Abstract
Background/Aims: Rheumatoid arthritis (RA) is associated with the emergence of cardiovascular disease, while chronic inflammation is considered a common denominator for their parallel progression. The Proprotein convertase subtilisin/kexin type 9 (PCSK9)/LDL-Receptor (LDLR) system is of high importance during atherogenesis, via regulating the clearance of LDL from the circulation; nevertheless the role of this molecular mechanism during RA-related atheromatosis is not known.Methods: Herein, high-resolution ultrasound measurements for arterial hypertrophy, atheromatosis and arterial stiffness as well as comprehensive biochemical profiling were performed in 85 RA patients. The circulating levels of PCSK9 and LDLR were measured and their potential associations as well as of the PCSK9/LDLR ratio with patients' characteristics and the degree of atherosclerosis were investigated.Results: Increased LDLR levels and decreased PCSK9/LDLR ratio were found in RA patients with at least 2 atheromatic plaques as compared to the ones without any plaques. In addition the levels of both PCSK9 and LDLR were positively correlated with the presence of atheromatic plaques as an age- and gender- adjusted multivariate analysis revealed.Conclusions: Our data imply that the PCSK9/LDLR system plays a significant role during RA-related atherosclerosis and may therefore be used as a screening tool for disease progression in the future.
Highlights
Rheumatoid arthritis (RA) is a systemic inflammatory disease with considerable prevalence worldwide, characterized by arthritis mainly of the peripheral joints
Mainly due to familial forms of hyperlipidemia, is a major disorder leading to increased plasma levels of atherogenic low-density lipoprotein cholesterol (LDLC) and to accelerated atherosclerosis and cardiovascular disease (CVD)
No association was observed for any of the arterial stiffness indices under study (Figure 2 and Supplementary Table 1). This is the first study to examine the correlation of PCSK9, as well as LDL receptor (LDLR), and markers of subclinical CVD, including pulse wave velocity (PWV) and AIx, in RA
Summary
Rheumatoid arthritis (RA) is a systemic inflammatory disease with considerable prevalence worldwide, characterized by arthritis mainly of the peripheral joints. RA associates with increased cardiovascular disease (CVD), which is a main cause of morbidity and mortality in these patients. While classical CVD risk factors—namely arterial hypertension, hyperlipidemia and insulin resistance—are of higher frequency and severity in these patients compared to the general population, they account for part of the accelerated CVD in RA [1,2,3,4]. Mainly due to familial forms of hyperlipidemia, is a major disorder leading to increased plasma levels of atherogenic low-density lipoprotein cholesterol (LDLC) and to accelerated atherosclerosis and CVD. To this end, LDL is a primary therapeutic target for reducing CVD risk [8, 9]
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