Citations

Objectives Rheumatoid factor (RF) and anticitrullinated protein antibodies (ACPA) are linked to disease activity, severity and cardiovascular risk in rheumatoid arthritis (RA). Since RA-related inflammation associates with cardiovascular disease, we investigated whether RF and ACPA status influence the relationship between RA activity and event risk. Methods We assessed 3952 cardiovascular disease-free patients with prevalent RA registered in an international observational consortium between 1985 and 2012. Main outcome was a first major adverse cardiovascular event (MACE) including myocardial infarction, stroke and cardiovascular death. Follow-up accrued from enrolment until first MACE or censoring. Multivariable Cox models stratified by centre risk evaluated disease activity, RF, ACPA and their interactions. Results We recorded 184 first MACE events over 22 981 patient-years. Disease activity associated with MACE (HR 1.18 (95% CI 1.03 to 1.35)), whereas RF (HR 1.26 (0.82 to 1.94)) and ACPA (HR 1.25 (0.85 to 1.83)) did not reach statistical significance, though CIs were wide and a clinically meaningful association cannot be excluded. A three-way interaction between disease activity, RF and ACPA on MACE (p for interaction=0.044) was observed. RA activity associated with MACE in seronegative and double seropositive (p≤0.047), but not single RF-positive or ACPA-positive patients. Among RF-negative participants, RA activity was linked to MACE in ACPA-negative but not positive ones (p for interaction=0.003). Among ACPA-positive patients, disease activity was linked to MACE in RF-positive but not RF-negative ones (p for interaction=0.040). Conclusions Disease activity may better discriminate inflammation-driven cardiovascular risk in seronegative and double seropositive than single RF-positive or ACPA-positive patients. Risk protection through lowering disease activity may be serostatus dependent.

Objectives Female sex and anticitrullinated protein antibodies (ACPA) are associated with higher disease activity in rheumatoid arthritis (RA). Since disease-related inflammation is linked to cardiovascular risk, we explored whether sex and ACPA influenced the association between disease activity at study entry and cardiovascular risk in established RA. Methods We evaluated 4008 patients with prevalent RA from an international observational cohort enrolled between 1985 and 2012. Outcomes included major adverse cardiovascular events (MACE: cardiovascular death, myocardial infarction and stroke) and ischaemic cardiovascular events (iCVE: MACE, angina, revascularisation, transient ischaemic attack and peripheral arterial disease). Follow-up accrued from enrolment until the first event or censoring. Multivariable Cox models stratified by centre risk evaluated disease activity, sex, ACPA and their interactions. Results We documented 193 MACE and 299 iCVE. Disease activity and sex were associated with MACE (all p≤0.017) and iCVE (p≤0.005) but ACPA was only associated with MACE (p=0.043). A three-way interaction on MACE (p=0.034) but not iCVE was noted. Among ACPA-negative patients, disease activity was associated with MACE in males (HR 1.57 (95% CI 1.14 to 2.16)) but not females (p-for-interaction=0.022). Among ACPA-positive patients, neither the disease activity x sex interaction (p=0.929), nor main effect of disease activity on MACE (p=0.124) was significant, but male sex was (HR 1.61 (95% CI 1.15 to 2.27)). Among females, neither disease activity x ACPA interaction (p=0.523) nor disease activity (p=0.319) was significant for MACE, but ACPA was (HR 1.57 (95% CI 1.02 to 2.42)). Conclusions The effect of disease activity at enrolment on cardiovascular risk in prevalent RA varies across patient groups with different sex and ACPA characteristics.

Objectives The impact of body mass index (BMI) on cardiovascular risk in rheumatoid arthritis (RA) is unclear. RA characteristics may influence the association between BMI and risk. Disease activity, which predicts cardiovascular risk, is associated with obesity only among anticitrullinated antibody (ACPA)-positive patients. Biologics alter body composition and mitigate cardiovascular risk in RA. We explored the association of BMI with cardiovascular risk and whether this varied across ACPA status and biologic use. Methods We evaluated 3982 patients from an international observational cohort. Outcomes included (a) first major adverse cardiovascular event (MACE) encompassing myocardial infarction, stroke or cardiovascular death; and (b) all events comprising MACE, angina, revascularisation, transient ischaemic attack, peripheral arterial disease and heart failure. Multivariable Cox models stratified by centre risk evaluated the impact of BMI, ACPA, biologics and their two- and three-way interactions on outcomes. Results We recorded 192 MACE and 319 total events. No main effects of BMI, ACPA or biologics were observed. A three-way interaction between them on MACE (p-interaction<0.001) and all events (p-interaction=0.028) was noted. Among ACPA negative patients, BMI was inversely associated with MACE (HR 0.38 (95% CI 0.25 to 0.57)) and all events (HR 0.67 (0.49 to 0.92)) in biologic users but not non-users (p-for-interaction <0.001 and 0.012). Among ACPA-positive patients, BMI was associated with MACE (HR 1.04 [1.01–1.07]) and all events (HR 1.03 (1.00 to 1.06)) independently of biologic use. Conclusions BMI is inversely associated with cardiovascular risk only among ACPA-negative biologic users. In contrast, BMI is associated with cardiovascular risk in ACPA-positive patients independently of biologic use.

AbstractAimThis study aims to assess the association of obesity and CRP concentrations in adult patients with rheumatoid arthritis (RA), and its influence on measures of disease activity.MethodsA comprehensive search was performed using Scopus, Web of Science, MEDLINE, and EMBASE, from the time of their inception to November 2021. Observational studies that evaluated the association between CRP concentrations and obesity or overweight in patients with RA were considered eligible. Correlation coefficients were pooled using the inverse variance method, while effect sizes were pre‐calculated for adjusted standardized regression coefficients (β).ResultsA total of 10 studies, which comprised 4024 patients, were included in this systematic review. Individually, most studies report a significant association between CRP concentrations and a higher body mass index or other adiposity measures, but the statistical significance was not sustained when pooling their data together. Through the estimates provided in the present review, it is noted that CRP tends to be more elevated in female patients with RA that have a higher BMI. However, this association is not present in men.ConclusionCRP tends to be elevated in female patients with RA that have a higher BMI. Further research is required to assess this possible sex‐related difference and to aid shared decision‐making in order to avoid over‐treatment and increased burden in patients with obesity and RA.PROSPERO registration number: CRD42022314580.

Aim The objective was to examine the prevalence of atherosclerotic cardiovascular disease (ASCVD) and its risk factors among patients with RA with diabetes mellitus (RA-DM) and patients with RA without diabetes mellitus (RAwoDM), and to evaluate lipid and blood pressure (BP) goal attainment in RA-DM and RAwoDM in primary and secondary prevention. Methods The cohort was derived from the Survey of Cardiovascular Disease Risk Factors in Patients with Rheumatoid Arthritis from 53 centres/19 countries/3 continents during 2014–2019. We evaluated the prevalence of cardiovascular disease (CVD) among RA-DM and RAwoDM. The study population was divided into those with and without ASCVD, and within these groups we compared risk factors and CVD preventive treatment between RA-DM and RAwoDM. Results The study population comprised of 10 543 patients with RA, of whom 1381 (13%) had DM. ASCVD was present in 26.7% in RA-DM compared with 11.6% RAwoDM (p<0.001). The proportion of patients with a diagnosis of hypertension, hyperlipidaemia and use of lipid-lowering or antihypertensive agents was higher among RA-DM than RAwoDM (p<0.001 for all). The majority of patients with ASCVD did not reach the lipid goal of low-density lipoprotein cholesterol <1.8 mmol/L. The lipid goal attainment was statistically and clinically significantly higher in RA-DM compared with RAwoDM both for patients with and without ASCVD. The systolic BP target of <140 mm Hg was reached by the majority of patients, and there were no statistically nor clinically significant differences in attainment of BP targets between RA-DM and RAwoDM. Conclusion CVD preventive medication use and prevalence of ASCVD were higher in RA-DM than in RAwoDM, and lipid goals were also more frequently obtained in RA-DM. Lessons may be learnt from CVD prevention programmes in DM to clinically benefit patients with RA .