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Browsing by Author "Creager, Mark A."
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Item Effect of angiotensin receptor blockade on insulin sensitivity and endothelial function in abdominally obese hypertensive patients with impaired fasting glucose(Portland Press, 2012-02) Perlstein, Todd S.; Henry, Robert R.; Mather, Kieren J.; Rickels, Michael R.; Abate, Nicola I.; Grundy, Scott M.; Mai, Yabing; Albu, Jeanine B.; Marks, Jennifer B.; Pool, James L.; Creager, Mark A.; Department of Endodontics, IU School of DentistryAngII (angiotensin II) may contribute to cardiovascular risk in obesity via adverse effects on insulin sensitivity and endothelial function. In the present study, we examined the effects of ARB (angiotensin receptor blocker) therapy (losartan, 100 mg/day) on insulin sensitivity and endothelial function in 53 subjects with stage I hypertension, abdominal obesity and impaired fasting glucose. The study design was a randomized double-blinded parallel design placebo-controlled multi-centre trial of 8 weeks duration. We used the hyperinsulinaemic-euglycaemic clamp technique to measure insulin sensitivity (expressed as the 'M/I' value) and RH-PAT (reactive hyperaemia-peripheral arterial tonometry) to measure endothelial function. Additional measures included HOMA (homoeostasis model assessment)-B, an index of pancreatic β-cell function, and markers of inflammation [e.g. CRP (C-reactive protein)] and oxidative stress (e.g. F2-isoprostanes). ARB therapy did not alter insulin sensitivity [5.2 (2.7) pre-treatment and 4.6 (1.6) post-treatment] compared with placebo therapy [6.1 (2.9) pre-treatment and 5.3 (2.7) post-treatment; P value not significant], but did improve the HOMA-B compared with placebo therapy (P=0.05). ARB therapy also did not change endothelial function [RH-PAT, 2.15 (0.7) pre-treatment and 2.11 (0.7) post-treatment] compared with placebo therapy [RH-PAT, 1.81 (0.5) pre-treatment and 1.76 (0.7) post-treatment; P value not significant]. Markers of inflammation and oxidative stress were not significantly changed by ARB therapy. In conclusion, ARB therapy did not alter peripheral insulin sensitivity or endothelial function in this cohort of patients with essential hypertension, abdominal obesity and impaired fasting glucose, but did improve pancreatic β-cell function.Item Surgery or Endovascular Therapy for Chronic Limb-Threatening Ischemia(Massachusetts Medical Society, 2022-11-07) Farber, Alik; Menard, Matthew T.; Conte, Michael S.; Kaufman, John A.; Powell, Richard J.; Choudhry, Niteesh K.; Hamza, Taye H.; Assmann, Susan F.; Creager, Mark A.; Cziraky, Mark J.; Dake, Michael D.; Jaff, Michael R.; Reid, Diane; Siami, Flora S.; Sopko, George; White, Christopher J.; van Over, Max; Strong, Michael B.; Villarreal , Maria F.; McKean, Michelle; Azene, Ezana; Azarbal, Amir; Barleben, Andrew; Chew, David K.; Clavijo, Leonardo C.; Douville, Yvan; Findeiss, Laura; Garg, Nitin; Gasper, Warren; Giles, Kristina A.; Goodney, Philip P.; Hawkins, Beau M.; Herman, Christine R.; Kalish, Jeffrey A.; Koopmann, Matthew C.; Laskowski, Igor A.; Mena-Hurtado, Carlos; Motaganahalli, Raghu; Rowe, Vincent L.; Schanzer, Andres; Schneider, Peter A.; Siracuse, Jeffrey J.; Venermo, Maarit; Rosenfield, Kenneth; BEST-CLI Investigators; Surgery, School of MedicineBACKGROUND Patients with chronic limb-threatening ischemia (CLTI) require revascularization to improve limb perfusion and thereby limit the risk of amputation. It is uncertain whether an initial strategy of endovascular therapy or surgical revascularization for CLTI is superior for improving limb outcomes. METHODS In this international, randomized trial, we enrolled 1830 patients with CLTI and infrainguinal peripheral artery disease in two parallel-cohort trials. Patients who had a single segment of great saphenous vein that could be used for surgery were assigned to cohort 1. Patients who needed an alternative bypass conduit were assigned to cohort 2. The primary outcome was a composite of a major adverse limb event — which was defined as amputation above the ankle or a major limb reintervention (a new bypass graft or graft revision, thrombectomy, or thrombolysis) — or death from any cause. RESULTS In cohort 1, after a median follow-up of 2.7 years, a primary-outcome event occurred in 302 of 709 patients (42.6%) in the surgical group and in 408 of 711 patients (57.4%) in the endovascular group (hazard ratio, 0.68; 95% confidence interval [CI], 0.59 to 0.79; P<0.001). In cohort 2, a primary-outcome event occurred in 83 of 194 patients (42.8%) in the surgical group and in 95 of 199 patients (47.7%) in the endovascular group (hazard ratio, 0.79; 95% CI, 0.58 to 1.06; P=0.12) after a median follow-up of 1.6 years. The incidence of adverse events was similar in the two groups in the two cohorts. CONCLUSIONS Among patients with CLTI who had an adequate great saphenous vein for surgical revascularization (cohort 1), the incidence of a major adverse limb event or death was significantly lower in the surgical group than in the endovascular group. Among the patients who lacked an adequate saphenous vein conduit (cohort 2), the outcomes in the two groups were similar. (Funded by the National Heart, Lung, and Blood Institute; BEST-CLI ClinicalTrials.gov number, NCT02060630.)