Background-B-type natriuretic peptide (BNP) is a predictor of short-and medium-term prognosis across the spectrum of acute coronary syndromes (ACS). The N-terminal fragment of the BNP prohormone, N-BNP, may be an even stronger prognostic marker. We assessed the relation between subacute plasma N-BNP levels and long-term, all-cause mortality in a large, contemporary cohort of patients with ACS. Methods and Results-Blood samples for N-BNP determination were obtained in the subacute phase in 204 patients with ST-elevation myocardial infarction (MI): 220 with non-ST segment elevation MI and 185 with unstable angina in the subacute phase. After a median follow-up of 51 months, 86 patients (14%) had died. Median N-BNP levels were significantly lower in long-term survivors than in patients dying (442 versus 1306 pmol/L; PϽ0.0001). The unadjusted risk ratio of patients with supramedian N-BNP levels was 3.9 (95% confidence interval, 2.4 to 6.5).In a multivariate Cox regression model, N-BNP (risk ratio 2.1 [95% confidence interval, 1.1 to 3.9]) added prognostic information above and beyond Killip class, patient age, and left ventricular ejection fraction. Adjustment for peak troponin T levels did not markedly alter the relation between N-BNP and mortality. In patients with no evidence of clinical heart failure, N-BNP remained a significant predictor of mortality after adjustment for age and ejection fraction (risk ratio, 2.4 [95% confidence interval, 1.1 to 5.4]). Conclusions-N-BNP is a powerful indicator of long-term mortality in patients with ACS and provides prognostic information above and beyond conventional risk markers.

Interleukin (IL)-6 is a proinflammatory cytokine shown to modify insulin sensitivity. Elevated plasma levels of IL-6 are observed in insulin-resistant states. Interestingly, plasma IL-6 levels also increase during exercise, with skeletal muscle being the predominant source. Thus, IL-6 has also been suggested to promote insulin-mediated glucose utilization. In this study, we determined the direct effects of IL-6 on glucose transport and signal transduction in human skeletal muscle. Skeletal muscle strips were prepared from vastus lateralis biopsies obtained from 22 healthy men. Muscle strips were incubated with or without IL-6 (120 ng/ml). We found that IL-6 increased glucose transport in human skeletal muscle 1.3-fold (P < 0.05). A 30-min pre-exposure to IL-6 did not affect insulin-stimulated glucose transport. IL-6 also increased skeletal muscle glucose incorporation into glycogen, as well as glucose oxidation (1.5-and 1.3-fold, respectively; P < 0.05). IL-6 increased phosphorylation of STAT3 (signal transducer and activator of transcription 3; P < 0.05), AMP-activated protein kinase (P ‫؍‬ 0.063), and p38 mitogen-activated protein kinase (P < 0.05) and reduced phosphorylation of S6 ribosomal protein (P < 0.05). In contrast, phosphorylation of protein kinase B/Akt, AS160 (Akt substrate of 160 kDa), and GSK3␣/␤ (glycogen synthase kinase 3␣/␤) as well as insulin receptor substrate 1-associated phosphatidylinositol 3-kinase activity remained unaltered. In conclusion, acute IL-6 exposure increases glucose metabolism in resting human skeletal muscle. Insulin-stimulated glucose transport and insulin signaling were unchanged after IL-6 exposure. Diabetes 56: [1630][1631][1632][1633][1634][1635][1636][1637] 2007 O besity is associated with an inflammatory state of adipose tissue. Pro-inflammatory cytokines, such as tumor necrosis factor-␣ and interleukin (IL)-6, have been suggested to contribute to the manifestation of whole-body insulin resistance (1). Although several lines of evidence implicate tumor necrosis factor-␣ as a contributing factor in the manifestation of peripheral insulin resistance (2), the role of IL-6 has been challenged (3,4).Adipocytes, monocytes/macrophages, fibroblasts, and vascular endothelial cells are important sources of IL-6 production, with adipocytes secreting up to 35% of total circulating levels (5,6). In type 2 diabetic and nondiabetic obese humans, adipose tissue IL-6 content correlates with impaired insulin-mediated glucose uptake (5,7). Moreover, plasma IL-6 is inversely related to insulin sensitivity in healthy subjects (8). However, in people with type 2 diabetes, the circulating IL-6 concentration is correlated with adipose tissue mass, rather than whole-body insulin sensitivity (9), suggesting that IL-6 may be a marker of obesity without any direct contribution to the development of insulin resistance. IL-6 has also been proposed to enhance glucose uptake and metabolism in skeletal muscle after exercise. During exercise, plasma IL-6 levels increase in an intensity-and duration...