Improvement of lipid profile is accompanied by atheroprotective alterations in high‐density lipoprotein composition upon tumor necrosis factor blockade: A prospective cohort study in ankylosing spondylitis

Abstract

Objective. Cardiovascular mortality is increased in ankylosing spondylitis (AS), and inflammation plays an important role. Inflammation deteriorates the lipid profile and alters high-density lipoprotein cholesterol (HDL-c) composition, reflected by increased concentrations of serum amyloid A (SAA) within the particle. Anti-tumor necrosis factor (anti-TNF) treatment may improve these parameters. We therefore undertook the present study to investigate the effects of etanercept on lipid profile and HDL composition in AS.Methods. In 92 AS patients, lipid levels and their association with the inflammation markers C-reactive protein (CRP), erythrocyte sedimentation rate, and SAA were evaluated serially during 3 months of etanercept treatment. HDL composition and its relationship to inflammation markers was determined in a subgroup of patients, using surface-enhanced laser desorption/ ionization time-of-flight analysis.Results. With anti-TNF treatment, levels of all parameters of inflammation decreased significantly, whereas total cholesterol, HDL-c, and apolipoprotein A-I (Apo A-I) levels increased significantly. This resulted in a better total cholesterol:HDL-c ratio (from 3.9 to 3.7) (although the difference was not statistically significant), and an improved Apo B:Apo A-I ratio, which decreased by 7.5% over time (P ‫؍‬ 0.008). In general, increases in levels of all lipid parameters were associated with reductions in inflammatory activity. In addition, SAA was present at high levels within HDL particles from AS patients with increased CRP levels and disappeared during treatment, in parallel with declining plasma levels of SAA.Conclusion. Our results show for the first time that during anti-TNF therapy for AS, along with favorable changes in the lipid profile, HDL composition is actually altered whereby SAA disappears from the HDL particle, increasing its atheroprotective ability. These findings demonstrate the importance of understanding the role of functional characteristics of HDL-c in cardiovascular diseases related to chronic inflammatory conditions.

Targeting inflammation in the prevention of cardiovascular disease in patients with inflammatory arthritis

“…76 In patients with AS, 77,78 although significant increase in HDL was reported, the TC to HDL ratio remained unchanged. 77 Meanwhile, apo B to apo A ratio decreased significantly. 77 Three studies analyzed patients with mixed inflammatory arthritis also showed inconsistent or even contradictory results.…”

“…77 Meanwhile, apo B to apo A ratio decreased significantly. 77 Three studies analyzed patients with mixed inflammatory arthritis also showed inconsistent or even contradictory results. [79][80][81] Differences in the study population, follow-up duration, and anti-TNF agents (included IFX, ETN, and ADA) may be responsible for these discrepancies.…”

“…72 Data from PsA and AS are limited and controversial. [73][74][75][76][77][78][79][80][81] In a randomized controlled trial (RCT) including 127 patients with PsA assigned to onercept (a recombinant human soluble TNF receptor) 50 mg, 100 mg, and placebo groups for 12 weeks, no significant change was found in TC and HDL after treatment with onercept. 73 Apo A and apo B increased significantly in the onercept 100 mg group, whereas TG increased in both onercept groups.…”

Editorial: Lipid Changes With Different Antiinflammatory Regimens in Rheumatoid Arthritis: Developing a Pragmatic Approach to Complex Data

“…It is not yet established that all modes of antiinflammatory action mediate similar magnitudes of change in lipid metabolism for a given change in systemic inflammation levels. Moreover, the picture becomes even more complex in RA, where there is evidence of 1) compositional changes in high-density lipoprotein (HDL) particles with inflammation (5) and 2) reversal of some of these changes with certain antiinflammatory therapies (6). Thus, interpretation of results that include data only on concentrations of, and not composition of, lipid particles is challenging, and elucidation of likely net effects on CVD risk in the context of an "inflammation-lipid paradox" is hazardous.…”

TNF-α in the cardiovascular system: from physiology to therapy

“…[194][195][196] Similar beneficial effects of etanercept treatment on the lipid profile were observed in patients with ankylosing spondylitis. 197 The detailed interplay of the proinflammatory activity of TNF-α with insulin resistance and lipid metabolism in the context of atherosclerosis and cardiometabolic disorders thus warrants further investigation.…”