age, cardiovascular risk factors and (2) further adjusted for drug use. Population attributable fractions were estimated for each exposure. Results Data were collected from 991,546 participants. The risk of cardiovascular disease was increased in systemic connective tissue disorders [Model 1: HR=1.38 (95% confidence interval=1.21-1.57) and 2: HR=1.31 (1.15-1.49)], rheumatoid arthritis [HR=1.43 (1.26-1.62) and HR=1.31 (1.15-1.49)] and inflammatory bowel diseases [HR=1.18 (1.06-1.32) and HR=1.12 (1.01-1.25)]. The effect of anti-inflammatory treatment was significant in all instances [HR=1.50 (1.24-1.81); HR=1.47 (1.23-1.75); HR=1.43 (1.19-1.73), respectively]. The population attributable fractions for all three disorders were 13.4%, 15.7%, and 10.7%, respectively. Conclusion Systemic connective tissue disorders and rheumatoid arthritis conferred the highest cardiovascular risk and population impact, followed by inflammatory bowel diseases

A cost-utility analysis of increasing percutaneous coronary intervention use in elderly patients with acute coronary syndromes in six European countries

Aims Percutaneous coronary intervention reduces mortality in acute coronary syndrome patients but the cost-utility of increasing its use in elderly acute coronary syndrome patients is unknown. Methods We assessed the efficiency of increased percutaneous coronary intervention use compared to current practice in patients aged >= 75 years admitted for acute coronary syndrome in France, Germany, Greece, Italy, Portugal and Spain with a semi-Markov state transition model. In-hospital mortality reduction estimates by percutaneous coronary intervention use and costs were derived from the EUROpean Treatment & Reduction of Acute Coronary Syndromes cost analysis EU project (n = 28,600). Risk of recurrence and out-of-hospital all-cause mortality were obtained from the Information System for the Development of Research in Primary Care (SIDIAP) database from North-Eastern Spain (n = 55,564). In-hospital mortality was modelled using stratified propensity score analysis. The 8-year acute coronary syndrome recurrence risk and out-of-hospital mortality were estimated with a multistate survival model. The scenarios analysed were to increase percutaneous coronary intervention use among patients with the highest, moderate and lowest probability of receiving percutaneous coronary intervention based on the propensity score analysis. Results France, Greece and Portugal showed similar total costs/1000 individuals (7.29-11.05 m euro); while in Germany, Italy and Spain, costs were higher (13.53-22.57 m euro). Incremental cost-utility ratios of providing percutaneous coronary intervention to all patients ranged from 2262.8 euro/quality adjusted life year gained for German males to 6324.3 euro/quality adjusted life year gained for Italian females. Increasing percutaneous coronary intervention use was cost-effective at a willingness-to-pay threshold of 10,000 euro/quality adjusted life year gained for all scenarios in the six countries, in males and females. Conclusion Compared to current clinical practice, broadening percutaneous coronary intervention use in elderly acute coronary syndrome patients would be cost-effective across different healthcare systems in Europe, regardless of the selected strategy

Effectiveness of statins as primary prevention in people with gout: A population-based cohort study

Background: Cardiovascular guidelines do not give firm recommendations on statin therapy in patients with gout because evidence is lacking. Aim: To analyze the effectiveness of statin therapy in primary prevention of coronary heart disease (CHD), ischemic stroke (IS), and all-cause mortality in a population with gout. Methods: A retrospective cohort study (July 2006 to December 2017) based on Information System for the Development of Research in Primary Care (SIDIAPQ), a research-quality database of electronic medical records, included primary care patients (aged 35-85 years) without previous cardiovascular disease (CVD). Participants were categorized as nonusers or new users of statins (defined as receiving statins for the first time during the study period). Index date was first statin invoicing for new users and randomly assigned to nonusers. The groups were compared for the incidence of CHD, IS, and all-cause mortality, using Cox proportional hazards modeling adjusted for propensity score. Results: Between July 2006 and December 2008, 8018 individuals were included; 736 (9.1%) were new users of statins. Median follow-up was 9.8 years. Crude incidence of CHD was 8.16 (95% confidence interval [CI]: 6.25-10.65) and 6.56 (95% CI: 5.85-7.36) events per 1000 person-years in new users and nonusers, respectively. Hazard ratios were 0.84 (95% CI: 0.60-1.19) for CHD, 0.68 (0.44-1.05) for IS, and 0.87 (0.67-1.12) for all-cause mortality. Hazard for diabetes was 1.27 (0.99-1.63). Conclusions: Statin therapy was not associated with a clinically significant decrease in CHD. Despite higher risk of CVD in gout populations compared to general population, patients with gout from a primary prevention population with a low-to-intermediate incidence of CHD should be evaluated according to their cardiovascular risk assessment, lifestyle recommendations, and preferences, in line with recent European League Against Rheumatism recommendations.</p

Quantification of Mesenchymal Stem Cell (MSC) Delivery to a Target Site Using In Vivo Confocal Microscopy

The ability to deliver cells to appropriate target tissues is a prerequisite for successful cell-based therapy. To optimize cell therapy it is therefore necessary to develop a robust method of in vivo cell delivery quantification. Here we examine Mesenchymal Stem Cells (MSCs) labeled with a series of 4 membrane dyes from which we select the optimal dye combination for pair-wise comparisons of delivery to inflamed tissue in the mouse ear using confocal fluorescence imaging. The use of an optimized dye pair for simultaneous tracking of two cell populations in the same animal enables quantification of a test population that is referenced to an internal control population, thereby eliminating intra-subject variations and variations in injected cell numbers. Consistent results were obtained even when the administered cell number varied by more than an order of magnitude, demonstrating an ability to neutralize one of the largest sources of in vivo experimental error and to greatly reduce the number of cells required to evaluate cell delivery. With this method, we are able to show a small but significant increase in the delivery of cytokine pre-treated MSCs (TNF-α & IFN-γ) compared to control MSCs. Our results suggest future directions for screening cell strategies using our in vivo cell delivery assay, which may be useful to develop methods to maximize cell therapeutic potential.Sanofi Aventis (Firm