Decreased high-density lipoprotein cholesterol level is an independent correlate of circulating tumor necrosis factor-α in a general population

Abstract

Background: Recent studies implicate a pathophysiological role of tumor necrosis factor-α (TNF-α) in atherosclerosis, thus suggesting that serum TNF-α levels may be one of the biomarkers for future cardiovascular events. However, which anthropometric, metabolic, and inflammatory variables could regulate circulating TNF-α levels in humans is not fully understood. In this study, we examined the independent determinants of serum TNF-α levels in a Japanese general population. Hypothesis: Anthropometric, metabolic , and inflammatory variables could regulate TNF-α. Methods: A total of 213 Japanese subjects underwent a complete history, physical examination, and determination of blood chemistries, including TNF-α levels. Univariate and multivariate analyses were applied for the determinants of TNF-α levels. Results: The average TNF-α levels were 13.4±0.81 pg/ml inmales and 13.9±4.5 pg/ml in females, respectively. Univariate analysis showed that TNF-α levels were associated with age (P = 0.007), body mass index (P = 0.034),waist circumference (P<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-α 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-α in the Japanese general population. Elevation of TNF-α may partly explain the increased risk of cardiovascular events in patients with low HDL-C levels. © 2009 Wiley Periodicals, Inc.