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.

Hypothesis: 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.