Introduction: Social determinants of health (SDOH) can critically impact healthcare access and outcomes. However, few studies have examined geospatial relationships between SDOH and healthcare util...
Abnormal endothelial function promotes atherosclerotic vascular disease in diabetes. Experimental studies indicate that disruption of endothelial insulin signaling, through the activity of protein kinase C-β (PKCβ) and nuclear factor κB, reduces nitric oxide availability. We sought to establish whether similar mechanisms operate in the endothelium in human diabetes mellitus.We measured protein expression and insulin response in freshly isolated endothelial cells from patients with type 2 diabetes mellitus (n=40) and nondiabetic controls (n=36). Unexpectedly, we observed 1.7-fold higher basal endothelial nitric oxide synthase (eNOS) phosphorylation at serine 1177 in patients with diabetes mellitus (P=0.007) without a difference in total eNOS expression. Insulin stimulation increased eNOS phosphorylation in nondiabetic subjects but not in diabetic patients (P=0.003), consistent with endothelial insulin resistance. Nitrotyrosine levels were higher in diabetic patients, indicating endothelial oxidative stress. PKCβ expression was higher in diabetic patients and was associated with lower flow-mediated dilation (r=-0.541, P=0.02). Inhibition of PKCβ with LY379196 reduced basal eNOS phosphorylation and improved insulin-mediated eNOS activation in patients with diabetes mellitus. Endothelial nuclear factor κB activation was higher in diabetes mellitus and was reduced with PKCβ inhibition.We provide evidence for the presence of altered eNOS activation, reduced insulin action, and inflammatory activation in the endothelium of patients with diabetes mellitus. Our findings implicate PKCβ activity in endothelial insulin resistance.
Background: Hospitalization for Acute Decompensated Heart Failure (ADHF) carries a high rate of All-Cause Readmission (ACR). While isolated interventions may reduce HF-related readmission, methods ...
Background: Community health workers (CHW) are specially trained lay-people often used as liaisons between underserved communities and the health care system. Prior studies suggest that use of CHWs can improve patient outcomes and reduce costs in a variety of illnesses. The role of CHW in managing patients with heart failure however has not been studied. This pilot study assesses the effect of CHW on hospital readmissions and Emergency Department (ED) visits for heart failure patients in an urban setting. Methods: Patients admitted to the hospital with a primary diagnosis of acute decompensated heart failure between April 2016 and March 2017 were screened for a pilot program to receive weekly home visits by a CHW. Visits included standardized assessment of overall well-being, vital signs, weight management, symptom control, medication compliance, diet education, and healthcare appointment reminders. Abnormal findings were reported to a cardiology nurse practitioner who triaged complaints and made appropriate changes. For this pilot study, enrolled patients were matched using 31 variables with retrospective control patients admitted with heart failure who did not receive a CHW. Hospital admissions and ED visits were compared for the 6 months following the index admission vs. the 6 months prior. Results: Sixteen patients received weekly visits from a CHW for 6 months after hospital admission. These were matched with 16 control patients who did not receive a CHW. Patients who received a CHW experienced a 36% decrease in Emergency Department (ED) visits in the 6 months after enrollment compared with the 6 months before. Control patients, however, experienced a 40% increase in ED visits over the same period. Similarly, patients with a CHW experienced a 42% decrease in hospital readmissions while control patients experienced a 28% increase. There was no significant difference in mortality between the groups. Conclusions: This pilot study suggests that CHW may reduce healthcare utilization for patients with heart failure without negatively impacting mortality. Based on these findings, a larger study is warranted to assess the efficacy and cost-efficiency of CHWs in helping to manage patients with heart failure.
Background: Low-socioeconomic, urban, minority patients with heart failure (HF) often have unique barriers to care. Community health workers (CHWs) are specially trained laypeople who serve as liaisons between underserved communities and the health system. It is not known whether CHWs improve outcomes in low-socioeconomic, urban, minority patients with HF. Hypothesis: CHWs reduce rehospitalizations, emergency department (ED) visits, and healthcare costs for low-socioeconomic urban patients with HF. Methods: Patients admitted with acute decompensated HF were assigned to receive weekly visits by CHW after discharge. Patients were propensity score matched with controls who received usual care. HF-related rehospitalizations, ED visits, and inpatient costs were compared for 12 months following index admission versus the same period before. Results: Twenty-eight patients who received weekly visits from a CHW for 12 months after discharge were matched with 28 control patients who did not receive CHWs. Patients who received a CHW had a 75% decrease in HF-related ED visits (0.71 vs. 0.18 visits per patient, P < 0.001), an 89% decrease in HF-related readmissions (0.64 vs. 0.07 admissions per patient, P < 0.005), and a significant decrease in inpatient cost for HF-related visits. In controls receiving usual care, there was no significant change in hospitalizations, ED visits, or costs. Conclusions: In conclusion, CHWs are associated with reduced rehospitalizations, ED visits, and inpatient costs in low-socioeconomic, urban, minority patients with HF. CHWs may be a cost-effective method to reduce health care utilization and improve outcomes for this population.
Inflammation is critical for atherosclerosis development and may be a target for risk-reduction therapy. In experimental studies, activation of the inflammatory regulator, nuclear factor kappa B (NFlB), contributes to endothelial activation and reduced nitric oxide production. We treated patients with coronary artery disease with sulfasalazine, an inhibitor of NFκB, and placebo in a randomized, double-blind, crossover study design. Brachial artery flow-mediated dilation (FMD) and digital vascular function were measured at baseline and after each 6-week treatment period. Of the 53 patients enrolled in the crossover study, 32 (age 60 ± 10, 22% female) completed all the visits, with a high rate of study withdrawal due to gastrointestinal side effects. In a subset of 10 participants, we compared the effects of 4 days of sulfasalazine treatment ( n = 5) to no treatment ( n = 5) on NFκB-regulated gene expression in peripheral blood mononuclear cells. Tumor necrosis factor α-stimulated expression of CD69 and NFlB subunit p50 was significantly blunted after 4 days of sulfasalazine treatment but not after no treatment. However, FMD and digital vasodilator response did not significantly change from baseline with long-term sulfasalazine treatment. Short-term sulfasalazine inhibited NFlB activity; however, long-term treatment was poorly tolerated and did not improve endothelial function. Our findings suggest that sulfasalazine therapy is not the optimal anti-inflammatory treatment for reversing endothelial dysfunction in cardiovascular disease. Further studies are warranted to investigate the potential for NFlB inhibition to reduce cardiovascular risk.
