Disease activity trajectories in rheumatoid arthritis: a tool for prediction of outcome.

Objective: Predicting treatment response and disease progression in rheumatoid arthritis (RA) remains an elusive endeavour. Identifying subgroups of patients with similar progression is essential for understanding what hinders improvement. However, this cannot be achieved with response criteria based on current versus previous Disease Activity Scores, as they lack the time component. We propose a longitudinal approach that identifies subgroups of patients while capturing their evolution across several clinical outcomes simultaneously (multi-trajectories). Method: For exploration, the RA cohort BARFOT (n = 2829) was used to identify 24 month post-diagnosis simultaneous trajectories of 28-joint Disease Activity Score and its components. Measurements were available at inclusion (0), 3, 6, 12, 24, and 60 months. Multi-trajectories were found with latent class growth modelling. For validation, the TIRA-2 cohort (n = 504) was used. Radiographic changes, assessed by the modified Sharp van der Heijde score, were correlated with trajectory membership. Results: Three multi-trajectories were identified, with 39.6% of the patients in the lowest and 18.9% in the highest (worst) trajectory. Patients in the worst trajectory had on average eight tender and six swollen joints after 24 months. Radiographic changes at 24 and 60 months were significantly increased from the lowest to the highest trajectory. Conclusion: Multi-trajectories constitute a powerful tool for identifying subgroups of RA patients and could be used in future studies searching for predictive biomarkers for disease progression. The evolution and shape of the trajectories in TIRA-2 were very similar to those in BARFOT, even though TIRA-2 is a newer cohort.

Low vitamin D status in relation to cardiovascular disease and mortality in Swedish women - Effect of extended follow-up.

BACKGROUND AND AIMS: The impact of vitamin D concentrations on subsequent cardiovascular disease (CVD) and overall mortality has been generally examined for periods under two decades. The magnitude of the association may depend on follow-up length. We aimed to investigate the relationship between baseline vitamin D and risk of total CVD, stroke and all-cause mortality over three decades of follow-up. Secondly, we aimed to assess how follow-up affects the associations. METHODS AND RESULTS: Concentrations of 25-hydroxyvitamin D (25D) were measured in a population-based sample of 1227 middle-aged women using serum collected at baseline and categorized into low (lowest 25D quartile) vs high 25D status (upper three 25D quartiles). Hazard ratio (HR) of the endpoints was estimated for low 25D. The impact of follow-up was examined in intermediary analyses where follow-up was interrupted up to four times, each time decreasing it by five years. There were 596 cardiovascular events and 635 participants died. During the first 17 years, the low 25D group experienced a 29% higher CVD risk and 3.3-fold higher stroke risk after accounting for confounders. Longer follow-up diminished significantly these risks and 25D status had no contribution at 32 years. For mortality, the decline over time was less dramatic, with HR = 1.96 (1.25; 3.08) at 17 years and HR = 1.42 (1.17; 1.72) at 37 years. CONCLUSION: Low 25D status increased the risk for all endpoints, but a lengthy follow-up diminished these risks towards the null. The impact of follow-up depends on the outcome. Future studies of 25D and disease should use repeated 25D assessments.

Serum 25-hydroxy vitamin D levels in middle-aged women in relationship to adiposity and height trajectories over three decades.

BACKGROUND/OBJECTIVES: The long-term chronology of the association between low serum concentrations of 25-hydroxy vitamin D (25(OH)D) and weight status is unclear. We examined whether lower 25(OH)D in middle-aged women drives upwards the weight, body mass index (BMI) and waist-hip ratio (WHR) over the next 32 years, and whether higher 25(OH)D might predict less decline in the mid- to late-life height trajectory. SUBJECTS/METHODS: The Population Study of Women in Gothenburg started in 1968-1969 (the baseline) in 38-60-year-old women residing in Gothenburg, Sweden. Anthropometric measures were taken at baseline and 4 re-examinations until 2000-2003. Levels of 25(OH)D were analyzed in serum stored since baseline in 1227 (84%) women. Repeated measures analyses were used to model associations between 25(OH)D (dichotomized, cut point 51.45 nmol/l) at baseline and anthropometric trajectories, adjusting for fixed and time-dependent covariates. RESULTS: At baseline, mean BMI was 25.2 kg/m(2) in women with low 25(OH)D and 23.8 kg/m(2) in the remaining women (P<0.001), but this difference did not increase over 32 years and longitudinal differences were explained by the baseline BMI. Similar results were observed for weight and WHR. In contrast, no association was seen for height at baseline or longitudinally. CONCLUSIONS: No relationship was observed between 25(OH)D height trajectory, but lower 25(OH)D was associated with higher BMI, weight and WHR differences that were maintained over three decades. This provides no evidence for the direction of causality, but for a life-long difference in adiposity-related measures according to the 25D level in middle-aged women.