Abstract 833: Heart Failure Severity Is Indicated by Circulating T Cell Osteopontin Expression Levels
Osteopontin (OPN) is abundantly produced in activated T cells. In heart failure (HF) patients, T cells in the peripheral blood reflect a systemic inflammatory response. It has been reported that OPN was dramatically increased in the left ventricular myocardium of HF model rats, in the kidneys of renal failure rats, and that plasma OPN level was markedly higher in patients with renal dysfunction; therefore, we sought to examine the influence of HF and renal function on plasma OPN levels and the frequencies of OPN expressing CD4+ T cells (OPN-T cell levels). Blood was collected from 131 subjects: 93 heart disease; and, 38 controls. The 93 heart disease patients were classified according to the New York Heart Association (NYHA) functional classification system. Left ventricular ejection fraction (LVEF) was calculated using a modified Simpson’s Rule. The glomerular filtration rate (GFR) was estimated utilizing a formula created by the Modification of Diet in Renal Disease Study. Plasma OPN levels were measured utilizing ELISA kits. OPN-T cell levels were quantified by flow cytometry. Plasma OPN levels (ng/ml) and OPN-T cell levels (%) were higher in HF patients than in the controls (800 ± 554, 575 ± 229, p=0.016 and 27.3 ± 12.2, 16.7 ± 10.0, p <0.001, respectively); furthermore, the plasma OPN levels (ng/ml) and the OPN-T cell levels (%) increased in proportion to the severity of the NYHA functional class (plasma (T cell); NYHA I: 604 ± 253 (25.7 ± 11.7); NYHA II: 787 ± 499 (26.3 ± 13.0); NYHA III-IV: 997 ± 707 (29.9 ± 12.2), respectively). The OPN-T cell levels were significantly correlated with LVEF (r=−0.336, p=0.0048) and log plasma brain natriuretic peptide (BNP) levels (r=0.305, p=0.0025). The plasma OPN levels were significantly correlated with estimated GFR (r=−0.356, p<0.0001) and log plasma BNP levels (r=0.339, p=0.0002). Multiple logistic regression analysis revealed that BNP levels, LVEF, and OPN-T cell levels were determinants of HF independent of age, gender, heart rate, blood pressure, estimated GFR, or plasma OPN. The OPN-T cell levels were associated with markers of HF and were independent determinants of HF. Evaluating OPN-T cell levels in HF patients would be clinically useful for confirming the severity of the HF.