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C-C chemokines are essential factors in the recruitment and activation of leukocytes from the circulation into inflamed tissue and may play a role in ischemia-induced myocardial injury and left ventricular remodeling after acute myocardial infarction (AMI). We investigated the kinetics of three major C-C chemokines, macrophage chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1 alpha (MIP-1 alpha), and regulated on activation normally T cell expressed and secreted (RANTES), in the sera of AMI patients and correlated the findings with the severity of the disease. Serum levels of C-C chemokines were determined in 35 AMI patients by ELISA assays serially during the first week of hospitalization and 1 month after hospital admission. Patients (n = 18) with uncomplicated AMI (Killip class I) were classified as group A, patients (n = 17) with AMI complicated by heart failure manifestations (Killip classes II and III) were classified as group B, and 15 age-matched and sex-matched volunteers were used as healthy controls. A sustained increase in serum C-C chemokines was observed in both AMI groups during the 7-day hospitalization period. Peaks of these inflammatory factors were significantly higher in group B than in group A (MCP-1, 295 +/- 11 vs. 203 +/- 9 pg/ml, p < 0.01; MIP-1 alpha, 30 +/- 1 vs. 24 +/- 2 pg/ml, p < 0.05; RANTES, 32 +/- 2 vs. 16 +/- 1 ng/ml, p < 0.01) and healthy controls (MCP-1, 125 +/- 7 pg/ml, p < 0.001; MIP-1 alpha, 14 +/- 1 pg/ml, p < 0.001; RANTES, 12 +/- 1 ng/ml, p < 0.001). In group B, significant correlations were found between the peak of MCP-1 and the peak of C-reactive protein levels (r = 0.55, p < 0.02) as well as wedge pressure (r = 0.40, p < 0.05). In the same group, the peak of MIP-1 alpha levels was also significantly correlated with the peak of serum creatine kinase-myocardial band (MB) (r = 0.51, p < 0.04) and left ventricular ejection fraction (LVEF) (r = -0.45, p < 0.05). After 1 month, AMI patients (n = 14) with severe left ventricular dysfunction (LVEF < or = 35%) exhibited significantly higher levels of C-C chemokines (all p < 0.05) than the other AMI patients (n = 21) (LVEF > 35%). A significant correlation was found between MIP-1 alpha levels and left ventricular end-diastolic diameter (r = 0.47, p < 0.03) in this patient population. In conclusion, we have detected a significant elevation of major C-C chemokines during the course of AMI, with the highest levels in patients with AMI complicated by heart failure manifestations and severe left ventricular dysfunction. The elevation of these chemotactic inflammatory factors may actively contribute to the pathophysiology of the disease and the subsequent left ventricular remodeling.

AimsClinicians lack a generally accepted means for health status assessment in chronic heart failure (CHF). We investigated the correlation between health status and inflammation burden as well as its long-term prognostic value in CHF outpatients. Methods and ResultsKansas City Cardiomyopathy Questionnaires (KCCQ) were completed by 137 CHF outpatients (aged 64 + 12 years, mean ejection fraction 27 + 7%). Inflammatory markers [interleukin (IL)-6, IL-10, TNF-a, soluble Fas, Fas ligand, ICAM-1, VCAM-1], plasma B-type natriuretic peptide (BNP), 6 min walk test (6MWT), Zung self-rating depression scale, and Beck Depression Inventory were also assessed. Patients were followed for major cardiovascular events (death or hospitalization for disease progression) for up to 250 days. Patients with worse KCCQ-summary (KCCQ-s , 50) score had lower 6MWT (P , 0.05), and higher BNP (P , 0.05) and pro-inflammatory markers (P , 0.05) than those with KCCQ-s 50. Worse health status was also associated with shorter event-free survival (115 + 12 days for KCCQ-s , 50 vs. 214 + 15 days for KCCQ-s 50, P ¼ 0.0179). Separating patients according KCCQ-functional score (KCCQ-f, cut-off 50) showed similar results. In multivariate Cox regression analysis, only LVEF (HR ¼ 0.637, 95% CI 0.450-0.900, P ¼ 0.011) and KCCQ-f (HR ¼ 0.035, 95% CI 0.002-0.824, P ¼ 0.037) were independent predictors of event-free survival at 250 days. ConclusionKCCQ-s reflects neurohormonal and inflammatory burden in CHF. Among studied questionnaires, only KCCQ-f is an independent predictor of long-term event-free survival in CHF.--