Elsevier

Atherosclerosis

Volume 207, Issue 2, December 2009, Pages 502-506
Atherosclerosis

Atherogenic lipoprotein phenotype and LDL size and subclasses in drug-naïve patients with early rheumatoid arthritis

https://doi.org/10.1016/j.atherosclerosis.2009.07.015Get rights and content

Abstract

Objective

: Subjects with rheumatoid arthritis (RA) have increased cardiovascular risk and may show atherogenic forms of dyslipidemia. The present study investigated whether patients with early RA, beyond alterations in plasma lipids, also show lower LDL size and altered LDL subclass distribution.

Design and Methods

We identified 25 subjects with RA (47 ± 8 years, body mass index (BMI) 25 ± 4 kg/m2) by the American College of Rheumatology diagnostic criteria, with a disease durations <1 year and no prior treatment against it. In patients and 22 healthy subjects matched for age and BMI (controls) we measured plasma lipids and LDL size and subclasses by gradient gel electrophoresis.

Results

As compared to controls RA patients had higher plasma triglycerides (1.8 ± 0.5 vs. 1.0 ± 0.5 mmol/L, p < 0.0001) and lower HDL-cholesterol concentrations (1.2 ± 0.2 vs. 1.4 ± 0.2 mmol/L, p = 0.0027), while total- and LDL-cholesterol concentrations were similar. LDL particle size was lower in RA patients than controls (264 ± 7 vs. 281 ± 9 Å, p < 0.0001), due to less LDL-I (31 ± 6 vs. 38 ± 7%, p = 0.0004) and LDL-IIA (14 ± 3 vs. 16 ± 3%, p = 0.0182), and more LDL-IIIB (7 ± 1 vs. 5 ± 1%), -IVA (11 ± 2 vs. 8 ± 2%) and -IVB particles (12 ± 2 vs. 9 ± 2%,) (p < 0.0001 for all). Further, about 1/3 of patients showed the complete “atherogenic-lipoprotein-phenotype” (e.g. the concomitant presence of high triglycerides, low HDL-cholesterol and elevated small, dense LDL).

Conclusions

Beyond plasma lipids, increased levels of small, dense LDL seems to be common in drug-naïve patients with early RA. Yet, whether these findings affect the atherogenic process and the clinical endpoints in these subjects remains to be determined by future prospective studies.

Introduction

Patients with rheumatoid arthritis (RA) have increased cardiovascular morbidity and mortality as compared to the general population [1], [2], [3]. Among the traditional cardiovascular risk factors, the lipid profile in RA has often been described as “pro-atherogenic” based on decreased HDL-cholesterol and increased LDL:HDLcholesterol ratio [4], [5]. In recent years it has become evident that the lipid triad or “atherogenic lipoprotein phenotype” (ALP), characterized by decreased HDL-cholesterol, moderately raised triglycerides and increased levels of small, dense LDL, is linked to increased cardiovascular risk, beyond LDL-cholesterol levels [6], [7], [8]. In fact, a number of evidences suggest that the quality, and not only the quantity, of LDL exerts a direct influence on cardiovascular risk [9] and the predominance of small dense LDL has been accepted as an emerging cardiovascular risk factor by the National Cholesterol Education Program Adult Treatment Panel III [10].

It has been reported in a previous study that patients with long-term RA may show lower LDL size due to increased levels of small, dense LDL particles [11]. Yet, this has not been further investigated in patients with early RA, without prior treatment for it, which limits the utility of the information we have on atherogenic dyslipidemia in RA. In fact, although drug treatment in RA is in general beneficial on plasma lipids, it seems that long-term anti-tumor necrosis factor-alpha therapies may induce some pro-atherogenic changes in lipid profile [12], [13], [14]. Therefore, we included in the present study a group of patients with early RA, without treatment, as well as a control group of healthy subjects, matched for age and body mass index (BMI) used as controls, in order to investigate (1) whether patients with early RA have lower LDL size; (2) whether their LDL subclass distribution is altered (i.e. increased levels of small, dense LDL); (3) the prevalence of ALP.

Section snippets

Subjects and study protocol

We included in the present study a group of drug-naïve patients with early RA who consecutively underwent a clinical examination at the Department of Rheumatology, Ankara Numune Education and Research Hospital, Ankara, Turkey between January and June 2008. Inclusion criteria were the fulfillment of the American College of Rheumatology diagnostic criteria for RA [15] and a disease durations <1 year. Disease activity was assessed by measuring the 28 joint indices score (DAS-28) [16]. According to

Results

All patients with early RA were rheumatoid factor positive (rheumatoid factor: 279 ± 116 IU/mL) and displayed high disease activity scores (DAS-28: 6.2 ± 1.6) (data not shown). According to the inclusion criteria, patients with early RA and controls were matched for age and BMI (Table 1). Expectedly, patients had higher CRP concentrations than controls (median 1.80 vs. 0.35 mg/L, p < 0.0001), triglyceride levels were also higher (1.8 ± 0.5 vs. 1.0 ± 0.5 mmol/L, p < 0.0001) and HDL-cholesterol concentrations

Discussion

It has been shown that subjects with early RA may have an atherogenic lipid profile, with increased LDL-cholesterol and LDL:HDLcholesterol ratio [5]. In the present study we have extended such preliminary observation investigating in this category of patients LDL size and all seven LDL subclasses, as well as the full ALP. In fact, LDL are very heterogeneous particles and comprise multiple distinct subclasses that differ in size, density, physicochemical composition, metabolic behaviour and

Acknowledgements

We wish to thank Cornelia Zwimpfer for laboratory skills in performing gradient gel electrophoresis. M. Rizzo and G.B. Rini were recipients of the “ex-60%” grant from University of Palermo, Italy.

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    These two authors contributed equally to the present work.

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