Lipoprotein Subclasses Determined by Nuclear Magnetic Resonance Spectroscopy and Coronary Atherosclerosis in Patients with Rheumatoid Arthritis

OBJECTIVE: Patients with rheumatoid arthritis (RA) are at increased risk of atherosclerosis, but routine lipid measurements differ little from those of people without RA. We examined the hypothesis that lipid subclasses determined by nuclear magnetic resonance spectroscopy (NMR) differed in patients with RA compared to controls and are associated with disease activity and the presence of coronary-artery atherosclerosis. METHODS: We measured lipoprotein subclasses by NMR in 139 patients with RA and 75 control subjects. Lipoproteins were classified as large low-density lipoprotein (LDL; diameter range 21.2–27.0 nm), small LDL (18.0–21.2 nm), large high-density lipoprotein (HDL; 8.2–13.0 nm), small HDL (7.3–8.2 nm), and total very low-density lipoprotein (VLDL; ≥ 27 nm). All subjects underwent an interview and examination; disease activity was quantified by the 28-joint Disease Activity Score (DAS28) and coronary artery calcification (CAC) was measured with electron-beam computed tomography. RESULTS: Concentrations of small HDL particles were lower in patients with RA (18.2 ± 5.4 nmol/l) than controls (20.0 ± 4.4 nmol/l; p = 0.003). In patients with RA, small HDL concentrations were inversely associated with DAS28 (rho = –0.18, p = 0.04) and C-reactive protein (rho = –0.25, p = 0.004). Concentrations of small HDL were lower in patients with coronary calcification (17.4 ± 4.8 nmol/l) than in those without (19.0 ± 5.8 nmol/l; p = 0.03). This relationship remained significant after adjustment for the Framingham risk score and DAS28 (p = 0.025). Concentrations of small LDL particles were lower in patients with RA (1390 ± 722 nmol/l) than in controls (1518 ± 654 nmol/l; p = 0.05), but did not correlate with DAS28 or CAC. CONCLUSION: Low concentrations of small HDL particles may contribute to increased coronary atherosclerosis in patients with RA.