Attenuation of type-1 diabetes-induced cardiovascular dysfunctions by direct thrombin inhibitor in rats: a mechanistic study.

Chronic diabetes is associated with ventricular dysfunctions in the absence of hypertension and coronary artery diseases. This condition is termed as diabetic cardiomyopathy (DCM). There is no favourable treatment available for the management of diabetic cardiomyopathy. Recent studies have reported increase in circulating thrombin level among diabetic patients which is responsible for hypercoagulability of blood. Thrombin induces inflammation and fibrosis, and enhances cardiac cell growth and contractility in vitro. In this study, we have investigated the effects of argatroban; a direct thrombin inhibitor against DCM in streptozotocin-induced type-1 diabetes. Diabetes was induced by single dose of streptozotocin (STZ; 50 mg/kg, i.p.) in male Sprague-Dawley rats. After 4 weeks of diabetes induction, the animals were treated with argatroban (0.3 and 1 mg/kg, i.p. daily) for the next 4 weeks. The effect of argatroban was evaluated against diabetes-associated cardiac dysfunction, structural alteration and protein expression. STZ-induced diabetic rats exhibited significant decline in left ventricular functions. Four weeks of treatments with argatroban significantly improved ventricular functions without affecting heart rate. Further, it also protected heart against structural changes induced by diabetes as shown by reduction in fibrosis, hypertrophy and apoptosis. The improvement in cardiac functions and structural changes was associated with significant reduction in left ventricular expression of thrombin receptor also termed as protease-activated receptor-1 or PAR1, p-AKT (ser-473), p-50 NFκB and caspase-3 proteins. This study demonstrates beneficial effects of argatroban via improvement in cardiac functions and structural changes in STZ-induced DCM. These effects may be attributed through reduction in cardiac inflammation, fibrosis and apoptosis.

Underestimated prognostic value of depression in patients with obstructive coronary artery disease.

Objective: The aim of this study was to explore the different predictive values of depression among patients with different cardiac systolic function levels. Methods: Four hundred eighty-three consecutive patients with obstructive coronary artery disease (CAD) were included the depressive state was assessed using the Chinese version of the Patient Health Questionnaire 9 (PHQ-9). Depression was defined as have depressive symptoms with a PHQ-9 score ≥5. The level of cardiac systolic function was classified as left ventricular ejection fraction (LVEF) ≥50 and <50%. Results: Over a median of 26.2 months, 421 patients completed the follow-up and experienced 101 major adverse cardiovascular events (MACEs), 45 non-cardiac rehospitalizations, and 17 deaths. Predictors for clinical outcomes in patients with different cardiac systolic function levels were not the same. For participants with preserved LVEF, depression was associated with increased risks for cardiovascular events and composite outcomes. However, when focusing the whole population, predictive values of depression for MACEs, non-cardiac rehospitalizations, and composite endpoints all dropped. Receiver operating characteristic (ROC) analyses further confirmed that depression was the one of the main predictors for all clinical outcomes. With the combination of other simple features, area under curve (AUC) could reach 0.64-0.67. Conclusions: Inconsistent with the general impression, depression is found to have a closer linkage with clinical outcomes in CAD patients with preserved LVEF rather than in those with decreased LVEF. These findings appeal for more attention on CAD patients with depressive symptoms and comparatively normal LVEF. Including psychological factors may be a good attempt when constructing risk prediction models.

Serum Prealbumin: a potential predictor of Right Ventricular Dysfunction in patients receiving programmed hemodialysis

SUMMARY OBJECTIVE: Prealbumin has been a reliable marker to predict protein energy malnutrition and hypercatabolic state. In this analysis, we particularly aimed to investigate the potential association between serum prealbumin levels and right ventricular dysfunction in patients receiving programmed hemodialysis. METHODS: A total of 57 subjects were included in the analysis. The subjects were then categorized into two groups: right ventricular dysfunction (n=18) and non-right ventricular dysfunction (n=39) groups. In all patients, detailed transthoracic echocardiography (following hemodialysis) were performed along with the evaluation of complete blood count, routine biochemistry parameters, and, in particular, serum prealbumin levels. RESULTS: Mortality rate at 3 years was found to be significantly higher in the right ventricular dysfunction group (p=0.042). Serum prealbumin levels were also significantly lower in the right ventricular dysfunction group compared with the non-right ventricular dysfunction group (23.83±8.50 mg/dL versus 31.38±6.81 mg/dL, p=0.001). In the receiver operating characteristics curve analysis, a prealbumin cutoff value of <28.5 mg/dL was found to predict right ventricular dysfunction, with a sensitivity of 67% and a specificity of 62% (area under the curve: 0.744). In the correlation analysis, a moderate yet significant positive correlation was demonstrated between serum prealbumin and tricuspid annular plane systolic excursion (r=0.365, p=0.005). CONCLUSION: This study suggests that low serum prealbumin might serve as a potential predictor of right ventricular dysfunction (and its clinical consequences) in patients receiving programmed hemodialysis.