BackgroundPatients with unprovoked venous thromboembolism (VTE) are at an increased risk of mortality, but whether their cardiovascular risks also increase remains to be determined. We aimed to investigate the factors associated with overall mortality and major adverse cardiovascular events in patients with unprovoked VTE.Methods and ResultsWe identified 2154 patients newly diagnosed with unprovoked VTE from Taiwan's National Health Insurance Database between 2000 and 2013, excluding those with reversible etiologies, underlying cancer, or autoimmune diseases. These patients with VTE were compared with an age‐, sex‐, and cardiovascular risk‐matched cohort of 4308 controls. The risk of mortality and major adverse cardiovascular events in patients with VTE was 2.23 (CI, 1.93–2.57; P<0.0001) and 1.86 (CI, 1.65–2.09; P<0.0001) times, respectively, higher than that of the conditions in controls. These events mostly occurred during the first year after the diagnosis of unprovoked VTE. Among patients with VTE, advanced age, male sex, and comorbid diabetes mellitus indicated a higher incidence of mortality and major adverse cardiovascular events. Conversely, comorbid hyperlipidemia attenuated these risks.ConclusionsThis nation‐wide cohort study revealed that patients with unprovoked VTE, particularly older males with diabetes mellitus, had an elevated risk of both mortality and cardiovascular events. Risk of mortality and major adverse cardiovascular events were highest within the first year after diagnosis and persisted during the 10 years of follow‐up.

Transthoracic Doppler echocardiography (TTDE) is a clinically useful, noninvasive tool for studying coronary artery flow velocity and coronary flow reserve (CFR) in humans. Reduced CFR is accompanied by marked intramyocardial and pericoronary fibrosis and is used as an indication of the severity of dysfunction. This study explores, step-by-step, the real-time changes measured in the coronary flow velocity, CFR and systolic to diastolic peak velocity (S/D) ratio in the setting of an aortic banding model in mice. By using a Doppler transthoracic imaging technique that yields reproducible and reliable data, the method assesses changes in flow in the septal coronary artery (SCA), for a period of over two weeks in mice, that previously either underwent aortic banding or thoracotomy.During imaging, hyperemia in all mice was induced by isoflurane, an anesthetic that increased coronary flow velocity when compared with resting flow. All images were acquired by a single imager. Two ratios, (1) CFR, the ratio between hyperemic and baseline flow velocities, and (2) systolic (S) to diastolic (D) flow were determined, using a proprietary software and by two independent observers. Importantly, the observed changes in coronary flow preceded LV dysfunction as evidenced by normal LV mass and fractional shortening (FS).The method was benchmarked against the current gold standard of coronary assessment, histopathology. The latter technique showed clear pathologic changes in the coronary artery in the form of peri-coronary fibrosis that correlated to the flow changes as assessed by echocardiography.The study underscores the value of using a non-invasive technique to monitor coronary circulation in mouse hearts. The method minimizes redundant use of research animals and demonstrates that advanced ultrasound-based indices, such as CFR and S/D ratios, can serve as viable diagnostic tools in a variety of investigational protocols including drug studies and the study of genetically modified strains. Video LinkThe video component of this article can be found at

BackgroundMetabolic syndrome (MS) is known to be associated with hypertension, insulin resistance, and dyslipidemia, and it raises the risk for cardiovascular diseases and diabetes mellitus. Telmisartan is used in clinic as an angiotensin II receptor blocker and it is also identified as activating peroxisome proliferator-activated receptors δ (PPARδ). Activation of PPARδ produced beneficial effects on fatty acid metabolism and glucose metabolism. This study aims to investigate the effects of telmisartan on the modulation of MS in rats fed a high-fat/high-sodium diet.MethodsRats were fed with a high-fat/high-sodium diet and received injections of streptozotocin at low dose to induce MS. Then, rats with MS were treated with telmisartan. The weight, glucose tolerance, and insulin sensitivity were measured. The lipid profiles were also obtained. The weights of retroperitoneal and epididymal fat pads were determined. The role of PPARδ in telmisartan treatment was identified in rats pretreated with the specific antagonist GSK0660.ResultsThe results showed that telmisartan, but not losartan, significantly reduced plasma glucose and plasma insulin, and improved insulin resistance in rats with MS. Telmisartan also decreased blood pressure and lipids more significantly than losartan. Moreover, GSK0660 effectively reversed the effects of telmisartan in the MS rats. In the MS group, telmisartan activated PPARδ to enhance the levels of phosphorylated GLUT4 in muscle or the expression of phosphoenolpyruvate carboxykinase (PEPCK) in the liver, which was also abolished by GSK0660. Telmisartan is useful to ameliorate hypertension and insulin resistance in rats with MS. Telmisartan improves the insulin resistance through increased expression of GLUT4 and down-regulation of PEPCK via PPARδ-dependent mechanisms.ConclusionTelmisartan has been proven to ameliorate MS, particularly in the prediabetes state. Therefore, telmisartan is suitable to develop for the management of MS in clinics.