Smoking cessation is associated with lower disease activity and predicts cardiovascular risk reduction in rheumatoid arthritis patients

Objectives: Smoking is a major risk factor for the development of both cardiovascular disease (CVD) and RA and may cause attenuated responses to anti-rheumatic treatments. Our aim was to compare disease activity, CVD risk factors and CVD event rates across smoking status in RA patients. Methods: Disease characteristics, CVD risk factors and relevant medications were recorded in RA patients without prior CVD from 10 countries (Norway, UK, Netherlands, USA, Sweden, Greece, South Africa, Spain, Canada and Mexico). Information on CVD events was collected. Adjusted analysis of variance, logistic regression and Cox models were applied to compare RA disease activity (DAS28), CVD risk factors and event rates across categories of smoking status. Results: Of the 3311 RA patients (1012 former, 887 current and 1412 never smokers), 235 experienced CVD events during a median follow-up of 3.5 years (interquartile range 2.5-6.1). At enrolment, current smokers were more likely to have moderate or high disease activity compared with former and never smokers (P < 0.001 for both). There was a gradient of worsening CVD risk factor profiles (lipoproteins and blood pressure) from never to former to current smokers. Furthermore, former and never smokers had significantly lower CVD event rates compared with current smokers [hazard ratio 0.70 (95% CI 0.51, 0.95), P = 0.02 and 0.48 (0.34, 0.69), P < 0.001, respectively]. The CVD event rates for former and never smokers were comparable. Conclusion: Smoking cessation in patients with RA was associated with lower disease activity and improved lipid profiles and was a predictor of reduced rates of CVD events

The impact of biologics and tofacitinib on cardiovascular risk factors and outcomes in patients with rheumatic disease: a systematic literature review

Introduction Rheumatic diseases are autoimmune, inflammatory diseases often associated with cardiovascular (CV) disease, a major cause of mortality in these patients. In recent years, treatment with biologic and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs), either as monotherapy or in combination with other drugs, have become the standard of treatment. In this systematic literature review, we evaluated the effect of treatment with biologic or tofacitinib on the CV risk and outcomes in these patients. Methods A systematic search was performed in MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews for articles reporting on CV risk and events in patients with rheumatic disease treated with a biologic agent or tofacitinib. Articles identified were subjected to two levels of screening. Articles that passed the first level based on title and abstract were assessed on full-text evaluation. The quality of randomized clinical trials was assessed by Jadad scoring system and the quality of the other studies and abstracts was assessed using the Downs and Black instrument. The data extracted included study design, baseline patient characteristics, and measurements of CV risk and events. Results Of the 5722 articles identified in the initial search, screening yielded 105 unique publications from 90 unique studies (33 clinical trials, 39 prospective cohort studies, and an additional 18 retrospective studies) that reported CV risk outcomes. A risk of bias analysis for each type of report indicated that they were of good or excellent quality. Importantly, despite some limitations in data reported, there were no indications of significant increase in adverse CV events or risk in response to treatment with the agents evaluated. Conclusions Treatment with biologic or tofacitinib appears to be well-tolerated with respect to CV outcomes in these patients

Excess Heart Disease Risk Associated with Arthritis in the Canadian General Population

This thesis, through three manuscripts, aims to clarify to what extent arthritis may be an independent risk factor for developing heart disease in the general population, underlying mechanisms of the relationship, and who may be most at-risk. Manuscript 1 is a systematic review and meta-analysis of population-based studies that estimated risk of incident myocardial infarction (MI) associated with five major types of arthritis. Results showed that MI-risk was consistently increased across arthritis and was partially explained by a higher prevalence of traditional heart disease risk factors in each type of arthritis. Knowledge gaps from the review were used to inform subsequent secondary analyses of the longitudinal Canadian National Population Health Survey (NPHS) with 16-years of follow up. Manuscript 2 used discrete time survival analysis with time-varying lagged predictors to estimate effects of arthritis on first heart disease event occurrence. Potential variations by age, sex and activity limitation were examined. Results showed that arthritis was independently associated with incident heart disease in all women, with more marked risk in women who also reported activity limitation, but only in men with activity limitation. Manuscript 3 used a novel approach to estimate potential mediating and moderating effects of activity limitation in the arthritis-heart disease relationship and possible differences by obesity and sex/gender in the same longitudinal health survey as manuscript 2. Results showed the proportion of heart disease risk explained by activity limitation varied between men and women, and between obese and non-obese women. Activity limitation explained nearly all of the heart disease risk associated with arthritis in men (90%), most of the heart disease risk in obese women (54%), and part of the heart disease risk in non-obese women (23%). Overall, the thesis results are important for increasing public and healthcare-provider awareness of excess heart disease risk generally associated with arthritis, highlighting sex/gender disparities, and identifying activity limitation as a modifiable intermediate target for prevention strategies to help reduce heart disease risk in people with arthritis.Ph.D

Prevalence, severity and clinical correlates of pain in patients with Systemic Sclerosis

Systemic Sclerosis (SSc) is a highly heterogeneous multi-system disease characterized by vasculopathy, immune system activation and fibrosis. Patients are classified into limited or diffuse SSc disease subsets according to the extent of skin involvement. This was the first study to use a large multi-center convenience sample of SSc patients (N=585) to estimate prevalence, severity and associations between clinical variables and pain in SSc and, separately in limited and diffuse subsets. Results from the present study draw attention to the high prevalence of pain in SSc and associations between specific clinical variables and pain, including more frequent episodes of Raynaud's phenomenon, active ulcers, worse synovitis and gastrointestinal symptoms, which may represent potential clinical intervention targets. Subsetting by the extent of skin involvement was only minimally related to pain severity and did not affect associations with clinical variables. More attention to pain and how to best manage it is needed in SSc.La sclérose systémique (SSc) se caractérise par une vasculopathie, une dysfonction auto-immune, et une fibrose diffuse. Les personnes atteintes de SSc sont classifiées comme ayant la SSc limitée ou diffuse selon l'étendue de l'atteinte cutanée. Notre étude est la première grande recherche multicentrique d'un échantillon de convenance (N=585) à estimer la prévalence, la sévérité et les associations entre les manifestations cliniques de la SSc et la douleur. Les résultats démontrent que la prévalence de la douleur est élevée, et que certaines variables cliniques sont associées à celle-ci (syndrome de Raynaud, ulcérations actives, synovites et symptômes gastro-intestinaux) et pourraient donc représenter des cibles d'intervention. L'étendue de l'atteinte cutanée affecte très peu ou pas du tout la sévérité de la douleur et les associations observées avec les variables cliniques. Plus d'attention à la douleur et à des stratégies thérapeutiques qui pourraient diminuer son intensité est nécessaire pour les personnes atteintes de SSc