Association of tumor necrosis factor-alpha with early target organ damage in newly diagnosed patients with essential hypertension

Abstract

Objectives: To investigate the relationship between inflammatory parameters [high-sensitivity C-reactive protein (hs-CRP), serum tumor necrosis factor-alpha (TNF-alpha) and urinary TNF-alpha] with subclinical cardiac and renal markers of early target organ damage (TOD) in essential hypertension.

Methods: Preclinical TOD [left ventricular hypertrophy (LVH) and microalbuminuria (MAB)] was evaluated in 40 newly diagnosed never-treated patients with essential hypertension. Serum and urinary TNF-alpha and hs-CRP were measured as inflammatory parameters. Twenty-one BMI-matched and sex-matched normotensive, healthy individuals were included as control group.

Results: The serum levels of hs-CRP and the urinary TNF-alpha excretion were higher in hypertensive patients with MAB, whereas patients with LVH presented higher levels of urinary TNF-alpha. The only difference between hypertensive patients without TOD and healthy controls was the higher urinary excretion of TNF-alpha. Partial correlation analysis showed a significant association between urinary albumin excretion (UAE) and systolic blood pressure (r=0.62, P<0.0001), hs-CRP (r=0.64, P<0.001), urinary TNF-alpha (r=0.55, P=0.001) and Cornell product (r=0.33, P<0.05), whereas the Cornell product was related to UAE (r=0.34, P<0.05), urinary TNF-alpha (r=0.45, P<0.01), and hs-CRP (r=0.32, P<0.05). Multiple regression analysis demonstrated that the parameters independently correlated with UAE were mean blood pressure, Cornell product, hs-CRP and urinary TNF-alpha (adjusted R2=0.77, P<0.001), whereas UAE, urinary TNF-alpha and hs-CRP were independently correlated with Cornell product (adjusted R2=0.66, P<0.001). Multiple logistic regression analysis with TOD as the dependent variable showed that hs-CRP [2.24 (1.17-4.28), P<0.05] and urinary TNF-alpha [1.21 (1.02-1.44), P<0.05] were independently related to TOD.

Conclusion: Urinary TNF-alpha is independently correlated with UAE and Cornell product in essential hypertension, suggesting that inflammation may participate in the development of TOD. In addition, urinary excretion of TNF-alpha might be an early marker of preclinical TOD in hypertensive patients. Finally, these results may be a basis to study the effect of the blockade of TNF-alpha activity on the development and progression of TOD in essential hypertension.