Abstract
Dyslipidemia has been implicated in various musculoskeletal diseases, including rheumatoid arthritis (RA). Evidence is emerging that there might be a pathogenic interaction among inflammation, dyslipidemia, and adipokines. We prospectively investigated the association of cumulative lipid levels with radiographic progression of RA. RA patients (n = 242) underwent plasma cholesterol assessment at four visits. Disease activity parameters and X-rays of the hands and feet were also serially monitored in these patients. The cumulative inflammatory burden and lipid levels were estimated by time-integrated values. Serum leptin and adiponectin concentrations were determined by ELISA. When patients were divided into three groups according to time-integrated lipid levels, as expected, patients with LDL cholesterol and/or triglyceride levels in the third tertile had persistently higher ESR and CRP levels. In parallel, a more rapid radiographic progression over two years was observed in patients with higher LDL cholesterol and/or triglyceride levels. In multivariate analysis, time-integrated LDL cholesterol was independently associated with radiographic progression. Particularly, the risk of radiographic progression was 5.6-fold in a subgroup with both LDL cholesterol and triglyceride levels in the third tertile. Moreover, LDL cholesterol synergistically increased the adjusted probability of radiographic progression in patients with high serum leptin levels but not in those without. These results demonstrate that LDL cholesterolemia is a novel serum marker that can be used to predict radiographic progression of RA, which seems to be related to circulatory leptin levels. We suggest that personalized and more aggressive anti-rheumatic therapy is required for dyslipidemic subgroups in RA patients.
Highlights
Dyslipidemia has been associated with a variety of types of inflammatory arthritis such as gout and familial hypercholesterolemia with migratory polyarthritis [1]
As reported previously [24,25,26], when we compared plasma lipid levels between rheumatoid arthritis (RA) patients and age- and gendermatched healthy controls, low density lipoprotein (LDL) cholesterol levels and triglyceride levels were increased, but high density lipoprotein (HDL) cholesterol levels were decreased in RA patients (Figure S1)
Dyslipidemia and RA Disease Activity Since lipid levels are influenced by disease activity [12], we studied whether lipid levels correlated with RA activity in our cohort
Summary
Dyslipidemia has been associated with a variety of types of inflammatory arthritis such as gout and familial hypercholesterolemia with migratory polyarthritis [1]. Earlier studies have demonstrated that obese people are at an increased risk of developing rheumatoid arthritis (RA) and psoriatic arthritis [2,3,4]. Oxidized low density lipoprotein (LDL) is increased in inflamed synovial fluid [7], and both intracellular and extracellular oxidized LDL are detected in the rheumatoid synovium [8]. We have shown that there is a common genetic predisposition for the synchronicity of RA and dyslipidemia [9,10]. Together, these observations suggest that dyslipidemia is linked to the pathogenesis of RA
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