THU0139 STATINS MODERATE THE EFFECT OF INFLAMMATION ON CORONARY PLAQUE PROGRESSION AND CARDIOVASCULAR DISEASE RISK IN RHEUMATOID ARTHRITIS
Authors: G. Karpouzas, S. Ormseth, E. Hernandez, M. Budoff
Journal: Annals of the Rheumatic Diseases (2020)

Background: Cumulative inflammation correlates with coronary plaque increase and cardiovascular disease (CVD) events in rheumatoid arthritis (RA). Coronary plaque progression predicts CVD risk beyond baseline burden in general patients. Statins inhibit plaque progression and are effective for CVD prevention in general patients. Nevertheless, their impact on coronary plaque trajectory and CVD risk in RA are less clear. Objectives: To explore if statin treatment may reduce CVD event risk, inhibit new plaque formation or promote the regression or protective calcification of prevalent atherosclerotic lesions in RA. We also evaluated whether statins moderate the effects of inflammation (CRP) on CVD risk and on coronary plaque progression. Methods: One hundred-fifty patients underwent computed tomography angiography for coronary atherosclerosis evaluation (total, non-calcified, mixed/calcified plaque); 101 had repeat assessments within 6.9±0.3 years to evaluate plaque progression. CVD events were prospectively recorded, including cardiac death, myocardial infarction, unstable angina, revascularization, stroke, claudication, and heart failure hospitalization. Framingham-D’Agostino score assessed clinical risk. Plaque burden was measured as segment stenosis score (cumulative stenosis). Robust cox proportional hazards regression models evaluated the effects of time-varying statin use, log-transformed time-varying CRP (mg/dL) and their interaction on CVD risk controlling for Framingham-D’Agostino score, plaque burden and time-varying bDMARD use. Per-segment robust logistic regression assessed the effect of statin duration (years), log-transformed time-averaged CRP, and their interaction on likelihood of plaque formation in segments without plaque, and plaque regression or calcification in segments with non-calcified lesions. Models accounted for clustering of coronary segments within patients and controlled for Framingham-D’Agostino score, total prednisone dose, bDMARD duration, and time between scans. Results: Sixteen patients incurred 19 CVD events. There was no main effect of current statin use on CVD risk (adjusted HR 1.10, 95% CI 0.33-3.67). However, there was an interaction between current statin use and time-varying CRP (p-interaction=0.030); higher time-varying CRP predicted greater CVD risk in patients not receiving statins (adjusted HR 2.78, 95% CI 1.01-7.65), but not current statin users (Figure 1A). Likewise, current statin use associated with lower CVD risk when patients had higher time-varying CRP (&gt;0.5 mg/dL) but not when CRP was lower (&lt;0.5 mg/dL, Figure 1B). Statin duration had no main effect on new plaque formation in segments without plaque at baseline (adjusted OR 1.13, 95% CI 0.95-1.05); however, statin use moderated the effect of time-averaged CRP on new plaque formation (p-interaction=0.030, Figure 2A). Time-averaged CRP associated with a higher likelihood of new plaque in patients receiving statins less than one year (adjusted OR 1.75, 95% CI 1.38-2.20) but not those treated for longer (adjusted OR 1.26, 95% CI 0.78-2.02). In segments with non-calcified plaque, longer statin duration predicted protective calcification (adjusted OR 1.28, 95% CI 1.07-1.53, Figure 2B). Conclusion: In RA, statins moderated the effect of CRP on CVD event risk and new plaque formation in coronary segments without plaque. Longer statin duration was also associated with an increased likelihood of protective calcification of non-calcified plaque. Disclosure of Interests: George Karpouzas Grant/research support from: Pfizer, Consultant of: Sanofi-Genzyme-Regeneron, Janssen, Speakers bureau: Sanofi-Genzyme-Regeneron, BMS, Sarah Ormseth: None declared, Elizabeth Hernandez: None declared, Matthew Budoff: None declared