Usefulness of Type D Personality and Kidney Dysfunction as Predictors of Interpatient Variability in Inflammatory Activation in Chronic Heart Failure

Abstract

Tumor necrosis factor-alpha (TNF-alpha), soluble TNF-alpha receptors 1 and 2 (sTNFR1/2), and interleukin (IL)-6 are powerful predictors of mortality in chronic heart failure (CHF). Little is known, however, about the origins of proinflammatory cytokine production or the determinants of substantial interpatient variability in inflammatory activation. We prospectively examined kidney dysfunction and Type D personality (tendency to experience and inhibit emotional distress) as predictors of interpatient variability in these markers of inflammatory activation. At baseline, 125 patients with CHF were assessed for kidney dysfunction and Type D. Serum levels of proinflammatory cytokines (TNF-alpha, sTNFR1, sTNFR2, IL-6), the anti-inflammatory cytokines IL-10, and IL-1 receptor antagonist were measured at 1-year follow-up. Type D patients had higher levels of sTNFR1 (p = 0.009) and sTNFR2 (p = 0.001) and lower levels of IL-10 (p = 0.006) than patients without Type D and kidney dysfunction. Patients with kidney dysfunction also had elevated levels of sTNFR1 and sTNFR2 (p <0.0001), but their IL-10 level was not decreased. Type D personality and kidney dysfunction predicted increased sTNFR1/IL-10 and sTNFR2/IL-10 ratios (p < or =0.007); Type D also predicted an increased IL-6/IL-10 ratio (p = 0.013). Other predictors were spironolactone and older age. After adjusting for these variables, the odds for elevated ratios (highest 20%) were still increased in Type D patients (all odd ratios >3.00). In conclusion, Type D personality and kidney dysfunction independently predicted unfavorable cytokine profiles in patients with CHF and may enhance our understanding of interpatient variability in inflammatory activation in these patients.