OBJECTIVEThe inflammatory and immune systems are altered in type 2 diabetes. Here, the aim was to profile the immune and inflammatory response in subjects with prediabetes and diabetes in a large population-representative sample. RESEARCH DESIGN AND METHODSIn total, 15,010 individuals were analyzed from the population-based Gutenberg Health Study. Glucose status was classified according to HbA 1c concentration and history of diagnosis. All samples were analyzed for white blood cells (WBCs), granulocytes, lymphocytes, monocytes, platelets, C-reactive protein (CRP), albumin, fibrinogen, and hematocrit. Interleukin-18 (IL-18), IL-1 receptor antagonist (IL-1RA), and neopterin concentrations were determined in a subcohort. RESULTSIn total, 7,584 men and 7,426 women were analyzed (range 35-74 years), with 1,425 and 1,299 having prediabetes and diabetes, respectively. Biomarkers showed varying dynamics from normoglycemic via subjects with prediabetes to subjects with diabetes: 1) gradual increase (WBCs, granulocytes, monocytes, IL-1RA, IL-18, and fibrinogen), 2) increase with subclinical disease only (lymphocytes and CRP), 3) increase from prediabetes to diabetes only (neopterin), and 4) no variation with glucose status (hematocrit). The strongest relative differences were found for CRP, IL-1RA, and fibrinogen concentrations. Several inflammatory and immune markers were associated with the glucose status independent from cardiovascular risk factors and comorbidities, varied with disease severity and the presence of disease-specific complications in the diabetes subcohort. CONCLUSIONSThe inflammatory and immune biomarker profile varies with the development and progression of type 2 diabetes. Markers of inflammation and immunity enable differentiation between the early preclinical and clinical phases of the disease, disease complications, and progression.Type 2 diabetes and its disease-associated complications represent an important and increasing public health burden worldwide (1). Obesity, which leads to metabolic and adipocyte stress, is the most important predisposing factor for type 2 diabetes (2). Obesity-associated insulin resistance, activation of the innate immune system, and chronic increased production of cytokines and adipokines are an

Background-Osteopontin, a glycoprotein that can be detected in plasma, was found to be upregulated in several animal models of cardiac failure and may thus represent a new biomarker that facilitates risk stratification in patients with heart failure. We therefore tested whether osteopontin plasma levels are elevated in patients with chronic heart failure and whether they provide independent prognostic information. Methods and Results-We analyzed osteopontin plasma levels in 420 patients with chronic heart failure due to significantly impaired left ventricular systolic function and correlated the results with disease stage and prognostic information (median follow-up of 43 months). We found that osteopontin plasma levels were significantly elevated in patients with heart failure as compared with healthy control subjects (532 versus 382 ng/mL, Pϭ0.008), irrespective of heart failure origin (ischemic versus dilated cardiomyopathy). Furthermore, osteopontin levels were higher in patients with moderate to severe heart failure than in patients with no or mild symptoms (672 ng/mL for New York Heart Association class III/IV versus 479 ng/mL for class I/II, PϽ0.0001). Estimated 4-year death rates in patients with osteopontin levels above or below a cutoff value derived from receiver operating characteristic analyses were 56.5% and 28.4%, respectively (hazard ratio 3.4, 95% confidence interval 2.2 to 5.3, PϽ0.0001). In a multivariable model that included demographic, clinical, and biochemical parameters such as N-terminal prohormone brain natriuretic peptide, osteopontin emerged as an independent predictor of death (hazard ratio 2.3, 95% confidence interval 1.4 to 3.5, PϽ0.001). Conclusion-Our findings suggest that osteopontin might be useful as a novel prognostic biomarker in patients with chronic heart failure. (Circ Heart Fail. 2008;1:43-49.)Key Words: heart failure Ⅲ prognosis Ⅲ biomarker H eart failure is a highly prevalent syndrome throughout the industrialized world and is associated with significant morbidity and mortality. In the United States, heart failure affects more than 5 million people and is responsible for nearly 50 000 deaths each year. 1 Furthermore, annual hospitalizations for heart failure have increased over the past 20 years, from 377 000 to almost 1 million. 2 Clinical Perspective p 49Thus, in patients with heart failure, an accurate diagnosis and prognostic evaluation are critical to identify those at greatest risk for cardiac decompensation and death. Traditional risk stratification by clinical parameters and assessment of left ventricular ejection fraction has proved helpful in the clinical management of heart failure patients. 3 More recently, the natriuretic peptides, in particular brain natriuretic peptide (BNP) or its fragment N-terminal prohormone BNP (NT-pro-BNP), have emerged as biomarkers that convey additional information for diagnosis and prognostication of death. 4 However, even when clinical information is combined with BNP levels, there is considerable variation in the outcome. 5 A...

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The prevalence of CTOs in patients with stable angina pectoris is high, and it influences the clinical outcome within the first year. The therapeutic strategy is influenced towards a rather conservative approach and lower rates of interventional therapy.