Lipid levels and CVD outcome in RA patients across different <i>APOE</i> genotype groups.

<p>LDL: low density lipoproteins, HDL; High density lipoproteins, IMT; intima-media thickness (mm), CVD event; cardiovascular disease event (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0060970#s2" target="_blank">Methods</a> sections). All lipids are measured in mmol/L. Lipid levels and IMT were compared using ANCOVA, and unadjusted mean values with standard deviation (sd) are given in column 2, 3 and 4. CVD outcomes, which included previous CVD events or carotid plaques present on ultrasound (or both) were compared using Chi-square test; and the number of individuals affected with percentages [%] are given in column 2, 3 and 4. Multivariate analyses were adjusted for age, sex and current statin use. Not all patients had data on all variables and patients with genotype ε2/ε4 (n = 4) were omitted from the analyses.</p>*<p>p-values were corrected for multiple testing using Dunnets-Hsu adjustment.</p>$<p>Exact test.</p

Demographic and baseline clinical data on patients included in the Norwegian longitudinal analyses (EURIDISS cohort), grouped by APOE genotype.

<p>sd; standard deviation, Disease duration; disease duration at baseline in years, ACPA; anti-citrullinated protein antibodies, RF; rheumatoid factor, CRP; C-reactive protein (mg/L), ESR; erythrocyte sedimentation rate (mm/hour), HAQ; Health Assessment Questionnaire, LnSHS; log transformed Sharp van der Heijde score, sDMARD; synthetic disease-modifying anti rheumatic drugs.</p>*<p>The three genotype groups (ε2 carriers, ε3/ε3, and ε4 carriers) were compared by ANOVA or Chi-square test.</p>£<p>For RF and ACPA, patients were viewed as positive if they had at least one positive test during the 10 year follow-up.</p

Longitudinal analyses of <i>APOE</i> genotype and radiographic score, CRP and ESR as dependent variables in the EURIDISS cohort.

<p>SHS, CRP and ESR have all been log-transformed.</p>¥<p>Models were adjusted for: a = time, b = time, age, sex, disease duration, ACPA and DMARD treatment (ever/never).</p>¤<p>Model B with SHS outcome was also adjusted for CRP. For the models investigating CRP or ESR n = 207, while for joint damage (SHS) n = 176. Patients with genotype ε2/ε4 were omitted from the analyses.</p>£<p>In the analyses where <i>APOE</i> genotype is a categorical factor, ε3/ε3 is the reference group.</p>$<p>In the linear analyses (<i>APOE</i> linear), ε2, ε3/ε3, and ε4 are coded 0, 1 and 2 respectively.</p>§<p>Overall p-value.</p>*<p>P-values corrected for multiple testing using Sidaks’ adjustment.</p

Demographics and clinical measures of the 136 patients included in the lipid and CVD analyses.

<p>sd; standard deviation, Disease duration; disease duration in years at follow-up in 2007, ACPA; anti-citrullinated protein antibodies, RF; rheumatoid factor, CDAI; Clinical Disease Activity Index, DAS28; Diseases Activity Score 28, HAQ; Health Assessment Questionnaire, Statins; lipid lowering medications, sDMARD and bDMARD; synthetic and biologic disease-modifying antirheumatic drug,</p>*<p>The three genotype groups (ε2carriers, ε3/ε3, and ε4 carriers) were compared by ANOVA or chi square test.</p>¤<p>Not all patients had data available for all analyses, but the maximum number of patients in each group was ε2 n = 15, ε3/ε3 n = 81, ε4 n = 40. Patients with ε2/ε4 gentoype were excluded (n = 4).</p

<i>APOE</i> genotypes in RA patients and controls.

<p>ACPA; anti-citrullinated protein antibodies, RF; rheumatoid factor. Frequencies of genotypes were compared between all patients or subsets of patients (i.e. ACPA positive patients) and controls using chi square test.</p>*<p>Odds ratios were calculated using ε3/ε3 as the reference group.</p

Longitudinal analyses and meta-analyses for <i>APOE</i> and radiographic joint damage for 3 cohorts.

<p>For <i>APOE</i>, the three genotype groups, ε2 carrier, ε3/ε3, and ε4 carrier are coded 0, 1 and 2 respectively. The coefficient estimates and 95% confidence interval (95% CI) from the longitudinal analyses give a measure of the difference in radiographic joint damage score of adjacent <i>APOE</i> genotype groups within each cohort. E.g. in the Norwegian cohort individuals with ε3/ε3 genotype had 0.36 lower radiographic joint damage score than individuals carrying ε2. The coefficient estimates are given on the natural log (ln) scale for radiographic joint damage score. Longitudinal analyses were adjusted for time, age, gender and treatment. Additional adjustments including presence of anti citrullinated protein antibodies and disease duration at baseline were included in the analyses of the Norwegian cohort. A fixed effect meta-analysis was carried out and the p-value is shown.</p

Mean radiographic joint damage in patients with RA in the three different cohorts grouped by <i>APOE</i> genotype.

<p>A = Norway, B = Lund (Sweden) and C = Leiden (Netherland). The Y-axes shows radiographic damage, either as log-transformed van der Heijde Sharp score or log transformed Larsen score (Lund). The x-axes show years of follow-up. Number of patients included: Norway (EURIDISS); n = 176, Leiden n = 621, Lund n = 138.</p