Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Hypercholesterolemia: HELP
Articles from Rhode Island
Based on 33 articles published since 2010
||||

These are the 33 published articles about Hypercholesterolemia that originated from Rhode Island during 2010-2020.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Guideline Cardiac risk factors: new cholesterol and blood pressure management guidelines. 2014

Anthony, David / George, Paul / Eaton, Charles B. ·Memorial Hospital of Rhode Island, 111 Brewster St., Pawtucket, RI 02903, USA. david_anthony@brown.edu · Warren Alpert Medical School of Brown University, 222 Richmond Street, Providence, RI 02903, USA. Paul-George@Brown.edu · Warren Alpert Medical School of Brown University, 222 Richmond Street, Providence, RI 02903, USA. Charles_Eaton@Brown.edu ·FP Essent · Pubmed #24936717.

ABSTRACT: The 2013 American College of Cardiology/American Heart Association cholesterol guidelines depart from low-density lipoprotein (LDL) treatment targets and recommend treating four specific patient groups with statins. Statins are the only cholesterol-lowering drugs with randomized trial evidence of benefit for preventing atherosclerotic cardiovascular disease (ASCVD). The groups are patients with clinical ASCVD; patients ages 40 to 75 years with diabetes and LDL of 70 to 189 mg/dL but no clinical ASCVD; patients 21 years or older with LDL levels of 190 mg/dL or higher; and patients ages 40 to 75 years with LDL of 70 to 189 mg/dL without clinical ASCVD or diabetes but with 10-year ASCVD risk of 7.5% or higher. Ten-year ASCVD risk may be calculated using the Pooled Cohort Equations. The Eighth Joint National Committee (JNC 8) guidelines for blood pressure management recommend a blood pressure goal of less than 140/90 mm Hg for all adults except those 60 years or older. For the latter group, the JNC 8 recommends a systolic blood pressure goal of less than 150 mm Hg. In another notable change from prior guidelines, the JNC 8 recommends relaxing the systolic blood pressure goal for patients with diabetes and chronic kidney disease to less than 140 mm Hg from less than 130 mm Hg.

2 Review Stroke: subacute/inpatient management of acute ischemic stroke. 2014

Silver, Brian / Wulf Silver, Rachel. ·Warren Alpert Medical School of Brown University, 110 Lockwood Street #324, Providence, RI 02903, brian_silver@brown.edu. · Sturdy Memorial Hospital, 211 Park St, Attleboro, MA 02703. ·FP Essent · Pubmed #24818556.

ABSTRACT: A stroke unit is a designated hospital area in which patients with stroke are evaluated and treated. Such units have been proven to reduce mortality and disability more than hospitalization in a general medical ward. Diagnostic testing for a patient with stroke includes complete blood count, urine toxicology screening, brain imaging, imaging of neck and cerebral arteries, and cardiac evaluation (including prolonged outpatient rhythm monitoring). Inpatient management should include dysphagia screening and prophylaxis for venous thromboembolism. Lower extremity compression stockings do not prevent venous thromboembolism in stroke patients, but intermittent pneumatic compression devices are of proven value. Patients who do not receive thrombolytic therapy should receive aspirin. A statin should be started if the patient's low-density lipoprotein cholesterol level is 100 mg/dL or higher. Delirium occurs commonly in patients with stroke and more commonly with increased age and stroke severity. Interventions, such as routine oxygen supplementation, prophylactic antibiotics, empiric antipyretic management, and early mobilization, are under investigation. Patients with arterial dissection and patent foramen ovale typically have good prognoses and can be treated medically.

3 Review Stroke: transient ischemic attack. 2014

Silver, Brian / Wulf Silver, Rachel. ·Warren Alpert Medical School of Brown University, 110 Lockwood Street #324, Providence, RI 02903, brian_silver@brown.edu. · Sturdy Memorial Hospital, 211 Park St, Attleboro, MA 02703. ·FP Essent · Pubmed #24818554.

ABSTRACT: The definitions of transient ischemic attack (TIA) and stroke have evolved with advancements in medical imaging. Approximately one-third of events that last less than 24 hours are associated with new infarctions on modern imaging sequences. These events, previously called apoplexy, are now called strokes. Approximately 10% of patients with TIA will have a stroke within 90 days without urgent evaluation and management; 50% of these events will occur within the first 48 hours. The ABCD(2) and ABCD(3)-I scores are validated measures that can help predict which patients are at greatest risk. With urgent evaluation and management, the rate of stroke after TIA can be reduced by up to 80%. Measures that reduce the rate of recurrence include rapid diagnosis and management of atrial fibrillation, identification and repair of carotid artery stenosis, early antithrombotic management, and use of statins for appropriate patients. Dual antiplatelet management with aspirin and clopidogrel may be useful in the first 30 days after TIA, but these drugs should not be used in combination after that time. Adverse events, including major bleeding and mortality, occur more frequently than with monotherapy with no reduction in ischemic events. Patients also should be encouraged to adopt lifestyle changes, such as regular exercise and weight loss.

4 Article Calpain inhibition decreases myocardial fibrosis in chronically ischemic hypercholesterolemic swine. 2020

Potz, Brittany A / Sabe, Ashraf A / Sabe, Sharif A / Lawandy, Isabella J / Abid, M Ruhul / Clements, Richard T / Sellke, Frank W. ·Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI. · Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI. Electronic address: fsellke@lifespan.org. ·J Thorac Cardiovasc Surg · Pubmed #32359903.

ABSTRACT: OBJECTIVES: Calpain activation during ischemia is known to play critical roles in myocardial remodeling. We hypothesize that calpain inhibition (CI) may serve to reverse and/or prevent fibrosis in chronically ischemic myocardium. METHODS: Yorkshire swine were fed a high-cholesterol diet for 4 weeks followed by placement of an ameroid constrictor on the left circumflex artery to induce myocardial ischemia. 3 weeks later, animals received either: no drug; high-cholesterol control group (CON; n = 8); low-dose CI (0.12 mg/kg; LCI, n = 9); or high-dose CI (0.25 mg/kg; HCI, n = 8). The high-cholesterol diet and CI were continued for 5 weeks, after which myocardial tissue was harvested. Tissue samples were analyzed by western blot for changes in protein content. RESULTS: In the setting of hypercholesterolemia and chronic myocardial ischemia, CI decreased the expression of collagen in ischemic and nonischemic myocardial tissue. This reduced collagen content was associated with a corresponding decrease in Jak/STAT/MCP-1 signaling pathway, suggesting a role for Jak 2 signaling in calpain activity. CI also decreases the expression of focal adhesion proteins (vinculin) and stabilizes the expression of cytoskeletal and structural proteins (N-cadherin, α-fodrin, desmin, vimentin, filamin, troponin-I). CI had no significant effect on metabolic and hemodynamic parameters. CONCLUSIONS: Calpain inhibition may be a beneficial medical therapy to decrease collagen formation in patients with coronary artery disease and associated comorbidities.

5 Article Enhancing the value of PCSK9 monoclonal antibodies by identifying patients most likely to benefit. A consensus statement from the National Lipid Association. 2019

Robinson, Jennifer G / Jayanna, Manju Bengularu / Brown, Alan S / Aspry, Karen / Orringer, Carl / Gill, Edward A / Goldberg, Anne / Jones, Laney K / Maki, Kevin / Dixon, Dave L / Saseen, Joseph J / Soffer, Daniel. ·Division of Cardiology, Departments of Epidemiology and Internal Medicine, University of Iowa, Iowa City, IA, USA. Electronic address: Jennifer-g-robinson@uiowa.edu. · Division of Cardiology, Departments of Epidemiology and Internal Medicine, University of Iowa, Iowa City, IA, USA. · Division of Cardiology, Advocate Heart Institute at Advocate Lutheran General Hospital, Park Ridge, IL, USA. · Brown University, Alpert Medical School, Lifespan Cardiovascular Institute, RI, USA. · University of Miami Miller School of Medicine, Miami, FL, USA. · Division of Cardiology, University of Colorado School of Medicine, Aurora, CO, USA. · Professor of Medicine, Washington University School of Medicine, St. Louis, MO, USA. · Genomic Medicine Institute, Danville, PA, USA. · Midwest Biomedical Research, Center for Metabolic and Cardiovascular Health, Wheaton, IL, USA. · Department of Pharmacotherapy & Outcomes Science, Virginia Commonwealth University, Richmond, VA, USA. · University of Colorado Anschutz Medical Campus, Aurora, CO, USA. · Department of Internal Medicine, University of Pennsylvania Health System, Philadelphia, PA, USA. ·J Clin Lipidol · Pubmed #31281070.

ABSTRACT: Acquisition costs and cost-effectiveness have limited access and recommendations to use proprotein convertase subtilisin/kexin type 9 (PCSK9)-inhibiting monoclonal antibodies (mAbs). Recently, prices were reduced by 60% for alirocumab and evolocumab. This statement systematically reviewed subgroup analyses from statin and PCSK9 mAb trials to identify higher risk groups for which PCSK9 mAbs at the new price could be considered a reasonable (Patients with heterozygous familial hypercholesterolemia or severe hypercholesterolemia with untreated LDL-C levels ≥220 mg/dL also should experience reasonable or high value from PCSK9 mAbs when LDL-C is ≥100 mg/dL for primary prevention and ≥70 mg/dL for secondary prevention.

6 Article Cholesteroloma of the breast: A 10 year retrospective review of 79 cases with radiology correlation. 2019

Nam, Gahie / Singer, Tisha M / Lourenco, Ana P / Wang, Yihong. ·Department of Pathology and Laboratory Medicine, Rhode Island Hospital and Lifespan Medical Center, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA. · Department of Diagnostic Imaging, Rhode Island Hospital and Lifespan Medical Center, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA. ·Breast J · Pubmed #31280486.

ABSTRACT: A cholesteroloma or cholesterol granuloma of the breast is an uncommon lesion representing an inflammatory/reactive process with unclear etiology. In this study, we reviewed our 10-year experience with cholesteroloma of the breast with clinical, radiologic, and histopathological correlation. Seventy-nine cases were selected. The mean patient age was 57.7 (range 25-90) years old. Patients had hypercholesterolemia with mean blood cholesterol level of 201 mg/dL (P < 0.001). The mean body mass index (BMI) was 26.7 kg/m

7 Article Complementary and alternative medicine use among persons with multiple chronic conditions: results from the 2012 National Health Interview Survey. 2018

Mbizo, Justice / Okafor, Anthony / Sutton, Melanie A / Leyva, Bryan / Stone, Leauna M / Olaku, Oluwadamilola. ·Department of Public Health, University of West Florida, 11000 University Parkway, Bldg. 38/Room 127, Pensacola, FL, 32514, USA. jmbizo@uwf.edu. · Department of Mathematics and Statistics, University of West Florida, Pensacola, FL, USA. · Department of Public Health, University of West Florida, 11000 University Parkway, Bldg. 38/Room 127, Pensacola, FL, 32514, USA. · Warren Alpert Medical School, Brown University, Providence, RI, USA. · Office of Cancer Complementary and Alternative Medicine, National Cancer Institute, Bethesda, MD, USA. · Kelly Government Solutions, Bethesda, MD, USA. ·BMC Complement Altern Med · Pubmed #30340577.

ABSTRACT: BACKGROUND: Although a quarter of Americans are estimated to have multiple chronic conditions, information on the impact of chronic disease dyads and triads on use of complementary and alternative medicine (CAM) is scarce. The purpose of this study is to: 1) estimate the prevalence and odds of CAM use among participants with hypercholesterolemia, hypertension, diabetes, and obesity; and 2) examine the effects of chronic condition dyads and triads on the use of CAM modalities, specifically manipulative and body-based methods, biological treatments, mind-body interventions, energy therapies, and alternative medical systems. METHODS: Data were obtained from the 2012 National Health Interview Survey and the Adult Alternative Medicine supplement. Statistical analyses were restricted to persons with self-reported hypercholesterolemia, hypertension, diabetes, or obesity (n = 15,463). RESULTS: Approximately 37.2% of the participants had just one of the four chronic conditions, while 62.4% self-reported multiple comorbidities. CAM use among participants was as follows (p < 0.001): hypercholesterolemia (31.5%), hypertension (28.3%), diabetes (25.0%), and obesity (10.8%). All combinations of disease dyads and triads were consistently and significantly associated with the use of mind-body interventions (2-4%, p < 0.001). Two sets of three dyads were associated with use of manipulative methods (23-27%, p < 0.05) and energy therapies (0.2-0.3%, p < 0.05). Use of biological treatments (0.04%, p < 0.05) and alternative systems (3%, p < 0.05) were each significant for one dyad. One triad was significant for use of manipulative methods (27%, p < 0.001). CONCLUSIONS: These findings point to future directions for research and have practical implications for family practitioners treating multimorbid patients.

8 Article Statin use and risk of skin cancer. 2018

Lin, Brian M / Li, Wen-Qing / Cho, Eunyoung / Curhan, Gary C / Qureshi, Abrar A. ·Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts. Electronic address: brian_lin@meei.harvard.edu. · Department of Dermatology, Warren Alpert Medical School, Providence, Rhode Island; Department of Epidemiology, School of Public Health, Brown University, Providence, Rhode Island. · Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Dermatology, Warren Alpert Medical School, Providence, Rhode Island; Department of Epidemiology, School of Public Health, Brown University, Providence, Rhode Island. · Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. ·J Am Acad Dermatol · Pubmed #29208416.

ABSTRACT: BACKGROUND: Statins are among the most commonly used medications in the United States, and statin use is associated with increased risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). However, previous studies are limited by lack of adjustment for important confounders. OBJECTIVE: Examine the relation between statins and skin cancer risk in the Nurses' Health Study and Health Professionals Follow-up Study. METHODS: Cox proportional hazards regression was used to evaluate associations. RESULTS: During follow-up (2000-2010), we documented 10,201 BCC, 1393 SCC, and 333 melanoma cases. History of high cholesterol level was not associated with risk of BCC (pooled multivariable-adjusted hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.00-1.09), SCC (HR, 0.95; 95% CI, 0.85-1.06), or melanoma (HR, 0.87; 95% CI, 0.64-1.19). Statin use was not associated with risk of BCC (HR, 1.04; 95% CI, 0.99-1.09]), SCC (HR, 1.08; 95% CI, 0.94-1.24), or melanoma (HR, 1.04; 95% CI, 0.78-1.38). There was a trend toward higher BCC risk with longer duration of statin use in men (P trend = .003) but not in women (P trend = .86). LIMITATIONS: Lack of treatment data. CONCLUSION: History of high cholesterol level was not associated with skin cancer risk. Longer duration of statin use was associated with a trend toward higher BCC risk in men.

9 Article Clinical efficacy and safety of achieving very low LDL-cholesterol concentrations with the PCSK9 inhibitor evolocumab: a prespecified secondary analysis of the FOURIER trial. 2017

Giugliano, Robert P / Pedersen, Terje R / Park, Jeong-Gun / De Ferrari, Gaetano M / Gaciong, Zbigniew A / Ceska, Richard / Toth, Kalman / Gouni-Berthold, Ioanna / Lopez-Miranda, Jose / Schiele, François / Mach, François / Ott, Brian R / Kanevsky, Estella / Pineda, Armando Lira / Somaratne, Ransi / Wasserman, Scott M / Keech, Anthony C / Sever, Peter S / Sabatine, Marc S / Anonymous7260917. ·TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, USA. Electronic address: rgiugliano@bwh.harvard.edu. · Oslo University Hospital, Ullevål and Medical Faculty, University of Oslo, Oslo, Norway. · TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, USA. · Department of Molecular Medicine, University of Pavia and Cardiac Intensive Care Unit and Laboratories for Experimental Cardiology, IRCCS Fondazione Policlinico San Matteo, Pavia, Italy. · Department of Internal Medicine, Hypertension and Vascular Diseases, The Medical University of Warsaw, Warsaw, Poland. · Center of Preventive Cardiology, 3rd Department Internal Medicine, University General Hospital and 1st Medical Faculty, Prague, Czech Republic. · 1st Department of Medicine, University of Pécs, Pécs, Hungary. · Polyclinic for Endocrinology, Diabetes, and Preventive Medicine, University of Cologne, Cologne, Germany. · Lipids and Atherosclerosis Unit, Maimonides Biomedical Research Institute of Cordoba, Reina Sofia University Hospital, University of Cordoba, CIBEROBN, Cordoba, Spain. · University Hospital Center Besançon, Besançon, France. · Hopital Cantonal, Hopitaux Universitaires de Geneva, Geneva, Switzerland. · Rhode Island Hospital, Department of Neurology, Alpert Medical School of Brown University, Providence, RI, USA. · Amgen, Thousand Oaks, CA, USA. · Sydney Medical School, National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia. · International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London, London, UK. ·Lancet · Pubmed #28859947.

ABSTRACT: BACKGROUND: LDL cholesterol is a well established risk factor for atherosclerotic cardiovascular disease. How much one should or safely can lower this risk factor remains debated. We aimed to explore the relationship between progressively lower LDL-cholesterol concentrations achieved at 4 weeks and clinical efficacy and safety in the FOURIER trial of evolocumab, a monoclonal antibody to proprotein convertase subtilisin-kexin type 9 (PCSK9). METHODS: In this prespecified secondary analysis of 25 982 patients from the randomised FOURIER trial, the relationship between achieved LDL-cholesterol concentration at 4 weeks and subsequent cardiovascular outcomes (primary endpoint was the composite of cardiovascular death, myocardial infarction, stroke, coronary revascularisation, or unstable angina; key secondary endpoint was the composite of cardiovascular death, myocardial infarction, or stroke) and ten prespecified safety events of interest was examined over a median of 2·2 years of follow-up. We used multivariable modelling to adjust for baseline factors associated with achieved LDL cholesterol. This trial is registered with ClinicalTrials.gov, number NCT01764633. FINDINGS: Between Feb 8, 2013, and June 5, 2015, 27 564 patients were randomly assigned a treatment in the FOURIER study. 1025 (4%) patients did not have an LDL cholesterol measured at 4 weeks and 557 (2%) had already had a primary endpoint event or one of the ten prespecified safety events before the week-4 visit. From the remaining 25 982 patients (94% of those randomly assigned) 13 013 were assigned evolocumab and 12 969 were assigned placebo. 2669 (10%) of 25 982 patients achieved LDL-cholesterol concentrations of less than 0·5 mmol/L, 8003 (31%) patients achieved concentrations between 0·5 and less than 1·3 mmol/L, 3444 (13%) patients achieved concentrations between 1·3 and less than 1·8 mmol/L, 7471 (29%) patients achieved concentrations between 1·8 to less than 2·6 mmol/L, and 4395 (17%) patients achieved concentrations of 2·6 mmol/L or higher. There was a highly significant monotonic relationship between low LDL-cholesterol concentrations and lower risk of the primary and secondary efficacy composite endpoints extending to the bottom first percentile (LDL-cholesterol concentrations of less than 0·2 mmol/L; p=0·0012 for the primary endpoint, p=0·0001 for the secondary endpoint). Conversely, no significant association was observed between achieved LDL cholesterol and safety outcomes, either for all serious adverse events or any of the other nine prespecified safety events. INTERPRETATION: There was a monotonic relationship between achieved LDL cholesterol and major cardiovascular outcomes down to LDL-cholesterol concentrations of less than 0·2 mmol/L. Conversely, there were no safety concerns with very low LDL-cholesterol concentrations over a median of 2·2 years. These data support further LDL-cholesterol lowering in patients with cardiovascular disease to well below current recommendations. FUNDING: Amgen.

10 Article Statin Use and the Risk of Type 2 Diabetes Mellitus in Children and Adolescents. 2017

Joyce, Nina R / Zachariah, Justin P / Eaton, Charles B / Trivedi, Amal N / Wellenius, Gregory A. ·Department of Epidemiology, Brown University School of Public Health, Providence, RI; Department of Health Care Policy, Harvard Medical School, Boston, Mass. Electronic address: joyce@hcp.med.harvard.edu. · Lillie Frank Abercrombie Section of Pediatric Cardiology, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, Tex. · Department of Epidemiology, Brown University School of Public Health, Providence, RI. · Department of Health Services, Policy and Practice, Brown University, Providence, RI. ·Acad Pediatr · Pubmed #28232259.

ABSTRACT: OBJECTIVE: There is increasing evidence of an association between statin use and type 2 diabetes mellitus (T2DM) in adults, yet this relationship has never been studied in children or adolescents and may have important implications for assessing risks and benefits of treatment in this population. We estimated the association between statin use and the risk of T2DM in children with and without a dyslipidemia diagnosis. METHODS: Propensity scores were used to match new users of statins with a minimum 50 percent of days covered (PDC) in the first year of use to up to 10 nonusers. Analyses were stratified by a dyslipidemia diagnosis based on recent evidence suggesting a potentially protective effect of familial hypercholesterolemia on T2DM. In sensitivity analyses, we varied this period of exclusion and PDC. Cox proportional hazard models compared the hazard of the outcome between the exposed and unexposed patients. RESULTS: A total of 21,243,305 patients met the eligibility criteria, 2085 (0.01%) of whom met the exposure definition and 1046 (50%) of whom had a dyslipidemia diagnosis. Statin use was associated with an increased risk of T2DM in children without dyslipidemia (hazard ratio 1.96, 95% confidence interval 1.20-3.22), but not in children with dyslipidemia (hazard ratio 1.11, 95% confidence interval 0.65-1.90). The results were consistent across variations in the exclusion period and PDC. CONCLUSIONS: Statin use was associated with an increased likelihood of developing T2DM in children without dyslipidemia. Physicians and patients need to weigh the possible risk of T2DM against the long-term benefits of statin therapy at a young age.

11 Article Glycogen Synthase Kinase 3β Inhibition Improves Myocardial Angiogenesis and Perfusion in a Swine Model of Metabolic Syndrome. 2016

Potz, Brittany A / Sabe, Ashraf A / Elmadhun, Nassrene Y / Clements, Richard T / Robich, Michael P / Sodha, Neel R / Sellke, Frank W. ·Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI. · Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI fsellke@lifespan.org. ·J Am Heart Assoc · Pubmed #27405812.

ABSTRACT: BACKGROUND: Inhibition of glycogen synthase kinase 3β (GSK-3β) has been reported to be cardioprotective during stressful conditions. METHODS AND RESULTS: Pigs were fed a high-fat diet for 4 weeks to develop metabolic syndrome, then underwent placement of an ameroid constrictor to their left circumflex artery to induce chronic myocardial ischemia. Two weeks later, animals received either: no drug (high cholesterol control group [HCC]) or a GSK-3β inhibitor (GSK-3β inhibited group [GSK-3βI]), which were continued for 5 weeks, followed by myocardial tissue harvest. Coronary blood flow and vessel density were significantly increased in the GSK-3βI group compared to the HCC group. Expression levels of the following proteins were greater in the GSK-3βI group compared to the HCC group: vascular endothelial growth factor receptor 1 , vascular endothelial cadherin, γ-catenin, β-catenin, protein kinase B, phosphorylated forkhead box O1, and superoxide dismutase 2. CONCLUSIONS: In the setting of metabolic syndrome, inhibition of GSK-3β increases blood flow and vessel density in chronically ischemic myocardium. We identified several angiogenic, cell survival, and differentiation pathways that include β-catenin signaling and AKT/FOXO1, through which GSK-3β appears to improve vessel density and blood flow. These results may provide a potential mechanism for medical therapy of patients suffering from coronary artery disease and metabolic syndrome.

12 Article Alcohol modulates autophagy and apoptosis in pig liver tissue. 2016

Potz, Brittany A / Lawandy, Isabella J / Clements, Richard T / Sellke, Frank W. ·Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, Rhode Island. · Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, Rhode Island. Electronic address: fsellke@lifespan.org. ·J Surg Res · Pubmed #27338546.

ABSTRACT: BACKGROUND: Autophagy serves as a cellular protective mechanism against alcohol-induced tissue injury but excessive autophagy can also be detrimental leading to apoptosis. Our laboratory has previously shown that moderate alcohol consumption alters expression of proteins in the insulin signaling pathway and worsens glucose metabolism in the liver in a swine model of metabolic syndrome. We examined the effect of alcohol consumption on apoptosis and autophagy signaling in the liver in our clinically relevant animal model of chronic hypercholesterolemia. MATERIAL AND METHODS: Twenty-six Yorkshire swine were fed a high-fat diet for 4 wks and were then split into three groups: hypercholesterolemic diet alone (HCC, n = 9), hypercholesterolemic diet with vodka (hypercholesterolemic vodka [HCV], n = 9), and hypercholesterolemic diet with wine (hypercholesterolemic wine [HCW], n = 8) for 7 wks. Animals underwent euthanasia, and liver tissue samples were harvested for analysis. Liver tissue was analyzed via Western blot analysis. Protein density data were normalized to GAPDH and is reported as fold-change values ± standard error of the mean compared to the high-cholesterol diet control group. A Kruskal-Wallis test with a Dunn's multiple comparison test was used to compare the means among groups. RESULTS: The HCV group showed significant increases in several proapoptotic proteins (including caspase 3, caspase 8, caspase 9, and cleaved caspase 9) compared with the HCC group. There was a decrease in the proapoptotic protein (BAD) and an increase in anti-apoptotic signal (B-cell lymphoma-2) in the HCW group compared with HCC control. There were increases in pro-survival proteins (AKT, p-AKT, mTOR, p-mTOR) in the HCW and the HCV group compared with control (HCC). There were decreases in autophagy protein LCB-3 in the HCW and HCV compared with the control. CONCLUSIONS: We found that moderate alcohol consumption altered protein expression related to apoptosis and autophagy signaling in pig liver in the setting of hypercholesterolemia. Interestingly, vodka may induce proapoptotic pathways in liver tissue, whereas wine may induce anti-apoptotic signaling. These results provide a mechanism by which vodka may contribute to alcoholic liver disease and supports the notion that wine, containing resveratrol, may prevent cellular apoptosis in liver tissue in the setting of hypercholesterolemia.

13 Article Calpain inhibition improves collateral-dependent perfusion in a hypercholesterolemic swine model of chronic myocardial ischemia. 2016

Sabe, Ashraf A / Potz, Brittany A / Elmadhun, Nassrene Y / Liu, Yuhong / Feng, Jun / Abid, M Ruhul / Abbott, Jinnette D / Senger, Donald R / Sellke, Frank W. ·Division of Cardiothoracic Surgery, Cardiovascular Research Center, Warren Alpert School of Medicine, Brown University, Providence, RI. · Division of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Harvard University, Boston, Mass. · Division of Cardiothoracic Surgery, Cardiovascular Research Center, Warren Alpert School of Medicine, Brown University, Providence, RI. Electronic address: fsellke@lifespan.org. ·J Thorac Cardiovasc Surg · Pubmed #26478238.

ABSTRACT: PURPOSE: Calpain overexpression is implicated in aberrant angiogenesis. We hypothesized that calpain inhibition (MDL28170) would improve collateral perfusion in a swine model with hypercholesterolemia and chronic myocardial ischemia. METHODS: Yorkshire swine fed a high cholesterol diet for 4 weeks underwent surgical placement of an ameroid constrictor to their left circumflex coronary artery. Three weeks later, animals received no drug, high cholesterol control group (n = 8); low-dose calpain inhibition (0.12 mg/kg; n = 9); or high-dose calpain inhibition (0.25 mg/kg; n = 8). The heart was harvested after 5 weeks. RESULTS: Myocardial perfusion in ischemic myocardium significantly improved with high-dose calpain inhibition at rest and with demand pacing (P = .016 and .011). Endothelium-dependent microvessel relaxation was significantly improved with low-dose calpain inhibition (P = .001). There was a significant increase in capillary density, with low-dose calpain inhibition and high-dose calpain inhibition (P = .01 and .01), and arteriolar density with low-dose calpain inhibition (P = .001). Calpain inhibition significantly increased several proangiogenic proteins, including vascular endothelial growth factor (P = .02), vascular endothelial growth factor receptor 1 (P = .003), vascular endothelial growth factor receptor 2 (P = .003), and talin, a microvascular structural protein (P = .0002). There was a slight increase in proteins implicated in endothelial-dependent (nitric oxide mediated) relaxation, including extracellular signal-regulated kinase, phosphorylated extracellular signal-regulated kinase, and inducible nitric oxide synthase with calpain inhibition. CONCLUSIONS: In the setting of hypercholesterolemia, calpain inhibition improved perfusion, with a trend toward increased collateralization on angiography and increased capillary and arteriolar densities in ischemic myocardium. Calpain inhibition also improved endothelium-dependent microvessel relaxation and increased expression of proteins implicated in angiogenesis and vasodilatation.

14 Article Reducing LDL with PCSK9 Inhibitors--The Clinical Benefit of Lipid Drugs. 2015

Everett, Brendan M / Smith, Robert J / Hiatt, William R. ·From Harvard Medical School and Divisions of Cardiovascular and Preventive Medicine, Department of Medicine, Brigham and Women's Hospital - both in Boston (B.M.E.) · the Department of Medicine, Alpert Medical School, and the Department of Health Services, Policy, and Practice, School of Public Health, Brown University · and Ocean State Research Institute, Providence VA Medical Center - all in Providence, RI (R.J.S.) · and the Department of Medicine, Division of Cardiology, University of Colorado School of Medicine, and CPC Clinical Research - both in Aurora (W.R.H.). All three authors participated as voting members of the FDA Endocrinologic and Metabolic Drugs Advisory Committee meeting on alirocumab, and Drs. Smith and Hiatt participated as voting members of the Advisory Committee meeting on evolocumab. ·N Engl J Med · Pubmed #26444323.

ABSTRACT: -- No abstract --

15 Article Calpain inhibition decreases myocardial apoptosis in a swine model of chronic myocardial ischemia. 2015

Potz, Brittany A / Sabe, Ashraf A / Elmadhun, Nassrene Y / Feng, Jun / Liu, Yuhong / Mitchell, Hunter / Quesenberry, Peter / Abid, M Ruhul / Sellke, Frank W. ·Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI. · Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI. Electronic address: fsellke@lifespan.org. ·Surgery · Pubmed #25991048.

ABSTRACT: INTRODUCTION: Calpain is a family of cysteine proteases that has an important role in the initiation, regulation, and execution of cell death. Our recent studies using a hypercholesterolemic swine model demonstrated that in the setting of the metabolic syndrome, calpain inhibition (CI) improved collateral-dependent perfusion and increased expression of proteins implicated in angiogenesis and vasodilation. In this study, we hypothesized that CI (by MLD28170) would decrease myocardial apoptosis in the same model. METHODS: Yorkshire swine, all fed a high-cholesterol diet for 4 weeks underwent placement of an ameroid constrictor on the left circumflex coronary artery. Three weeks later, animals received either no drug, termed the high-cholesterol control group (HCC; n = 8); low-dose CI (0.12 mg/kg; LCI, n = 9); or high-dose CI (0.25 mg/kg; HCI, n = 8). The high-cholesterol diet and the CI were continued for 5 weeks, after which the pig was humanely killed and the left ventricular myocardium was harvested and analyzed via terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, oxyblot analysis, and Western blots. Data were analyzed using the Kruskal-Wallis test. RESULTS: The percentage of apoptotic cells to total cells in ischemic myocardial territory was decreased in the LCI and HCI groups compared with the HCC group as shown by TUNEL staining (P = .018). There was a decrease in proapoptotic proteins, including cleaved caspase 3, caspase 9, cleaved caspase 9, Bax, BAD, p-BAD, and Erk 1/2 (P ≤ .049 each), but no decrease in caspase 3 (P = .737). There was also an increase in antiapoptotic proteins, including BCL-2 and p-BCL2 (P ≤ .025 each). In the ischemic myocardium, several proangiogenic proteins were increased in the LCI and HCI groups compared with the HCC group, including p-AKT, p-eNOS, and eNOS (P ≤ .006 each) but there was no increase in AKT (P = .311). CI decreased tissue oxidative stress in both the LCI and HCI groups compared to the HCC group as shown by oxyblot analysis (P = .021). CONCLUSION: In the setting of hypercholesterolemia, CI decreases apoptosis and the expression of proteins in proapoptotic signaling pathways. CI also increased expression of proteins implicated in anti apoptotic pathways and improves oxidative stress in ischemic myocardial tissue.

16 Article Rheumatoid Arthritis, Anti-Cyclic Citrullinated Peptide Positivity, and Cardiovascular Disease Risk in the Women's Health Initiative. 2015

Mackey, Rachel H / Kuller, Lewis H / Deane, Kevin D / Walitt, Brian T / Chang, Yue-Fang / Holers, V Michael / Robinson, William H / Tracy, Russell P / Hlatky, Mark A / Eaton, Charles B / Liu, Simin / Freiberg, Matthew S / Talabi, Mehret Birru / Schelbert, Erik B / Moreland, Larry W. ·University of Pittsburgh, Pittsburgh, Pennsylvania. · University of Colorado, Denver. · Washington Hospital Center, Washington, DC. · Stanford University, Stanford, California, and VA Palo Alto Health Care System, Palo Alto, California. · University of Vermont, Burlington. · Stanford University, Stanford, California. · Brown University, Providence, Rhode Island. · Vanderbilt University and Nashville VA Medical Center, Nashville, Tennessee. ·Arthritis Rheumatol · Pubmed #25988241.

ABSTRACT: OBJECTIVE: To evaluate the incidence of cardiovascular disease (CVD) morbidity and mortality over the course of 10 years among the more than 160,000 postmenopausal women in the Women's Health Initiative (WHI) in relation to self-reported rheumatoid arthritis (RA), taking disease-modifying antirheumatic drugs (DMARDs), anti-cyclic citrullinated peptide (anti-CCP) positivity, rheumatoid factor (RF) positivity, CVD risk factors, joint pain, and inflammation (white blood cell count and interleukin-6 levels). METHODS: Anti-CCP and RF were measured in a sample of WHI participants with self-reported RA (n = 9,988). RA was classified as self-reported RA plus anti-CCP positivity and/or taking DMARDs. Anti-CCP-negative women with self-reported RA and not taking DMARDs were classified as having "unverified RA." RESULTS: Age-adjusted rates of coronary heart disease (CHD), stroke, CVD, fatal CVD, and total mortality were higher in women with RA than in women with no reported RA, with multivariable-adjusted hazard ratios of 1.46 (95% confidence interval [95% CI] 1.17-1.83) for CHD and 2.55 (95% CI 1.86-3.51) for fatal CVD. Among women with RA, anti-CCP positivity and RF positivity were not significantly associated with higher risk of any outcomes, despite slightly higher risk of death for those who were anti-CCP positive than for those who were anti-CCP negative. Joint pain severity and CVD risk factors were strongly associated with CVD risk, even in women with no reported RA. CVD incidence was increased in women with RA versus women with no reported RA at almost all risk factor levels, except for low levels of joint pain or inflammation. Among women with RA, inflammation was more strongly associated with fatal CVD and total mortality than with CHD or CVD. CONCLUSION: Among postmenopausal women, RA was associated with 1.5-2.5-fold higher CVD risk. CVD risk was strongly associated with CVD risk factors, joint pain severity, and inflammation, but not with anti-CCP positivity or RF positivity.

17 Article Type of Insurance and Use of Preventive Health Services Among Older Adults in Mexico. 2015

Rivera-Hernandez, Maricruz / Galarraga, Omar. ·Bio Med Gerontology Health, Brown University, Providence, RI, USA Maricruz_Rivera-Hernandez@Brown.edu. · Department of Health Services, Policy and Practice Brown University, Providence, RI, USA. ·J Aging Health · Pubmed #25804897.

ABSTRACT: OBJECTIVE: The main purpose of this article was to assess the differences between Seguro Popular (SP) and employer-based health insurance in the use of preventive services, including screening tests for diabetes, cholesterol, hypertension, cervical cancer, and prostate cancer among older adults at more than a decade of health care reform in Mexico. METHOD: Logistic regression models were used with data from the Mexican Health and Nutrition Survey, 2012. RESULTS: After adjusting for other factors influencing preventive service utilization, SP enrollees were more likely to use screening tests for diabetes, cholesterol, hypertension, and cervical cancer than the uninsured; however, those in employment-based and private insurances had higher odds of using preventive care for most of these services, except Pap smears. DISCUSSION: Despite all the evidence that suggests that SP has increased access to health insurance for the poor, inequalities in health care access and utilization still exist in Mexico.

18 Article The role of retail pharmacies in CVD prevention after the release of the ATP IV guidelines. 2014

Shrank, William H / Sussman, Andrew / Brennan, Troyen A. ·CVS Caremark Corporation, 100 Scenic View Rd, Cumberland, RI 02864. Email: william.shrank@cvscaremark.com. ·Am J Manag Care · Pubmed #25730347.

ABSTRACT: -- No abstract --

19 Article Assessing the clinical benefits of lipid-disorder drugs. 2014

Hiatt, William R / Smith, Robert J. ·From the Division of Cardiology and CPC Clinical Research, Department of Medicine, University of Colorado School of Medicine, Aurora (W.R.H.) · and the Alpert Medical School of Brown University and the Ocean State Research Institute, Providence Veterans Affairs Medical Center - both in Providence, RI (R.J.S.). ·N Engl J Med · Pubmed #24476429.

ABSTRACT: -- No abstract --

20 Article Resveratrol regulates autophagy signaling in chronically ischemic myocardium. 2014

Sabe, Ashraf A / Elmadhun, Nassrene Y / Dalal, Rahul S / Robich, Michael P / Sellke, Frank W. ·Division of Cardiothoracic Surgery, Cardiovascular Research Center, Brown University Warren Alpert School of Medicine, Providence, RI. · Division of Cardiothoracic Surgery, Cardiovascular Research Center, Brown University Warren Alpert School of Medicine, Providence, RI. Electronic address: fsellke@lifespan.org. ·J Thorac Cardiovasc Surg · Pubmed #24267781.

ABSTRACT: OBJECTIVE: Autophagy is a cellular process by which damaged components are removed. Although autophagy can result in cell death, when optimally regulated, it might be cardioprotective. Resveratrol is a naturally occurring polyphenol also believed to be cardioprotective. Using a clinically relevant swine model of metabolic syndrome, we investigated the effects of resveratrol on autophagy in the chronically ischemic myocardium. METHODS: Yorkshire swine were fed a regular diet (n = 7), a high cholesterol diet (n = 7), or a high cholesterol diet with supplemental resveratrol (n = 6). After 4 weeks, an ameroid constrictor was surgically placed on the left circumflex artery to induce chronic myocardial ischemia. The diets were continued another 7 weeks, and then the ischemic and nonischemic myocardium were harvested for protein analysis. RESULTS: In the ischemic myocardium, a high cholesterol diet partly attenuated the autophagy, as determined by an increase in phosphorylated mammalian target of rapamycin (p-mTOR) and a decrease in p70 S6 kinase (P70S6K), lysosome-associated membrane protein (LAMP)-2, and autophagy-related gene 12-5 conjugate (ATG 12-5; P < .05). The addition of resveratrol blunted many of these changes, because the p-mTOR, P70S6K, and LAMP-2 levels were not significantly altered from those of the pigs fed a regular diet. Other autophagy markers were increased with a high cholesterol diet, including light chain 3A-II and beclin 1 (P < .05). In the nonischemic myocardium, beclin 1 was decreased in the high cholesterol-fed pigs (P < .05); otherwise no significant changes in protein expression were noted among the 3 groups. CONCLUSIONS: In the chronically ischemic myocardium, resveratrol partly reversed the effects of a high cholesterol diet on autophagy. This might be a mechanism by which resveratrol exerts its cardioprotective effects.

21 Article Mechanism for reduced pericardial adhesion formation in hypercholesterolemic swine supplemented with alcohol. 2013

Lassaletta, Antonio D / Chu, Louis M / Elmadhun, Nassrene Y / Robich, Michael P / Hoffman, Zachary G / Kim, David J / Sellke, Frank W. ·Division of Cardiothoracic Surgery, Cardiovascular Research Center, Warren Alpert Medical School, Brown University, Providence, RI 02905, USA. ·Eur J Cardiothorac Surg · Pubmed #22991457.

ABSTRACT: OBJECTIVE: Previous experiments in Yorkshire swine demonstrated significantly fewer pericardial adhesions and intramyocardial collagen deposition at reoperative sternotomy in animals supplemented with vodka but not with red wine. The purpose of this experiment was to determine a mechanism for adhesion reduction. METHODS: Twenty-seven male Yorkshire swine were fed a high-cholesterol diet to simulate conditions of coronary artery disease followed by the surgical placement of an ameroid constrictor to the left circumflex coronary artery to induce chronic ischaemia. Postoperatively, control pigs continued their high-fat/cholesterol diet alone, whereas the two experimental groups had diets supplemented with either red wine or vodka for 7 weeks followed by reoperative sternotomy and cardiac harvest. RESULTS: The expression of related adhesion focal tyrosine kinase (RAFTK) and caspase 3 in the sodium dodecyl sulphate (SDS)-soluble myocardial fraction was significantly higher only in the vodka-supplemented group. In the more soluble fraction, the expression of caspase 3, cleaved caspase 3 and caspase 9 was lower in both the vodka and red wine treatment groups. CONCLUSIONS: In the SDS-soluble lysate fraction, likely representing the transmembrane/cell-extracellular matrix (ECM), a significant increase in RAFTK and caspase 3 expression was seen only in the vodka-treated animals, which may explain why this group demonstrated significantly fewer pericardial adhesions. Caspase expression/signalling was not increased in the more soluble myocardial lysate, suggesting that the increased apoptotic signalling was specific to the epicardial-ECM.

22 Article Effects of red wine and vodka on collateral-dependent perfusion and cardiovascular function in hypercholesterolemic swine. 2012

Chu, Louis M / Lassaletta, Antonio D / Robich, Michael P / Liu, Yuhong / Burgess, Thomas / Laham, Roger J / Sweeney, Joseph D / Shen, Tun-Li / Sellke, Frank W. ·Division of Cardiothoracic Surgery, Warren Alpert School of Medicine, Brown University, Providence, RI 02905, USA. ·Circulation · Pubmed #22965995.

ABSTRACT: BACKGROUND: Moderate consumption of alcohol, particularly red wine, has been shown to decrease cardiac risk. We used a hypercholesterolemic swine model of chronic ischemia to examine the effects of 2 alcoholic beverages on the heart. METHODS AND RESULTS: Yorkshire swine fed a high-cholesterol diet underwent left circumflex ameroid constrictor placement to induce chronic ischemia at 8 weeks of age. One group (HCC, n=9) continued on the diet alone, the second (HCW, n=8) was supplemented with red wine (pinot noir, 12.5% alcohol, 375 mL daily), and the third (HCV, n=9) was supplemented with vodka (40% alcohol, 112 mL daily). After 7 weeks, cardiac function was measured, and ischemic myocardium was harvested for analysis of perfusion, myocardial fibrosis, vessel function, protein expression, oxidative stress, and capillary density. Platelet function was measured by aggregometry. Perfusion to the ischemic territory as measured by microsphere injection was significantly increased in both HCW and HCV compared with HCC at rest, but in only the HCW group under ventricular pacing. Microvessel relaxation response to adenosine 5'-diphosphate was improved in the HCW group alone as was regional contractility in the ischemic territory, although myocardial fibrosis was decreased in both HCW and HCV. Expression of proangiogenic proteins phospho-endothelial nitric oxide synthase and vascular endothelial growth factor was increased in both HCW and HCV, whereas phospho-mammalian target of rapamycin was increased only in the HCV group. Expression of Sirt-1 and downstream antioxidant phospho-FoxO1 was increased only in the HCW group. Protein oxidative stress was decreased in the HCW group alone, whereas capillary density was increased only in the HCV group. There was no significant difference in platelet function between groups. CONCLUSION: Moderate consumption of red wine and vodka may reduce cardiovascular risk by improving collateral-dependent perfusion through different mechanisms. Red wine may offer increased cardioprotection related to its antioxidant properties.

23 Article Cardioprotective effects of red wine and vodka in a model of endothelial dysfunction. 2012

Lassaletta, Antonio D / Chu, Louis M / Elmadhun, Nassrene Y / Burgess, Thomas A / Feng, Jun / Robich, Michael P / Sellke, Frank W. ·Division of Cardiothoracic Surgery, Cardiovascular Research Center, Warren Alpert Medical School of Brown University, Providence, Rhode Island 02905, USA. ·J Surg Res · Pubmed #22748601.

ABSTRACT: BACKGROUND: Moderate alcohol consumption is largely believed to be cardioprotective, while red wine is hypothesized to offer benefit in part due to the proangiogenic and antioxidant properties of polyphenols. We investigated the cardiovascular effects of both red wine and vodka in a swine model of endothelial dysfunction. METHODS: Twenty-seven male Yorkshire swine fed a high-fat/cholesterol diet were divided into three groups and received either no alcohol (Control), red wine, or vodka. After 7 wk, myocardial perfusion was measured, and ventricular tissue was analyzed for microvascular reactivity and immunohistochemical studies. RESULTS: There were no differences in myocardial perfusion, in arteriolar or capillary density, or in VEGF expression among groups. Total protein oxidation as well as expression of superoxide dismutase-1 and -2 and NADPH oxidase was decreased in both treatment groups compared to controls. Endothelium-dependent microvessel relaxation, however, was significantly improved only in the red wine-supplemented group. CONCLUSIONS: Supplementation with both red wine and vodka decreased oxidative stress by several measures, implicating the effects of ethanol in reducing oxidative stress in the myocardium. However, it was only in the red wine-supplemented group that an improvement in microvessel function was observed. This suggests that a component of red wine, independent of ethanol, possibly a polyphenol such as resveratrol, may confer cardioprotection by normalizing endothelial dysfunction induced by an atherogenic diet.

24 Article Effects of alcohol on pericardial adhesion formation in hypercholesterolemic swine. 2012

Lassaletta, Antonio D / Chu, Louis M / Sellke, Frank W. ·Department of Surgery, Division of Cardiothoracic Surgery, Warren Alpert School of Medicine, Brown University, Providence, RI, USA. ·J Thorac Cardiovasc Surg · Pubmed #22244558.

ABSTRACT: OBJECTIVE: Reoperative cardiac surgery is complicated in part because of extensive adhesions encountered during the second operation. The purpose of this study was to examine the effects of alcohol with and without resveratrol (red wine vs vodka) on postoperative pericardial adhesion formation in a porcine model of hypercholesterolemia and chronic myocardial ischemia. METHODS: Male Yorkshire swine were fed a high-cholesterol diet to simulate conditions of coronary artery disease followed by surgical placement of an ameroid constrictor to induce chronic ischemia. Postoperatively, control pigs continued their high-cholesterol diet alone, whereas the 2 experimental groups had diets supplemented with red wine or vodka. Seven weeks after ameroid placement, all animals underwent reoperative sternotomy. RESULTS: Compared with controls, pericardial adhesion grade was markedly reduced in the vodka group, whereas there was no difference in the wine group. Intramyocardial fibrosis was significantly reduced in the vodka group compared with controls. There was no difference in expression of proteins involved in focal adhesion formation between any groups (focal adhesion kinase, integrin alpha-5, integrin beta-1, paxillin, vinculin, protein tyrosine kinase 2, protein kinase C ε, and phosphorylated protein kinase C ε). The wine group exhibited elevated C-reactive protein levels versus the control and vodka groups. CONCLUSIONS: Postoperative vodka consumption markedly reduced the formation of pericardial adhesions and intramyocardial fibrosis, whereas red wine had no effect. Analysis of protein expression did not reveal any obvious explanation for this phenomenon, suggesting a post-translational effect of alcohol on fibrous tissue deposition. The difference in adhesion formation in the vodka versus wine groups may be due to increased inflammation in the wine group.

25 Article Effects of cyclooxygenase inhibition on cardiovascular function in a hypercholesterolemic swine model of chronic ischemia. 2012

Chu, Louis M / Robich, Michael P / Bianchi, Cesario / Feng, Jun / Liu, Yuhong / Xu, Shu-Hua / Burgess, Thomas / Sellke, Frank W. ·Department of Surgery, Division of Cardiothoracic Surgery, Warren Alpert School of Medicine, Brown University, Providence, RI 02903, USA. ·Am J Physiol Heart Circ Physiol · Pubmed #22037194.

ABSTRACT: The cardiovascular effects of cyclooxygenase (COX) inhibition remain controversial, especially in the setting of cardiovascular comorbidities. We examined the effects of nonselective and selective COX inhibition on cardiovascular function in a hypercholesterolemic swine model of chronic ischemia. Twenty-four intact male Yorkshire swine underwent left circumflex ameroid constrictor placement and were subsequently given either no drug (HCC; n = 8), a nonselective COX inhibitor (440 mg/day naproxen; HCNS; n = 8), or a selective COX-2 inhibitor (200 mg/day celecoxib; HCCX; n = 8). After 7 wk, myocardial functional was measured and myocardium from the nonischemic ventricle and ischemic area-at-risk (AAR) were analyzed. Regional function as measured by segmental shortening was improved in the AAR of HCCX compared with HCC. There was no significant difference in perfusion to the nonischemic ventricle between groups, but myocardial perfusion in the AAR was significantly improved in the HCCX group compared with controls at rest and during pacing. Endothelium-dependent microvessel relaxation was diminished by ischemia in HCC animals, but both naproxen and celecoxib improved vessel relaxation in the AAR compared with controls, and also decreased the vasoconstrictive response to serotonin. Thromboxane levels in the AAR were decreased in both HCNS and HCCX compared with HCC, whereas prostacyclin levels were decreased only in HCNS, corresponding to a decrease in prostacyclin synthase expression. Chronic ischemia increased apoptosis in Troponin T negative cells and intramyocardial fibrosis, both of which were reduced by celecoxib administration in the AAR. Capillary density was decreased in both the HCNS and HCCX groups. Protein oxidative stress was decreased in both HCNS and HCCX, whereas lipid oxidative stress was decreased only in the HCCX group. Thus nonselective and especially selective COX inhibition may have beneficial myocardial effects in the setting of hypercholesterolemia and chronic ischemia. Whether these effects modulate cardiovascular risk in patients taking these drugs remains to be seen, but evidence to date suggests that they do not.

Next