Background/Purpose: Chronic inflammation yields higher risk of cardiovascular events (CVE) in patients with rheumatoid arthritis (RA). We recently reported that occult atherosclerosis burden on coronary computed tomography angiography (CCTA) predicted CVE in RA beyond cardiac risk factors or scores. We further showed that that higher cumulative inflammation independently predicted coronary plaque progression. We here explored whether statin exposure impacted plaque progression or incident CVE in RA; we further evaluated potential interactions of statin treatment with cumulative inflammation on both outcomes.

Methods: One hundred-fifty RA patients underwent a baseline CCTA and followed thereafter; 101 had a repeat scan within 83±3.6 months. Coronary artery calcium (CAC) was reported as Agatston score. Segment involvement score (SIS) reported numbers of coronary segments with plaque; segment stenosis score (SSS) reflected the cumulative plaque stenosis. Plaque composition was defined as non-calcified (NCP), mixed or calcified. Cox proportional hazards regression models with time-varying covariates evaluated predictors of CVE. Negative binomial regression was used to assess count outcomes and a generalized linear model with a Tweedie (Poisson-Gamma) error distribution for CAC change.

Results: Longer statin exposure independently inhibited NCP progression [OR=0.72 (0.57-0.90), p< 0.01]. An interaction between cumulative inflammation and duration of statin exposure on total SIS increase (p=0.017) as well as CAC increase (p=0.006) was observed independently of age, dyslipidemia, total prednisone and methotrexate dose and bDMARD duration (Figure 1A and B respectively); higher time-averaged CRP yielded significant plaque progression in patients not on statin [RR=1.48 (1.05-2.09), p=0.025] or those receiving statins< 50% of the study period [RR=1.31 (1.01-1.69), p=0.040]. In contrast, in subjects with statin exposure >50% of study time, such risk was not observed [RR=1.07 (0.93-1.22), p=0.35]. Similarly for CAC, higher time-averaged CRP yielded greater progression risk in statin unexposed patients [OR=2.33 (1.29-4.22), p=0.005]; in contrast, any statin exposure mitigated that risk [OR=1.17 (0.81-1.68), p=0.41 for exposure< 50% and OR=0.96 (0.44-2.17), p=0.98 for exposure >50%]. Sixteen RA patients incurred 19 CVEs. Higher cumulative inflammation yielded significantly higher CVE risk in patients not receiving statins vs. those who do [HR=1.34 (1.11-1.63), p=0.003 and 0.39 (0.05-2.91), p=0.36 respectively, p-interaction=0.05, Figure 1C].

Conclusion: Statin exposure moderates the effect of cumulative inflammation on coronary atherosclerosis progression and CVE risk in RA. The atheroprotective effect of statins may highlight potential local anti-inflammatory attributes at the plaque level independently of systemic inflammation.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/statin-exposure-moderates-the-effects-of-chronic-inflammation-on-coronary-atherosclerosis-progression-and-cardiovascular-events-in-rheumatoid-arthritis/