M. Nielen

Lipids and inflammation: serial measurements of the lipid profile of blood donors who later developed rheumatoid arthritis.

Background: Rheumatoid arthritis is characterised by inflammation and an increased cardiovascular risk. It was recently shown that active early rheumatoid arthritis is associated with dyslipidaemia, which may partially explain the enhanced cardiovascular risk. However, it is unknown when this dyslipidaemia starts. Objective: To investigate the progression of the lipid profile over time and the influence of inflammatory parameters on this lipid profile, in people who later developed rheumatoid arthritis. Methods: Levels of total cholesterol, high-density lipoprotein cholesterol (HDLc), triglycerides, apolipoprotein AI (apo AI), apolipoprotein B (apo B) and lipoprotein(a) (Lp(a)) were determined in 1078 stored, deep-frozen, serial blood bank samples, collected between 1984 and 1999, of 79 blood donors who later developed rheumatoid arthritis. These samples were compared with 1071 control samples of unselected blood donors, matched for age, sex and storage time. Results: Samples of patients who later developed rheumatoid arthritis showed, on average, 4% higher total cholesterol, 9% lower HDLc, 17% higher triglyceride and 6% higher apo B levels than matched controls (p⩽0.05). The magnitude of the differences in lipid levels between groups, explained by C reactive protein (CRP), was limited. For example, only 3.6% of the difference in HDLc levels between the groups was explained by the CRP concentrations. Conclusion: Patients who later develop rheumatoid arthritis have a considerably more atherogenic lipid profile than matched blood donors at least 10 years before onset of symptoms. As inflammation only marginally explains the differences between the two groups, a modulating effect of lipids on inflammatory processes is hypothesised.

DAS-driven therapy versus routine care in patients with recent-onset active rheumatoid arthritis.

Objectives: To compare the efficacy of Disease Activity Score (DAS)-driven therapy and routine care in patients with recent-onset rheumatoid arthritis. Methods: Patients with recent-onset rheumatoid arthritis receiving traditional antirheumatic therapy from either the BeSt study, a randomised controlled trial comparing different treatment strategies (group A), or two Early Arthritis Clinics (group B) were included. In group A, systematic DAS-driven treatment adjustments aimed to achieve low disease activity (DAS ⩽2.4). In group B, treatment was left to the discretion of the treating doctor. Functional ability (Health Assessment Questionnaire (HAQ)), Disease Activity Score in 28 joints (DAS28) and Sharp/van der Heijde radiographic score (SHS) were evaluated. Results: At baseline, patients in group A (n = 234) and group B (n = 201) had comparable demographic characteristics and a mean HAQ of 1.4. Group A had a longer median disease duration than group B (0.5 vs 0.4 years, p = 0.016), a higher mean DAS28 (6.1 vs 5.7, p<0.001), more rheumatoid factor-positive patients (66% vs 42%, p<0.001) and more patients with erosions (71% vs 53%, p<0.001). After 1 year, the HAQ improvement was 0.7 vs 0.5 (p = 0.029), and the percentage in remission (DAS28 <2.6) 31% vs 18% (p<0.005) in groups A and B, respectively. In group A, the median SHS progression was 2.0 (expected progression 7.0), in group B, the SHS progression was 1.0 (expected progression 4.4). Conclusions: In patients with recent-onset rheumatoid arthritis receiving traditional treatment, systematic DAS-driven therapy results in significantly better clinical improvement and possibly improves the suppression of joint damage progression.

Simultaneous development of acute phase response and autoantibodies in preclinical rheumatoid arthritis

Objective: To investigate the temporal relationship between onset of inflammation (as measured by secretory phospholipase A2 (sPLA2) and C reactive protein (CRP)) and the presence of autoantibodies (IgM rheumatoid factor (IgM RF) and antibodies against citrullinated peptides (anti-CCP)) in the preclinical phase of rheumatoid arthritis (RA). Methods: For 79 patients with RA who had been blood donors before the onset of disease, a median of 13 serum samples per patient was available. sPLA2 was measured in patient and matched control samples and related to previous CRP, IgM RF, and anti-CCP measurements. The temporal relationship between the increased markers of inflammation and autoantibodies was analysed with time lag analysis. Results: IgM RF and anti-CCP concentrations were significantly associated (p<0.001) with concentrations of sPLA2, CRP, and the combination of sPLA2 and CRP at the same time point. However, we found no stronger association between the two autoantibody tests and the three inflammation measures 1, 2, and 3 years before or after a time point than for measurements at the same time, in the whole group or in subgroups of IgM RF and anti-CCP positive patients. Conclusion: Both the acute phase response and autoantibody formation often develop years before the first symptoms of RA occur, and these phenomena are probably closely connected in time.

Ankylosing spondylitis: a risk factor for myocardial infarction?

Objective To ascertain the prevalence of myocardial infarction (MI) in ankylosing spondylitis (AS) relative to that in the general population. Methods A questionnaire was sent to 593 patients with AS, aged between 50 and 75 years and registered at the Jan van Breemen Institute or VU University Medical Centre. A total of 383 (65%) patients with AS returned their questionnaire that covered the primary outcome, (non-fatal) MI. The prevalence of MI was calculated with data from the general population provided by Netherlands Information Network of General Practice databases as reference. Results The overall prevalence for MI was 4.4% in patients with AS versus 1.2% in the general population, resulting in an age- and gender-adjusted odds ratio of 3.1 (95% CI 1.9 to 5.1) for patients with AS. When non-responders (35%) were considered as non-MI the odds ratio decreased to 1.9 (95% CI 1.2 to 3.2). Conclusions These observations indicate that the prevalence of MI is increased in patients with AS.

Antibodies to mutated citrullinated vimentin and disease activity score in early arthritis: a cohort study

IntroductionThe aim of our study was to investigate the association between arthritic disease activity and antibodies to mutated citrullinated vimentin (anti-MCV), because such a relation has been suggested.MethodsAnti-MCV levels were measured in 162 patients with early arthritis (123 with rheumatoid arthritis and 39 with undifferentiated arthritis) at baseline and at 1 and 2 years of follow up. Disease activity was measured using the disease activity score (Disease Activity Score based on 28 joints [DAS28]) and serum C-reactive protein. General estimation equation analysis was used to assess the relation between anti-MCV levels and DAS28 over time.ResultsBoth, anti-MCV levels and DAS28 exhibited a significant decrease during the first and second year. However, the association between anti-MCV levels and DAS28, adjusted for dependency on sequential measurements within one individual, was very low (β = 0.00075). In a population of patients with rheumatoid arthritis or undifferentiated arthritis, anti-MCV had a specificity of 92.3% and a sensitivity of 59.3% when using the recommended cut-off of 20 U/ml. Specificity and sensitivity of antibodies against second-generation cyclic citrullinated peptide, using the recommended cut-off value of 25 U/ml, were 92.1% and 55.3%, respectively. Anti-MCV-positive early arthritis patients had significantly higher Sharp-van der Heijde score, erythrocyte sedimentation rate and C-reactive protein levels than did anti-MCV-negative patients at all time points (P < 0.005), but DAS28 was higher in anti-MCV-positive patients at 2 years of follow up only (P < 0.05).ConclusionBecause the correlation between anti-MCV levels and parameters of disease activity was very low, we conclude that it is not useful to monitor disease activity with anti-MCV levels.

Aggressive therapy in patients with early arthritis results in similar outcome compared with conventional care: the STREAM randomized trial

Objective. To compare the effects of aggressive tight control therapy and conventional care on radiographic progression and disease activity in patients with early mild inflammatory arthritis. Methods. Patients with two to five swollen joints, Sharp–van der Heijde radiographic score (SHS) <5 and symptom duration ≤2 years were randomized between two strategies. Patients with a definite non-RA diagnosis were excluded. The protocol of the aggressive group aimed for remission (DAS < 1.6), with consecutive treatment steps: MTX, addition of adalimumab and combination therapy. The conventional care group followed a strategy with traditional DMARDs (no prednisone or biologics) without DAS-based guideline. Outcome measures after 2 years were SHS (primary), remission rate and HAQ score (secondary). Results. Eighty-two patients participated (60% ACPA positive). In the aggressive group (n = 42), 19 patients were treated with adalimumab. In the conventional care group (n = 40), 24 patients started with hydroxychloroquin (HCQ), 2 with sulfasalazine (SSZ) and 14 with MTX. After 2 years, the median SHS increase was 0 [interquartile range (IQR) 0–1.1] and 0.5 (IQR 0–2.5), remission rates were 66 and 49% and HAQ decreased with a mean of −0.09 (0.50) and −0.25 (0.59) in the aggressive and conventional care group, respectively. All comparisons were non-significant. Conclusion. In patients with early arthritis of two to five joints, both aggressive tight-control therapy including adalimumab and conventional therapy resulted in remission rates around 50%, low radiographic damage and excellent functional status after 2 years. However, full disease control including radiographic arrest in all patients remains an elusive target even in moderately active early arthritis. Trial registration. Dutch Trial Register, http://www.trialregister.nl/, NTR 144.

Bone metabolism is altered in preclinical rheumatoid arthritis

Radiographic damage and its progression in early rheumatoid arthritis (RA) can be predicted by markers and regulators of bone metabolism. Studies of bone formation in RA patients measuring osteocalcin or the N-terminal telopeptide of type I procollagen (P1NP) have produced varying results, whereas measurements of bone resorption using serum or urine C-terminal crosslink of type I collagen (β-CTX) mostly show increased values.1,–,3 RA patients often have elevated serum levels of the osteoclast-activating cytokine receptor activator of nuclear factor κB ligand (RANKL), as well as of osteoprotegerin, which prevents osteoclast activation.4 We previously reported increased levels of autoantibodies and acute phase reactants …

Cardiometabolic prevention consultation in the Netherlands: screening uptake and detection of cardiometabolic risk factors and diseases – a pilot study

BackgroundUntil now, cardiometabolic risk assessment in Dutch primary health care was directed at case-finding, and structured, programmatic prevention is lacking. Therefore, the Prevention Consultation cardiometabolic risk (PC CMR), a stepwise approach to identify and manage patients with cardiometabolic risk factors, was developed. The aim of this study was 1) to evaluate uptake rates of the two steps of the PC CMR, 2) to assess the rates of newly diagnosed hypertension, hypercholesterolemia, diabetes mellitus and chronic kidney disease and 3) to explore reasons for non-participation.MethodsSixteen general practices throughout the Netherlands were recruited to implement the PC CMR during 6 months. In eight practices eligible patients aged between 45 and 70 years without a cardiometabolic disease were actively invited by a personal letter (‘active approach’) and in eight other practices eligible patients were informed about the PC CMR only by posters and leaflets in the practice (‘passive approach’). Participating patients completed an online risk estimation (first step). Patients estimated as having a high risk according to the online risk estimation were advised to visit their general practice to complete the risk profile with blood pressure measurements and blood tests for cholesterol and glucose and to receive recommendations about risk lowering interventions (second step).ResultsThe online risk estimation was completed by 521 (33%) and 96 (1%) of patients in the practices with an active and passive approach, respectively. Of these patients 392 (64%) were estimated to have a high risk and were referred to the practice; 142 of 392 (36%) consulted the GP. A total of 31 (22%) newly diagnosed patients were identified. Hypertension, hypercholesterolemia, diabetes and chronic kidney disease were diagnosed in 13%, 11%, 1% and 0%, respectively. Privacy risks were the most frequently mentioned reason not to participate.ConclusionsOne third of the patients responded to an active invitation to complete an online risk estimation. A passive invitation resulted in only a small number of participating patients. Two third of the participants of the online risk estimation had a high risk, but only one third of them attended the GP office. One in five visiting patients had a diagnosed cardiometabolic risk factor or disease.

Effect of an evidence-based website on healthcare usage: an interrupted time-series study

Objectives Healthcare costs and usage are rising. Evidence-based online health information may reduce healthcare usage, but the evidence is scarce. The objective of this study was to determine whether the release of a nationwide evidence-based health website was associated with a reduction in healthcare usage. Design Interrupted time series analysis of observational primary care data of healthcare use in the Netherlands from 2009 to 2014. Setting General community primary care. Population 912 000 patients who visited their general practitioners 18.1 million times during the study period. Intervention In March 2012, an evidence-based health information website was launched by the Dutch College of General Practitioners. It was easily accessible and understandable using plain language. At the end of the study period, the website had 2.9 million unique page views per month. Main outcomes measures Primary outcome was the change in consultation rate (consultations/1000 patients/month) before and after the release of the website. Additionally, a reference group was created by including consultations about topics not being viewed at the website. Subgroup analyses were performed for type of consultations, sex, age and socioeconomic status. Results After launch of the website, the trend in consultation rate decreased with 1.620 consultations/1000 patients/month (p<0.001). This corresponds to a 12% decline in consultations 2 years after launch of the website. The trend in consultation rate of the reference group showed no change. The subgroup analyses showed a specific decline for consultations by phone and were significant for all other subgroups, except for the youngest age group. Conclusions Healthcare usage decreased by 12% after providing high-quality evidence-based online health information. These findings show that e-Health can be effective to improve self-management and reduce healthcare usage in times of increasing healthcare costs.

Duration of pre-rheumatoid arthritis anti-cyclic citrullinated peptide positivity is positively associated with age at seroconversion.

Majka et al 1 have recently shown that higher age at the time of diagnosis of rheumatoid arthritis (RA) is associated with an increased period of prediagnosis antibody positivity for rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP). We have extended this observation using a previously described RA cohort (n = 79) in which serial preclinical serum samples were available, in most cases preceding and following seroconversion, thereby enabling approximation of the age at seroconversion.2 A total of 32 patients were anti-CCP positive and 22 patients were IgM-RF positive in the preclinical period. The age at seroconversion and the period of seropositivity before onset of …