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.
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.


CONCLUSIONS
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.
van Eijk
I C
IC
Jan van Breemen Institute, Amsterdam, The Netherlands.
de Vries
M K
MK
Levels
J H M
JH
Peters
M J L
MJ
Huizer
E E
EE
Dijkmans
B A C
BA
van der Horst-Bruinsma
I E
IE
Hazenberg
B P C
BP
van de Stadt
R J
RJ
Wolbink
G J
GJ
Nurmohamed
M T
MT
D000328:Adult; D016632:Apolipoprotein A-I / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood*; D015331:Cohort Studies; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology*; D008297:Male; D011446:Prospective Studies; D018124:Receptors, Tumor Necrosis Factor; D000685:Serum Amyloid A Protein / Q000032:analysis*; D013167:Spondylitis, Ankylosing / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D000685:Serum Amyloid A Protein; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D000068800:Etanercept