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Background Our objective was to determine if patients who later develop inflammatory bowel disease (IBD) show signs of increased inflammatory activity in plasma measured with high sensitivity C-reactive protein (CRP), calprotectin, and albumin before the clinical onset of IBD. Methods We identified 96 subjects who later developed IBD (70 ulcerative colitis [UC] and 26 Crohn’s disease [CD]). High sensitivity CRP, calprotectin, and albumin were analyzed in frozen plasma, donated from cases and sex–age matched controls 1–15 years before diagnosis. Results We found that subjects who later developed UC had lower albumin levels, and subjects who later developed CD had higher CRP levels than controls. Multivariable conditional logistic regression with albumin, calprotectin, and CRP showed a lower risk for developing IBD and UC with higher albumin levels (odds ratio [OR] 0.79, confidence interval [CI] 0.69–0.90; respective OR 0.77, CI 0.66–0.91). Higher CRP levels were associated with an increased risk of developing CD (OR 1.314, CI 1.060–1.630). When adjusting for body mass index or smoking in the logistic regression model, similar results were found. Plasma calprotectin levels in the preclinical period among patients with IBD did not differ from controls. Conclusions In this nested case–control study, subjects who later developed IBD had signs of low-grade systemic inflammation, indicated by significantly higher CRP plasma levels in CD and lower albumin plasma levels in UC, before the onset of clinical disease.

Background Chronic kidney disease (CKD) has a complicated relationship with the heart, leading to many adverse outcomes. Purpose The aim of the study was to evaluate the relationship between CKD and the incidence of atrial fibrillation (AF) and heart failure (HF) along with mortality as a competing risk in general population cohorts. Methods This study was conducted as part of the BiomarCaRE project using harmonised data from 12 population-based cohorts (n=40,212) from Europe. Cox proportional hazards models were used to determine hazard ratios (HRs) for the incidence of AF and HF in CKD and with competing mortality risk after adjusting for covariates. Results Mean age at baseline was 51.1 (standard deviation 11.9) years, and 49.3% were men. Overall, 3.5% had CKD at baseline. The rate for incident AF was 3.9 per 1000 person-years during follow-up. The HR for AF for those with CKD compared with those without was 1.23 (95% CI 1.00–1.52, p=0.0465) after adjustment for covariates. The rate for incident HF was 3.9 per 1000 person-years and the associated risk in the presence of CKD was HR 1.67 (95% CI 1.39–2.01). In subjects with CKD, N-terminal pro-B-type natriuretic peptide (NT-proBNP) showed an association with AF, while NT-proBNP and C-reactive protein (CRP) showed an association with HF. Conclusion CKD is an independent risk factor for subsequent AF and even more so for HF. In patients with CKD, NT-proBNP was clearly associated with subsequent risk of AF. In addition to this marker, hs-CRP was also associated with risk of subsequent HF. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): 7th framework programme collaborative project, grant agreement no. HEALTH-F2-2011_278913. Atrial Fibrillation and HF in CKD

Objective High-sensitivity troponin T (hs-TnT) and high-sensitivity C-reactive protein (hs-CRP) may convey prognostic information in patients with aortic stenosis (AS). However, many association studies were cross-sectional, and the presence of myocardial hypertrophy and concomitant coronary artery disease (CAD) were usually not described. This study evaluated if hs-TnT and hs-CRP relate to myocardial mass, and associate with risk of and time to future surgery for AS in patients with and without concomitant CAD. Design In total, 336 patients who underwent surgery due to AS after participation in large population surveys were identified. Median age [interquartile range] was 59.8 [10.3] years at survey and 68.3 [12.7] years at surgery, and 48% were women. The median time between survey and surgery was 10.9 [9.3] years. Preoperatively, myocardial mass and the presence of CAD were assessed. Two matched referents were allocated for each case, and hs-TnT and hs-CRP were determined in stored plasma samples from the baseline survey. Uni- and multivariable conditional logistic regression analyses were used to estimate the risk (odds ratio [95% confidence interval]) related to one (ln) standard deviation increase in hs-TnT and hs-CRP. Time to surgery was evaluated by Kaplan-Mayer analysis and Cox regression. Results Hs-TnT was independently associated with surgery for AS in patients with concomitant CAD (odds ratio [95% confidence interval]) (1.22 [1.02–1.46]) and without concomitant CAD (1.39 [1.05–1.84]). Hs-CRP was not associated with surgery for AS after adjustment for traditional cardiovascular risk factors (1.06 [0.92–1.23]). Patients with high hs-TnT levels had shorter time to surgery compared those with low levels (Figure, p Conclusions Hs-TnT – but not hs-CRP – was associated with increased risk for, and shorter time to future surgery for AS. Hs-TnT associated with myocardial mass at surgery which indicates that Hs-TnT may be used as a clinical tool and allow for identification of patients with AS who could benefit from earlier intervention. Time to surgery; tertiles of hs-TnT Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): The Swedish Heart–Lung Foundation

Background Coffee is known to impact on colon motility, alter gut-related immune response, and to affect symptoms among inflammatory bowel disease (IBD) patients. In spite of this, the role of coffee as a determinant of IBD is unclear. The aim of this study was to investigate how coffee correlates to the risk of developing late-onset IBD in general, and subdivided into Crohn’s disease and ulcerative colitis. Methods This nested case-control study within the large, population-based Northern Sweden Health and Disease Study (NSHDS), included data from 78 patients with IBD and 311 controls matched for age, sex, time and area of sample collection. Cases were included in NSHDS at least one year prior to IBD diagnosis. Coffee consumption was assessed by questionnaire-data, differing between drip-filtered and boiled unfiltered coffee. Risk associations were estimated through conditional logistic regressions. Results Results differed between different subgroups of IBD and coffee. Our main finding was a decreased risk of Crohn’s disease in subjects with a daily intake of drip-filtered coffee in comparison with subjects with a less frequent intake (Table). After adjustments for smoking, body-mass-index, educational level and marital status the results remained. Adjusted OR for Crohn’s disease was 0.22; 95% CI 0.07–0.76 Conclusion Our results indicate potential biochemical differences depending on coffee preparation technique on IBD risk, with possible implications for prevention or treatment. Further studies are warranted.

BackgroundWe aimed to determine whether patients who later develop IBD show signs of inflammatory activity in blood measured with high-sensitivity CRP, calprotectin and albumin before clinical onse ...

Background. Thrombocytopenia is a common finding during viral hemorrhagic fever, which includes hemorrhagic fever with renal syndrome (HFRS). The 2 main causes for thrombocytopenia are impaired thrombopoiesis and/or increased peripheral destruction of platelets. In addition, there is an increased intravascular coagulation risk during HFRS, which could be due to platelet activation. Methods. Thrombopoiesis was determined by quantification of platelet counts, thrombopoietin, immature platelet fraction, and mean platelet volume during HFRS. The in vivo platelet activation was determined by quantification of soluble P-selectin (sP-selectin) and glycoprotein VI (sGPVI). The function of circulating platelets was determined by ex vivo stimulation followed by flow cytometry analysis of platelet surface-bound fibrinogen and P-selectin exposure. Intravascular coagulation during disease was determined by scoring for disseminated intravascular coagulation (DIC) and recording thromboembolic complications. Results. The levels of thrombopoietin, immature platelet fraction, and mean platelet volume all indicate increased thrombopoiesis during HFRS. Circulating platelets had reduced ex vivo function during disease compared to follow-up. Most interestingly, we observed significantly increased in vivo platelet activation in HFRS patients with intravascular coagulation (DIC and thromboembolic complications) as shown by sP-selectin and sGPVI levels. Conclusions. HFRS patients have increased thrombopoiesis and platelet activation, which contributes to intravascular coagulation. Funding Agencies|Medical Faculty of Umea University; County Council of Vasterbotten [216851, 243061, 238461, 321411]; County Councils of Northern Sweden [296301]

Background and Aims: Population-based prospective cohort studies investigating fibre intake and development of inflammatory bowel disease are lacking. Our aim was to investigate the association between fibre intake and the development of Crohn's disease [CD] and ulcerative colitis [UC] in a large European population.Methods: In total, 401326 participants, aged 20-80 years, were recruited in eight countries in Europe between 1991 and 1998. At baseline, fibre intake [total fibres, fibres from fruit, vegetables and cereals] was recorded using food frequency questionnaires. The cohort was monitored for the development of inflammatory bowel disease. Each case was matched with four controls and odds ratios [ORs] for the exposures were calculated using conditional logistic regression. Sensitivity analyses according to smoking status were computed.Results: In total, 104 and 221 participants developed incident CD and UC, respectively. For both CD and UC, there were no statistically significant associations with either quartiles, or trends across quartiles, for total fibre or any of the individual sources. The associations were not affected by adjusting for smoking and energy intake. Stratification according to smoking status showed null findings apart from an inverse association with cereal fibre and CD in non-smokers [Quartile 4 vs 1 OR = 0.12, 95% confidence interval = 0.02-0.75, p = 0.023, OR trend across quartiles = 0.50, 95% confidence interval = 0.29-0.86, p = 0.017].Conclusion: The results do not support the hypothesis that dietary fibre is involved in the aetiology of UC, although future work should investigate whether there may be a protective effect of specific types of fibre according to smoking status in CD.

Higher plasma cotinine is associated with an increased risk for later developing IBD, especially among users of combusted tobacco