Björn Sundström

Interaction between dietary sodium and smoking increases the risk for rheumatoid arthritis: results from a nested case–control study

OBJECTIVE Recent studies in animal models and on human cells have shown an effect of sodium chloride (NaCl) on Th17 cells promoting inflammation. The aim of this study was to evaluate the impact of NaCl intake on the risk of development of RA. METHODS A nested case-control study was performed using population-based prospective data from the Västerbotten Intervention Programme. The study included 386 individuals who had stated their dietary habits as part of a community intervention programme a median of 7.7 years before the onset of symptoms of RA. For comparison, 1886 matched controls were identified from the same database and co-analysed. RESULTS No significant association was found between sodium intake and the development of RA when all of the individuals were included. In analyses stratified for smoking status at the time of the examination, sodium intake more than doubled the risk for RA among smokers [odds ratio (OR) 2.26 (95% CI 1.06, 4.81)]. This was not observed among non-smokers. Additive interaction analysis of smoking and cases with the highest tertile of sodium intake revealed that 54% of the increased risk of developing RA from these exposures was due to interaction between them [attributable proportion 0.54 (95% CI 0.26, 0.82)]. The risk was further increased for the development of anti-CCP-positive and/or HLA shared epitope-positive RA. CONCLUSION Although we were unable to confirm our stated hypothesis, our results that high sodium consumption among smokers was associated with the risk of RA may provide new insights into the impact of smoking in RA development.

Exercise habits among patients with ankylosing spondylitis. A questionnaire based survey in the County of Västerbotten, Sweden.

Objective: This study aimed at evaluating exercise habits among patients with ankylosing spondylitis, their clinical status and what mainly restrains these patients from exercising. Methods: In a cross-sectional design study 189 patients completed a self-administrated questionnaire regarding their exercise habits and their clinical status. Results: A majority of the patients reported that they performed exercises. The most popular form of exercise was walking. Pool exercise was perceived to relieve the symptoms more than any other exercise and was also rated as the most enjoyable form of exercise. The main obstacle to exercise was lack of time, followed by fatigue. A small number of patients experienced aggravation of symptoms with exercise. Conclusion: A majority of AS patients exercise, although the frequency of the exercise was low for many patients. The main obstacle to exercise was lack of time and fatigue.

Validity of ankylosing spondylitis and undifferentiated spondyloarthritis diagnoses in the Swedish National Patient Register

Objectives: Epidemiological studies of spondyloarthritis (SpA), using ICD codes from the Swedish National Patient Register (NPR), offer unique possibilities but hinge upon an understanding of the validity of the codes. The aim of this study was to validate the ICD codes for ankylosing spondylitis (AS) and undifferentiated SpA (uSpA) in the NPR against the established classification criteria [modified New York (mNY), Assessment of SpondyloArthritis international Society (ASAS), Amor, and European Spondyloarthropathy Study Group (ESSG) criteria]. Method: All patients with an ICD-8/9/10 code of AS or uSpA in the NPR 1966–2009 at a visit to a specialist in rheumatology or internal medicine or corresponding hospitalization, alive and living in Sweden 2009, were identified (n = 20 089). Following a structured procedure to achieve geographical representativeness, 500 random patients with a diagnosis of AS or uSpA in 2007–2009 were selected. Based on a structured review of clinical records, positive predictive values (PPVs) for fulfilling the criteria sets were calculated. Results: For those having received an ICD code for AS, the PPVs for fulfilling the mNY criteria or any set of SpA criteria were 70% and 89%, respectively. For those with an uSpA diagnosis (and never an AS diagnosis), the corresponding PPVs were 20% and 79%. The subset with both AS and uSpA diagnoses (overlap = 12%) were as likely to fulfil the mNY criteria as the group that had been coded as AS only. Conclusions: The diagnosis codes for AS or uSpA had high PPVs, suggesting that our case identification in the Swedish NPR can be used for nationwide, population-based, epidemiological studies of these diseases.

Supplementation of omega‐3 fatty acids in patients with ankylosing spondylitis

Objective: To study the effect of supplementation with omega‐3 fatty acids on disease variables and drug consumption in patients with ankylosing spondylitis (AS). Methods: Twenty‐four patients were randomized to either a low‐dose (1.95 g omega‐3/day) or a high‐dose (4.55 g omega‐3/day) supplement. Disease activity, functional impairment, erythrocyte sedimentation rate (ESR), and drug consumption were assessed during visits at baseline and at weeks 7, 14, and 21. Results: Eighteen patients completed the study, nine patients from each group. The patients in the high‐dose group exhibited a significant decrease in disease activity according to the Bath Ankylosing Disease Activity Index (BASDAI; p = 0.038), which was not seen in the low‐dose group. Significant differences were not found on drug consumption or in functional capacity in either of the groups. No significant differences were found when comparing the results between the high‐ and low‐dose groups. Conclusion: Omega‐3 fatty acids in adequate doses may have the capacity to decrease the disease activity of AS. However, larger and better controlled studies are needed before any further conclusions can be made on the extent of this capacity.

Diet, disease activity, and gastrointestinal symptoms in patients with ankylosing spondylitis

The aims of this study were to investigate, firstly, the relationship between diet and disease activity and, secondly, the presence of gastrointestinal symptoms and their relationship to diet among patients with ankylosing spondylitis (AS) using a cross-sectional design. One hundred sixty-five individuals diagnosed with AS were invited to complete a self-administered postal questionnaire regarding demographic data, diet, medication, and gastrointestinal symptoms in addition to two established disease assessment questionnaires, i.e., the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI). No significant correlation between diet and disease activity was found. Overall, 27% of the patients reported aggravating gastrointestinal problems when consuming certain foodstuff(s). The 30% of patients who reported suffering from gastrointestinal pain had significantly greater disease activity and poorer functional status according to their BASDAI and BASFI scores (p < 0.01 and p = 0.01, respectively). Patients who reported gastrointestinal pain had a significantly higher consumption of vegetables (p < 0.01) and lower consumption of milk and soured milk (p = 0.04). No significant correlation was found between the use of non-steroidal anti-inflammatory drugs (NSAID) and gastrointestinal symptoms. In multiple regression models, BASDAI and the consumption of vegetables were independent and statistically significant predictors of gastrointestinal pain. To conclude, in a group of Swedish AS patients, no correlation between diet and disease activity could be detected. There were, however, correlations between diet and gastrointestinal pain. Gastrointestinal problems were also found to be prevalent in AS, independent of NSAID usage.

Plasma phospholipid fatty acid content is related to disease activity in ankylosing spondylitis.

Objective. To investigate fatty acid composition in the diet, plasma phospholipids, and adipose tissue in a cohort of patients with ankylosing spondylitis (AS), and to determine their correlations to disease activity and blood lipids in a cross-sectional study. Methods. Diet was assessed using a food frequency questionnaire in 66 patients with AS. Polyunsaturated fatty acids in plasma phospholipids and gluteal adipose tissue were measured using gas chromatography. Disease status was quantified using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), erythrocyte sedimentation rate (ESR), high sensitivity C-reactive protein, and proinflammatory cytokines. Results. Diet did not correlate with disease activity assessed by the BASDAI, but there were negative correlations between the dietary intake of long-chain omega-3 fatty acids and ESR (rs = –0.27, p < 0.05). The plasma phospholipid content of arachidonic acid correlated significantly with the BASDAI score (rs = 0.39, p < 0.01). There were correlations between the intake of long-chain omega-3 fatty acids and high-density lipoproteins and serum triglycerides (rs = 0.26 and rs = –0.25, respectively, p < 0.05). Conclusion. There was a positive correlation between levels of arachidonic acid in plasma phospholipids and disease activity assessed by BASDAI in patients with AS. A Western diet does not appear to influence this correlation, but seems to affect blood lipids involved in atherogenic processes.

High sodium chloride consumption enhances the effects of smoking but does not interact with SGK1 polymorphisms in the development of ACPA-positive status in patients with RA

High sodium chloride consumption enhances the effects of smoking but does not interact with SGK1 polymorphisms in the development of ACPA-positive status in patients with RA

Modifiable cardiovascular risk factors in patients with ankylosing spondylitis

The aim of this study was to evaluate whether modifiable cardiovascular disease (CVD) risk factors, e.g. atherogenic blood lipids, hypertension and lifestyle-related factors such as smoking, diet and physical inactivity, differ among patients with ankylosing spondylitis (AS) in comparison to the general population. Eighty-eight patients diagnosed with AS were identified by analysis of the databases of a previous community intervention programme, the Västerbotten intervention programme. The patients were compared with 351 controls matched for age, sex and study period. These databases include the results of blood samples analysed for cholesterol, triglycerides and plasma glucose, as well as data on hypertension, height, weight, smoking and dietary habits and physical activity. No significant differences were found between patients and controls regarding hypertension, body mass index, physical activity, diet or smoking. Levels of serum triglycerides (p < 0.01) and cholesterol (p < 0.01) were significantly lower in the patient group. Among the patients, the level of triglycerides correlated inversely with the intake of total fat (rs = −0.25, p < 0.05), monounsaturated fats (rs = −0.29, p < 0.05) and positively correlated to the intake of carbohydrates (rs = 0.26, p < 0.05). These associations were not apparent among the controls. In the cohort of AS patients studied, no differences were found regarding the modifiable risk factors for CVD compared with the general population. Hence, the increased presence of CVD in patients with AS may be caused by other factors such as differences in metabolism and medication such as NSAID or the chronic low-grade inflammation present in the disease.

High sodium intake among smokers is a risk factor for acpa positivity in RA

Background Increased exposure to sodium chloride has been associated with an increased activation of Th17 cells and with increased risk of experimental encephalitis in mice as well as an increased T cell activation in humans [1,2]. Provided the postulated role of Th17 cells in rheumatoid arthritis (RA) [3], it is of interest to investigate the effects of sodium intake on risk for different variants of RA and other known risk factors such as smoking. Objectives To investigate the relationship between consumption of sodium chloride, smoking and seropositivity among individuals with RA. Methods Incident cases with early RA (n=1049) participating in the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) [4] cohort study were analysed. Presence of anti-citrullinated peptides antibodies (ACPA) and rheumatoid factor (RF) was assessed by standard laboratory procedures. Previous and present smoking was reported by the participants of the study in self-reporting questionnaires. Sodium intake was assessed on basis of food frequency questions and analysed as tertiles adjusted by total energy intake. The lowest tertile of sodium intake was used as reference and compared to the combined upper two tertiles. Odds ratios (ORs) were calculated with 95% confidence intervals (95% CIs) by means of logistic regression analysis with adjustment for age and sex. Results High consumption of sodium in current smokers was associated with an increased risk for ACPA positivity compared with smokers with low sodium intake (OR=2.21, 95% CI 1.26-3.89). There was a significant interaction between smoking and sodium intake using both additative and multiplicative methods for calculation (AP=0.55, 95% CI 0.25-0.85, RERI=1.41, 95% CI 0.28-2.55, MI p=0.046). There were no significant associations of RF positivity and sodium intake among smokers (OR=1.35, 95% CI 0.81-2.27). Nor were there any significant associations between ACPA or RF positivity and sodium intake among non-smokers (OR=0.96, 95% CI 0.64-1.46 for ACPA, and OR=0.98, 95% CI 0.58-1.66 for RF). Conclusions High dietary intake of sodium among smokers was associated with an increased risk to develop ACPA positive RA and there was a significant interaction between the two environmental factors – sodium intake and smoking in conferring to this increased disease risk. The present study thus extends a previous study from three of us (BS, IJ and SRD) on impact of sodium on risk for RA in a pre-RA cohort (5). The possibility that smoking may be involved in triggering of Th17 activation of pathogenic importance in ACPA positive RA, and that such events may be modified by dietary intake of sodium chloride now requires experimental studies for eventual molecular verification. If verified, these observations may provide leads for preventive as well as therapeutic efforts by means of dietary changes and/or targeting of sodium-chloride-dependent molecular pathways. References Wu C, Yosef N, Thalhamer T, et al. Nature. 2013;496:513-7 Kleinewietfeld M, Manzel A, Titze J, et al. Nature. 2013;496:518-22 Benedetti G, Miossec P. Eur J Immunol. 2013 Dec 5. Bengtsson C, Nordmark B, Klareskog L, et al. Ann Rheum Dis 2005;64:1588–94. Sundström B, Johansson I, Rantapää-Dahlqvist S. Arthritis Rheum 2013: 65: S966 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1592

Validity of ankylosing spondylitis and spondyloarthritis diagnoses in the Swedish National Patient Register

Background Epidemiological studies of spondyloarthritis (SpA) are scarce. Using ICD-codes from the Swedish National Patient Register (NPR) offers unique possibilities for such studies. For this purpose, the validity of these ICD-codes needs to be determined. Objectives To validate the ICD-codes for ankylosing spondylitis (AS) and SpA in the NPR against established classification criteria (modified New York (mNY), ASAS, Amor and ESSG criteria). Methods All patients with an ICD-code of AS or SpA in the NPR 1966-2009 at a visit to a specialist in rheumatology or internal medicine, or corresponding hospitalization, were identified (n=20074). Following a structured procedure to achieve geographical representativeness, 500 random patients with a registered diagnosis of AS or SpA in 2007-2009 were selected. A structured review of clinical records, with extraction of necessary information for the established classification criteria was performed and positive predictive values (PPV) were calculated. Results In this cohort 11472 (34% women) patients had received an AS diagnosis and 11004 (56% women) a SpA diagnosis. The overlap group having received both types of diagnoses had similar frequencies for fulfillment of mNY criteria, symptoms and signs of back disease as the group having been coded as AS only. Of those being coded as AS only, the PPV for fulfilling the mNY, any criteria set and any of the included criteria elements were 70%, 89% and 96% respectively. Of those with SpA (without AS ever) the corresponding PPV values were 20%, 79% and 99% respectively. Conclusions A diagnosis of AS or SpA (without AS) had a high validity, suggesting that case identification based on ICD-codes in the Swedish NPR can be used for epidemiological studies of these diseases. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2817