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1. Myocardial Work in Patients Hospitalized With COVID‐19: Relation to Biomarkers, COVID‐19 Severity, and All‐Cause Mortality

Author: Flemming Javier Olsen, Mats Christian Højbjerg Lassen, Kristoffer Grundtvig Skaarup, Jacob Christensen, Filip Soeskov Davidovski, Alia Saed Alhakak, Morten Sengeløv, Anne Bjerg Nielsen, Niklas Dyrby Johansen, Claus Graff, Henning Bundgaard, Christian Hassager, Reza Jabbari, Jørn Carlsen, Ole Kirk, Matias Greve Lindholm, Lothar Wiese, Ole Peter Kristiansen, Olav W. Nielsen, Birgitte Lindegaard, Niels Tønder, Charlotte Suppli Ulrik, Morten Lamberts, Pradeesh Sivapalan, Gunnar Gislason, Kasper Iversen, Jens Ulrik Stæhr Jensen, Morten Schou, Jesper Hastrup Svendsen, John Moene Aalen, Otto Armin Smiseth, Espen Wattenberg Remme, and Tor Biering‐Sørensen
Subjects: corona, COVID, myocardial work, pressure‐strain, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background COVID‐19 infection has been hypothesized to affect left ventricular function; however, the underlying mechanisms and the association to clinical outcome are not understood. The global work index (GWI) is a novel echocardiographic measure of systolic function that may offer insights on cardiac dysfunction in COVID‐19. We hypothesized that GWI was associated with disease severity and all‐cause death in patients with COVID‐19. Methods and Results In a multicenter study of patients admitted with COVID‐19 (n=305), 249 underwent pressure‐strain loop analyses to quantify GWI at a median time of 4 days after admission. We examined the association of GWI to cardiac biomarkers (troponin and NT‐proBNP [N‐terminal pro‐B‐type natriuretic peptide]), disease severity (oxygen requirement and CRP [C‐reactive protein]), and all‐cause death. Patients with elevated troponin (n=71) exhibited significantly reduced GWI (1508 versus 1707 mm Hg%; P=0.018). A curvilinear association to NT‐proBNP was observed, with increasing NT‐proBNP once GWI decreased below 1446 mm Hg%. Moreover, GWI was significantly associated with a higher oxygen requirement (relative increase of 6% per 100–mm Hg% decrease). No association was observed with CRP. Of the 249 patients, 37 died during follow‐up (median, 58 days). In multivariable Cox regression, GWI was associated with all‐cause death (hazard ratio, 1.08 [95% CI, 1.01–1.15], per 100–mm Hg% decrease), but did not increase C‐statistics when added to clinical parameters. Conclusions In patients admitted with COVID‐19, our findings indicate that NT‐proBNP and troponin may be associated with lower GWI, whereas CRP is not. GWI was independently associated with all‐cause death, but did not provide prognostic information beyond readily available clinical parameters. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04377035.
Published: 2022
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2. Excessive supraventricular ectopic activity and risk of incident atrial fibrillation in a consecutive population referred to ambulatory cardiac monitoring

Author: Bjørn Strøier Larsen, MD, Mark Aplin, MD, PhD, Olav Wendelboe Nielsen, MD, PhD, DMSc, Maria Helena Dominguez Vall-Lamora, MD, PhD, Nis Baun Høst, MD, PhD, Ole Peter Kristiansen, MD, DMSc, Hanne Kruuse Rasmusen, MD, PhD, Ulla Davidsen, MD, Finn Michael Karlsen, MD, PhD, Søren Højberg, MD, PhD, and Ahmad Sajadieh, MD, PhD, DMSc
Subjects: Atrial fibrillation, Epidemiology, Premature atrial contractions, Risk stratification, Survival analysis, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background: Excessive supraventricular ectopic activity (ESVEA), defined as ≥720 premature atrial contractions (PAC) per day or any runs of ≥20 PACs, has been proposed as a surrogate marker for paroxysmal atrial fibrillation (PAF). Objective: We aimed to estimate the prognostic impact of ESVEA on the future development of PAF in consecutive patients referred to ambulatory cardiac monitoring. Methods: The cohort consists of a population with comorbidities referred to 48-hour ambulatory electrocardiogram aged 30–98 (n = 1316) between 2009 and 2011. After exclusion of known or current atrial fibrillation (AF) (n = 527) and patients with pacemakers (n = 7), 782 patients were included, with a median follow-up of 8.1 years. Events of incident AF and death were retrieved from patient records. Results: Mean age was 58.6 ± 15.5 years and 56.5% were women. A total of 101 patients had ESVEA at baseline (12.9%). During follow-up, 69 (8.9%) developed incidental AF. Twenty-three patients with ESVEA developed AF (23%). Incidence rate of AF in patients with and without ESVEA was 37.1/1000 person-years and 9.1 per 1000 person-years, respectively (P < .001). ESVEA was associated with incident AF after adjustment for potential confounders in Cox regression analysis (hazard ratio [HR]: 2.39; 95% confidence interval [CI]: 1.40–4.09) and in competing risk analysis with death as competing risk (subdistribution HR: 2.35; 95% CI: 1.30–4.17). Conclusion: ESVEA increases the risk of incident AF substantially in a population referred to ambulatory cardiac monitoring.
Published: 2021
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3. Echocardiographic abnormalities and predictors of mortality in hospitalized COVID‐19 patients: the ECHOVID‐19 study

Author: Mats Christian Højbjerg Lassen, Kristoffer Grundtvig Skaarup, Jannie Nørgaard Lind, Alia Saed Alhakak, Morten Sengeløv, Anne Bjerg Nielsen, Caroline Espersen, Kirstine Ravnkilde, Raphael Hauser, Liv Borum Schöps, Eva Holt, Niklas Dyrby Johansen, Daniel Modin, Kasper Djernæs, Claus Graff, Henning Bundgaard, Christian Hassager, Reza Jabbari, Jørn Carlsen, Anne‐Mette Lebech, Ole Kirk, Uffe Bodtger, Matias Greve Lindholm, Gowsini Joseph, Lothar Wiese, Frank Vinholt Schiødt, Ole Peter Kristiansen, Emil Schwarz Walsted, Olav Wendelboe Nielsen, Birgitte Lindegaard Madsen, Niels Tønder, Thomas Benfield, Klaus Nielsen Jeschke, Charlotte Suppli Ulrik, Filip Krag Knop, Morten Lamberts, Pradeesh Sivapalan, Gunnar Gislason, Jacob Louis Marott, Rasmus Møgelvang, Gorm Jensen, Peter Schnohr, Peter Søgaard, Scott D. Solomon, Kasper Iversen, Jens Ulrik Stæhr Jensen, Morten Schou, and Tor Biering‐Sørensen
Subjects: COVID‐19, Echocardiography, Global longitudinal strain, Right ventricular strain, SARS‐CoV‐2, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Abstract Aims The present study had two aims: (i) compare echocardiographic parameters in COVID‐19 patients with matched controls and (2) assess the prognostic value of measures of left (LV) and right ventricular (RV) function in relation to COVID‐19 related death. Methods and results In this prospective multicentre cohort study, 214 consecutive hospitalized COVID‐19 patients underwent an echocardiographic examination (by pre‐determined research protocol). All participants were successfully matched 1:1 with controls from the general population on age, sex, and hypertension. Mean age of the study sample was 69 years, and 55% were male participants. LV and RV systolic function was significantly reduced in COVID‐19 cases as assessed by global longitudinal strain (GLS) (16.4% ± 4.3 vs. 18.5% ± 3.0, P
Published: 2020
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4. Liraglutide improves the beta-cell function without increasing insulin secretion during a mixed meal in patients, who exhibit well-controlled type 2 diabetes and coronary artery disease

Author: Christian Anholm, Preman Kumarathurai, Anders Jürs, Lene Rørholm Pedersen, Olav Wendelboe Nielsen, Ole Peter Kristiansen, Mogens Fenger, Jens Juul Holst, Sten Madsbad, Ahmad Sajadieh, and Steen Bendix Haugaard
Subjects: GLP1-receptor agonist, Diabetes mellitus type 2, Beta-cell function, Insulin sensitivity, Meal test, Insulin clearance, Nutritional diseases. Deficiency diseases, RC620-627
Abstract: Abstract Background Hyperinsulinemia aggravates insulin resistance and cardio-vascular disease. How the insulinotropic glucagon-like peptide-1 receptor agonist liraglutide in a physiologic post-prandial setting may act on pancreatic alpha and beta-cell function in patients with coronary artery disease (CAD) and type 2 diabetes (T2DM) is less clear. Methods Insulin resistant patients with established CAD and newly diagnosed well-controlled T2DM were recruited to a placebo-controlled, cross-over trial with two treatment periods of 12 weeks and a 2 weeks wash-out period before and in-between. Treatment was liraglutide or placebo titrated from 0.6 mg q.d. to 1.8 mg q.d. within 4 weeks and metformin titrated from 500 mg b.i.d to 1000 mg b.i.d. within 4 weeks. Before and after intervention in both 12 weeks periods insulin, C-peptide, glucose, and glucagon were measured during a meal test. Beta-cell function derived from the oral glucose tolerance setting was calculated as changes in insulin secretion per unit changes in glucose concentration (Btotal) and whole-body insulin resistance using ISIcomposite. Results Liraglutide increased the disposition index [Btotal × ISIcomposite, by 40% (n = 24, p
Published: 2019
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5. Cardiac Characteristics of the First Two Waves of COVID-19 in Denmark and the Prognostic Value of Echocardiography: The ECHOVID-19 Study

Author: Jacob Christensen, Filip Søskov Davidoski, Kristoffer Grundtvig Skaarup, Mats Christian Højbjerg Lassen, Alia Sead Alhakak, Morten Sengeløv, Anne Bjerg Nielsen, Niklas Dyrby Johansen, Henning Bundgaard, Christian Hassager, Reza Jabbari, Jørn Carlsen, Ole Kirk, Ole Peter Kristiansen, Olav Wendelboe Nielsen, Charlotte Suppli Ulrik, Pradeesh Sivapalan, Gunnar Gislason, Kasper Iversen, Jens Ulrik Stæhr Jensen, Morten Schou, Anders Hviid, Tyra Grove Krause, and Tor Biering-Sørensen
Subjects: Pharmacology (medical), Cardiology and Cardiovascular Medicine
Abstract: Introduction: COVID-19 has spread globally in waves, and Danish treatment guidelines have been updated following the first wave. We sought to investigate whether the prognostic values of echocardiographic parameters changed with updates in treatment guidelines and the emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, 20E (EU1) and alpha (B.1.1.7), and further to compare cardiac parameters between patients from the first and second wave. Methods: A total of 305 patients hospitalized with COVID-19 were prospectively included, 215 and 90 during the first and second wave, respectively. Treatment in the study was defined as treatment with remdesivir, dexamethasone, or both. Patients were assumed to be infected with the dominant SARS-CoV-2 variant at the time of their hospitalization. Results: Mean age for the first versus second wave was 68.7 ± 13.6 versus 69.7 ± 15.8 years, and 55% versus 62% were males. Left ventricular (LV) systolic and diastolic function was worse in patients hospitalized during the second wave (LV ejection fraction [LVEF] for first vs. second wave = 58.5 ± 8.1% vs. 52.4 ± 10.6%, p < 0.001; and global longitudinal strain [GLS] = 16.4 ± 4.3% vs. 14.2 ± 4.3%, p < 0.001). In univariable Cox regressions, reduced LVEF (hazard ratio [HR] = 1.07 per 1% decrease, p = 0.002), GLS (HR = 1.21 per 1% decrease, p < 0.001), and tricuspid annular plane systolic excursion (HR = 1.18 per 1 mm decrease, p < 0.001) were associated with COVID-related mortality, but only GLS remained significant in fully adjusted analysis (HR = 1.14, p = 0.02). Conclusion: Reduced GLS was associated with COVID-related mortality independently of wave, treatment, and the SARS-CoV-2 variant. LV function was significantly impaired in patients hospitalized during the second wave.
Published: 2022

6. Lung ultrasound findings in hospitalized COVID-19 patients in relation to venous thromboembolic events:the ECHOVID-19 study

Author: Kirstine Ravnkilde, Reza Jabbari, Olav W. Nielsen, Ole Peter Kristiansen, Jannik Langtved Pallisgaard, Mats Christian Højbjerg Lassen, Anne Bjerg Nielsen, Christian Hassager, Gunnar Gislason, Elke Platz, Raphael Hauser, Klaus Nielsen Jeschke, Birgitte Lindegaard, Charlotte Suppli Ulrik, Jørn Carlsen, Niklas Dyrby Johansen, Pradeesh Sivapalan, Kristoffer Grundtvig Skaarup, Morten Lamberts, Søren Helbo Skaarup, Lothar Wiese, Eva Holt, Morten Schou, Matias Greve Lindholm, Emil S. Walsted, Liv Borum Schöps, Kasper Iversen, Jannie Nørgaard Lind, Morten Sengeløv, Jens-Ulrik Stæhr Jensen, Niels Tønder, Ole Kirk, Alia Saed Alhakak, Caroline Espersen, Tor Biering-Sørensen, Uffe Bodtger, and Henning Bundgaard
Subjects: Adult, Male, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Article, B-lines, Internal medicine, Internal Medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, Prospective Studies, Lung, Pathological, Aged, Ultrasonography, Lung ultrasound, Proportional hazards model, business.industry, Venous thromboembolic events, COVID-19, Mean age, Venous Thromboembolism, General Medicine, medicine.disease, Thrombosis, Pulmonary embolism, Median time, Female, business
Abstract: Purpose: Several studies have reported thromboembolic events to be common in severe COVID-19 cases. We sought to investigate the relationship between lung ultrasound (LUS) findings in hospitalized COVID-19 patients and the development of venous thromboembolic events (VTE). Methods: A total of 203 adults were included from a COVID-19 ward in this prospective multi-center study (mean age 68.6 years, 56.7% men). All patients underwent 8-zone LUS, and all ultrasound images were analyzed off-line blinded. Several LUS findings were investigated (total number of B-lines, B-line score, and LUS-scores). Results: Median time from admission to LUS examination was 4 days (IQR: 2, 8). The median number of B-lines was 12 (IQR: 8, 18), and 44 (21.7%) had a positive B-line score. During hospitalization, 17 patients developed VTE (4 deep-vein thrombosis, 15 pulmonary embolism), 12 following and 5 prior to LUS. In fully adjusted multivariable Cox models (excluding participants with VTE prior to LUS), all LUS parameters were significantly associated with VTE (total number of B-lines: HR = 1.14, 95% CI (1.03, 1.26) per 1 B-line increase), positive B-line score: HR = 9.79, 95% CI (1.87, 51.35), and LUS-score: HR = 1.51, 95% CI (1.10, 2.07), per 1-point increase). The B-line score and LUS-score remained significantly associated with VTE in sensitivity analyses. Conclusion: In hospitalized COVID-19 patients, pathological LUS findings were common, and the total number of B-lines, B-line score, and LUS-score were all associated with VTE. These findings indicate that the LUS examination may be useful in risk stratification and the clinical management of COVID-19. These findings should be considered hypothesis generating. Clinicaltrials.gov ID: NCT04377035.
Published: 2022
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7. Lung ultrasound findings following COVID-19 hospitalization: A prospective longitudinal cohort study

Author: Caroline Espersen, Elke Platz, Alia Saed Alhakak, Morten Sengeløv, Jakob Øystein Simonsen, Niklas Dyrby Johansen, Filip Søskov Davidovski, Jacob Christensen, Henning Bundgaard, Christian Hassager, Reza Jabbari, Jørn Carlsen, Ole Kirk, Matias Greve Lindholm, Ole Peter Kristiansen, Olav Wendelboe Nielsen, Klaus Nielsen Jeschke, Charlotte Suppli Ulrik, Pradeesh Sivapalan, Kasper Iversen, Jens Ulrik Stæhr Jensen, Morten Schou, Søren Helbo Skaarup, Mats Christian Højbjerg Lassen, Kristoffer Grundtvig Skaarup, and Tor Biering-Sørensen
Subjects: Pulmonary and Respiratory Medicine, Adult, Male, Respiratory Distress Syndrome, Lung ultrasound, Longitudinal follow-up, COVID-19, Middle Aged, Cohort Studies, Hospitalization, Humans, Female, Longitudinal Studies, Prospective Studies, Lung, Ultrasonography
Abstract: Background: Lung ultrasound (LUS) is a useful tool for diagnosis and monitoring in patients with active COVID-19-infection. However, less is known about the changes in LUS findings after a hospitalization for COVID-19. Methods: In a prospective, longitudinal study in patients with COVID-19 enrolled from non-ICU hospital units, adult patients underwent 8-zone LUS and blood sampling both during the hospitalization and 2–3 months after discharge. LUS images were analyzed blinded to clinical variables and outcomes. Results: A total of 71 patients with interpretable LUS at baseline and follow up (mean age 64 years, 61% male, 24% with acute respiratory distress syndrome (ARDS)) were included. The follow-up LUS was performed a median of 72 days after the initial LUS performed during hospitalization. At baseline, 87% had pathologic LUS findings in ≥1 zone (e.g. ≥3 B-lines, confluent B-lines or subpleural or lobar consolidation), whereas 30% had pathologic findings at follow-up (p < 0.001). The total number of B-lines and LUS score decreased significantly from hospitalization to follow-up (median 17 vs. 4, p < 0.001 and 4 vs. 0, p < 0.001, respectively). On the follow-up LUS, 28% of all patients had ≥3 B-lines in ≥1 zone, whereas in those with ARDS during the baseline hospitalization (n = 17), 47% had ≥3 B-lines in ≥1 zone. Conclusion: LUS findings improved significantly from hospitalization to follow-up 2–3 months after discharge in COVID-19 survivors. However, persistent B-lines were frequent at follow-up, especially among those who initially had ARDS. LUS seems to be a promising method to monitor COVID-19 lung changes over time. Clinicaltrials.gov ID: NCT04377035.
Published: 2021
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8. Effects of liraglutide on diastolic function parameters in patients with type 2 diabetes and coronary artery disease:a randomized crossover study

Author: Ole Peter Kristiansen, Steen B. Haugaard, Ahmad Sajadieh, Christian Anholm, Preman Kumarathurai, and Olav W. Nielsen
Subjects: Male, medicine.medical_specialty, lcsh:Diseases of the circulatory (Cardiovascular) system, Time Factors, Diastolic function, Endocrinology, Diabetes and Metabolism, Denmark, Diastole, Type 2 diabetes, Coronary Artery Disease, Ventricular Function, Left, Coronary artery disease, Ventricular Dysfunction, Left, Double-Blind Method, Heart Rate, Internal medicine, Heart rate, medicine, Humans, Hypoglycemic Agents, Angiology, Aged, Original Investigation, Echocardiography, Doppler, Pulsed, GLP-1 receptor agonists, Ejection fraction, Cross-Over Studies, Liraglutide, business.industry, Diabetes, Stroke Volume, Middle Aged, medicine.disease, Crossover study, Echocardiography, Doppler, Color, Treatment Outcome, Diabetes Mellitus, Type 2, lcsh:RC666-701, Echocardiography, Cardiology, Disease Progression, Female, Cardiology and Cardiovascular Medicine, business, medicine.drug
Abstract: BackgroundDiastolic dysfunction is highly prevalent in patients with type 2 diabetes mellitus (T2DM) and is associated with overweight, glucose dysregulation and coronary artery disease (CAD). The GLP-1 receptor agonist, liraglutide, has shown to induce weight loss and improve metabolic factors, thus modulating factors associated with diastolic dysfunction. We have previously reported the effects of liraglutide on systolic function, and in this current study we explore the effects of liraglutide on diastolic function parameters in patients with stable CAD, preserved left ventricular ejection fraction (LVEF), and newly diagnosed T2DM.MethodsThirty subjects were randomized to liraglutide or placebo intervention for 12 + 12-weeks in this double-blind cross-over study. 2D-echocardiography using tissue velocity imaging was used for assessment of diastolic function parameters. Early diastolic filling velocity (E), late atrial filling velocity (A), E-wave deceleration time (EDT) and E/A ratio was assessed from the pulse wave (PW)-Doppler velocity recording of the mitral inflow. Peak early diastolic annular velocities (e′) was measured from color tissue doppler images.ResultsLiraglutide, when compared to placebo, induced a significant reduction in average e′ and lateral e′ velocities (– 0.57 cm/s [– 1.05 to − 0.08] and –0.74 cm/s [–1.32 to –0.15], respectively). Adjusted for the concomitant increase in HR (+ 6.16 bpm [0.79 to 11.54], the changes were not significant. No significant changes in other diastolic function parameters were observed.ConclusionsLiraglutide therapy did not improve any diastolic function parameters in subjects with T2DM, CAD, and preserved LVEF. Instead, a deterioration in e’ was observed, which was associated to an increase in heart rate induced by liraglutide therapy.Trial registrationClinical Trial Registration:http://www.clinicaltrials.gov(unique identifier: NCT01595789) (first submitted May 8, 2012)
Published: 2021
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9. Lung Ultrasound Findings Associated With COVID-19 ARDS, ICU Admission, and All-Cause Mortality

Author: Matias Greve Lindholm, Søren Helbo Skaarup, Reza Jabbari, Caroline Espersen, Tor Biering-Sørensen, Henning Bundgaard, Niklas Dyrby Johansen, Jørn Carlsen, Elke Platz, Ole Peter Kristiansen, Charlotte Suppli Ulrik, Ole Kirk, Alia Saed Alhakak, Christian Hassager, Anne Bjerg Nielsen, Klaus Nielsen Jeschke, Kristoffer Grundtvig Skaarup, Olav W. Nielsen, Pradeesh Sivapalan, Mats Christian Højbjerg Lassen, Gunnar Gislason, Jannie Nørgaard Lind, Morten Sengeløv, Jens-Ulrik Stæhr Jensen, Morten Schou, and Kasper Iversen
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, ARDS, Lung ultrasound, Coronavirus disease 2019 (COVID-19), business.industry, Incidence (epidemiology), COVID-19, Risk stratifi-cation, General Medicine, Critical Care and Intensive Care Medicine, medicine.disease, Logistic regression, Procalcitonin, In-hospital outcomes, Internal medicine, Cohort, Medicine, Observational study, business
Abstract: BACKGROUND: As lung ultrasound (LUS) has emerged as a diagnostic tool in patients with COVID-19, we sought to investigate the association between LUS findings and the composite in-hospital outcome of ARDS incidence, ICU admission, and all-cause mortality. METHODS: In this prospective, multi-center, observational study, adults with laboratory-confirmed SARS-CoV-2 infection were enrolled from non-ICU in-patient units. Subjects underwent an LUS evaluating a total of 8 zones. Images were analyzed off-line, blinded to clinical variables and outcomes. A LUS score was developed to integrate LUS findings: ≥ 3 B-lines corresponded to a score of 1, confluent B-lines to a score of 2, and subpleural or lobar consolidation to a score of 3. The total LUS score ranged from 0–24 per subject. RESULTS: Among 215 enrolled subjects, 168 with LUS data and no cur-rent signs of ARDS or ICU admission (mean age 59 y, 56% male) were included. One hundred thirty-six (81%) subjects had pathologic LUS findings in ≥ 1 zone (≥ 3 B-lines, confluent B-lines, or consolidations). Markers of disease severity at baseline were higher in subjects with the composite outcome (n = 31, 18%), including higher median C-reactive protein (90 mg/L vs 55, P
Published: 2021
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10. Recovery of cardiac function following COVID-19 - ECHOVID-19: a prospective longitudinal cohort study

Author: Rasmus Mogelvang, Morten Sengeløv, Reza Jabbari, Scott D. Solomon, Olav W. Nielsen, Tor Biering-Sørensen, Mats Christian Højbjerg Lassen, Kasper Iversen, Jørn Carlsen, Gunnar Gislason, Peter Søgaard, Ole Peter Kristiansen, Charlotte Suppli Ulrik, Anne Bjerg Nielsen, Jacob Christensen, Kristoffer Grundtvig Skaarup, Henning Bundgaard, Jakob Øystein Simonsen, Jannie Nørgaard Lind, Ole Kirk, Alia Saed Alhakak, Christian Hassager, Peter Schnohr, Matias Greve Lindholm, Morten Schou, Niklas Dyrby Johansen, Pradeesh Sivapalan, Jens-Ulrik Stæhr Jensen, Filip Søskov Davidovski, and Gorm B. Jensen
Subjects: Cardiac function curve, Male, medicine.medical_specialty, Longitudinal study, Coronavirus disease 2019 (COVID-19), medicine.drug_class, Ventricular Dysfunction, Right, Cohort Studies, Interquartile range, Internal medicine, Natriuretic peptide, Medicine, Humans, Longitudinal Studies, Prospective Studies, Longitudinal cohort, Aged, Heart Failure, Covid‐19, biology, business.industry, SARS-CoV-2, COVID-19, Middle Aged, medicine.disease, Troponin, Heart failure, Cardiology, biology.protein, Ventricular Function, Right, Female, Cardiology and Cardiovascular Medicine, business, Editorial Comment
Abstract: AIMS: The degree of cardiovascular sequelae following COVID-19 remains unknown. The aim of this study was to investigate whether cardiac function recovers following COVID-19. METHODS AND RESULTS: A consecutive sample of patients hospitalized with COVID-19 was prospectively included in this longitudinal study. All patients underwent an echocardiographic examination during hospitalization and 2 months later. All participants were successfully matched 1:1 with COVID-19-free controls by age and sex. A total of 91 patients were included (mean age 63 ± 12 years, 59% male). A median of 77 days (interquartile range: 72-92) passed between the two examinations. Right ventricular (RV) function improved following resolution of COVID-19: tricuspid annular plane systolic excursion (TAPSE) (2.28 ± 0.40 cm vs. 2.11 ± 0.38 cm, P < 0.001) and RV longitudinal strain (RVLS) (25.3 ± 5.5% vs. 19.9 ± 5.8%, P < 0.001). In contrast, left ventricular (LV) systolic function assessed by global longitudinal strain (GLS) did not significantly improve (17.4 ± 2.9% vs. 17.6 ± 3.3%, P = 0.6). N-terminal pro-B-type natriuretic peptide decreased between the two examinations [177.6 (80.3-408.0) ng/L vs. 11.7 (5.7-24.0) ng/L, P < 0.001]. None of the participants had elevated troponins at follow-up compared to 18 (27.7%) during hospitalization. Recovered COVID-19 patients had significantly lower GLS (17.4 ± 2.9% vs. 18.8 ± 2.9%, P < 0.001 and adjusted P = 0.004), TAPSE (2.28 ± 0.40 cm vs. 2.67 ± 0.44 cm, P < 0.001 and adjusted P < 0.001), and RVLS (25.3 ± 5.5% vs. 26.6 ± 5.8%, P = 0.50 and adjusted P < 0.001) compared to matched controls. CONCLUSION: Acute COVID-19 affected negatively RV function and cardiac biomarkers but recovered following resolution of COVID-19. In contrast, the observed reduced LV function during acute COVID-19 did not improve post-COVID-19. Compared to the matched controls, both LV and RV function remained impaired.
Published: 2021

11. Excessive supraventricular ectopic activity and risk of incident atrial fibrillation in a consecutive population referred to ambulatory cardiac monitoring

Author: Ahmad Sajadieh, Ole Peter Kristiansen, Hanne Rasmusen, Mark Aplin, Olav W. Nielsen, Maria Helena Dominguez Vall-Lamora, Ulla Davidsen, Bjørn Strøier Larsen, Finn M. Karlsen, Nis Baun Høst, and Søren Højberg
Subjects: medicine.medical_specialty, Premature atrial contraction, Epidemiology, Population, Premature atrial contractions, Clinical, Internal medicine, Atrial Fibrillation, Diseases of the circulatory (Cardiovascular) system, Medicine, education, Survival analysis, Risk stratification, education.field_of_study, business.industry, Surrogate endpoint, Atrial fibrillation, medicine.disease, RC666-701, Cohort, Cardiology, business, Ambulatory cardiac monitoring
Abstract: Background: Excessive supraventricular ectopic activity (ESVEA), defined as ≥720 premature atrial contractions (PAC) per day or any runs of ≥20 PACs, has been proposed as a surrogate marker for paroxysmal atrial fibrillation (PAF). Objective: We aimed to estimate the prognostic impact of ESVEA on the future development of PAF in consecutive patients referred to ambulatory cardiac monitoring. Methods: The cohort consists of a population with comorbidities referred to 48-hour ambulatory electrocardiogram aged 30–98 (n = 1316) between 2009 and 2011. After exclusion of known or current atrial fibrillation (AF) (n = 527) and patients with pacemakers (n = 7), 782 patients were included, with a median follow-up of 8.1 years. Events of incident AF and death were retrieved from patient records. Results: Mean age was 58.6 ± 15.5 years and 56.5% were women. A total of 101 patients had ESVEA at baseline (12.9%). During follow-up, 69 (8.9%) developed incidental AF. Twenty-three patients with ESVEA developed AF (23%). Incidence rate of AF in patients with and without ESVEA was 37.1/1000 person-years and 9.1 per 1000 person-years, respectively (P < .001). ESVEA was associated with incident AF after adjustment for potential confounders in Cox regression analysis (hazard ratio [HR]: 2.39; 95% confidence interval [CI]: 1.40–4.09) and in competing risk analysis with death as competing risk (subdistribution HR: 2.35; 95% CI: 1.30–4.17). Conclusion: ESVEA increases the risk of incident AF substantially in a population referred to ambulatory cardiac monitoring.
Published: 2021
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12. Myocardial Impairment and Acute Respiratory Distress Syndrome in Hospitalized Patients With COVID-19

Author: Mats Christian Højbjerg Lassen, Klaus Nielsen Jeschke, Olav Wendelboe Nielsen, Eva Holt, Morten Sengeløv, Niels Tønder, Anne-Mette Lebech, K Skaarup, Shreeya Sharma, Birgitte Lindegaard Madsen, Ole Peter Kristiansen, Emil Schwarz Walsted, Jannik Langtved Pallisgaard, Reza Jabbari, D Modin, Gunnar Gislason, Niklas Dyrby Johansen, Filip K. Knop, Raphael Hauser, Liv Borum Schöps, Jannie Nørgaard Lind, Morten Schou, Gowsini Joseph, Pradeesh Sivapalan, Frank Vinholt Schiødt, Matias Greve Lindholm, Jens-Ulrik Stæhr Jensen, Kasper Iversen, Ole Kirk, Thomas Benfield, Lothar Wiese, Alia Saed Alhakak, Scott D. Solomon, Anne Bjerg Nielsen, Caroline Espersen, Tor Biering-Sørensen, Claus Graff, Charlotte Suppli Ulrik, Morten Lamberts, Christian Hassager, Uffe Bodtger, and Henning Bundgaard
Subjects: Male, ARDS, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Heart Diseases, Hospitalized patients, Denmark, Acute respiratory distress, 030204 cardiovascular system & hematology, medicine.disease_cause, Risk Assessment, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, Risk Factors, Internal medicine, medicine, Prevalence, Humans, Radiology, Nuclear Medicine and imaging, Prospective Studies, Prospective cohort study, Coronavirus, Aged, Aged, 80 and over, business.industry, COVID-19, Middle Aged, medicine.disease, Prognosis, Hospitalization, Imail, Radiology Nuclear Medicine and imaging, Echocardiography, Predictive value of tests, Female, Cardiology and Cardiovascular Medicine, Complication, business
Abstract: Acute respiratory distress syndrome (ARDS) is the primary complication observed in Coronavirus disease-2019 (COVID-19)–related deaths ([1][1]). Additionally, studies have found cardiac biomarkers to be increased in a significant proportion of patients, emphasizing COVID-19–related cardiac injury
Published: 2020

13. Liraglutide in combination with metformin may improve the atherogenic lipid profile and decrease C-reactive protein level in statin treated obese patients with coronary artery disease and newly diagnosed type 2 diabetes: A randomized trial

Author: Preman Kumarathurai, Christian Anholm, Sten Madsbad, Olav W. Nielsen, Rosemary L. Walzem, Lene Rørholm Pedersen, Mogens Fenger, Amirsalar Samkani, Ahmad Sajadieh, Ole Peter Kristiansen, and Steen B. Haugaard
Subjects: Blood Glucose, Male, 0301 basic medicine, medicine.medical_specialty, Time Factors, Statin, medicine.drug_class, Denmark, Coronary Artery Disease, Type 2 diabetes, 030204 cardiovascular system & hematology, Gastroenterology, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Internal medicine, medicine, Humans, Hypoglycemic Agents, Obesity, Aged, Cross-Over Studies, medicine.diagnostic_test, business.industry, Liraglutide, nutritional and metabolic diseases, Middle Aged, medicine.disease, Lipids, Metformin, C-Reactive Protein, Treatment Outcome, 030104 developmental biology, Diabetes Mellitus, Type 2, Drug Therapy, Combination, Female, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Inflammation Mediators, Cardiology and Cardiovascular Medicine, Lipid profile, business, Biomarkers, Dyslipidemia, medicine.drug, Lipoprotein
Abstract: Background and aims Atherosclerosis in obesity and type 2 diabetes (T2DM) is associated with low-grade inflammation (LGI) and dyslipidemia, where especially small, dense lipoprotein particles are atherogenic. The glucagon-like peptide-1 receptor agonist, liraglutide, reduces cardiovascular events by poorly understood mechanisms. We investigated the effect of liraglutide combined with metformin on LGI and lipoprotein density profiles in patients with stable coronary artery disease (CAD) and newly diagnosed T2DM. Methods We conducted a randomized, double-blind, placebo-controlled, cross-over trial over a 12 + 12-week period, with ≥2-week wash-out. Intervention: liraglutide/metformin vs. placebo/metformin. Lipoproteins were separated by continuous density gradient ultracentrifugation, and LDL divided into five subfractions between 226 and 270 A, considering particle size ≤255 A as the atherogenic pattern. Plasma C-reactive protein and tumor necrosis factor-α were assessed by the enzyme-linked immunosorbent-assay. Results 28 out of 41 randomized patients completed all visits. Intention-to-treat analysis was performed but one patient had statin dosage and was excluded from the analysis. 95% of the patients were on statin therapy. Overall, liraglutide did not affect lipid subfractions or markers of LGI compared to placebo. The combination of liraglutide and metformin reduced the total LDL subfractions, primarily by reducing the most atherogenic subfraction LDL 5 , and reduced CRP but not TNF-α. Explorative analyses suggested that the subfraction LDL 5 during the wash-out period rebounded significantly at least in a per-protocol analysis of the sub-group of patients starting the liraglutide therapy. Conclusions In patients with CAD and newly diagnosed T2DM on stable statin therapy, liraglutide combined with metformin may improve the atherogenic LDL lipid profile and CRP.
Published: 2019
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14. Effect of liraglutide on estimates of lipolysis and lipid oxidation in obese patients with stable coronary artery disease and newly diagnosed type 2 diabetes: A randomized trial

Author: Steen B. Haugaard, Sten Madsbad, Christian Anholm, Lene Rørholm Pedersen, Ahmad Sajadieh, Mogens Fenger, Ole Peter Kristiansen, Olav W. Nielsen, Raymond C. Boston, Amirsalar Samkani, and Preman Kumarathurai
Subjects: Blood Glucose, Male, medicine.medical_specialty, endocrine system diseases, Lipolysis, Endocrinology, Diabetes and Metabolism, Blood sugar, 030209 endocrinology & metabolism, Coronary Artery Disease, Type 2 diabetes, Fatty Acids, Nonesterified, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, NEFA, Insulin resistance, Double-Blind Method, Lipid oxidation, Internal medicine, Internal Medicine, medicine, Humans, Hypoglycemic Agents, Obesity, Aged, Cross-Over Studies, medicine.diagnostic_test, business.industry, Liraglutide, Middle Aged, Lipid Metabolism, medicine.disease, Metformin, Treatment Outcome, Diabetes Mellitus, Type 2, Drug Therapy, Combination, Female, Lipid profile, business, Oxidation-Reduction, medicine.drug
Abstract: Elevated levels of non-esterified fatty acids (NEFA) play a role in insulin resistance, impaired beta-cell function and they are a denominator of the abnormal atherogenic lipid profile that characterizes obese patients with type 2 diabetes (T2DM). We hypothesized that the GLP-1 receptor agonist liraglutide, in combination with metformin, would reduce lipolysis. In a randomized, double-blind, placebo-controlled, cross-over trial, 41 T2DM patients with coronary artery disease were randomized and treated with liraglutide-metformin vs placebo-metformin during 12- + 12-week periods with a wash-out period of at least 2 weeks before and between the intervention periods. NEFA kinetics were estimated using the Boston Minimal Model of NEFA metabolism, with plasma NEFA and glucose levels measured during a standard 180-minute frequently sampled intravenous glucose tolerance test. Liraglutide-metformin reduced estimates of lipolysis. Furthermore, placebo-metformin increased estimates of lipid oxidation, while treatment with liraglutide eliminated this effect. We conclude that liraglutide exerts a clinically relevant reduction in estimates of lipolysis and lipid oxidation which is explained, in part, by improved insulin secretion, as revealed by an intravenous glucose tolerance test.
Published: 2019
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15. Prognostic Value of Coronary CT Angiography in Patients With Non–ST-Segment Elevation Acute Coronary Syndromes

Author: Klaus F. Kofoed, Susette K. Therkelsen, Rolf Steffensen, Henning Kelbæk, Lene Kløvgaard, Tem Jørgensen, Ida Hastrup Svendsen, Thomas Engstrøm, Ilan Raymond, Stig Lyngbæk, Steffen Helqvist, Frants Pedersen, Merete Heitmann, Peter Clemmensen, Jawdat Abdulla, Jørgen Tobias Kühl, Lene Holmvang, Christian Torp-Pedersen, Birgit Jurlander, Gunnar Gislason, Gitte G. Fornitz, Søren Galatius, Per E Sigvardsen, Kari Saunamäki, Jesper J. Linde, Lars Køber, Martina Chantal de Knegt, Ole Peter Kristiansen, Lia E. Bang, Jens D. Hove, Charlotte Kragelund, Dan Eik Høfsten, Peter Riis Hansen, Erik Jørgensen, Hanne Elming, Thomas Fritz-Hansen, Jan Bech, M H Domínguez Vall-Lamora, Ulrik Abildgaard, and Olav W. Nielsen
Subjects: Male, medicine.medical_specialty, Acute coronary syndrome, Computed Tomography Angiography, Myocardial Infarction, Myocardial Ischemia, risk stratification, 030204 cardiovascular system & hematology, Risk Assessment, Severity of Illness Index, acute coronary syndrome, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Internal medicine, medicine, Clinical endpoint, ST segment, Humans, angiography, 030212 general & internal medicine, cardiovascular diseases, Acute Coronary Syndrome, cardiac computed tomography, Aged, Heart Failure, medicine.diagnostic_test, business.industry, Hazard ratio, Coronary Stenosis, medicine.disease, Prognosis, Heart failure, Angiography, Cardiology, Female, prognosis, Cardiology and Cardiovascular Medicine, business
Abstract: Background Severity and extent of coronary artery disease (CAD) assessed by invasive coronary angiography (ICA) guide treatment and may predict clinical outcome in patients with non–ST-segment elevation acute coronary syndrome (NSTEACS). Objectives This study tested the hypothesis that coronary computed tomography angiography (CTA) is equivalent to ICA for risk assessment in patients with NSTEACS. Methods The VERDICT (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes) trial evaluated timing of treatment in relation to outcome in patients with NSTEACS and included a clinically blinded coronary CTA conducted prior to ICA. Severity of CAD was defined as obstructive (coronary stenosis ≥50%) or nonobstructive. Extent of CAD was defined as high risk (obstructive left main or proximal left anterior descending artery stenosis and/or multivessel disease) or non–high risk. The primary endpoint was a composite of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or heart failure. Results Coronary CTA and ICA were conducted in 978 patients. During a median follow-up time of 4.2 years (interquartile range: 2.7 to 5.5 years), the primary endpoint occurred in 208 patients (21.3%). The rate of the primary endpoint was up to 1.7-fold higher in patients with obstructive CAD compared with in patients with nonobstructive CAD as defined by coronary CTA (hazard ratio [HR]: 1.74; 95% confidence interval [CI]: 1.22 to 2.49; p = 0.002) or ICA (HR: 1.54; 95% CI: 1.13 to 2.11; p = 0.007). In patients with high-risk CAD, the rate of the primary endpoint was 1.5-fold higher compared with the rate in those with non–high-risk CAD as defined by coronary CTA (HR: 1.56; 95% CI: 1.18 to 2.07; p = 0.002). A similar trend was noted for ICA (HR: 1.28; 95% CI: 0.98 to 1.69; p = 0.07). Conclusions Coronary CTA is equivalent to ICA for the assessment of long-term risk in patients with NSTEACS. (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes [VERDICT]; NCT02061891 )
Published: 2021
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16. Night-time heart rate variability identifies high-risk people among people with uncomplicated type 2 diabetes mellitus

Author: Ahmad Sajadieh, Ole Peter Kristiansen, Steen B. Haugaard, Bjørn Strøjer Larsen, Philip Weber, Dorte Marie Stavnem, Olav W. Nielsen, and Rakin Hadad
Subjects: Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Population, Myocardial Infarction, 030209 endocrinology & metabolism, Type 2 diabetes, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Heart Rate, Internal medicine, Internal Medicine, medicine, Heart rate variability, Humans, 030212 general & internal medicine, Myocardial infarction, education, Stroke, Aged, education.field_of_study, business.industry, Hazard ratio, Middle Aged, medicine.disease, Confidence interval, Blood pressure, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Cardiology, Electrocardiography, Ambulatory, Female, business, Sleep, Follow-Up Studies
Abstract: Background Low heart rate variability (HRV) reflects cardiac autonomic neuropathy, which is associated with increased cardiovascular mortality in people with type 2 diabetes mellitus (T2DM). Measuring HRV is challenged by environmental noise, mental stress and physical activity during daytime. Night-time HRV during sleep may be a more valid tool to measure cardiac autonomic neuropathy and therefore may improve prediction of cardiovascular (CV) events in low-risk people with T2DM. Methods Copenhagen Holter Study included 678 community-dwelling participants aged 55-75 years who were free of previous CV disease. Day and night-time HRV were available for 653 participants. The population included 133 people with well-controlled T2DM and newly recognized T2DM (mean HbA1c 55 mmol/mol [7.2%]). HRV is defined as standard deviation for the mean value of normal-to-normal complexes (SDNN). Night-time HRV measurements were pre-defined from 2:00 to 2:15 AM. Cardiovascular events were defined as CV death, myocardial infarction, stroke or coronary revascularization. Results Median follow-up time was 14.4 years. During this period, 245 death and 149 CV events (CV death 36, myocardial infarction 42, revascularisation procedures 46, stroke 70) occurred in total. Among people with T2DM, 41 CV events were observed (CV death 13, myocardial infarction 13, revascularisation procedures 17, stroke 18). Night-time SDNN was inversely associated with CV events in people with T2DM, (hazard ratio [HR]: 0.74 95% confidence interval [CI]:0.61-0.89) for each 10-millisecond increment in SDNN after adjustment for the conventional risk factors sex, age, LDL cholesterol, smoking, systolic blood pressure and by also including glucose CRP and NT-proBNP in adjustment. Twenty-four-hour HRV was not associated with CV events, but associated with all-cause mortality in people with T2DM. Conventional risk factors had a receiver operating characteristic (ROC) value of 0.704 (95% CI 0.602-0.806) to predict CV events in people with T2DM. The prediction of CV events by conventional risk factors was improved in people with T2DM by the addition of night-time SDNN; ROC 0.765 (95% CI 0.669-0.862), p = 0.037, but ROC was not improved by addition of CRP and NT-proBNP in the model. In people with T2DM and night-time SDNN ≤30 ms, the 10-year risk of CV death and CV event rate was 12% and 45%, respectively, which re-allocated them to a 'very high-risk' group according to current guidelines. Conclusion Reduced night-time HRV predicts increased risk of CV events in people with well-controlled T2DM, thus night-time HRV may add to traditional risk factors in predicting CV events in people with T2DM.
Published: 2021

17. Echocardiographic abnormalities and predictors of mortality in hospitalized COVID-19 patients:the ECHOVID-19 study

Author: Birgitte Lindegaard Madsen, Niklas Dyrby Johansen, Ole Kirk, Morten Schou, Gorm Boje Jensen, Morten Sengeløv, Thomas Benfield, Mats Christian Højbjerg Lassen, Kasper Iversen, Henning Bundgaard, Peter Søgaard, Jens-Ulrik Stæhr Jensen, Morten Lamberts, Kristoffer Grundtvig Skaarup, Lothar Wiese, Caroline Espersen, Tor Biering-Sørensen, Uffe Bodtger, Frank V. Schiødt, Jacob Louis Marott, Filip K. Knop, Kasper Djernæs, Christian Hassager, Charlotte Suppli Ulrik, Niels Tønder, Emil S. Walsted, Rasmus Mogelvang, Jannie Nørgaard Lind, Jørn Carlsen, Klaus Nielsen Jeschke, Reza Jabbari, Peter Schnohr, Eva Holt, Liv Borum Schöps, Matias Greve Lindholm, Claus Graff, Daniel Modin, Raphael Hauser, Alia Saed Alhakak, Scott D. Solomon, Ole Peter Kristiansen, Pradeesh Sivapalan, Gunnar Gislason, Gowsini Joseph, Kirstine Ravnkilde, Anne Bjerg Nielsen, Anne-Mette Lebech, and Olav W. Nielsen
Subjects: Global longitudinal strain, STRAIN, medicine.medical_specialty, Heart disease, Coronavirus disease 2019 (COVID-19), Population, 030204 cardiovascular system & hematology, GUIDELINES, RECOMMENDATIONS, SARS‐CoV‐2, covid19, 03 medical and health sciences, 0302 clinical medicine, COVID‐19, Original Research Articles, Internal medicine, Diseases of the circulatory (Cardiovascular) system, Medicine, Original Research Article, 030212 general & internal medicine, education, AMERICAN SOCIETY, EUROPEAN ASSOCIATION, education.field_of_study, business.industry, Proportional hazards model, SARS-CoV-2, Hazard ratio, COVID-19, ADULTS, medicine.disease, Confidence interval, Right ventricular strain, Echocardiography, RC666-701, Heart failure, Cardiology, UPDATE, HEART, Cardiology and Cardiovascular Medicine, business, CARDIAC CHAMBER QUANTIFICATION, Cohort study
Abstract: Aims The present study had two aims: (i) compare echocardiographic parameters in COVID-19 patients with matched controls and (2) assess the prognostic value of measures of left (LV) and right ventricular (RV) function in relation to COVID-19 related death.Methods and results In this prospective multicentre cohort study, 214 consecutive hospitalized COVID-19 patients underwent an echocardiographic examination (by pre-determined research protocol). All participants were successfully matched 1:1 with controls from the general population on age, sex, and hypertension. Mean age of the study sample was 69 years, and 55% were male participants. LV and RV systolic function was significantly reduced in COVID-19 cases as assessed by global longitudinal strain (GLS) (16.4% +/- 4.3 vs. 18.5% +/- 3.0,P Conclusions RV and LV function are significantly impaired in hospitalized COVID-19 patients compared with matched controls. Furthermore, reduced TAPSE and GLS are independently associated with COVID-19-related death.
Published: 2020
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18. Early Versus Standard Care Invasive Examination and Treatment of Patients With Non-ST-Segment Elevation Acute Coronary Syndrome

Author: Ilan Raymond, Kari Saunamäki, Thomas Engstrøm, Peter Clemmensen, Erik Jørgensen, Ole Peter Kristiansen, Dan Eik Høfsten, Hanne Elming, Jan Skov Jensen, Olav W. Nielsen, Henning Kelbæk, Jens D. Hove, Jan Bech, Søren Galatius, Rolf Steffensen, Gunnar Gislason, Klaus F. Kofoed, Merete Heitmann, Lene Kløvgaard, Maria Helena Dominguez Vall-Lamora, Lars Køber, Gitte G. Fornitz, Ulrik Abildgaard, Charlotte Kragelund, Ida Hastrup Svendsen, Stig Lyngbæk, Lene Holmvang, Steffen Helqvist, Birgit Jurlander, Lia Bang, Peter Riis Hansen, Christian Torp-Pedersen, Susette K. Therkelsen, Frants Pedersen, Jesper J. Linde, Tem Jørgensen, Thomas Fritz Hansen, and Jawdat Abdulla
Subjects: Male, medicine.medical_specialty, Acute coronary syndrome, Troponin/metabolism, medicine.medical_treatment, clinical outcome, 030204 cardiovascular system & hematology, Revascularization, time factors, acute coronary syndrome, 03 medical and health sciences, 0302 clinical medicine, Standard care, Risk Factors, Physiology (medical), Internal medicine, medicine, Humans, ST segment, In patient, 030212 general & internal medicine, Percutaneous Coronary Intervention/adverse effects, Proportional Hazards Models, Aged, Coronary Angiography/methods, business.industry, Elevation, PCI, Middle Aged, medicine.disease, Acute Coronary Syndrome/diagnosis, Invasive coronary angiography, Heart Arrest/etiology, Treatment Outcome, Cardiology, Female, coronary revascularization, Cardiology and Cardiovascular Medicine, business
Abstract: Background: The optimal timing of invasive coronary angiography (ICA) and revascularization in patients with non-ST-segment elevation acute coronary syndrome is not well defined. We tested the hypothesis that a strategy of very early ICA and possible revascularization within 12 hours of diagnosis is superior to an invasive strategy performed within 48 to 72 hours in terms of clinical outcomes. Methods: Patients admitted with clinical suspicion of non-ST-segment elevation acute coronary syndrome in the Capital Region of Copenhagen, Denmark, were screened for inclusion in the VERDICT trial (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography) ( ClinicalTrials.gov NCT02061891). Patients with ECG changes indicating new ischemia or elevated troponin, in whom ICA was clinically indicated and deemed logistically feasible within 12 hours, were randomized 1:1 to ICA within 12 hours or standard invasive care within 48 to 72 hours. The primary end point was a combination of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or hospital admission for heart failure. Results: A total of 2147 patients were randomized; 1075 patients allocated to very early invasive evaluation had ICA performed at a median of 4.7 hours after randomization, whereas 1072 patients assigned to standard invasive care had ICA performed 61.6 hours after randomization. Among patients with significant coronary artery disease identified by ICA, coronary revascularization was performed in 88.4% (very early ICA) and 83.1% (standard invasive care). Within a median follow-up time of 4.3 (interquartile range, 4.1–4.4) years, the primary end point occurred in 296 (27.5%) of participants in the very early ICA group and 316 (29.5%) in the standard care group (hazard ratio, 0.92; 95% CI, 0.78–1.08). Among patients with a GRACE risk score (Global Registry of Acute Coronary Events) >140, a very early invasive treatment strategy improved the primary outcome compared with the standard invasive treatment (hazard ratio, 0.81; 95% CI, 0.67–1.01; P value for interaction=0.023). Conclusions: A strategy of very early invasive coronary evaluation does not improve overall long-term clinical outcome compared with an invasive strategy conducted within 2 to 3 days in patients with non-ST-segment elevation acute coronary syndrome. However, in patients with the highest risk, very early invasive therapy improves long-term outcomes. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02061891.
Published: 2018
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19. Liraglutide effects on beta-cell, insulin sensitivity and glucose effectiveness in patients with stable coronary artery disease and newly diagnosed type 2 diabetes

Author: Christian Anholm, Olav W. Nielsen, Mogens Fenger, Ole Peter Kristiansen, Lene Rørholm Pedersen, Sten Madsbad, Preman Kumarathurai, Steen B. Haugaard, and Ahmad Sajadieh
Subjects: Blood Glucose, Male, medicine.medical_specialty, endocrine system diseases, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Coronary Artery Disease, Type 2 diabetes, 030204 cardiovascular system & hematology, Overweight, Placebo, Gastroenterology, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Double-Blind Method, Weight loss, Insulin-Secreting Cells, Internal medicine, Internal Medicine, Humans, Hypoglycemic Agents, Medicine, Obesity, Aged, Cross-Over Studies, business.industry, Liraglutide, nutritional and metabolic diseases, Type 2 Diabetes Mellitus, Middle Aged, medicine.disease, Metformin, Diabetes Mellitus, Type 2, Female, Insulin Resistance, medicine.symptom, business, medicine.drug
Abstract: AIMS The aims of the study were to investigate the effects of the GLP-1 receptor agonist liraglutide as add-on to metformin on insulin sensitivity (Si) and glucose effectiveness (Sg) in addition to its positive effects on beta-cell function in overweight/obese patients with coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM). METHODS The design of the study was a randomized, double-blind, placebo-controlled, cross-over trial in patients with stable CAD and newly diagnosed well-controlled T2DM. Patients were treated with liraglutide/metformin vs placebo/metformin for a 12 + 12-week period with ≥2-week wash-out. First phase insulin secretion (AIRg), Si and Sg were estimated by the Bergman Minimal Model, enabling calculation of beta-cell function; Disposition Index (DI) = AIRg × Si. A total of 30 patients from among 41 randomized were available for paired analysis. RESULTS Baseline characteristics were: HbA1c 47 mmol/mol (SD 6), BMI 31.6 kg/m2 (SD 4.8), fasting plasma-glucose 6.9 mmol/L (IQR 6.1; 7.4) and HOMA-IR 4.9 (IQR 3.0; 7.5). Liraglutide treatment improved AIRg by 3-fold, 497 mU × L-1 × min (IQR 342; 626, P
Published: 2017
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20. Liraglutide improves the beta-cell function without increasing insulin secretion during a mixed meal in patients, who exhibit well-controlled type 2 diabetes and coronary artery disease

Author: Olav W. Nielsen, Anders Jürs, Ole Peter Kristiansen, Christian Anholm, Ahmad Sajadieh, Jens J. Holst, Steen B. Haugaard, Preman Kumarathurai, Lene Rørholm Pedersen, Sten Madsbad, and Mogens Fenger
Subjects: medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Beta-cell function, 030209 endocrinology & metabolism, Type 2 diabetes, Insulin clearance, 030204 cardiovascular system & hematology, Glucagon, 03 medical and health sciences, Diabetes mellitus type 2, 0302 clinical medicine, Insulin resistance, Diabetes mellitus, Internal medicine, Internal Medicine, Hyperinsulinemia, Medicine, lcsh:RC620-627, business.industry, Liraglutide, Research, Insulin, Meal test, Insulin sensitivity, medicine.disease, Metformin, lcsh:Nutritional diseases. Deficiency diseases, Endocrinology, business, GLP1-receptor agonist, medicine.drug
Abstract: Background Hyperinsulinemia aggravates insulin resistance and cardio-vascular disease. How the insulinotropic glucagon-like peptide-1 receptor agonist liraglutide in a physiologic post-prandial setting may act on pancreatic alpha and beta-cell function in patients with coronary artery disease (CAD) and type 2 diabetes (T2DM) is less clear. Methods Insulin resistant patients with established CAD and newly diagnosed well-controlled T2DM were recruited to a placebo-controlled, cross-over trial with two treatment periods of 12 weeks and a 2 weeks wash-out period before and in-between. Treatment was liraglutide or placebo titrated from 0.6 mg q.d. to 1.8 mg q.d. within 4 weeks and metformin titrated from 500 mg b.i.d to 1000 mg b.i.d. within 4 weeks. Before and after intervention in both 12 weeks periods insulin, C-peptide, glucose, and glucagon were measured during a meal test. Beta-cell function derived from the oral glucose tolerance setting was calculated as changes in insulin secretion per unit changes in glucose concentration (Btotal) and whole-body insulin resistance using ISIcomposite. Results Liraglutide increased the disposition index [Btotal × ISIcomposite, by 40% (n = 24, p Conclusions The insulinotropic drug liraglutide may without increasing the insulin concentration reduce postprandial glucose but not glucagon excursions and improve beta-cell function in newly diagnosed and well-controlled T2DM. Trial registration Clinicaltrials.gov ID: NCT01595789
Published: 2019
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21. RECOVERY OF CARDIAC FUNCTION FOLLOWING COVID-19 INFECTION: ECHOVID-19 - A LONGITUDINAL COHORT STUDY

Author: Morten Sengeløv, Jannie N. Nørgaard, Henning Bundgaard, Peter Schnohr, Ole Peter Kristiansen, Jakob Øystein Simonsen, Morten Schou, Ole Kirk, Jørn Carlsen, Christian Hassager, Alia Saed Alhakak, Charlotte Suppli Ulrik, Morten Lamberts, Mats Christian Højbjerg Lassen, Anne Orholm Nielsen, Reza Jabbari, Kristoffer Grundtvig Skaarup, Kasper Iversen, Rasmus Mogelvang, Olav W. Nielsen, Peter Søgaard, Gorm B. Jensen, Niklas Dyrby Johansen, and Jens U.S. Jensen
Subjects: Cardiac function curve, medicine.medical_specialty, Text mining, Spotlight on Special Topics, Coronavirus disease 2019 (COVID-19), business.industry, Internal medicine, Medicine, Longitudinal cohort, Cardiology and Cardiovascular Medicine, business
Published: 2021
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22. Early Versus Standard Care Invasive Examination and Treatment of Patients With Non-ST-Segment Elevation Acute Coronary Syndrome

Author: Klaus F, Kofoed, Henning, Kelbæk, Peter Riis, Hansen, Christian, Torp-Pedersen, Dan, Høfsten, Lene, Kløvgaard, Lene, Holmvang, Steffen, Helqvist, Erik, Jørgensen, Søren, Galatius, Frants, Pedersen, Lia, Bang, Kari, Saunamaki, Peter, Clemmensen, Jesper J, Linde, Merete, Heitmann, Olav, Wendelboe Nielsen, Ilan E, Raymond, Ole Peter, Kristiansen, Ida Hastrup, Svendsen, Jan, Bech, Maria Helena, Dominguez Vall-Lamora, Charlotte, Kragelund, Thomas Fritz, Hansen, Jens, Dahlgaard Hove, Tem, Jørgensen, Gitte G, Fornitz, Rolf, Steffensen, Birgit, Jurlander, Jawdat, Abdulla, Stig, Lyngbæk, Hanne, Elming, Susette Krohn, Therkelsen, Ulrik, Abildgaard, Jan Skov, Jensen, Gunnar, Gislason, Lars V, Køber, and Thomas, Engstrøm
Subjects: Male, Time Factors, Middle Aged, Coronary Angiography, Troponin, Heart Arrest, Percutaneous Coronary Intervention, Treatment Outcome, Risk Factors, Humans, Female, Acute Coronary Syndrome, Aged, Proportional Hazards Models
Abstract: The optimal timing of invasive coronary angiography (ICA) and revascularization in patients with non-ST-segment elevation acute coronary syndrome is not well defined. We tested the hypothesis that a strategy of very early ICA and possible revascularization within 12 hours of diagnosis is superior to an invasive strategy performed within 48 to 72 hours in terms of clinical outcomes.Patients admitted with clinical suspicion of non-ST-segment elevation acute coronary syndrome in the Capital Region of Copenhagen, Denmark, were screened for inclusion in the VERDICT trial (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography) ( ClinicalTrials.gov NCT02061891). Patients with ECG changes indicating new ischemia or elevated troponin, in whom ICA was clinically indicated and deemed logistically feasible within 12 hours, were randomized 1:1 to ICA within 12 hours or standard invasive care within 48 to 72 hours. The primary end point was a combination of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or hospital admission for heart failure.A total of 2147 patients were randomized; 1075 patients allocated to very early invasive evaluation had ICA performed at a median of 4.7 hours after randomization, whereas 1072 patients assigned to standard invasive care had ICA performed 61.6 hours after randomization. Among patients with significant coronary artery disease identified by ICA, coronary revascularization was performed in 88.4% (very early ICA) and 83.1% (standard invasive care). Within a median follow-up time of 4.3 (interquartile range, 4.1-4.4) years, the primary end point occurred in 296 (27.5%) of participants in the very early ICA group and 316 (29.5%) in the standard care group (hazard ratio, 0.92; 95% CI, 0.78-1.08). Among patients with a GRACE risk score (Global Registry of Acute Coronary Events)140, a very early invasive treatment strategy improved the primary outcome compared with the standard invasive treatment (hazard ratio, 0.81; 95% CI, 0.67-1.01; P value for interaction=0.023).A strategy of very early invasive coronary evaluation does not improve overall long-term clinical outcome compared with an invasive strategy conducted within 2 to 3 days in patients with non-ST-segment elevation acute coronary syndrome. However, in patients with the highest risk, very early invasive therapy improves long-term outcomes.URL: https://www.clinicaltrials.gov . Unique identifier: NCT02061891.
Published: 2018

23. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Author: Adrian F Hernandez, Jennifer B Green, Salim Janmohamed, Ralph B D'Agostino, Christopher B Granger, Nigel P Jones, Lawrence A Leiter, Anne E Rosenberg, Kristina N Sigmon, Matthew C Somerville, Karl M Thorpe, John J V McMurray, Stefano Del Prato, John J.V. McMurray, Ralph B. D'Agostino, Christopher B. Granger, Adrian F. Hernandez, Lawrence A. Leiter, Robert M Califf, Rury Holman, David DeMets, Matthew Riddle, Shaun Goodman, Darren McGuire, Karen Alexander, Adam Devore, Chiara Melloni, Chetan Patel, David Kong, Gerald Bloomfield, Matthew Roe, Pierluigi Tricoci, Rob Harrison, Renato Lopes, Robin Mathews, Rajendra Mehta, William Schuyler Jones, Sreekanth Vemulapalli, Thomas Povsic, Zubin Eapen, Keith Dombrowski, Brad Kolls, Dedrick Jordan, Andrew Ambrosy, Stephen Greene, Aditya Mandawat, Jay Shavadia, Lauren Cooper, Abhinav Sharma, Patricia Guimaraes, Daniel Friedman, Matt Wilson, Patricia Endsley, Tracy Gentry, Jeannie Collier, Kathleen Perez, Kourtnei James, Jennifer Roush, Connie Pope, Christina Howell, Megan Johnson, Matt Bailey, Joanna Cole, Teresa Akers, Beth Vandyne, Betsy Thomas, Jenny Rich, Susan Bartone, Gail Beaulieu, Kim Brown, Tuan Chau, Tamra Christian, Rebecca Coker, Deb Greene, Trevorlyn Haddock, Wendy Jenkins, Ghazala Haque, Marsha Marquess, Jean Pesarchick, Renee Rethaford, Allegra Stone, Firas Al Kawas, Michelle Anderson, Robert Enns, Isaac Sinay, Chantal Mathieu, Victor Yordanov, Irene Hramiak, Martin Haluzik, Søren Galatius, Bruno Guerci, Michael Nauck, Ilias Migdalis, Choon Beng Kathryn Tan, Gyozo Kocsis, Andrea Giaccari, Moon Kyu Lee, Ernesto German Cardona Muñoz, Jan Cornel, Kare Birkeland, Miguel Pinto, Louie Tirador, Martyna Olesinska-Mader, Marina Shestakova, Larry Distiller, Jose Lopez-Sendon, Bjorn Eliasson, Chern-En Chiang, Suphot Srimahachota, Boris Mankovsky, M Angelyn Bethel, Kathleen Dungan, Mikhail Kosiborod, Andres Alvarisqueta, Jorge Baldovino, Diego Besada, Pedro Calella, Maria Cecilia Cantero, Patricia Castaño, Alejandro Chertkoff, Jesus Cuadrado, Luis De Loredo, Andrea Dominguez, Maria Vanesa Español, Hernan Finkelstein, Gustavo Frechtel, Jose Fretes, Natalia Garrido Santos, Joaquin Gonzalez, Marcos Litvak, Juan Loureyro, Laura Maffei, Natacha Maldonado, Diego Mohr Gasparini, Silvia Orio, Federico Perez Manghi, Nelson Rodriguez Papini, Jorgelina Sala, Pablo Schygiel, Georgina Sposetti, Maria Ulla, Fernando Verra, Silvina Zabalua, Cesar Zaidman, Laurent Crenier, Corinne Debroye, Francis Duyck, André Scheen, Luc Van Gaal, Chris Vercammen, Velichka Damyanova, Stefan Dimitrov, Snezhina Kovacheva, Lachezar Lozanov, Viktor Margaritov, Rositsa Mihaylova-Shumkova, Antoaneta Nikolaeva, Zhasmina Stoyanova, Ronald Akhras, Yves Beaudry, Jacques Bedard, Joseph Berlingieri, Raja Chehayeb, Stephen Cheung, James Conway, Jean Cusson, Anthony Della Siega, Richard Dumas, Peter Dzongowski, Murdo Ferguson, Daniel Gaudet, Francois Grondin, Anil Gupta, Milan Gupta, Frank Halperin, Pierre-Alain Houle, Michael Jones, Simon Kouz, Christopher Kovacs, Daniel Landry, Eva Lonn, William O'Mahony, Sean Peterson, Dennis Reich, Alan Rosenbloom, Francois St-Maurice, Barna Tugwell, Saul Vizel, Vincent Woo, Tomas Brychta, Vladimir Cech, Eva Dvorakova, Tomas Edelsberger, Katarina Halciakova, Jarmila Krizova, Jiri Lastuvka, Martin Piperek, Vera Prymkova, Lea Raclavska, Elena Silhova, Robin Urbanek, Jan Vrkoc, Ulla Andersen, Jens Brønnum-Schou, Jens Hove, Jan Skov Jensen, Lars Kober, Ole Peter Kristiansen, Per Lund, Thomas Melchior, Ole Nyvad, Morten Schou, Alain Boye, Didier Cadinot, Didier Gouet, Patrick Henry, Laurence Kessler, Jean-Daniel Lalau, Catherine Petit, Jean-Francois Thuan, Christel Voinot, Julien Vouillarmet, Christoph Axthelm, Dirk Berger, Tasso Bieler, Andreas Birkenfeld, Jochen Bott, Klaus Busch, Karel Caca, Julia Chevts, Torsten Donaubauer, Rudolf Erlinger, Klaus Funke, Josef Grosskopf, Andreas Hagenow, Monika Hamann, Manfred Hartard, Peter Heymer, Wolfgang Huppertz, Gabriele Illies, Stephan Jacob, Thomas Jung, Gerd Kahrmann, Petra Kast, Monika Kellerer, Hans-Peter Kempe, Andrei Khariouzov, Gerhard Klausmann, Christiane Klein, Uwe Kleinecke-Pohl, Klaus Kleinertz, Thorsten Koch, Christine Kosch, Babette Lorra, Joerg Luedemann, Matthias Luttermann, Stephan Maxeiner, Karsten Milek, Andrea Moelle, Gerhard Neumann, Ruth Nischik, Edith Oehrig-Pohl, Georg Plassmann, Lars Pohlmeier, Felix Proepper, Stefan Regner, Werner Rieker, Ludger Rose, Holger Samer, Joachim Sauter, Frank Schaper, Clemens Schiffer, Juergen Schmidt, Bernd-M. Scholz, Joerg Schulze, Alexander Segner, Jochen Seufert, Helena Sigal, Joerg Steindorf, Juergen Stockhausen, Petra Stuebler, Heidrun Taeschner, Dietrich Tews, Diethelm Tschoepe, Karl Wilhelm, Helga Zeller-Stefan, Iakovos Avramidis, Stavros Bousboulas, Magdalini Bristianou, Georgios Dimitriadis, Moses Elisaf, Kalliopi Kotsa, Andreas Melidonis, Asimina Mitrakou, Emmanouil Pagkalos, Nikolaos Papanas, Angelos Pappas, Christos Sampanis, Nikolaos Tentolouris, Apostolos Tsapas, Glykeria Tzatzagou, Risa Ozaki, Csaba Hajdú, Eleonóra Harcsa, Laszlo Konyves, János Mucsi, Zsolt Pauker, Gizella Petró, Zsolt Plés, Katalin Revesz, Vangel Sándor, Viktor Vass, Angelo Avogaro, Massimo Boemi, Riccardo Bonadonna, Agostino Consoli, Salvatore De Cosmo, Paolo Di Bartolo, Francesco Dotta, Simona Frontoni, Marianna Galetta, Alessandra Gambineri, Carmine Gazzaruso, Francesco Giorgino, Davide Lauro, Emanuela Orsi, Giuseppe Paolisso, Gabriele Perriello, Piermarco Piatti, Antonio Pontiroli, Paola Ponzani, Angela Albarosa Rivellese, Giorgio Sesti, Giancarlo Tonolo, Roberto Trevisan, Chul Woo Ahn, Sei-Hyun Baik, Bong-Soo Cha, Choon-Hee Chung, Hak Chul Jang, Chong-Jin Kim, Hye Soon Kim, In Joo Kim, Eun Young Lee, Hyoung Woo Lee, Kwan-Woo Lee, Keon-Woong Moon, June Namgung, Kyong Soo Park, Soon Jib Yoo, Jaemyung Yu, Edmundo-Alfredo Bayram Llamas, Jose-Luis Cervantes-Escárcega, Luis Fernando Flota-Cervera, José Gerardo González-González, Sara Pascoe-Gonzalez, Emilia Susana Pelayo-Orozco, Santiago-Paulino Ramirez-Diaz, Arturo Saldana-Mendoza, Carlos Sánchez Jerjes-Díaz, Jose Juan Torres-Colores, Maricela Vidrio-Velázquez, Juan Villagordoa-Mesa, Hugo Peter Beijerbacht, Reginald G.E.J. Groutars, Boudewijn A Hoek, Pieter A.M. Hoogslag, Adriaan Kooy, Johannes A. Kragten, Aloysius G. Lieverse, Hendrik P. Swart, Eric P. Viergever, Jørn Ahlqvist, John Cooper, Hanne Gulseth, Gaute Guttormsen, Cecilie Wium, Hugo Arbañil, Jorge Calderon, Luis Camacho, Augusto Dextre Espinoza, Elizabeth Garrido, Alejandro Luna, Helard Manrique, Frederick Massucco Revoredo, Rolando Vargas Gonzales, Luis Zapata Rincon, Carlos Zubiate, Geraldine Ebo, Ellen Morales-Palomares, Malgorzata Arciszewska, Marek Banach, Renata Bijata-Bronisz, Tadeusz Derezinski, Waldemar Gadzinski, Jacek Gajek, Katarzyna Klodawska, Ewa Krzyzagorska, Andrzej Madej, Pawel Miekus, Jaroslaw Opiela, Piotr Romanczuk, Anna Siegel, Ewa Skokowska, Andrzej Stankiewicz, Teresa Stasinska, Iwona Trznadel-Morawska, Robert Witek, Sergey Aksentyev, Irina Bondar, Irina Demidova, Alexander Dreval, Olga Ershova, Gagik Galstyan, Alla Garganeeva, Nadezhda Izmozherova, Victoria Karetnikova, Marina Kharakhulakh, Aleksandr Khokhlov, Zhanna Kobalava, Olga Koshelskaya, Elena Kosmacheva, Vladimir Kostin, Natalia Koziolova, Anatoly Kuzin, Victor Lesnov, Tatyana Lysenko, Valentin Markov, Alexander Mayorov, Sergey Moiseev, Svetlana Myasoedova, Nina Petunina, Andrey Rebrov, Ludmila Ruyatkina, Julia Samoylova, Olga Sazonova, Natalia Shilkina, Nadezhda Sokolova, Olga Vasilevskaya, Nelli Verbovaya, Elena Vishneva, Sergey Vorobyev, Natalya Vorokhobina, Olga Zanozina, Elena Zhdanova, Tatyana Zykova, Lesley Burgess, Kathleen Coetzee, Saleem Dawood, Landman Lombard, Ellen Makotoko, Rajendran Moodley, Wessels Oosthuysen, Mohamed Sarvan, Carlos Calvo Gómez, Isidoro Cano Rodríguez, Almudena Castro Conde, Angel Cequier Fillat, Guillem Cuatrecasas Cambra, Fernando de Álvaro Moreno, Luis De Teresa Parreño, Javier Delgado Lista, José Ramón Domínguez Escribano, Santiago Durán García, Javier Elvira González, José María Fernández Rodríguez, Alberto Goday Arno, Ricardo Gomez Huelgas, José Ramón González Juanatey, Antonio Hernandez Mijares, Víctor Alfonso Jiménez Díaz, Esteban Jodar Gimeno, Tomás Lucas Morante, Monica Marazuela, Nieves Martell Claros, Didac Mauricio Puente, Elena Mena Ribas, Juan Francisco Merino Torres, Pedro Mezquita Raya, Andreu Nubiola Calonge, Xavier Ordoñez Sánchez, Jose Maria Pascual Izuel, Verónica Perea Castilla, Antonio Pérez Pérez, Isabel Perez Soto, Miguel Quesada Charneco, Angustias Quesada Simón, Josep Redón Mas, Antonia Rego Iraeta, Maria Rodriguez Alvarez, Irene Rodríguez Rodríguez, José Sabán Ruiz, Alfonso Soto González, Francisco Tinahones Madueno, Carlos Trescoli Serrano, Angels Ulied Armiñana, Erasmus Bachus, Katarina Berndtsson Blom, Ken Eliasson, Pekka Koskinen, Hans Larnefeldt, Cornelia Lif-Tiberg, Carina Linderfalk, Gustav Lund, Pia Lundman, Linda Moris, Åke Olsson, Staffan Salmonsson, Johan Sanmartin Berglund, Folke Sjöberg, Stefan Söderberg, Ingemar Torstensson, Jung-Fu Chen, Kai Jen Tien, Shih-Ting Tseng, Shih-Te Tu, Chih-Yuan Wang, Ji-Hung Wang, Arintaya Phrommintikul, Sukit Yamwong, Woravut Jintapakorn, Pisit Hutayanon, Nakarin Sansanayudh, Larysa Bazhan, Ivan Fushtey, Mariya Grachova, Vitaliy Katerenchuk, Vadym Korpachev, Nonna Kravchun, Oleksandr Larin, Galyna Mykhalchyshyn, Halyna Myshanych, Olga Oleksyk, Valeriia Orlenko, Nataliia Pashkovska, Nataliia Pertseva, Olena Petrosyan, Ivan Smirnov, Maryna Vlasenko, Tetiana Zlova, Myint Aye, Arun Baksi, Mathangi Balasubramani, Ronnie Beboso, Mark Blagden, Charles Bundy, Tobias Cookson, Allan Copland, Alistair Emslie-Smith, Fiona Green, Anthony Gunstone, Basil Issa, Ewart Jackson-Voyzey, Andrew Johnson, Malcolm Maclean, John McKnight, Solomon Muzulu, Ian O'Connell, Babatunde Oyesile, Catherine Patterson, Ewan Pearson, Sam Philip, Paul Smith, Usha Sukumaran, Jalal Abbas, Gaurav Aggarwala, Faiq Akhter, James Andersen, Moise Anglade, Georges Argoud, Mehrdad Ariani, Reswan Ashdji, Ladan Bakhtari, Subhash Banerjee, Andrew Bartlett, Howard Baum, Harold Bays, Richard Beasley, Renata Belfort de Aguiar, Sabrina Benjamin, Ravi Bhagwat, Anuj Bhargava, Bruce Bode, Christina Bratcher, Toby Briskin, Andrew Brockmyre, Raymond Broughton, Judith Brown, Madhusudan Budhraja, Kevin Cannon, Jewell Carr, Harold Cathcart, Arvind Cavale, Louis Chaykin, Deanna Cheung, Richard Childress, Allan Cohen, Jonathan Condit, Erin Cooksey, George Mitchell Cornett, Ira Dauber, William Davila, Luis De Armas, Julius Dean, Robert Detweiler, Ernesto Diaz, Michael Di Giovanna, Isaac Dor, Waymon Drummond, Donald Eagerton, John Earl, Charles Eaton, Howard Ellison, Neil Farris, Thomas Fiel, Anthony Firek, Brian First, Les Forgosh, William French, Winston Gandy, Ronald Garcia, Santosh Gill, Murray Gordon, Michael Guice, Siva Gummadi, Jonathan Hackenyos, Kristen Hairston, Lenita Hanson, Lindsay Harrison, Israel Hartman, John Heitner, Srini Hejeebu, Paul Hermany, Carlos Hernandez-Cassis, Horacio Hidalgo, Alexander Higgins, Hassan Ibrahim, Shahram Jacobs, David Johnson, Parag Joshi, Steven Kaster, Daniel Kellum, Christopher Kim, Ellen Kim, William Kirby, Albert Knouse, Steven Kulback, Mariananda Kumar, Tulsidas Kuruvanka, Ajay Labroo, William Lasswell, John Lentz, Thomas Lenzmeier, David Lewis, Zhaoping Li, Michael Lillestol, Raymond Little, Richard Lorraine, Cecilia McKeown-Biagas, Robert McNeill, Anand Mehta, Alan Miller, Joseph Moran, Emily Morawski, Venkatesh Nadar, Thomas O'Connor, Alberto Odio, Reginald Parker, Rajesh Patel, Lawrence Phillips, George Raad, Aref Rahman, Marina Raikhel, Ajit Raisinghani, Raj Rajan, Neda Rasouli, Frank Rauzi, Kathryn Rohr, Hal Roseman, Sergio Rovner, Fadi Saba, Richard Sachson, Alex Schabauer, Ricky Schneider, Timothy Schuchard, John Sensenbrenner, Yshay Shlesinger, Narendra Singh, Kanagaratnam Sivalingam, Larry Stonesifer, Daniel Storey, David Suh, Mohammed Tahir, Anjanette Tan, Marilyn Tan, Alain Taylon, Maitreya Thakkar, Devjit Tripathy, Gabriel Uwaifo, Amarnath Vedere, Chandra Venugopal, Anthony Vo, Michelle Welch, James Welker, Alexander White, John Willis, Alan Wynne, Shahram Yazdani, Anne Rosenberg, Lauren Price, Kristina Sigmon, Yuliya Lokhngina, Weibing Xing, Robert Overton, Murray Stewart, Janet Stead, Alistair Lindsay, Vickas Patel, Jorge Ross, Joseph Soffer, Shruti Daga, Margaret Sowell, Prashant Patel, Louisa Garvey, Jessica Ackert, Sybil Abraham, Mary Beth Sabol, Desma Altobelli, JuYoung Ha, Mangesh Kulkarni, Matthew Somerville, Drusilla Noronha, Ed Casson, Eddie Zang, Chamandeep Sandhu, Rakesh Kumar, David Chen, Lin Taft, Rajivkumar Patel, June Ye, Jennifer Shannon, Tim Wilson, Charleen Babi, Diane Miller, Karl Thorpe, Rachael Russell, Georgina Bull, Belinda Hereghty, Eva Fernandez-Salazar, Troy Longley, Jill Donaldson, Marie Jarosz, Karen Murphy, Patricia Adams, Peter Smith, Rachel James, Jackie Richards, Sangeeta Sedani, Denise Althouse, David Watson, Jamie Lorimer, Steven Lauder, Ron Schultheis, Terese Womer, Ella Wraight, Wenyan Li, Emma Price-Olsen, Anthony Watson, Aoife Kelly, Patricia McLaughlin, John Fleming, Jessica Schubert, Debra Schleiden, Tara Harris, Rahul Prakash, Jody Breneman, Sameer Deshpande, Aarti Saswadkar, Aditi Kumari, Aditi Shitut, Amruta Raorane, Anisha Karmalkar, Ankita Mhambrey, Archana Bhosale, Ashok Vaphare, Ashwini P Patil, Chaitali Khandelwal, Fayaz Shaik, Madhumitha Nadar, Mounika Karka, Neha Kadgaonkar, Nikita Gupta, Nutan Aher, Omkar Potnis, Pallavi Naicker, Rakesh Shinde, Richa Sharma, Rupali Godse, Sheetal Solanki, Shruti Sahu, Snehal Dumbre, Somesh Kumar, Suradnya Patil, Trisha Mandal, Hernandez, Adrian F, Green, Jennifer B, Janmohamed, Salim, D'Agostino, Ralph B, Granger, Christopher B, Jones, Nigel P, Leiter, Lawrence A, Rosenberg, Anne E, Sigmon, Kristina N, Somerville, Matthew C, Thorpe, Karl M, Mcmurray, John J V, Del Prato, Stefano, Mcmurray, John J. V., D'Agostino, Ralph B., Granger, Christopher B., Hernandez, Adrian F., Leiter, Lawrence A., Califf, Robert M, Holman, Rury, Demets, David, Riddle, Matthew, Goodman, Shaun, Mcguire, Darren, Alexander, Karen, Devore, Adam, Melloni, Chiara, Patel, Chetan, Kong, David, Bloomfield, Gerald, Roe, Matthew, Tricoci, Pierluigi, Harrison, Rob, Lopes, Renato, Mathews, Robin, Mehta, Rajendra, Schuyler Jones, William, Vemulapalli, Sreekanth, Povsic, Thoma, Eapen, Zubin, Dombrowski, Keith, Kolls, Brad, Jordan, Dedrick, Ambrosy, Andrew, Greene, Stephen, Mandawat, Aditya, Shavadia, Jay, Cooper, Lauren, Sharma, Abhinav, Guimaraes, Patricia, Friedman, Daniel, Wilson, Matt, Endsley, Patricia, Gentry, Tracy, Collier, Jeannie, Perez, Kathleen, James, Kourtnei, Roush, Jennifer, Pope, Connie, Howell, Christina, Johnson, Megan, Bailey, Matt, Cole, Joanna, Akers, Teresa, Vandyne, Beth, Thomas, Betsy, Rich, Jenny, Bartone, Susan, Beaulieu, Gail, Brown, Kim, Chau, Tuan, Christian, Tamra, Coker, Rebecca, Greene, Deb, Haddock, Trevorlyn, Jenkins, Wendy, Haque, Ghazala, Marquess, Marsha, Pesarchick, Jean, Rethaford, Renee, Stone, Allegra, Al Kawas, Fira, Anderson, Michelle, Enns, Robert, Sinay, Isaac, Mathieu, Chantal, Yordanov, Victor, Hramiak, Irene, Haluzik, Martin, Galatius, Søren, Guerci, Bruno, Nauck, Michael, Migdalis, Ilia, Tan, Choon Beng Kathryn, Kocsis, Gyozo, Giaccari, Andrea, Lee, Moon Kyu, Muñoz, Ernesto German Cardona, Cornel, Jan, Birkeland, Kare, Pinto, Miguel, Tirador, Louie, Olesinska-Mader, Martyna, Shestakova, Marina, Distiller, Larry, Lopez-Sendon, Jose, Eliasson, Bjorn, Chiang, Chern-En, Srimahachota, Suphot, Mankovsky, Bori, Bethel, M Angelyn, Dungan, Kathleen, Kosiborod, Mikhail, Alvarisqueta, Andre, Baldovino, Jorge, Besada, Diego, Calella, Pedro, Cantero, Maria Cecilia, Castaño, Patricia, Chertkoff, Alejandro, Cuadrado, Jesu, De Loredo, Lui, Dominguez, Andrea, Español, Maria Vanesa, Finkelstein, Hernan, Frechtel, Gustavo, Fretes, Jose, Garrido Santos, Natalia, Gonzalez, Joaquin, Litvak, Marco, Loureyro, Juan, Maffei, Laura, Maldonado, Natacha, Mohr Gasparini, Diego, Orio, Silvia, Perez Manghi, Federico, Rodriguez Papini, Nelson, Sala, Jorgelina, Schygiel, Pablo, Sposetti, Georgina, Ulla, Maria, Verra, Fernando, Zabalua, Silvina, Zaidman, Cesar, Crenier, Laurent, Debroye, Corinne, Duyck, Franci, Scheen, André, Van Gaal, Luc, Vercammen, Chri, Damyanova, Velichka, Dimitrov, Stefan, Kovacheva, Snezhina, Lozanov, Lachezar, Margaritov, Viktor, Mihaylova-Shumkova, Rositsa, Nikolaeva, Antoaneta, Stoyanova, Zhasmina, Akhras, Ronald, Beaudry, Yve, Bedard, Jacque, Berlingieri, Joseph, Chehayeb, Raja, Cheung, Stephen, Conway, Jame, Cusson, Jean, Della Siega, Anthony, Dumas, Richard, Dzongowski, Peter, Ferguson, Murdo, Gaudet, Daniel, Grondin, Francoi, Gupta, Anil, Gupta, Milan, Halperin, Frank, Houle, Pierre-Alain, Jones, Michael, Kouz, Simon, Kovacs, Christopher, Landry, Daniel, Lonn, Eva, O'Mahony, William, Peterson, Sean, Reich, Denni, Rosenbloom, Alan, St-Maurice, Francoi, Tugwell, Barna, Vizel, Saul, Woo, Vincent, Brychta, Toma, Cech, Vladimir, Dvorakova, Eva, Edelsberger, Toma, Halciakova, Katarina, Krizova, Jarmila, Lastuvka, Jiri, Piperek, Martin, Prymkova, Vera, Raclavska, Lea, Silhova, Elena, Urbanek, Robin, Vrkoc, Jan, Andersen, Ulla, Brønnum-Schou, Jen, Hove, Jen, Jensen, Jan Skov, Kober, Lar, Kristiansen, Ole Peter, Lund, Per, Melchior, Thoma, Nyvad, Ole, Schou, Morten, Boye, Alain, Cadinot, Didier, Gouet, Didier, Henry, Patrick, Kessler, Laurence, Lalau, Jean-Daniel, Petit, Catherine, Thuan, Jean-Francoi, Voinot, Christel, Vouillarmet, Julien, Axthelm, Christoph, Berger, Dirk, Bieler, Tasso, Birkenfeld, Andrea, Bott, Jochen, Busch, Klau, Caca, Karel, Chevts, Julia, Donaubauer, Torsten, Erlinger, Rudolf, Funke, Klau, Grosskopf, Josef, Hagenow, Andrea, Hamann, Monika, Hartard, Manfred, Heymer, Peter, Huppertz, Wolfgang, Illies, Gabriele, Jacob, Stephan, Jung, Thoma, Kahrmann, Gerd, Kast, Petra, Kellerer, Monika, Kempe, Hans-Peter, Khariouzov, Andrei, Klausmann, Gerhard, Klein, Christiane, Kleinecke-Pohl, Uwe, Kleinertz, Klau, Koch, Thorsten, Kosch, Christine, Lorra, Babette, Luedemann, Joerg, Luttermann, Matthia, Maxeiner, Stephan, Milek, Karsten, Moelle, Andrea, Neumann, Gerhard, Nischik, Ruth, Oehrig-Pohl, Edith, Plassmann, Georg, Pohlmeier, Lar, Proepper, Felix, Regner, Stefan, Rieker, Werner, Rose, Ludger, Samer, Holger, Sauter, Joachim, Schaper, Frank, Schiffer, Clemen, Schmidt, Juergen, Scholz, Bernd-M., Schulze, Joerg, Segner, Alexander, Seufert, Jochen, Sigal, Helena, Steindorf, Joerg, Stockhausen, Juergen, Stuebler, Petra, Taeschner, Heidrun, Tews, Dietrich, Tschoepe, Diethelm, Wilhelm, Karl, Zeller-Stefan, Helga, Avramidis, Iakovo, Bousboulas, Stavro, Bristianou, Magdalini, Dimitriadis, Georgio, Elisaf, Mose, Kotsa, Kalliopi, Melidonis, Andrea, Mitrakou, Asimina, Pagkalos, Emmanouil, Papanas, Nikolao, Pappas, Angelo, Sampanis, Christo, Tentolouris, Nikolao, Tsapas, Apostolo, Tzatzagou, Glykeria, Ozaki, Risa, Hajdú, Csaba, Harcsa, Eleonóra, Konyves, Laszlo, Mucsi, Jáno, Pauker, Zsolt, Petró, Gizella, Plés, Zsolt, Revesz, Katalin, Sándor, Vangel, Vass, Viktor, Avogaro, Angelo, Boemi, Massimo, Bonadonna, Riccardo, Consoli, Agostino, De Cosmo, Salvatore, Di Bartolo, Paolo, Dotta, Francesco, Frontoni, Simona, Galetta, Marianna, Gambineri, Alessandra, Gazzaruso, Carmine, Giorgino, Francesco, Lauro, Davide, Orsi, Emanuela, Paolisso, Giuseppe, Perriello, Gabriele, Piatti, Piermarco, Pontiroli, Antonio, Ponzani, Paola, Rivellese, Angela Albarosa, Sesti, Giorgio, Tonolo, Giancarlo, Trevisan, Roberto, Ahn, Chul Woo, Baik, Sei-Hyun, Cha, Bong-Soo, Chung, Choon-Hee, Jang, Hak Chul, Kim, Chong-Jin, Kim, Hye Soon, Kim, In Joo, Lee, Eun Young, Lee, Hyoung Woo, Lee, Kwan-Woo, Moon, Keon-Woong, Namgung, June, Park, Kyong Soo, Yoo, Soon Jib, Yu, Jaemyung, Llamas, Edmundo-Alfredo Bayram, Cervantes-Escárcega, Jose-Lui, Flota-Cervera, Luis Fernando, González-González, José Gerardo, Pascoe-Gonzalez, Sara, Pelayo-Orozco, Emilia Susana, Ramirez-Diaz, Santiago-Paulino, Saldana-Mendoza, Arturo, Jerjes-Díaz, Carlos Sánchez, Torres-Colores, Jose Juan, Vidrio-Velázquez, Maricela, Villagordoa-Mesa, Juan, Beijerbacht, Hugo Peter, Groutars, Reginald G. E. J., Hoek, Boudewijn A, Hoogslag, Pieter A. M., Kooy, Adriaan, Kragten, Johannes A., Lieverse, Aloysius G., Swart, Hendrik P., Viergever, Eric P., Ahlqvist, Jørn, Cooper, John, Gulseth, Hanne, Guttormsen, Gaute, Wium, Cecilie, Arbañil, Hugo, Calderon, Jorge, Camacho, Lui, Espinoza, Augusto Dextre, Garrido, Elizabeth, Luna, Alejandro, Manrique, Helard, Revoredo, Frederick Massucco, Gonzales, Rolando Varga, Rincon, Luis Zapata, Zubiate, Carlo, Ebo, Geraldine, Morales-Palomares, Ellen, Arciszewska, Malgorzata, Banach, Marek, Bijata-Bronisz, Renata, Derezinski, Tadeusz, Gadzinski, Waldemar, Gajek, Jacek, Klodawska, Katarzyna, Krzyzagorska, Ewa, Madej, Andrzej, Miekus, Pawel, Opiela, Jaroslaw, Romanczuk, Piotr, Siegel, Anna, Skokowska, Ewa, Stankiewicz, Andrzej, Stasinska, Teresa, Trznadel-Morawska, Iwona, Witek, Robert, Aksentyev, Sergey, Bondar, Irina, Demidova, Irina, Dreval, Alexander, Ershova, Olga, Galstyan, Gagik, Garganeeva, Alla, Izmozherova, Nadezhda, Karetnikova, Victoria, Kharakhulakh, Marina, Khokhlov, Aleksandr, Kobalava, Zhanna, Koshelskaya, Olga, Kosmacheva, Elena, Kostin, Vladimir, Koziolova, Natalia, Kuzin, Anatoly, Lesnov, Victor, Lysenko, Tatyana, Markov, Valentin, Mayorov, Alexander, Moiseev, Sergey, Myasoedova, Svetlana, Petunina, Nina, Rebrov, Andrey, Ruyatkina, Ludmila, Samoylova, Julia, Sazonova, Olga, Shilkina, Natalia, Sokolova, Nadezhda, Vasilevskaya, Olga, Verbovaya, Nelli, Vishneva, Elena, Vorobyev, Sergey, Vorokhobina, Natalya, Zanozina, Olga, Zhdanova, Elena, Zykova, Tatyana, Burgess, Lesley, Coetzee, Kathleen, Dawood, Saleem, Lombard, Landman, Makotoko, Ellen, Moodley, Rajendran, Oosthuysen, Wessel, Sarvan, Mohamed, Calvo Gómez, Carlo, Cano Rodríguez, Isidoro, Castro Conde, Almudena, Cequier Fillat, Angel, Cuatrecasas Cambra, Guillem, de Álvaro Moreno, Fernando, De Teresa Parreño, Lui, Delgado Lista, Javier, Domínguez Escribano, José Ramón, Durán García, Santiago, Elvira González, Javier, Fernández Rodríguez, José María, Goday Arno, Alberto, Gomez Huelgas, Ricardo, González 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B., Altobelli, D., Ha, J., Kulkarni, M., Noronha, D., Casson, E., Zang, E., Sandhu, C., Kumar, R., Chen, D., Taft, L., Ye, J., Shannon, J., Wilson, T., Babi, C., Miller, D., Russell, R., Bull, G., Hereghty, B., Fernandez-Salazar, E., Longley, T., Donaldson, J., Jarosz, M., Murphy, K., Adams, P., James, R., Richards, J., Sedani, S., Althouse, D., Watson, D., Lorimer, J., Lauder, S., Schultheis, R., Womer, T., Wraight, E., Li, W., Price-Olsen, E., Watson, A., Kelly, A., Mclaughlin, P., Fleming, J., Schubert, J., Schleiden, D., Harris, T., Prakash, R., Breneman, J., Deshpande, S., Saswadkar, A., Kumari, A., Shitut, A., Raorane, A., Karmalkar, A., Mhambrey, A., Bhosale, A., Vaphare, A., Patil, A. P., Khandelwal, C., Shaik, F., Nadar, M., Karka, M., Kadgaonkar, N., Gupta, N., Aher, N., Potnis, O., Naicker, P., Shinde, R., Sharma, R., Godse, R., Solanki, S., Sahu, S., Dumbre, S., Kumar, S., Patil, S., Mandal, T., Skin function and permeability, Dermatology, Hernandez, A, Green, J, Janmohamed, S, D'Agostino, R, Granger, C, Jones, N, Leiter, L, Rosenberg, A, Sigmon, K, Somerville, M, Thorpe, K, Mcmurray, J, Del Prato, S, Califf, R, Holman, R, Demets, D, Riddle, M, Goodman, S, Mcguire, D, Alexander, K, Devore, A, Melloni, C, Patel, C, Kong, D, Bloomfield, G, Roe, M, Tricoci, P, Harrison, R, Lopes, R, Mathews, R, Mehta, R, Schuyler Jones, W, Vemulapalli, S, Povsic, T, Eapen, Z, Dombrowski, K, Kolls, B, Jordan, D, Ambrosy, A, Greene, S, Mandawat, A, Shavadia, J, Cooper, L, Sharma, A, Guimaraes, P, Friedman, D, Wilson, M, Endsley, P, Gentry, T, Collier, J, Perez, K, James, K, Roush, J, Pope, C, Howell, C, Johnson, M, Bailey, M, Cole, J, Akers, T, Vandyne, B, Thomas, B, Rich, J, Bartone, S, Beaulieu, G, Brown, K, Chau, T, Christian, T, Coker, R, Greene, D, Haddock, T, Jenkins, W, Haque, G, Marquess, M, Pesarchick, J, Rethaford, R, Stone, A, Al Kawas, F, Anderson, M, Enns, R, Sinay, I, Mathieu, C, Yordanov, V, Hramiak, I, Haluzik, M, Galatius, S, Guerci, B, Nauck, M, Migdalis, I, Tan, C, Kocsis, G, Giaccari, A, Lee, M, Munoz, E, Cornel, J, Birkeland, K, Pinto, M, Tirador, L, Olesinska-Mader, M, Shestakova, M, Distiller, L, Lopez-Sendon, J, Eliasson, B, Chiang, C, Srimahachota, S, Mankovsky, B, Bethel, M, Dungan, K, Kosiborod, M, Alvarisqueta, A, Baldovino, J, Besada, D, Calella, P, Cantero, M, Castano, P, Chertkoff, A, Cuadrado, J, De Loredo, L, Dominguez, A, Espanol, M, Finkelstein, H, Frechtel, G, Fretes, J, Garrido Santos, N, Gonzalez, J, Litvak, M, Loureyro, J, Maffei, L, Maldonado, N, Mohr Gasparini, D, Orio, S, Perez Manghi, F, Rodriguez Papini, N, Sala, J, Schygiel, P, Sposetti, G, Ulla, M, Verra, F, Zabalua, S, Zaidman, C, Crenier, L, Debroye, C, Duyck, F, Scheen, A, Van Gaal, L, Vercammen, C, Damyanova, V, Dimitrov, S, Kovacheva, S, Lozanov, L, Margaritov, V, Mihaylova-Shumkova, R, Nikolaeva, A, Stoyanova, Z, Akhras, R, Beaudry, Y, Bedard, J, Berlingieri, J, Chehayeb, R, Cheung, S, Conway, J, Cusson, J, Della Siega, A, Dumas, R, Dzongowski, P, Ferguson, M, Gaudet, D, Grondin, F, Gupta, A, Gupta, M, Halperin, F, Houle, P, Jones, M, Kouz, S, Kovacs, C, Landry, D, Lonn, E, O'Mahony, W, Peterson, S, Reich, D, Rosenbloom, A, St-Maurice, F, Tugwell, B, Vizel, S, Woo, V, Brychta, T, Cech, V, Dvorakova, E, Edelsberger, T, Halciakova, K, Krizova, J, Lastuvka, J, Piperek, M, Prymkova, V, Raclavska, L, Silhova, E, Urbanek, R, Vrkoc, J, Andersen, U, Bronnum-Schou, J, Hove, J, Jensen, J, Kober, L, Kristiansen, O, Lund, P, Melchior, T, Nyvad, O, Schou, M, Boye, A, Cadinot, D, Gouet, D, Henry, P, Kessler, L, Lalau, J, Petit, C, Thuan, J, Voinot, C, Vouillarmet, J, Axthelm, C, Berger, D, Bieler, T, Birkenfeld, A, Bott, J, Busch, K, Caca, K, Chevts, J, Donaubauer, T, Erlinger, R, Funke, K, Grosskopf, J, Hagenow, A, Hamann, M, Hartard, M, Heymer, P, Huppertz, W, Illies, G, Jacob, S, Jung, T, Kahrmann, G, Kast, P, Kellerer, M, Kempe, H, Khariouzov, A, Klausmann, G, Klein, C, Kleinecke-Pohl, U, Kleinertz, K, Koch, T, Kosch, C, Lorra, B, Luedemann, J, Luttermann, M, Maxeiner, S, Milek, K, Moelle, A, Neumann, G, Nischik, R, Oehrig-Pohl, E, Plassmann, G, Pohlmeier, L, Proepper, F, Regner, S, Rieker, W, Rose, L, Samer, H, Sauter, J, Schaper, F, Schiffer, C, Schmidt, J, Scholz, B, Schulze, J, Segner, A, Seufert, J, Sigal, H, Steindorf, J, Stockhausen, J, Stuebler, P, Taeschner, H, Tews, D, Tschoepe, D, Wilhelm, K, Zeller-Stefan, H, Avramidis, I, Bousboulas, S, Bristianou, M, Dimitriadis, G, Elisaf, M, Kotsa, K, Melidonis, A, Mitrakou, A, Pagkalos, E, Papanas, N, Pappas, A, Sampanis, C, Tentolouris, N, Tsapas, A, Tzatzagou, G, Ozaki, R, Hajdu, C, Harcsa, E, Konyves, L, Mucsi, J, Pauker, Z, Petro, G, Ples, Z, Revesz, K, Sandor, V, Vass, V, Avogaro, A, Boemi, M, Bonadonna, R, Consoli, A, De Cosmo, S, Di Bartolo, P, Dotta, F, Frontoni, S, Galetta, M, Gambineri, A, Gazzaruso, C, Giorgino, F, Lauro, D, Orsi, E, Paolisso, G, Perriello, G, Piatti, P, Pontiroli, A, Ponzani, P, Rivellese, A, Sesti, G, Tonolo, G, Trevisan, R, Ahn, C, Baik, S, Cha, B, Chung, C, Jang, H, Kim, C, Kim, H, Kim, I, Lee, E, Lee, H, Lee, K, Moon, K, Namgung, J, Park, K, Yoo, S, Yu, J, Llamas, E, Cervantes-Escarcega, J, Flota-Cervera, L, Gonzalez-Gonzalez, J, Pascoe-Gonzalez, S, Pelayo-Orozco, E, Ramirez-Diaz, S, Saldana-Mendoza, A, Jerjes-Diaz, C, Torres-Colores, J, Vidrio-Velazquez, M, Villagordoa-Mesa, J, Beijerbacht, H, Groutars, R, Hoek, B, Hoogslag, P, Kooy, A, Kragten, J, Lieverse, A, Swart, H, Viergever, E, Ahlqvist, J, Cooper, J, Gulseth, H, Guttormsen, G, Wium, C, Arbanil, H, Calderon, J, Camacho, L, Espinoza, A, Garrido, E, Luna, A, Manrique, H, Revoredo, F, Gonzales, R, Rincon, L, Zubiate, C, Ebo, G, Morales-Palomares, E, Arciszewska, M, Banach, M, Bijata-Bronisz, R, Derezinski, T, Gadzinski, W, Gajek, J, Klodawska, K, Krzyzagorska, E, Madej, A, Miekus, P, Opiela, J, Romanczuk, P, Siegel, A, Skokowska, E, Stankiewicz, A, Stasinska, T, Trznadel-Morawska, I, Witek, R, Aksentyev, S, Bondar, I, Demidova, I, Dreval, A, Ershova, O, Galstyan, G, Garganeeva, A, Izmozherova, N, Karetnikova, V, Kharakhulakh, M, Khokhlov, A, Kobalava, Z, Koshelskaya, O, Kosmacheva, E, Kostin, V, Koziolova, N, Kuzin, A, Lesnov, V, Lysenko, T, Markov, V, Mayorov, A, Moiseev, S, Myasoedova, S, Petunina, N, Rebrov, A, Ruyatkina, L, Samoylova, J, Sazonova, O, Shilkina, N, Sokolova, N, Vasilevskaya, O, Verbovaya, N, Vishneva, E, Vorobyev, S, Vorokhobina, N, Zanozina, O, Zhdanova, E, Zykova, T, Burgess, L, Coetzee, K, Dawood, S, Lombard, L, Makotoko, E, Moodley, R, Oosthuysen, W, Sarvan, M, Calvo Gomez, C, Cano Rodriguez, I, Castro Conde, A, Cequier Fillat, A, Cuatrecasas Cambra, G, de Alvaro Moreno, F, De Teresa Parreno, L, Delgado Lista, J, Dominguez Escribano, J, Duran Garcia, S, Elvira Gonzalez, J, Fernandez Rodriguez, J, Goday Arno, A, Gomez Huelgas, R, Gonzalez Juanatey, J, Hernandez Mijares, A, Jimenez Diaz, V, Jodar Gimeno, E, Lucas Morante, T, Marazuela, M, Martell Claros, N, Mauricio Puente, D, Mena Ribas, E, Merino Torres, J, Mezquita Raya, P, Nubiola Calonge, A, Ordonez Sanchez, X, Pascual Izuel, J, Perea Castilla, V, Perez Perez, A, Perez Soto, I, Quesada Charneco, M, Quesada Simon, A, Redon Mas, J, Rego Iraeta, A, Rodriguez Alvarez, M, Rodriguez Rodriguez, I, Saban Ruiz, J, Soto Gonzalez, A, Tinahones Madueno, F, Trescoli Serrano, C, Ulied Arminana, A, Bachus, E, Berndtsson Blom, K, Eliasson, K, Koskinen, P, Larnefeldt, H, Lif-Tiberg, C, Linderfalk, C, Lund, G, Lundman, P, Moris, L, Olsson, A, Salmonsson, S, Sanmartin Berglund, J, Sjoberg, F, Soderberg, S, Torstensson, I, Chen, J, Tien, K, Tseng, S, Tu, S, Wang, C, Wang, J, Phrommintikul, A, Yamwong, S, Jintapakorn, W, Hutayanon, P, Sansanayudh, N, Bazhan, L, Fushtey, I, Grachova, M, Katerenchuk, V, Korpachev, V, Kravchun, N, Larin, O, Mykhalchyshyn, G, Myshanych, H, Oleksyk, O, Orlenko, V, Pashkovska, N, Pertseva, N, Petrosyan, O, Smirnov, I, Vlasenko, M, Zlova, T, Aye, M, Baksi, A, Balasubramani, M, Beboso, R, Blagden, M, Bundy, C, Cookson, T, Copland, A, Emslie-Smith, A, Green, F, Gunstone, A, Issa, B, Jackson-Voyzey, E, Johnson, A, Maclean, M, Mcknight, J, Muzulu, S, O'Connell, I, Oyesile, B, Patterson, C, Pearson, E, Philip, S, Smith, P, Sukumaran, U, Abbas, J, Aggarwala, G, Akhter, F, Andersen, J, Anglade, M, Argoud, G, Ariani, M, Ashdji, R, Bakhtari, L, Banerjee, S, Bartlett, A, Baum, H, Bays, H, Beasley, R, Belfort de Aguiar, R, Benjamin, S, Bhagwat, R, Bhargava, A, Bode, B, Bratcher, C, Briskin, T, Brockmyre, A, Broughton, R, Brown, J, Budhraja, M, Cannon, K, Carr, J, Cathcart, H, Cavale, A, Chaykin, L, Cheung, D, Childress, R, Cohen, A, Condit, J, Cooksey, E, Cornett, G, Dauber, I, Davila, W, De Armas, L, Dean, J, Detweiler, R, Diaz, E, Di Giovanna, M, Dor, I, Drummond, W, Eagerton, D, Earl, J, Eaton, C, Ellison, H, Farris, N, Fiel, T, Firek, A, First, B, Forgosh, L, French, W, Gandy, W, Garcia, R, Gill, S, Gordon, M, Guice, M, Gummadi, S, Hackenyos, J, Hairston, K, Hanson, L, Harrison, L, Hartman, I, Heitner, J, Hejeebu, S, Hermany, P, Hernandez-Cassis, C, Hidalgo, H, Higgins, A, Ibrahim, H, Jacobs, S, Johnson, D, Joshi, P, Kaster, S, Kellum, D, Kim, E, Kirby, W, Knouse, A, Kulback, S, Kumar, M, Kuruvanka, T, Labroo, A, Lasswell, W, Lentz, J, Lenzmeier, T, Lewis, D, Li, Z, Lillestol, M, Little, R, Lorraine, R, McKeown-Biagas, C, Mcneill, R, Mehta, A, Miller, A, Moran, J, Morawski, E, Nadar, V, O'Connor, T, Odio, A, Parker, R, Patel, R, Phillips, L, Raad, G, Rahman, A, Raikhel, M, Raisinghani, A, Rajan, R, Rasouli, N, Rauzi, F, Rohr, K, Roseman, H, Rovner, S, Saba, F, Sachson, R, Schabauer, A, Schneider, R, Schuchard, T, Sensenbrenner, J, Shlesinger, Y, Singh, N, Sivalingam, K, Stonesifer, L, Storey, D, Suh, D, Tahir, M, Tan, A, Tan, M, Taylon, A, Thakkar, M, Tripathy, D, Uwaifo, G, Vedere, A, Venugopal, C, Vo, A, Welch, M, Welker, J, White, A, Willis, J, Wynne, A, Yazdani, S, Price, L, Lokhngina, Y, Xing, W, Overton, R, Stewart, M, Stead, J, Lindsay, A, Patel, V, Ross, J, Soffer, J, Daga, S, Sowell, M, Patel, P, Garvey, L, Ackert, J, Abraham, S, Sabol, M, Altobelli, D, Ha, J, Kulkarni, M, Noronha, D, Casson, E, Zang, E, Sandhu, C, Kumar, R, Chen, D, Taft, L, Ye, J, Shannon, J, Wilson, T, Babi, C, Miller, D, Russell, R, Bull, G, Hereghty, B, Fernandez-Salazar, E, Longley, T, Donaldson, J, Jarosz, M, Murphy, K, Adams, P, James, R, Richards, J, Sedani, S, Althouse, D, Watson, D, Lorimer, J, Lauder, S, Schultheis, R, Womer, T, Wraight, E, Li, W, Price-Olsen, E, Watson, A, Kelly, A, Mclaughlin, P, Fleming, J, Schubert, J, Schleiden, D, Harris, T, Prakash, R, Breneman, J, Deshpande, S, Saswadkar, A, Kumari, A, Shitut, A, Raorane, A, Karmalkar, A, Mhambrey, A, Bhosale, A, Vaphare, A, Patil, A, Khandelwal, C, Shaik, F, Nadar, M, Karka, M, Kadgaonkar, N, Gupta, N, Aher, N, Potnis, O, Naicker, P, Shinde, R, Sharma, R, Godse, R, Solanki, S, Sahu, S, Dumbre, S, Kumar, S, Patil, S, and Mandal, T
Subjects: Male, Placebo-controlled study, Myocardial Infarction, alanine aminotransferase, albiglutide, bilirubin, placebo, antidiabetic agent, glucagon like peptide 1, rGLP-1 protein, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Glucagon-Like Peptide 1, Cardiovascular Disease, Medicine(all), education.field_of_study, Subcutaneous, Medicine (all), albigutide, Hazard ratio, General Medicine, Middle Aged, Albiglutide, Stroke, Treatment Outcome, Tolerability, Cardiovascular Diseases, Female, type 2 diabetes, Type 2, Human, Adult, medicine.medical_specialty, Injections, Subcutaneous, Population, 030209 endocrinology & metabolism, Placebo, Injections, Subcutaneou, Drug Administration Schedule, Injections, 03 medical and health sciences, Double-Blind Method, Internal medicine, Diabetes Mellitus, medicine, Humans, Hypoglycemic Agents, education, Aged, Diabetes Mellitus, Type 2, Hypoglycemic Agent, business.industry, Semaglutide, Settore MED/13 - ENDOCRINOLOGIA, Harmony, business
Abstract: Background: \ud Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke.\ud \ud Methods: \ud We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515.\ud \ud Findings: \ud Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p
Published: 2018

24. Effects of the glucagon-like peptide-1 receptor agonist liraglutide on 24-h ambulatory blood pressure in patients with type 2 diabetes and stable coronary artery disease: a randomized, double-blind, placebo-controlled, crossover study

Author: Christian Anholm, Sten Madsbad, Preman Kumarathurai, Ole Peter Kristiansen, Andreas Fabricius-Bjerre, Olav W. Nielsen, Ahmad Sajadieh, and Steen B. Haugaard
Subjects: Male, medicine.medical_specialty, Ambulatory blood pressure, Physiology, 030209 endocrinology & metabolism, Blood Pressure, Type 2 diabetes, Coronary Artery Disease, 030204 cardiovascular system & hematology, Placebo, Glucagon-Like Peptide-1 Receptor, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Heart Rate, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Humans, Hypoglycemic Agents, Glucagon-like peptide 1 receptor, Aged, Cross-Over Studies, Liraglutide, business.industry, Blood Pressure Monitoring, Ambulatory, Middle Aged, medicine.disease, Crossover study, Metformin, Blood pressure, Endocrinology, Diabetes Mellitus, Type 2, Cardiology, Drug Therapy, Combination, Female, Cardiology and Cardiovascular Medicine, business, medicine.drug
Abstract: Objective The glucagon-like peptide-1 receptor agonist liraglutide has been shown to reduce blood pressure (BP) in clinical trials using office BP measurements. However, the effects of liraglutide on 24-h BP and on the diurnal variation in BP have not been explored sufficiently. Methods Forty-one patients with type 2 diabetes and stable coronary artery disease were randomized to receive liraglutide or placebo to a backbone therapy of metformin in this double-blind, placebo-controlled 12 along with 12 weeks crossover study. Ambulatory blood pressure monitoring (ABPM) was performed at the start and end of each intervention. Results Twenty-four individuals completed all 24-h BP measurements. Liraglutide, when compared with placebo, did not induce any significant changes in mean 24-h SBP [difference +1.8 mmHg (95% confidence interval, 95% CI: -4.33 to 7.93)] or DBP [+4.2 mmHg (-0.74 to 9.17)]. Twenty-four-hour BP profiles revealed a trend for increase in evening SBP and DBP [+9.2 mmHg (95% CI: 1.1-17.2) and +9.7 mmHg (95% CI: 3.9-15.5), respectively]. Mean heart rate significantly increased after liraglutide [+7.6 bpm (95% CI: 2.56-12.62)]. Liraglutide did not affect the BP variability or the nocturnal BP dipping. Conclusions We could not demonstrate any BP-lowering effect of liraglutide when using 24-h ABPM. Liraglutide exhibited diurnal variation in the effect on BP without affecting the BP variability or nocturnal BP dipping.
Published: 2017

25. Effects of Liraglutide on Heart Rate and Heart Rate Variability: A Randomized, Double-Blind, Placebo-Controlled Crossover Study

Author: Ahmad Sajadieh, Christian Anholm, Preman Kumarathurai, Sten Madsbad, Ole Peter Kristiansen, Bjørn Strøier Larsen, Rasmus Huan Olsen, Steen B. Haugaard, and Olav W. Nielsen
Subjects: Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Type 2 diabetes, Coronary Artery Disease, 030204 cardiovascular system & hematology, Placebo, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Weight loss, Heart Rate, Internal medicine, Heart rate, Internal Medicine, Medicine, Heart rate variability, Humans, Hypoglycemic Agents, Aged, Advanced and Specialized Nursing, Cross-Over Studies, business.industry, Liraglutide, Middle Aged, Overweight, medicine.disease, Crossover study, Metformin, Circadian Rhythm, Diabetes Mellitus, Type 2, Anesthesia, Cardiology, Electrocardiography, Ambulatory, Drug Therapy, Combination, Female, medicine.symptom, business, medicine.drug
Abstract: OBJECTIVE Reduced heart rate variability (HRV) and increased heart rate (HR) have been associated with cardiovascular mortality. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) increase HR, and studies have suggested that they may reduce HRV. We examined the effect of the GLP-1 RA liraglutide on HRV and diurnal variation of HR in overweight patients with newly diagnosed type 2 diabetes (T2D) and stable coronary artery disease (CAD). RESEARCH DESIGN AND METHODS Liraglutide or placebo was administrated to a backbone therapy of metformin in this double-blind, placebo-controlled 12 + 12–week crossover study. SD of beat-to-beat (NN) intervals (SDNN) was assessed by 24-h Holter monitoring as a measure of HRV. Diurnal HR variation and sympathovagal balance analyzed by root mean square of successive differences (RMSSD) in NN intervals and high-frequency (HF) and low-frequency (LF) power were assessed. RESULTS Compared with placebo, liraglutide decreased SDNN in 27 subjects (−33.9 ms; P < 0.001, paired analysis); decreased RMSSD (−0.3 log-ms; P = 0.025); and increased the mean HR (8.1 beats/min; P = 0.003), daytime HR (5.7; P = 0.083), and nighttime HR (6.3; P = 0.026). In a multivariable regression analysis, the decrease in SDNN remained significant after adjustment for metabolic and HR changes. Liraglutide reduced HF power (−0.7 log-ms2; P = 0.026) without any change in LF/HF ratio. CONCLUSIONS In overweight patients with CAD and newly diagnosed T2D, liraglutide increased HR and reduced HRV despite significant weight loss and improvement in metabolic parameters. The increase in nightly HR in conjunction with a decrease in parameters of parasympathetic activity suggests that liraglutide may affect sympathovagal balance.
Published: 2016

26. Effects of the glucagon-like peptide-1 receptor agonist liraglutide on systolic function in patients with coronary artery disease and type 2 diabetes: a randomized double-blind placebo-controlled crossover study

Author: Christian Anholm, Olav W. Nielsen, Steen B. Haugaard, Sten Madsbad, Ahmad Sajadieh, Preman Kumarathurai, Ole Peter Kristiansen, and Jens Mølvig
Subjects: Blood Glucose, Male, medicine.medical_specialty, Left ventricular ejection fraction, Endocrinology, Diabetes and Metabolism, Heart Ventricles, 030209 endocrinology & metabolism, Type 2 diabetes, Coronary Artery Disease, 030204 cardiovascular system & hematology, Placebo, Glucagon-Like Peptide-1 Receptor, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Double-Blind Method, Internal medicine, medicine, Humans, Exercise, Aged, Original Investigation, Ejection fraction, Cross-Over Studies, Liraglutide, business.industry, Middle Aged, medicine.disease, Crossover study, Dobutamine stress echocardiography, medicine.anatomical_structure, Diabetes Mellitus, Type 2, Ventricle, Cardiology, Female, business, Cardiology and Cardiovascular Medicine, GLP-1, Biomarkers, medicine.drug
Abstract: Background Patients with type 2 diabetes (T2D) and coronary artery disease (CAD) have increased risk of cardiac dysfunction. The diabetic heart is characterized by increased fatty acid oxidation and reduced glucose uptake resulting in reduced cardiac efficiency. Glucagon-like peptide-1 (GLP-1) has shown to increase myocardial glucose uptake and to improve myocardial function. We examined the effect of the GLP-1 receptor agonist, liraglutide, on the systolic function of the left ventricle (LV) in patients with T2D and stable CAD. Methods In this placebo-controlled crossover study, 41 subjects with T2D and stable CAD were randomized to liraglutide or placebo and underwent dobutamine stress echocardiography (DSE) and exercise tolerance test at beginning and end of each intervention. The primary endpoint was changes in LV ejection fraction. Secondary endpoints were exercise capacity and other measures of systolic function: wall motion score index (WMSI), global longitudinal strain (GLS) and strain rate (GLSR). Results Liraglutide, when compared to placebo, did not improve LV ejection fraction at rest (+0.54 %; 95 % CI 2.38–3.45), at low stress (+0.03 %; 95 % CI 3.25–3.32), at peak stress (+1.12 %; 95 % CI 3.45–5.69), or at recovery (+4.06 %; 95 % CI 0.81–8.93). No significant changes in WMSI were observed at any stress levels. GLS and GLSR at rest did not improve. The maximal exercise capacity estimated by metabolic equivalents was not affected by liraglutide. Conclusion In conclusion, liraglutide did not improve the systolic function of the left ventricle during DSE or the exercise capacity in patients with T2D and stable CAD. Clinical Trial Registrationhttp://www.clinicaltrials.gov (unique identifier: NCT01595789) Electronic supplementary material The online version of this article (doi:10.1186/s12933-016-0425-2) contains supplementary material, which is available to authorized users.
Published: 2016

27. Is Puberty an Accelerator of Type 1 Diabetes in IL6-174CC Females?

Author: Virginie M. Betin, Edwin A M Gale, Thomas Mandrup-Poulsen, Kathleen M Gillespie, R. Nolsoe, Polly J. Bingley, and Ole Peter Kristiansen
Subjects: Male, medicine.medical_specialty, Adolescent, Genotype, medicine.drug_class, Endocrinology, Diabetes and Metabolism, Population, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Cohort Studies, Sex Factors, Internal medicine, Internal Medicine, medicine, Humans, SNP, Age of Onset, Child, education, education.field_of_study, Type 1 diabetes, Interleukin-6, Puberty, Estrogens, medicine.disease, Diabetes Mellitus, Type 1, Endocrinology, Estrogen, Cohort, Female, Age of onset
Abstract: The pubertal peak in onset of type 1 diabetes occurs earlier in girls than boys. We postulated that this sex difference might be mediated in part by estrogen or by genes regulated by estrogen, such as the interleukin-6 (IL6) gene. Previous studies concerning the role of an estrogen-sensitive single nucleotide polymorphism (SNP) in the IL6 promoter in type 1 diabetes have proved contradictory. We therefore selected a large, genetically homogenous population-based cohort, analyzed by age at onset and sex, to test the hypothesis that the IL6-174G>C SNP affects age at onset of type 1 diabetes in females but not in males. We found that the IL6-174CC genotype was significantly less frequent in females diagnosed after than in those diagnosed before the age of 10 years (19 vs. 13%, P = 0.016). No genotype difference was observed in males stratified for age at onset. Among children diagnosed after age 10, the median age of onset was 11.9 years (intraquartile range 10.7–14.6) in 34 girls homozygous for IL6-174C compared with 13.2 years (11.6–15.4) in 229 girls with other genotypes and 13.5 years (12.0–15.6) in 339 males with any IL6-174 genotype (P = 0.012). These data support the hypothesis that pubertal changes may contribute to accelerated onset of type 1 diabetes in genetically susceptible females. This phenomenon may be orchestrated by the action of estrogen on the IL6 promoter.
Published: 2005
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28. NON-MHC genes in type 1 diabetes. Family-based association studies and functional studies of disease-associated polymorphisms

Author: Ole Peter, Kristiansen
Subjects: Polymorphism, Genetic, HLA-A Antigens, Genetic Linkage, Denmark, Siblings, Minisatellite Repeats, Linkage Disequilibrium, Cohort Studies, Diabetes Mellitus, Type 1, Mutation, Diseases in Twins, Humans, Genetic Predisposition to Disease, Age of Onset, Polymorphism, Single-Stranded Conformational
Published: 2006

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28 results on '"Ole Peter Kristiansen"'

1. Myocardial Work in Patients Hospitalized With COVID‐19: Relation to Biomarkers, COVID‐19 Severity, and All‐Cause Mortality

2. Excessive supraventricular ectopic activity and risk of incident atrial fibrillation in a consecutive population referred to ambulatory cardiac monitoring

3. Echocardiographic abnormalities and predictors of mortality in hospitalized COVID‐19 patients: the ECHOVID‐19 study

4. Liraglutide improves the beta-cell function without increasing insulin secretion during a mixed meal in patients, who exhibit well-controlled type 2 diabetes and coronary artery disease

5. Cardiac Characteristics of the First Two Waves of COVID-19 in Denmark and the Prognostic Value of Echocardiography: The ECHOVID-19 Study

6. Lung ultrasound findings in hospitalized COVID-19 patients in relation to venous thromboembolic events:the ECHOVID-19 study

7. Lung ultrasound findings following COVID-19 hospitalization: A prospective longitudinal cohort study

8. Effects of liraglutide on diastolic function parameters in patients with type 2 diabetes and coronary artery disease:a randomized crossover study

9. Lung Ultrasound Findings Associated With COVID-19 ARDS, ICU Admission, and All-Cause Mortality

10. Recovery of cardiac function following COVID-19 - ECHOVID-19: a prospective longitudinal cohort study

11. Excessive supraventricular ectopic activity and risk of incident atrial fibrillation in a consecutive population referred to ambulatory cardiac monitoring

12. Myocardial Impairment and Acute Respiratory Distress Syndrome in Hospitalized Patients With COVID-19

13. Liraglutide in combination with metformin may improve the atherogenic lipid profile and decrease C-reactive protein level in statin treated obese patients with coronary artery disease and newly diagnosed type 2 diabetes: A randomized trial

14. Effect of liraglutide on estimates of lipolysis and lipid oxidation in obese patients with stable coronary artery disease and newly diagnosed type 2 diabetes: A randomized trial

15. Prognostic Value of Coronary CT Angiography in Patients With Non–ST-Segment Elevation Acute Coronary Syndromes

16. Night-time heart rate variability identifies high-risk people among people with uncomplicated type 2 diabetes mellitus

17. Echocardiographic abnormalities and predictors of mortality in hospitalized COVID-19 patients:the ECHOVID-19 study

18. Early Versus Standard Care Invasive Examination and Treatment of Patients With Non-ST-Segment Elevation Acute Coronary Syndrome

19. Liraglutide effects on beta-cell, insulin sensitivity and glucose effectiveness in patients with stable coronary artery disease and newly diagnosed type 2 diabetes

20. Liraglutide improves the beta-cell function without increasing insulin secretion during a mixed meal in patients, who exhibit well-controlled type 2 diabetes and coronary artery disease

21. RECOVERY OF CARDIAC FUNCTION FOLLOWING COVID-19 INFECTION: ECHOVID-19 - A LONGITUDINAL COHORT STUDY

22. Early Versus Standard Care Invasive Examination and Treatment of Patients With Non-ST-Segment Elevation Acute Coronary Syndrome

23. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

24. Effects of the glucagon-like peptide-1 receptor agonist liraglutide on 24-h ambulatory blood pressure in patients with type 2 diabetes and stable coronary artery disease: a randomized, double-blind, placebo-controlled, crossover study

25. Effects of Liraglutide on Heart Rate and Heart Rate Variability: A Randomized, Double-Blind, Placebo-Controlled Crossover Study

26. Effects of the glucagon-like peptide-1 receptor agonist liraglutide on systolic function in patients with coronary artery disease and type 2 diabetes: a randomized double-blind placebo-controlled crossover study

27. Is Puberty an Accelerator of Type 1 Diabetes in IL6-174CC Females?

28. NON-MHC genes in type 1 diabetes. Family-based association studies and functional studies of disease-associated polymorphisms

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