Decreased high-density lipoprotein cholesterol level is an independent correlate of circulating tumor necrosis factor-alpha in a general population.
BACKGROUND
Recent studies implicate a pathophysiological role of tumor necrosis factor-alpha (TNF-alpha) in atherosclerosis, thus suggesting that serum TNF-alpha levels may be one of the biomarkers for future cardiovascular events. However, which anthropometric, metabolic, and inflammatory variables could regulate circulating TNF-alpha levels in humans is not fully understood. In this study, we examined the independent determinants of serum TNF-alpha levels in a Japanese general population.


OBJECTIVE
Anthropometric, metabolic , and inflammatory variables could regulate TNF-alpha.


METHODS
A total of 213 Japanese subjects underwent a complete history, physical examination, and determination of blood chemistries, including TNF-alpha levels. Univariate and multivariate analyses were applied for the determinants of TNF-alpha levels.


RESULTS
The average TNF-alpha levels were 13.4 +/- 0.81 pg/ml in males and 13.9 +/- 4.5 pg/ml in females, respectively. Univariate analysis showed that TNF-alpha levels were associated with age (P = 0.007), body mass index (P = 0.034), waist circumference (<0.001), high-density lipoprotein cholesterol (HDL-C; inversely, P < 0.001), triglycerides (P < 0.001), creatinine (P < 0.001), uric acids (P < 0.001), insulin (P = 0.008), homeostasis model assessment of insulin resistance (HOMA-IR; P = 0.015), high sensitivity C-reactive protein (hs-CRP; P < 0.001), and fibrinogen (P = 0.009). By the use of multiple stepwise regression analyses, HDL-C (inversely, P < 0.001) and hs-CRP (P < 0.001) remained significant and were independently related to TNF-alpha levels (R2 = 0.153).


CONCLUSIONS
The present study is the first demonstration that besides hs-CRP, a decreased HDL-C level is an independent determinant of circulating TNF-alpha in the Japanese general population. Elevation of TNF-alpha may partly explain the increased risk of cardiovascular events in patients with low HDL-C levels.
Yamagishi
Sho-ichi
S
Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan. shoichi@med.kurume-u.ac.jp
Adachi
Hisashi
H
Matsui
Takanori
T
Nakamura
Kazuo
K
Enomoto
Mika
M
Fukami
Ako
A
Otsuka
Maki
M
Kumagae
Shun-ichi
S
Nanjo
Yasuki
Y
Imaizumi
Tsutomu
T
D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology* / Q000276:immunology; D008076:Cholesterol, HDL / Q000097:blood*; D003430:Cross-Sectional Studies; D015536:Down-Regulation; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D007564:Japan; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011159:Population Surveillance; D018570:Risk Assessment; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*; D015854:Up-Regulation
D015415:Biomarkers; D008076:Cholesterol, HDL; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein