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

2010 ◽  
Vol 37 (8) ◽  
pp. 1633-1638 ◽  
Author(s):  
CECILIA P. CHUNG ◽  
ANNETTE OESER ◽  
PAOLO RAGGI ◽  
TUULIKKI SOKKA ◽  
THEODORE PINCUS ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Nuclear Magnetic Resonance ◽  
Coronary Artery ◽  
Disease Activity ◽  
Coronary Atherosclerosis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Resonance Spectroscopy ◽  
Low Density ◽  
Lipoprotein Subclasses

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.

scholarly journals OP0104 DIFFERENCES IN LOW-DENSITY LIPOPROTEIN (LDL) PARTICLE COMPOSITION AND OXIDATION MAY UNDERLIE THE PARADOXICAL ASSOCIATION OF LOW LDL WITH HIGHER CORONARY ATHEROSCLEROSIS BURDEN IN RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 58.1-58
Author(s):  
G. Karpouzas ◽  
S. Ormseth ◽  
E. Hernandez ◽  
M. Budoff
Keyword(s):  
Rheumatoid Arthritis ◽  
Coronary Atherosclerosis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Relative Content ◽  
Low Density ◽  
Cvd Risk ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Background:The association between cholesterol and cardiovascular disease (CVD) risk is attenuated in Rheumatoid arthritis (RA). In fact, RA patients in the lowest low-density lipoprotein (LDL) group (<70mg/dl) may experience unexpectedly high CVD risk.Objectives:We here explored whether patients with LDL<70mg/dl (Group 1) had higher coronary atherosclerosis burden compared to other LDL groups (Group 2: 70≤LDL≤130 and Group 3: LDL>130), as a reason for this risk. We further evaluated whether low LDL in group 1 associated with differences in inflammation, LDL particle composition or oxidation.Methods:One hundred fifty RA patients without symptoms or history of CVD underwent coronary atherosclerosis evaluation with computed tomography angiography. Coronary artery calcium (CAC), number of segments with plaque (segment involvement score), stenotic severity (segment stenosis score), and extensive (>4 segments with plaque) or obstructive disease (>50% stenosis) were assessed. Lipoprotein classes and subclasses were directly measured. Oxidized LDL (oxLDL) was measured with monoclonal antibody E06. Chemiluminescence Elisa quantified IgG and IgM antibodies to oxLDL (anti-oxLDL) and apoB100 immune complexes (IC). Proinflammatory cytokines were measured with Erenna Immunoassay. Robust linear and logistic regression models- adjusted for Framingham D’Agostino score, obesity, disease activity, bDMARD and statin treatment- evaluated associations between LDL groups and plaque outcomes. Similar models evaluated adjusted differences in LDL subclasses, oxLDL, anti-oxLDL, anti-ApoB100 IC, and cytokines across LDL groups.Results:Group 1 patients had higher coronary plaque burden (Figure 1A) and 2.8 times greater risk of extensive or obstructive disease (adjusted OR 2.82 [95% CI 1.12-7.17], P = 0.031) compared to LDL>70 groups. Among statin naïve patients, those with LDL<70 also had higher oxLDL (log-transformed adjusted mean 2.55 [95% CI 2.34-2.77] versus 2.27 [95% CI 2.19-2.36], P = 0.018 for LDL>70). Notably, Group 1 patients also had higher anti-oxLDL IgG and anti-ApoB100 IgG IC levels compared to other groups (Figure 1B). LDL subclass relative content in the LDL particle differed across groups (Figure 1C). Lp(a) was higher in LDL particles in Group 1 (adjusted mean 16.04% [95% CI 11.75-20.33], versus 10.48% [95% CI 8.20-12.75] in Group 2, P = 0.026 and 7.41% [95% CI 0.77-14.04] in Group 3, P = 0.033). Notably, Lp(a) content strongly associated with oxLDL overall (r = 0.83, P < 0.0001). This association was stronger for Group 1 compared to others (P < 0.005, Figure 1D). No differences in RA activity, CRP, TNF-α, IL-17A, or IL-17F were seen across groups. However, Group 1 had higher IL-6 (log-transformed adjusted mean 1.98 [95% CI 1.64- 2.32] versus 1.57 [95% CI 1.45-1.70], P = 0.028 in Group 2 and 1.32 [95% CI 0.84-1.80], P = 0.031 in Group 3). IL-6 associated with both IgG anti-oxLDL (P = 0.015) and anti-apoB100 IC (P = 0.016). Log-transformed IL-6 further associated with higher log-transformed CAC (adjusted B 0.41 [95% CI 0.01-0.81], P = 0.049).Conclusion:RA patients with LDL<70 mg/dl had higher coronary atherosclerosis burden. Low circulating LDL in that group may reflect higher oxidation; this was mostly linked to the larger Lp(a) relative content of LDL and its significantly higher oxidation potential in that group. OxLDL immune recognition was linked to higher IgG anti-oxLDL Ab and anti-ApoB100 IC levels in the LDL<70 group, which further associated with higher IL-6 elaboration and atherosclerosis burden.Disclosure of Interests:George Karpouzas Speakers bureau: Sanofi/ Genzyme/ Regeneron, Consultant of: Sanofi/ Genzyme/ Regeneron, Grant/research support from: Pfizer, Sarah Ormseth: None declared, Elizabeth Hernandez: None declared, Matthew Budoff Consultant of: Pfizer

Sign in / Sign up

Export Citation Format

Share Document