Abnormal Remodeling of Subcutaneous Small Arteries Is Associated With Early Diastolic Impairment in Metabolic Syndrome

Background Small artery pathophysiology is frequently invoked as a cause of obesity‐related diastolic heart failure. However, evidence to support this hypothesis is scant, particularly in humans. Methods and Results To address this, we studied human small artery structure and function in obesity and looked for correlations between vascular parameters and diastolic function. Seventeen obese patients with metabolic syndrome and 5 control participants underwent echocardiography and subcutaneous gluteal fat biopsy. Small arteries were isolated from the biopsy and pressure myography was used to study endothelial function and wall structure. In comparison with the control group, small arteries from obese participants exhibited significant endothelial dysfunction, assessed as the vasodilatory response to acetylcholine and also pathological growth of the wall. For the obese participants, multiple regression analysis revealed an association between left atrial volume and both the small artery wall thickness (β=0.718, P =0.02) and wall‐to‐lumen ratio (β=0.605, P =0.02). Furthermore, the E:E′ ratio was associated with wall‐to‐lumen ratio (β=0.596, P =0.02) and inversely associated with interleukin‐6 (β=−0.868, P =0.03). By contrast, endothelial function did not correlate with any of the echocardiographic parameters studied. Conclusions Although the small arteries studied were not cardiac in origin, our results support a role for small artery remodeling in the development of diastolic dysfunction in humans. Further direct examination of the structure and function of the myocardial resistance vasculature is now warranted, to elucidate the temporal association between metabolic risk factors, small artery injury, and diastolic impairment. </jats:sec

Preoperative Hematocrit Concentration and the Risk of Stroke in Patients Undergoing Isolated Coronary-Artery Bypass Grafting

Background. Identification and management of risk factors for stroke following isolated coronary artery bypass grafting (CABG) could potentially lower the risk of such serious morbidity. Methods. We retrieved data for 30-day stroke incidence and perioperative variables for patients undergoing isolated CABG and used multivariate logistic regression to assess the adjusted effect of preoperative hematocrit concentration on stroke incidence. Results. In 2,313 patients (mean age 65.9 years, 73.6% men), 43 (1.9%, 95% CI: 1.4-2.5) developed stroke within 30 days following CABG (74.4% within 6 days). After adjustment for a priori defined potential confounders, each 1% drop in preoperative hematocrit concentration was associated with 1.07 (95% CI: 1.01-1.13) increased odds for stroke (men, OR: 1.08, 95% CI: 1.01-1.16; women, OR: 1.02, 95% CI: 0.91-1.16). The predicted probability of stroke for descending preoperative hematocrit concentration exceeded 2% for values &lt;37% (&lt;37% for men (adjusted OR: 2.39, 95% CI: 1.08-5.26) and &lt;38% for women (adjusted OR: 2.52, 95% CI: 0.53-11.98), with a steeper probability increase noted in men). The association between lower preoperative hematocrit concentration and stroke was evident irrespective of intraoperative transfusion use. Conclusion. Screening and management of patients with low preoperative hematocrit concentration may alter postoperative stroke risk in patients undergoing isolated CABG

Relating the microscopic rules in coalescence-fragmentation models to the macroscopic cluster size distributions which emerge

Coalescence-fragmentation problems are of great interest across the physical, biological, and recently social sciences. They are typically studied from the perspective of the rate equations, at the heart of such models are the rules used for coalescence and fragmentation. Here we discuss how changes in these microscopic rules affect the macroscopic cluster-size distribution which emerges from the solution to the rate equation. More generally, our work elucidates the crucial role that the fragmentation rule can play in such dynamical grouping models. We focus on two well-known models whose fragmentation rules lie at opposite extremes setting the models within the broader context of binary coalescence-fragmentation models. Further, we provide a range of generalizations and new analytic results for a well-known model of social group formation [V. M. Eguiluz and M. G. Zimmermann, Phys. Rev. Lett. 85, 5659 (2000)]. We develop analytic perturbation treatment of the original model, and extend the mathematical to the treatment of growing and declining populations

Diabetic cardiomyopathy

Diabetic cardiomyopathy is a distinct primary disease process, independent of coronary artery disease, which leads to heart failure in diabetic patients. Epidemiological and clinical trial data have confirmed the greater incidence and prevalence of heart failure in diabetes. Novel echocardiographic and MR (magnetic resonance) techniques have enabled a more accurate means of phenotyping diabetic cardiomyopathy. Experimental models of diabetes have provided a range of novel molecular targets for this condition, but none have been substantiated in humans. Similarly, although ultrastructural pathology of the microvessels and cardiomyocytes is well described in animal models, studies in humans are small and limited to light microscopy. With regard to treatment, recent data with thiazoledinediones has generated much controversy in terms of the cardiac safety of both these and other drugs currently in use and under development. Clinical trials are urgently required to establish the efficacy of currently available agents for heart failure, as well as novel therapies in patients specifically with diabetic cardiomyopathy