Atherogenic lipoprotein phenotype and LDL size and subclasses in drug-naïve patients with early rheumatoid arthritis
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.
References (38)
- et al.
Effect of anti TNFalpha therapy on arterial diameter and wall shear stress and HDL cholesterol
Atherosclerosis
(2004) - et al.
Effects of repeated infliximab therapy on serum lipid profile in patients with refractory rheumatoid arthritis B
Clin Chim Acta
(2006) - et al.
Atherogenic lipoprotein phenotype and LDL size and subclasses in patients with peripheral arterial disease
Atherosclerosis
(2008) - et al.
Is there a simple way to identify insulin-resistant individuals at increased risk of cardiovascular disease?
Am J Cardiol
(2005) - et al.
Identification of multiple subclasses of plasma low density lipoproteins in normal humans
J Lipid Res
(1982) - et al.
Metabolic origins and clinical significance of LDL heterogeneity
J Lipid Res
(2002) - et al.
The plasma parameter log (TG/HDL-C) as an atherogenic index: correlation with lipoprotein particle size and esterification rate in apoB-lipoprotein-depleted plasma (FER(HDL))
Clin Biochem
(2001) - et al.
Apolipoprotein A-I inhibits the production of interleukin-1beta and tumor necrosis factor-alpha by blocking contact-mediated activation of monocytes by T lymphocytes
Blood
(2001) - et al.
Cardiovascular morbidity and mortality in patients with seropositive rheumatoid arthritis in Northern Sweden
J Rheumatol
(1997) - et al.
High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors
Arthritis Rheum
(2001)
Making an impact on mortality in rheumatoid arthritis: targeting cardiovascular comorbidity
Arthritis Rheum
Accelerated atherosclerosis: an extraarticular feature of rheumatoid arthritis?
Arthritis Rheum
Atherogenic lipid profile is a feature of patients with early rheumatoid arthritis: effect of early treatment–a prospective, controlled study
Arthritis Res Ther
Atherogenic lipoprotein phenotype. A proposed genetic marker for coronary heart disease risk
Circulation
Beyond LDL cholesterol reduction
Circulation
Beyond low-density lipoprotein: addressing the atherogenic lipid triad in type 2 diabetes mellitus and the metabolic syndrome
Am J Cardiovasc Drugs
Low-density-lipoproteins size and cardiovascular risk assessment
QJM–Int J Med
Elevated levels of small, low-density lipoprotein with high affinity for arterial matrix components in patients with rheumatoid arthritis: possible contribution of phospholipase A2 to this atherogenic profile
Arthritis Rheum
Cited by (0)
- 1
These two authors contributed equally to the present work.