Common atherosclerosis genetic risk factors and subclinical atherosclerosis in rheumatoid arthritis: the relevance of disease duration

Bartłomiej Kisiel,Małgorzata Tłustochowicz,Witold Tłustochowicz,Marek Saracyn,Rafał Płoski,Konrad Szymański,Aleksandra Juszkiewicz,Krzysztof Kłos,Katarzyna Kisiel,Anna Raczkiewicz,Robert Kruszewski,Artur Maliborski,Artur Bachta,Stanisław Niemczyk,Krzysztof Duda

doi:10.1007/s00296-018-4186-y

Abstract

Rheumatoid arthritis (RA) is a common systemic autoimmune disease characterized by increased cardiovascular morbidity. Several previous studies assessed associations between common atherosclerotic genetic risk factors and subclinical atherosclerosis (SA) in RA patients, yet most of them gave negative results. We undertook a cross-sectional study to evaluate the association between previously reported SNPs and subclinical atherosclerosis in a cohort of Polish RA patients. 29 SNPs associated with atherosclerosis in general population were genotyped in 289 RA patients: 116 patients with SA (increased carotid intima–media thickness and/or presence of carotid plaque) and 173 patients without SA. To assess the cumulative effect of SNPs we calculated 3 weighted genetic risk scores: GRSIMT, GRSCP and GRSCAD, comprising intima–media thickness-associated SNPs, carotid plaque-associated SNPs and coronary artery disease-associated SNPs, respectively. None of the SNPs showed a significant association with SA. However, we found an association between SA and GRSIMT. Interestingly, this association was limited to patients with short disease duration (P = 0.00004 vs. P > 0.5, for comparison of GRSIMT among patients within the 1st quartile of disease duration vs. others, respectively). Patients within the 1st quartile of disease duration were more frequently disease modifying anti-rheumatic drugs (DMARDs)-naïve and less frequently treated with biologics. Our study suggests that in patients with early RA subclinical atherosclerosis may be driven by similar genetic factors as in general population, while in long-lasting disease, the role common genetic risk factors may decrease. Possibly, this effect may be due to the influence of DMARDs.

Highlights

Rheumatoid arthritis (RA) is a common systemic autoimmune disease characterized by chronic joint inflammation and extra-articular manifestations
Hamrefors et al found that a myocardial infarction Genetic risk scores (GRSs) was associated with markers of carotid atherosclerosis (i.e., CIMT and plaque) [19], and Salfati et al showed that a GRS for clinical Coronary artery disease (CAD) was associated with advanced coronary atherosclerosis [20]
A large-scale study performed in three Finnish cohorts showed that none of the 24 genomewide significant coronary artery disease risk variants was associated with subclinical atherosclerosis and a GRS combining those variants did not improve the prediction of subclinical atherosclerosis [21]

Summary

Introduction

Rheumatoid arthritis (RA) is a common systemic autoimmune disease characterized by chronic joint inflammation and extra-articular manifestations. It is well known that cardiovascular disease (CVD) morbidity and mortality rates are increased in RA patients as compared to general population. Extended author information available on the last page of the article [1]. It has been shown that the excess of cardiovascular (CV) risk in RA persists after adjustment for classical CV risk factors [2], RA is considered as an independent CV risk factor. A systematic review and meta-analysis by Lorenz et al showed that CIMT predicts future vascular events in healthy individuals [3]. Tyrrell et al found in their meta-analysis that CIMT is increased in RA [4]

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