miological studies have reported positive associations between the risk of coronary heart disease (CHD) and plasma fibrinogen levels. Fibrinogen is the major coagulation protein in blood by mass, the precursor of fibrin, and an important determinant of blood viscosity and platelet aggregation. [38][39][40][41] Because fibrinogen levels can be reduced considerably by lifestyle interventions that also affect levels of established risk factors (such as regular exercise, smoking cessation, and moderate alcohol consumption), there is interest in the possibility that measurement (or modification) of fibrinogen may help in disease prediction or prevention. [38][39][40]42 A meta-analysis of published data from 18 such studies, involving about 4000 CHD cases, indicated a relative risk of 1.8 (95% confidence interval [CI], 1.6-2.0) per 1-g/L increase in plasma fibrinogen level. 43 However, such analyses are not able to provide detailed assessments of the nature of any independent association of fibrinogen level with CHD or with other vascular and nonvascular outcomes. [43][44][45] This meta-analysis differs from previous analyses in several ways that should increase its reliability and scientific value. First, it is large and comprehensive: the data comprise 6944 first nonfatal myocardial infarction (MI) or stroke events and 13 210 deaths (cause-*The Authors/Writing Committee, Authors/Members, and Other Members of the Fibrinogen Studies Collaboration are listed at the end of this article.

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Objective-Adiponectin is adipose-specific secretory protein and acts as anti-diabetic and anti-atherosclerotic molecule.We previously found peroxisome proliferators response element in adiponectin promoter region, suggesting that peroxisome proliferator-activated receptor (PPAR) ligands elevate adiponectin. Fibrates are known to be PPAR␣ ligands and were shown to reduce risks of diabetes and cardiovascular disease. Effect of fibrates on adiponectin has not been clarified, whereas thiazolidinediones enhance adiponectin. Thus, we explored the possibility and mechanism that fibrates enhance adiponectin in humans, mice, and cells. Methods and Results-Significant increase of serum adiponectin was observed in bezafibrate-treated subjects compared with placebo group in patients enrolled in The Bezafibrate Infarction Prevention study. Higher baseline adiponectin levels were strongly associated with reduced risk of new diabetes. Fibrates, bezafibrate and fenofibrate, significantly elevated adiponectin levels in wild-type mice and 3T3-L1 adipocytes. Such an effect was not observed in PPAR␣-deficient mice and adipocytes. Fibrates activated adiponectin promoter but failed to enhance its activity when the point mutation occurred in peroxisome proliferators response element site and the endogenous PPAR␣ was knocked down by PPAR␣-RNAi. Conclusions-Our results suggest that fibrates enhance adiponectin partly through adipose PPAR␣ and measurement of adiponectin might be a useful tool for searching subjects at high risk for diabetes. Key Words: adipocyte Ⅲ adiponectin Ⅲ fibrate Ⅲ metabolic syndrome Ⅲ peroxisome proliferator-activated receptor F ibrates have been used in clinical practice for Ͼ4 decades as a class of agents known to decrease triglyceride levels. Fibrates are also known to be peroxisome proliferator-activated receptor (PPAR)␣ ligands. Several clinical studies of fibrates have been performed in large populations. The Bezafibrate Infarction Prevention study (BIP) suggested that bezafibrate prevented cardiovascular events in the subgroup of coronary artery disease patients with high triglycerides. 1 Moreover, further subanalyses demonstrated that the administrations of bezafibrate significantly reduced new-onset diabetes 2,3 and myocardial infarction in the patients with the metabolic syndrome (MS). 4 The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study showed that fenofibrate significantly reduced nonfatal myocardial infarctions and coronary revascularizations, a secondary endpoint, among patients with type 2 diabetes. 5 These favorable clinical outcomes in fibrate studies might be explained by not only its triglyceride-lowering effect but also its various PPAR␣-mediated pleiotropic effects.Adiponectin is an adipose-specific secretory protein and acts as an anti-diabetic and anti-atherosclerotic molecule. 6 Furthermore, a number of clinical trials showed that subjects with high levels of circulating adiponectin tend to be protected against type 2 diabetes and myocardial infarction. 7,8 Thiazolidi...

BackgroundThe efficacy of disease management programs in improving the outcome of heart failure patients remains uncertain and may vary across health systems. This study explores whether a countrywide disease management program is superior to usual care in reducing adverse health outcomes and improving well-being among community-dwelling adult patients with moderate-to-severe chronic heart failure who have universal access to advanced health-care services and technologies.MethodsIn this multicenter open-label trial, 1,360 patients recruited after hospitalization for heart failure exacerbation (38%) or from the community (62%) were randomly assigned to either disease management or usual care. Disease management, delivered by multi-disciplinary teams, included coordination of care, patient education, monitoring disease symptoms and patient adherence to medication regimen, titration of drug therapy, and home tele-monitoring of body weight, blood pressure and heart rate. Patients assigned to usual care were treated by primary care practitioners and consultant cardiologists.The primary composite endpoint was the time elapsed till first hospital admission for heart failure exacerbation or death from any cause. Secondary endpoints included the number of all hospital admissions, health-related quality of life and depression during follow-up. Intention-to-treat comparisons between treatments were adjusted for baseline patient data and study center.ResultsDuring the follow-up, 388 (56.9%) patients assigned to disease management and 387 (57.1%) assigned to usual care had a primary endpoint event. The median (range) time elapsed until the primary endpoint event or end of study was 2.0 (0–5.0) years among patients assigned to disease management, and 1.8 (0–5.0) years among patients assigned to usual care (adjusted hazard ratio, 0.908; 95% confidence interval, 0.788 to 1.047). Hospital admissions were mostly (70%) unrelated to heart failure.Patients assigned to disease management had a better health-related quality of life and a lower depression score during follow-up.ConclusionsThis comprehensive disease management intervention was not superior to usual care with respect to the primary composite endpoint, but it improved health-related quality of life and depression. A disease-centered approach may not suffice to make a significant impact on hospital admissions and mortality in patients with chronic heart failure who have universal access to health care.Clinical trial registrationClinicaltrials.gov identifier: NCT00533013. Trial registration date: 9 August 2007. Initial protocol release date: 20 September 2007.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-017-0855-z) contains supplementary material, which is available to authorized users.