The Association Between Reduction in Inflammation and Changes in Lipoprotein Levels and HDL Cholesterol Efflux Capacity in Rheumatoid Arthritis

Abstract

BackgroundPotent anti‐inflammatory rheumatoid arthritis (RA) treatments are associated with reduced cardiovascular risk as well as increases in low‐density lipoprotein (LDL) cholesterol. This apparent paradox may be explained by favorable changes in other lipid measurements. The objective of this study was to determine the longitudinal association between changes in inflammation with advanced lipoprotein measurements and high‐density lipoprotein (HDL) cholesterol efflux capacity.Methods and ResultsWe conducted this study in a longitudinal RA cohort from a large academic center, including subjects with high‐sensitivity C‐reactive protein (hs‐CRP) reduction ≥10 mg/L at 2 time points 1 year apart. Subjects receiving statins during the study period or preceding 6 months were excluded. We compared total cholesterol, LDL cholesterol, HDL cholesterol, apolipoprotein B, and apolipoprotein A1 levels and HDL cholesterol efflux capacity at baseline and 1‐year follow‐up by using the paired t test. We also assessed the correlations between reductions in hs‐CRP with percentage change in lipid parameters. We studied 90 RA subjects (mean age 57 years, 89% female), all of whom were receiving disease‐modifying antirheumatic drugs. We observed a 7.2% increase in LDL cholesterol levels (P=0.02) and improvement in efflux capacity by 5.7% (P=0.002) between baseline and follow‐up, with a median hs‐CRP reduction of 23.5 mg/L. We observed significant correlations between reductions in hs‐CRP with increases in apolipoprotein A1 (r=0.27, P=0.01) and HDL cholesterol efflux capacity (r=0.24, P=0.02).ConclusionAmong RA subjects experiencing reductions in hs‐CRP, we observed increased LDL cholesterol levels and concomitant improvements in HDL cholesterol efflux capacity. These findings provide further insight into lipid modulation and the beneficial effect of reduction in inflammation on lipids in vivo.

Associations between disease activity, markers of HDL functionality and arterial stiffness in patients with rheumatoid arthritis

“…In this context, the finding of a significant association between apo A-I levels and cf-PWV can be a consequence of increased vascular damage in RA patients with decreased apo A-I concentration. In fact, a recent study showed that antiinflammatory treatment was associated with an increase in HDL cholesterol efflux capacity and apo A-I levels in RA patients [38].…”

Increased cardiovascular risk in rheumatoid arthritis: mechanisms and implications

“…In an observational study of rheumatoid arthritis patients with visits one year apart, reductions in high sensitivity (hs)CRP of more than 10 mg/dL were strongly associated with increases in LDL, apolipoprotein A1, HDL, and HDL cholesterol efflux capacity 71. No associations were seen with changes in hsCRP and apolipoprotein B or atherogenic indices (total cholesterol/HDL and apoliporotein B/A1).…”

Through the looking glass of rheumatoid arthritis to study inflammation and high-density lipoprotein

“…As expected, elevated levels of LDL-C are associated with increased CV risk in RA; however, low LDL-C is also associated with increased CV risk 2. Subjects with RA who experience a reduction in inflammation, considered beneficial for CV risk, have concomitant increases in LDL-C,3 suggesting the opposite effect of increased CV risk. Post hoc studies of lipids from randomised controlled trials of RA therapies have shown that increases in LDL-C occur across different classes of RA therapies 4.…”

“…While the expected relationship of higher HDL-C levels and reduced CV risk is preserved in RA, cholesterol efflux capacity is impaired in RA subjects. Furthermore, a reduction in inflammation is associated with significant improvements in cholesterol efflux capacity,3 suggesting that HDL dysfunction may explain some of the excess CV risk in RA. Studying HDL function is a focus of the study presented by O'Neill et al 6 in this journal .…”