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Zhang C, Yu P, Liu M, Zhang L, Li X, Jiang H. Can electrocardiographic repolarization predict diabetes incidence: the Atherosclerosis Risk in Communities Study. J Electrocardiol 2025; 89:153885. [PMID: 39892035 DOI: 10.1016/j.jelectrocard.2025.153885] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Revised: 01/01/2025] [Accepted: 01/21/2025] [Indexed: 02/03/2025]
Abstract
BACKGROUND Diabetes is marked by metabolic dysregulation and high cardiovascular risk. Preceding diabetes onset, cardiac change markers often appear, yet predicting occurrence of diabetes remains challenging. METHODS The study included 11,297 ARIC Study participants aged 45-64 without baseline diabetes or heart disease, with 12‑lead ECGs recorded. Cox regression models were used to analyze repolarization parameters (QTc intervals, J-point level, T-wave amplitude, T-wave to R-wave (T/R) ratio) in relation to diabetes risk. Correlation analyses explored links between ECG findings, metabolic parameters, and myocardial fat content. RESULTS Over 23 years, 3338 participants (29.5 %) developed type 2 diabetes. A reduced T/R ratio showed dose-response relationship with diabetes risk, notably in lead I (HR 1.22, 95 % CI 1.15-1.31) and lead V5 (HR 1.15, 95 % CI 1.07-1.24) per standard deviation (SD) decrease after adjustment for common covariates. J-point level and T-wave amplitude also exhibited associations, though weaker. Negative correlations were found between repolarization markers, including T-wave amplitude, T/R ratio with metabolic parameters. CONCLUSIONS ECG parameters, especially T-wave amplitude and T/R ratio, predict incident type 2 diabetes and serve as potential early biomarkers for metabolic-induced cardiac change. These findings underscore their clinical relevance in identifying individuals at risk for diabetes.
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Affiliation(s)
- Chunyu Zhang
- Shanghai Institute of Cardiovascular Diseases, Shanghai Engineering Research Center of AI Technology for Cardiopulmonary Diseases, Zhongshan Hospital, Shanghai Medical College of Fudan University, Shanghai, China
| | - Peng Yu
- Department of Endocrinology, Shanghai Geriatric Medical Center, Shanghai, China; Department of Endocrinology, Zhongshan Hospital, Shanghai Medical College of Fudan University, Shanghai, China
| | - Ming Liu
- Department of Health Management Center, Zhongshan Hospital, Shanghai Medical College of Fudan University, Shanghai, China
| | - Lei Zhang
- Department of Endocrinology, Shanghai Geriatric Medical Center, Shanghai, China; Department of Endocrinology, Zhongshan Hospital, Shanghai Medical College of Fudan University, Shanghai, China
| | - Xiaomu Li
- Department of Endocrinology, Zhongshan Hospital, Shanghai Medical College of Fudan University, Shanghai, China.
| | - Hong Jiang
- Shanghai Institute of Cardiovascular Diseases, Shanghai Engineering Research Center of AI Technology for Cardiopulmonary Diseases, Zhongshan Hospital, Shanghai Medical College of Fudan University, Shanghai, China.
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2
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Isaksen JL, Sivertsen CB, Jensen CZ, Graff C, Linz D, Ellervik C, Jensen MT, Jørgensen PG, Kanters JK. Electrocardiographic markers in patients with type 2 diabetes and the role of diabetes duration. J Electrocardiol 2024; 84:129-136. [PMID: 38663227 DOI: 10.1016/j.jelectrocard.2024.04.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Revised: 04/01/2024] [Accepted: 04/14/2024] [Indexed: 06/16/2024]
Abstract
BACKGROUND The association between type 2 diabetes and electrocardiographic (ECG) markers are incompletely explored and the dependence on diabetes duration is largely unknown. We aimed to investigate the electrocardiographic (ECG) changes associated with type 2 diabetes over time. METHODS In this cross-sectional study, we matched people with type 2 diabetes 1:1 on sex, age, and body mass index with people without diabetes from the general population. We regressed ECG markers with the presence of diabetes and the duration of clinical diabetes, respectively, adjusted for sex, age, body mass index, smoking, heart rate, diabetes medication, renal function, hypertension, and myocardial infarction. RESULTS We matched 988 people with type 2 diabetes (332, 34% females) with as many controls. Heart rate was 8 bpm higher (p < 0.001) in people with vs. without type 2 diabetes, but the difference declined with increasing diabetes duration. For most depolarization markers, the difference between people with and without type 2 diabetes increased progressively with diabetes duration. On average, R-wave amplitude was 6 mm lower in lead V5 (p < 0.001), P-wave duration was 5 ms shorter (p < 0.001) and QRS duration was 3 ms (p = 0.03). Among repolarization markers, T-wave amplitude (measured in V5) was lower in patients with type 2 diabetes (1 mm lower, p < 0.001) and the QRS-T angle was 10 degrees wider (p = 0.002). We observed no association between diabetes duration and repolarization markers. CONCLUSIONS Type 2 diabetes was independently associated with electrocardiographic depolarization and repolarization changes. Differences in depolarization markers, but not repolarization markers, increased with increasing diabetes duration.
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Affiliation(s)
- Jonas L Isaksen
- Laboratory of Experimental Cardiology, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
| | - Christian B Sivertsen
- Laboratory of Experimental Cardiology, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Christian Zinck Jensen
- Laboratory of Experimental Cardiology, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Claus Graff
- Department of Health Science and Technology, Aalborg University, Aalborg, Denmark
| | - Dominik Linz
- Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Christina Ellervik
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Department of Data and Data Support, Region Zealand, Sorø, Denmark
| | | | - Peter G Jørgensen
- Department of Cardiology, Herlev and Gentofte University Hospital, Copenhagen, Denmark
| | - Jørgen K Kanters
- Laboratory of Experimental Cardiology, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark; Center of Physiological Research, University of California San Francisco, San Francisco, USA
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Chambers ME, Nuibe EH, Reno-Bernstein CM. Brain Regulation of Cardiac Function during Hypoglycemia. Metabolites 2023; 13:1089. [PMID: 37887414 PMCID: PMC10608630 DOI: 10.3390/metabo13101089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 10/02/2023] [Accepted: 10/16/2023] [Indexed: 10/28/2023] Open
Abstract
Hypoglycemia occurs frequently in people with type 1 and type 2 diabetes. Hypoglycemia activates the counter-regulatory response. Besides peripheral glucose sensors located in the pancreas, mouth, gastrointestinal tract, portal vein, and carotid body, many brain regions also contain glucose-sensing neurons that detect this fall in glucose. The autonomic nervous system innervates the heart, and during hypoglycemia, can cause many changes. Clinical and animal studies have revealed changes in electrocardiograms during hypoglycemia. Cardiac repolarization defects (QTc prolongation) occur during moderate levels of hypoglycemia. When hypoglycemia is severe, it can be fatal. Cardiac arrhythmias are thought to be the major mediator of sudden death due to severe hypoglycemia. Both the sympathetic and parasympathetic nervous systems of the brain have been implicated in regulating these arrhythmias. Besides cardiac arrhythmias, hypoglycemia can have profound changes in the heart and most of these changes are exacerbated in the setting of diabetes. A better understanding of how the brain regulates cardiac changes during hypoglycemia will allow for better therapeutic intervention to prevent cardiovascular death associated with hypoglycemia in people with diabetes. The aim of this paper is to provide a narrative review of what is known in the field regarding how the brain regulates the heart during hypoglycemia.
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Affiliation(s)
| | | | - Candace M. Reno-Bernstein
- Division of Endocrinology, Metabolism, and Diabetes, University of Utah School of Medicine, Salt Lake City, UT 84112, USA (E.H.N.)
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Welten SJGC, van der Heijden AA, Remmelzwaal S, Blom MT, Nijpels G, Rutters F, Beulens JWJ, Elders PJM. Prolongation of the QTc interval is associated with an increased risk of cardiovascular diseases: The Hoorn study. J Electrocardiol 2023; 80:133-138. [PMID: 37352635 DOI: 10.1016/j.jelectrocard.2023.06.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 05/12/2023] [Accepted: 06/04/2023] [Indexed: 06/25/2023]
Abstract
BACKGROUND/OBJECTIVE Prolonged heart rate-corrected QT interval (QTc) on the electrocardiogram (ECG) is maybe associated with the occurrence of cardiovascular diseases (CVD), but the evidence is inconsistent. Therefore, we investigated whether baseline prolongation of the QTc interval is associated with CVD morbidity and mortality and its subtypes and whether glucose tolerance modifies this association in a population-based cohort study with a mean follow-up of 10.8 years. METHODS We analyzed a glucose tolerance stratified sample (N = 487) from the longitudinal population-based Hoorn Study cohort (age 64 ± 7 years, 48% female). Cox regression was used to investigate the association between sex-specific baseline QTc quartiles and CVD morbidity and mortality. The risk was also estimated per 10 ms increase in QTc. All analyses were adjusted for age, sex, smoking status, systolic blood pressure, prevalent CVD, glucose tolerance status, hypertension and total cholesterol. In addition, stratified analyses were conducted for glucose tolerance status. RESULTS During a mean follow-up of 10.8 years, 351 CVD events were observed. The adjusted hazard ratios (95% CI) for each 10 ms increase in QTc interval were 1.06 (95% CI: 1.02-1.10) for CVD, 1.06 (95% CI: 0.97-1.15) for acute myocardial infarction, 1.07 (95% CI: 1.01-1.13) for stroke, 1.12 (95% CI: 1.06-1.19) for heart failure, 1.04 (95% CI: 0.96-1.12) for peripheral arterial disease and 1.01 (95% CI:0.95-1.08) for coronary heart disease. Glucose tolerance status did not modify the association (P > 0.2). CONCLUSION/INTERPRETATION Prolongation of the QTc interval is associated with morbidity and mortality due to general CVD. Glucose tolerance status did not modify these associations.
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Affiliation(s)
- Sabrina J G C Welten
- Amsterdam UMC location Vrije Universiteit Amsterdam, Department of General Practice, de Boelelaan 1117, Amsterdam, Netherlands; Amsterdam Public Health Research Institute, Health Behaviors & Chronic Diseases, Amsterdam, the Netherlands
| | - Amber A van der Heijden
- Amsterdam UMC location Vrije Universiteit Amsterdam, Department of General Practice, de Boelelaan 1117, Amsterdam, Netherlands; Amsterdam Public Health Research Institute, Health Behaviors & Chronic Diseases, Amsterdam, the Netherlands
| | - Sharon Remmelzwaal
- Amsterdam UMC location Vrije Universiteit Amsterdam, Department of General Practice, de Boelelaan 1117, Amsterdam, Netherlands; Amsterdam Public Health Research Institute, Health Behaviors & Chronic Diseases, Amsterdam, the Netherlands; Department of Epidemiology and Data science, Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
| | - Marieke T Blom
- Amsterdam UMC location Vrije Universiteit Amsterdam, Department of General Practice, de Boelelaan 1117, Amsterdam, Netherlands; Amsterdam Public Health Research Institute, Health Behaviors & Chronic Diseases, Amsterdam, the Netherlands
| | - Giel Nijpels
- Amsterdam UMC location Vrije Universiteit Amsterdam, Department of General Practice, de Boelelaan 1117, Amsterdam, Netherlands; Amsterdam Public Health Research Institute, Health Behaviors & Chronic Diseases, Amsterdam, the Netherlands
| | - Femke Rutters
- Amsterdam Public Health Research Institute, Health Behaviors & Chronic Diseases, Amsterdam, the Netherlands; Department of Epidemiology and Data science, Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
| | - Joline W J Beulens
- Amsterdam Public Health Research Institute, Health Behaviors & Chronic Diseases, Amsterdam, the Netherlands; Department of Epidemiology and Data science, Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands; Julius Centre for Health Sciences and Primary Care, University Medical Centre, Utrecht University, Utrecht, the Netherlands
| | - Petra J M Elders
- Amsterdam UMC location Vrije Universiteit Amsterdam, Department of General Practice, de Boelelaan 1117, Amsterdam, Netherlands; Amsterdam Public Health Research Institute, Health Behaviors & Chronic Diseases, Amsterdam, the Netherlands
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Christou MA, Christou PA, Kyriakopoulos C, Christou GA, Tigas S. Effects of Hypoglycemia on Cardiovascular Function in Patients with Diabetes. Int J Mol Sci 2023; 24:9357. [PMID: 37298308 PMCID: PMC10253702 DOI: 10.3390/ijms24119357] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 05/21/2023] [Accepted: 05/25/2023] [Indexed: 06/12/2023] Open
Abstract
Hypoglycemia is common in patients with type 1 and type 2 diabetes (T1D, T2D), treated with insulin or sulfonylureas, and has multiple short- and long-term clinical implications. Whether acute or recurrent, hypoglycemia significantly affects the cardiovascular system with the potential to cause cardiovascular dysfunction. Several pathophysiological mechanisms have been proposed linking hypoglycemia to increased cardiovascular risk, including hemodynamic changes, myocardial ischemia, abnormal cardiac repolarization, cardiac arrhythmias, prothrombotic and proinflammatory effects, and induction of oxidative stress. Hypoglycemia-induced changes can promote the development of endothelial dysfunction, which is an early marker of atherosclerosis. Although data from clinical trials and real-world studies suggest an association between hypoglycemia and cardiovascular events in patients with diabetes, it remains uncertain whether this association is causal. New therapeutic agents for patients with T2D do not cause hypoglycemia and have cardioprotective benefits, whereas increasing the use of new technologies, such as continuous glucose monitoring devices and insulin pumps, has the potential to reduce hypoglycemia and its adverse cardiovascular outcomes in patients with T1D.
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Affiliation(s)
- Maria A. Christou
- Department of Endocrinology, University of Ioannina Faculty of Medicine, 45500 Ioannina, Greece; (M.A.C.); (P.A.C.)
| | - Panagiota A. Christou
- Department of Endocrinology, University of Ioannina Faculty of Medicine, 45500 Ioannina, Greece; (M.A.C.); (P.A.C.)
| | - Christos Kyriakopoulos
- Department of Respiratory Medicine, University of Ioannina Faculty of Medicine, 45500 Ioannina, Greece;
| | - Georgios A. Christou
- Laboratory of Physiology, University of Ioannina Faculty of Medicine, 45500 Ioannina, Greece;
| | - Stelios Tigas
- Department of Endocrinology, University of Ioannina Faculty of Medicine, 45500 Ioannina, Greece; (M.A.C.); (P.A.C.)
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Aburisheh K, AlKheraiji MF, Alwalan SI, Isnani AC, Rafiullah M, Mujammami M, Alfadda AA. Prevalence of QT prolongation and its risk factors in patients with type 2 diabetes. BMC Endocr Disord 2023; 23:50. [PMID: 36859297 PMCID: PMC9976503 DOI: 10.1186/s12902-022-01235-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Accepted: 11/30/2022] [Indexed: 03/03/2023] Open
Abstract
BACKGROUND QT prolongation increases cardiovascular mortality in diabetes. The risk factors for QT prolongation vary across different studies. There is no data on the QT prolongation in patients with diabetes from the Arab region, where diabetes is highly prevalent. Here we aimed to assess the prevalence of QT prolongation and its associated risk factors in patients with type 2 diabetes from Saudi Arabia. METHOD This was a retrospective, cross-sectional, hospital-based file review study. Data were collected from the medical records of patients with type 2 diabetes aged above 14 years and underwent ECG examination, and laboratory investigations were done within one month of ECG. RESULTS The study included 782 patients with a prevalence of QTc prolongation of 13%. Patients with prolonged QTc interval were characterized by older age, higher BMI, longer diabetes duration, lower total cholesterol and LDL-C, and more diabetic nephropathy, hypertension, and CVD cases. They were also more in insulin treatment, antihypertensive medications, loop diuretics, and potassium-sparring diuretics. Logistic regression analysis revealed the odds of prolonged QTc interval increased significantly with CVD (OR = 1.761, 95% CI:1.021-3.036, p = 0.042), and usage of loop diuretics (OR = 2.245, 95% CI:1.023-4.923, p = 0.044) after adjusting for age, gender, and duration of diabetes. CONCLUSION The risk factors associated with QTc prolongation in patients with type 2 diabetes are CVD, and loop diuretics. Age, BMI, and diabetes duration were more in people with QTc prolongation, whereas total cholesterol and LDL-C levels were lower. More patients had diabetic nephropathy, hypertension, and CVD with prolonged QTc.
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Affiliation(s)
- Khaled Aburisheh
- University Diabetes Center, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
| | - Mohammad F AlKheraiji
- University Diabetes Center, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
| | - Saleh I Alwalan
- University Diabetes Center, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
| | - Arthur C Isnani
- Obesity Research Center, College of Medicine, King Saud University, P.O. Box 2925, Riyadh, 11461, Saudi Arabia
| | - Mohamed Rafiullah
- Strategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Muhammad Mujammami
- University Diabetes Center, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
- Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Assim A Alfadda
- Obesity Research Center, College of Medicine, King Saud University, P.O. Box 2925, Riyadh, 11461, Saudi Arabia.
- Strategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
- Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
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Zayas-Arrabal J, Alquiza A, Rodríguez-de-Yurre A, Echeazarra L, Fernández-López V, Gallego M, Casis O. Kv1.3 Channel Blockade Improves Inflammatory Profile, Reduces Cardiac Electrical Remodeling, and Prevents Arrhythmia in Type 2 Diabetic Rats. Cardiovasc Drugs Ther 2023; 37:63-73. [PMID: 34623540 PMCID: PMC9834174 DOI: 10.1007/s10557-021-07264-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/16/2021] [Indexed: 01/16/2023]
Abstract
PURPOSE Kv1.3 channel regulates the activity of lymphocytes, macrophages, or adipose tissue and its blockade reduces inflammatory cytokine secretion and improves insulin sensitivity in animals with metabolic syndrome and in genetically obese mice. Thus, Kv1.3 blockade could be a strategy for the treatment of type 2 diabetes. Elevated circulating levels of TNFα and IL-1b mediate the higher susceptibility to cardiac arrhythmia in type 2 diabetic rats. We hypothesized that Kv1.3 channel blockade with the psoralen PAP1 could have immunomodulatory properties that prevent QTc prolongation and reduce the risk of arrhythmia in type 2 diabetic rats. METHODS Type 2 diabetes was induced to Sprague-Dawley rats by high-fat diet and streptozotocin injection. Diabetic animals were untreated, treated with metformin, or treated with PAP1 for 4 weeks. Plasma glucose, insulin, cholesterol, triglycerides, and cytokine levels were measured using commercial kits. ECG were recorded weekly, and an arrhythmia-inducing protocol was performed at the end of the experimental period. Action potentials were recorded in isolated ventricular cardiomyocytes. RESULTS In diabetic animals, PAP1 normalized glycaemia, insulin resistance, adiposity, and lipid profile. In addition, PAP1 prevented the diabetes-induced repolarization defects through reducing the secretion of the inflammatory cytokines IL-10, IL-12p70, GM-CSF, IFNγ, and TNFα. Moreover, compared to diabetic untreated and metformin-treated animals, those treated with PAP1 had the lowest risk of developing the life-threatening arrhythmia Torsade de Pointes under cardiac challenge. CONCLUSION Kv1.3 inhibition improves diabetes and diabetes-associated low-grade inflammation and cardiac electrical remodeling, resulting in more protection against cardiac arrhythmia compared to metformin.
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Affiliation(s)
- Julián Zayas-Arrabal
- Department of Physiology, Faculty of Pharmacy, University of the Basque Country UPV/EHU, Paseo de la Universidad 7, 01006, Vitoria-Gasteiz, Spain
| | - Amaia Alquiza
- Department of Physiology, Faculty of Pharmacy, University of the Basque Country UPV/EHU, Paseo de la Universidad 7, 01006, Vitoria-Gasteiz, Spain
| | - Ainhoa Rodríguez-de-Yurre
- Department of Physiology, Faculty of Pharmacy, University of the Basque Country UPV/EHU, Paseo de la Universidad 7, 01006, Vitoria-Gasteiz, Spain
| | - Leyre Echeazarra
- Department of Physiology, Faculty of Pharmacy, University of the Basque Country UPV/EHU, Paseo de la Universidad 7, 01006, Vitoria-Gasteiz, Spain
| | - Víctor Fernández-López
- Department of Physiology, Faculty of Pharmacy, University of the Basque Country UPV/EHU, Paseo de la Universidad 7, 01006, Vitoria-Gasteiz, Spain
| | - Mónica Gallego
- Department of Physiology, Faculty of Pharmacy, University of the Basque Country UPV/EHU, Paseo de la Universidad 7, 01006, Vitoria-Gasteiz, Spain
| | - Oscar Casis
- Department of Physiology, Faculty of Pharmacy, University of the Basque Country UPV/EHU, Paseo de la Universidad 7, 01006, Vitoria-Gasteiz, Spain.
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Welten SJGC, Elders PJM, Remmelzwaal S, Doekhie R, Kee KW, Nijpels G, van der Heijden AA. Prolongation of the heart rate-corrected QT interval is associated with cardiovascular diseases: Systematic review and meta-analysis. Arch Cardiovasc Dis 2023; 116:69-78. [PMID: 36690508 DOI: 10.1016/j.acvd.2022.11.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Revised: 11/03/2022] [Accepted: 11/07/2022] [Indexed: 01/09/2023]
Abstract
BACKGROUND Conflicting findings have described the association between prolonged heart rate-corrected QT interval (QTc) and cardiovascular disease. AIMS To identify articles investigating the association between QTc and cardiovascular disease morbidity and mortality, and to summarize the available evidence for the general and type 2 diabetes populations. METHODS A systematic search was performed in PubMed and Embase in May 2022 to identify studies that investigated the association between QTc prolongation and cardiovascular disease in both the general and type 2 diabetes populations. Screening, full-text assessment, data extraction and risk of bias assessment were performed independently by two reviewers. Effect estimates were pooled across studies using random-effect models. RESULTS Of the 59 studies included, 36 qualified for meta-analysis. Meta-analysis of the general population studies showed a significant association for: overall cardiovascular disease (fatal and non-fatal) (hazard ratio [HR] 1.68, 95% confidence interval [CI] 1.33-2.12; I2=69%); coronary heart disease (fatal and non-fatal) in women (HR 1.27, 95% CI 1.08-1.50; I2=38%; coronary heart disease (fatal and non-fatal) in men (HR 2.07, 95% CI 1.26-3.39; I2=78%); stroke (HR 1.59, 95% CI 1.29-1.96; I2=45%); sudden cardiac death (HR 1.60, 95% CI 1.14-2.25; I2=68%); and atrial fibrillation (HR 1.55, 95% CI 1.31-1.83; I2=0.0%). No significant association was found for cardiovascular disease in the type 2 diabetes population. CONCLUSION QTc prolongation was associated with risk of cardiovascular disease in the general population, but not in the type 2 diabetes population.
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Affiliation(s)
- Sabrina J G C Welten
- Department of General Practice, Amsterdam University Medical Centre, Vrije Universiteit Amsterdam, 1081 BT Amsterdam, The Netherlands; Health Behaviours & Chronic Diseases, Amsterdam Public Health Research Institute, 1081 BT Amsterdam, The Netherlands.
| | - Petra J M Elders
- Department of General Practice, Amsterdam University Medical Centre, Vrije Universiteit Amsterdam, 1081 BT Amsterdam, The Netherlands; Health Behaviours & Chronic Diseases, Amsterdam Public Health Research Institute, 1081 BT Amsterdam, The Netherlands
| | - Sharon Remmelzwaal
- Department of General Practice, Amsterdam University Medical Centre, Vrije Universiteit Amsterdam, 1081 BT Amsterdam, The Netherlands; Health Behaviours & Chronic Diseases, Amsterdam Public Health Research Institute, 1081 BT Amsterdam, The Netherlands; Department of Epidemiology and Data Science, Amsterdam University Medical Centre, Vrije Universiteit Amsterdam, Amsterdam Public Health Research Institute, 1081 HV Amsterdam, The Netherlands
| | - Roos Doekhie
- Department of General Practice, Amsterdam University Medical Centre, Vrije Universiteit Amsterdam, 1081 BT Amsterdam, The Netherlands
| | - Kok Wai Kee
- National Healthcare Group Polyclinics, Singapore, 138543
| | - Giel Nijpels
- Department of General Practice, Amsterdam University Medical Centre, Vrije Universiteit Amsterdam, 1081 BT Amsterdam, The Netherlands; Health Behaviours & Chronic Diseases, Amsterdam Public Health Research Institute, 1081 BT Amsterdam, The Netherlands
| | - Amber A van der Heijden
- Department of General Practice, Amsterdam University Medical Centre, Vrije Universiteit Amsterdam, 1081 BT Amsterdam, The Netherlands; Health Behaviours & Chronic Diseases, Amsterdam Public Health Research Institute, 1081 BT Amsterdam, The Netherlands
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9
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Lin N, Zhang H, Li X, Niu Y, Gu H, Lu S, Yang Z, Su Q, Qin L. The influence of different glucose tolerance on QTc interval: a population-based study. BMC Cardiovasc Disord 2023; 23:47. [PMID: 36698056 PMCID: PMC9875502 DOI: 10.1186/s12872-023-03081-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2022] [Accepted: 01/19/2023] [Indexed: 01/27/2023] Open
Abstract
BACKGROUND Corrected QT (QTc) interval has been reported to be associated with type 2 diabetes. This study aimed to explore the relationship between different glucose tolerance and QTc intervals among middle-aged and older Chinese individuals. METHODS We conducted a cross-sectional analysis that included 9898 subjects (3194 men and 6704 women) in a Chinese population. Glucose tolerance was studied during the oral glucose tolerance test (OGTT). Insulin, blood pressure, hemoglobin A1c (HbA1c), serum lipids, hepatic transaminases and waist-to-hip ratio were assessed. The QTc interval was derived from ECG recordings, and the subjects were stratified based on different glucose tolerance. RESULTS QTc interval levels were increased significantly in the subjects with abnormal glucose metabolism compared with the normal glucose regulation group. Multiple regression analyses showed that the QTc interval was significantly associated with fasting plasma glucose, 2-h OGTT plasma glucose and HbA1c. The odds ratio of prolonged QTc was 1.396 for impaired glucose regulation (IFG)/impaired fasting glucose (IGT) (95% CI 0.126-1.730), and 1.342 for type 2 diabetes (95% CI 0.142-1.577) after all potential confounders were adjusted. CONCLUSIONS Impaired glucose tolerance (IGR) and diabetes are associated with prolonged QTc intervals among middle-aged and older Chinese individuals. Abnormal glucose regulation can be used to monitor the QTc interval in the population.
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Affiliation(s)
- Ning Lin
- grid.412987.10000 0004 0630 1330Department of Endocrinology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China ,grid.284723.80000 0000 8877 7471Department of Endocrinology, Shenzhen Hospital, Southern Medical University, Shenzhen, China
| | - Hongmei Zhang
- grid.412987.10000 0004 0630 1330Department of Endocrinology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaoyong Li
- grid.412987.10000 0004 0630 1330Department of Endocrinology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yixin Niu
- grid.412987.10000 0004 0630 1330Department of Endocrinology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hongxia Gu
- grid.39436.3b0000 0001 2323 5732Department of Endocrinology, Chongming Hospital affiliated to Shanghai University of Health & Medicine Science, Shanghai, China
| | - Shuai Lu
- grid.39436.3b0000 0001 2323 5732Department of Endocrinology, Chongming Hospital affiliated to Shanghai University of Health & Medicine Science, Shanghai, China
| | - Zhen Yang
- grid.412987.10000 0004 0630 1330Department of Endocrinology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qing Su
- grid.412987.10000 0004 0630 1330Department of Endocrinology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Li Qin
- grid.39436.3b0000 0001 2323 5732Department of Endocrinology, Chongming Hospital affiliated to Shanghai University of Health & Medicine Science, Shanghai, China
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Cha SA. Heart rate-corrected QT interval prolongation is associated with decreased heart rate variability in patients with type 2 diabetes. Medicine (Baltimore) 2022; 101:e31511. [PMID: 36397376 PMCID: PMC9666134 DOI: 10.1097/md.0000000000031511] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
We investigated the association between the heart rate-corrected QT interval (QTc interval) measured by standard electrocardiography and heart rate variability (HRV) in patients with type 2 diabetes mellitus (T2DM). From March 1, 2009, to December 12, 2009, 411 patients with T2DM who underwent resting 12-lead electrocardiography and cardiovascular autonomic function testing concurrently without the exclusion criteria were consecutively recruited in this cross-sectional study. Time- and frequency-domain HRV variables were assessed for 5 minutes by beat-to-beat HRV recording. The QT interval was corrected for the heart rate using Bazett's formula. QTc interval measurements of >440 ms were considered abnormally prolonged. The mean age and diabetes duration were 56.3 ± 10.6 years and 9.6 ± 7.3 years, respectively. A total of 90 patients had QTc interval prolongation (21.9%). The participants with a prolonged QTc interval were older (59.4 ± 10.1 years vs 55.5 ± 10.6 years, P = .002), were more likely to be a woman (72.2% vs 51.7%, P = .001), had a higher prevalence of hypertension (46.7% vs 33.4%, P = .022), had a higher hemoglobin A1c level (8.8% ± 2.2% vs 8.2% ± 1.8%, P = .045), and had decreased values for the variables measuring HRV, except for the low frequency (LF)/high frequency (HF) ratio (total power [TP], 147.7 [74.1-335.9] ms vs 328.7 [185.7-721.7] ms, P = .002). After adjusting for multiple confounders, QTc interval prolongation was associated with the lowest quartile of the HRV parameters of TP (odds ratio [OR] = 3.99; 95% confidence interval [CI]: 2.29-6.96), HF (OR = 3.20; 95% CI: 1.84-5.58), LF (OR = 3.68; 95% CI: 2.10-6.43), standard deviation of the normal-to-normal interval (OR = 3.31; 95% CI: 1.89-5.77), and root-mean-square of the successive differences (OR = 1.98; 95% CI: 1.13-3.47) in patients with T2DM. Decreased values for the variables measuring HRV, except for the LF/HF ratio, might be associated with QTc interval prolongation in patients with T2DM.
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Affiliation(s)
- Seon-Ah Cha
- Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Wonkwang University Sanbon Hospital, Gunpo, Republic of Korea
- *Correspondence: Seon-Ah Cha, Division of Endocrinology and Metabolism, Department of Internal Medicine, Wonkwang University Sanbon Hospital, 321 Sanbon-ro, Gunpo, Gyeonggi-do 15865, Republic of Korea (e-mail: )
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Cha SA, Yun JS, Kim GH, Ahn YB. Impact of hypoglycemia at the time of hospitalization for heart failure from emergency department on major adverse cardiovascular events in patients with and without type 2 diabetes. Cardiovasc Diabetol 2022; 21:218. [PMID: 36271363 PMCID: PMC9585717 DOI: 10.1186/s12933-022-01651-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Accepted: 09/23/2022] [Indexed: 11/15/2022] Open
Abstract
Background Few studies have examined the association between hypoglycemic episodes among people with type 2 diabetes (T2DM) at the time of hospitalization for heart failure (HF) and cardiovascular outcomes. Methods From March 2016 to June 2018, we conducted a retrospective cohort study to investigate hypoglycemia during HF hospitalization in the emergency department, three-point major adverse cardiovascular events (3P-MACE), and all-cause mortality; these were followed up through June 2021. HF hospitalization was defined according to American Heart Association criteria. Hypoglycemia was defined as a glucose level < 3.9 mmol/L at the time of HF hospitalization. We classified the enrolled patients into three groups (reference group, those without T2DM or hypoglycemia; those diagnosed with T2DM without hypoglycemia; and those with hypoglycemia and T2DM). We used Cox proportional hazard regression analysis to investigate the association between the three groups and the development of the first occurrence of 3P-MACE and all-cause mortality. Results During a median of 25 months of follow-up, a total of 783 patients admitted due to HF were analyzed. In total, 159 (20.3%) cases of 3P-MACE were identified, and the mortality rate was 20.2% (n = 158). The median age of patients was 76.0 (65.0–82.0) years, and 49.0% were men. Patients with 3P-MACE had a lower body mass index (22.6 [20.4–25.1] vs. 23.8 [21.3–26.7]), higher frequency of previous history of HF (24.5% vs. 15.7%), T2DM (64.2% vs. 47.3%), higher rates of hypoglycemia at the time of HF hospitalization (19.5% vs. 7.7%), and lower eGFR levels (61.1 [36.0–80.7] mL/min/1.73 m2 vs. 69.2 [45.8–89.5] mL/min/1.73 m2) than those without 3P-MACE. The multivariable adjusted HR of 3P-MACE was as follows: group with hypoglycemia and T2DM: HR, 2.29; 95% CI: 1.04–5.06; group with T2DM without hypoglycemia: HR: 1.42; 95% CI: 0.86–2.33; and all-cause mortality group with hypoglycemia and T2DM: HR: 2.58; 95% CI: 1.26–5.31, group with T2DM without hypoglycemia: HR: 1.32; 95% CI: 0.81–2.16; compared to the reference group (group without T2DM or hypoglycemia). Conclusions T2DM and hypoglycemia are independent risk factors for 3P-MACE and all-cause mortality compared to those without hypoglycemia during HF hospitalization.
Supplementary Information The online version contains supplementary material available at 10.1186/s12933-022-01651-0.
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Affiliation(s)
- Seon-Ah Cha
- Division of Endocrinology & Metabolism, Department of Internal Medicine, College of Medicine, St. Vincent's Hospital, The Catholic University of Korea, 93 Jungbu-daero, Paldal-gu, Seoul, Republic of Korea.,Division of Endocrinology and Metabolism, Department of Internal Medicine, Wonkwang University Sanbon Hospital, Gunpo, Republic of Korea
| | - Jae-Seung Yun
- Division of Endocrinology & Metabolism, Department of Internal Medicine, College of Medicine, St. Vincent's Hospital, The Catholic University of Korea, 93 Jungbu-daero, Paldal-gu, Seoul, Republic of Korea
| | - Gee-Hee Kim
- Division of Cardiology, Department of Internal Medicine, College of Medicine, St. Vincent's Hospital, The Catholic University of Korea, Seoul, Republic of Korea
| | - Yu-Bae Ahn
- Division of Endocrinology & Metabolism, Department of Internal Medicine, College of Medicine, St. Vincent's Hospital, The Catholic University of Korea, 93 Jungbu-daero, Paldal-gu, Seoul, Republic of Korea.
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Rupee S, Rupee K, Singh RB, Hanoman C, Ismail AMA, Smail M, Singh J. Diabetes-induced chronic heart failure is due to defects in calcium transporting and regulatory contractile proteins: cellular and molecular evidence. Heart Fail Rev 2022; 28:627-644. [PMID: 36107271 DOI: 10.1007/s10741-022-10271-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/07/2022] [Indexed: 11/04/2022]
Abstract
Heart failure (HF) is a major deteriorating disease of the myocardium due to weak myocardial muscles. As such, the heart is unable to pump blood efficiently around the body to meet its constant demand. HF is a major global health problem with more than 7 million deaths annually worldwide, with some patients dying suddenly due to sudden cardiac death (SCD). There are several risk factors which are associated with HF and SCD which can negatively affect the heart synergistically. One major risk factor is diabetes mellitus (DM) which can cause an elevation in blood glucose level or hyperglycaemia (HG) which, in turn, has an insulting effect on the myocardium. This review attempted to explain the subcellular, cellular and molecular mechanisms and to a lesser extent, the genetic factors associated with the development of diabetes- induced cardiomyopathy due to the HG which can subsequently lead to chronic heart failure (CHF) and SCD. The study first explained the structure and function of the myocardium and then focussed mainly on the excitation-contraction coupling (ECC) processes highlighting the defects of calcium transporting (SERCA, NCX, RyR and connexin) and contractile regulatory (myosin, actin, titin and troponin) proteins. The study also highlighted new therapies and those under development, as well as preventative strategies to either treat or prevent diabetic cardiomyopathy (DCM). It is postulated that prevention is better than cure.
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Effect of hyperglycaemia in combination with moxifloxacin on cardiac repolarization in male and female patients with type I diabetes. Clin Res Cardiol 2022; 111:1147-1160. [PMID: 35596784 PMCID: PMC9525410 DOI: 10.1007/s00392-022-02037-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Accepted: 05/05/2022] [Indexed: 11/20/2022]
Abstract
Background Patients with Type 1 diabetes mellitus have been shown to be at a two to ten-fold higher risk of sudden cardiac death (SCD) (Svane et al., Curr Cardiol 2020; 22:112) than the general population, but the underlying mechanism is unclear. Hyperglycaemia is a recognised cause of QTc prolongation; a state patients with type 1 diabetes are more prone to, potentially increasing their risk of ventricular arrhythmia. Understanding the QTc prolongation effect of both hyperglycaemia and the concomitant additive risk of commonly prescribed QTc-prolonging drugs such as Moxifloxacin may help to elucidate the mechanism of sudden cardiac death in this cohort. This single-blinded, placebo-controlled study investigated the extent to which hyperglycaemia prolongs the QTc in controlled conditions, and the potential additive risk of QTc-prolonging medications. Methods 21 patients with type 1 diabetes mellitus were enrolled to a placebo-controlled crossover study at a single clinical trials unit. Patients underwent thorough QTc assessment throughout the study. A ‘hyperglycaemic clamp’ of oral and intravenous glucose was administered with a target blood glucose of > 25 mM and maintained for 2 h on day 1 and day 3, alongside placebo on day 1 and moxifloxacin on day 3. Day 2 served as a control day between the two active treatment days. Thorough QTc assessment was conducted at matched time points over 3 days, and regular blood sampling was undertaken at matched time intervals for glucose levels and moxifloxacin exposure. Results Concentration-effect modelling showed that acute hyperglycaemia prolonged the QTc interval in female and male volunteers with type 1 diabetes by a peak mean increase of 13 ms at 2 h. Peak mean QTc intervals after the administration of intravenous Moxifloxacin during the hyperglycaemic state were increased by a further 9 ms at 2 h, to 22 ms across the entire study population. Regression analysis suggested this additional increase was additive, not exponential. Hyperglycaemia was associated with a significantly greater mean QTc-prolonging effect in females, but the mean peak increase with the addition of moxifloxacin was the same for males and females. This apparent sex difference was likely due to the exclusive use of basal insulin in the male patients, which provided a low level of exogenous insulin during the study assessments thereby mitigating the effects of hyperglycaemia on QTc. This effect was partially overcome by Moxifloxacin administration, suggesting both hyperglycaemia and moxifloxacin prolong QTc by different mechanisms, based on subinterval analysis. Conclusions Hyperglycaemia was found to be a significant cause of QTc prolongation and the additional effect of a QTc-prolonging positive control (moxifloxacin) was found to be additive. Given the high risk of sudden cardiac death in type 1 diabetes mellitus, extra caution should be exercised when prescribing any medication in this cohort for QTc effects, and further research needs to be undertaken to elucidate the exact mechanism underlying this finding and explore the potential prescribing risk in diabetes. Trial Registration NCT number: NCT01984827. Graphical abstract ![]()
Supplementary Information The online version contains supplementary material available at 10.1007/s00392-022-02037-8.
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14
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Jiang A, Gu H, Feng Z, Ding Y, Xu X, Yin G, Zhang W, Shen Z, Li Q. Heart rate-corrected QT interval: A novel diagnostic biomarker for diabetic peripheral neuropathy. J Diabetes Investig 2022; 13:850-857. [PMID: 34932277 PMCID: PMC9077736 DOI: 10.1111/jdi.13738] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 12/15/2021] [Accepted: 12/17/2021] [Indexed: 11/28/2022] Open
Abstract
AIMS/INTRODUCTION To explore the relationship between heart rate-corrected QT (QTc) interval and diabetic peripheral neuropathy (DPN), and whether QTc interval has diagnostic utility for DPN beyond nerve conduction velocity. MATERIALS AND METHODS A total of 965 patients with diabetes, including 473 patients with DPN and 492 patients without DPN, underwent standard 12-lead electrocardiography and detailed assessments of peripheral neuropathy. RESULTS Patients with DPN had longer QTc intervals than those without. Among participants, from the first to fourth quartile of QTc interval, the proportion of patients with DPN appreciably increased and the nerve conduction velocity obviously decreased (P for trend <0.001). The univariate and multivariate analyses showed that prolonged QTc interval was closely associated with increased risk of DPN (univariable odds ratio 1.112, 95% confidence interval 1.097-1.127, P < 0.001; multivariable odds ratio 1.118, 95% confidence interval 1.099-1.137, P < 0.001). Receiver operating characteristic analysis for the diagnosis of DPN showed a greater area under the curve for QTc interval of 0.894 than the median nerve motor conduction velocity of 0.691, median nerve sensory conduction velocity of 0.664 and peroneal nerve motor conduction velocity of 0.692. The optimal cut-off point of QTc interval for DPN was 428.5 ms with sensitivity of 0.715 and specificity of 0.920 (P < 0.001). The combination of QTc interval and nerve conduction testing increased the area under the curve for the diagnosis of DPN (from 0.736 to 0.916; P < 0.001). CONCLUSIONS QTc interval with 428.5 ms has more reliable diagnostic utility for DPN than nerve conduction velocity, and prolonged QTc interval is closely associated with an increased risk of DPN.
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Affiliation(s)
- Ai‐jun Jiang
- Department of Endocrinology, Nanjing First HospitalNanjing Medical UniversityNanjingChina
| | - Heng Gu
- Nanjing Medical UniversityNanjingChina
| | - Zhan‐rong Feng
- Department of EndocrinologyShuyang Hospital of Traditional Chinese MedicineSuqianChina
| | - Ying Ding
- Department of EndocrinologyShuyang Hospital of Traditional Chinese MedicineSuqianChina
| | - Xiao‐hua Xu
- Department of Endocrinology, Nanjing First HospitalNanjing Medical UniversityNanjingChina
| | - Guo‐ping Yin
- Department of Endocrinology, Nanjing First HospitalNanjing Medical UniversityNanjingChina
| | - Wen‐li Zhang
- Department of Endocrinology, Nanjing First HospitalNanjing Medical UniversityNanjingChina
| | - Zi‐yang Shen
- Department of Endocrinology, Nanjing First HospitalNanjing Medical UniversityNanjingChina
| | - Qian Li
- Department of Endocrinology, Nanjing First HospitalNanjing Medical UniversityNanjingChina
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15
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Valentin JP, Hoffmann P, Ortemann-Renon C, Koerner J, Pierson J, Gintant G, Willard J, Garnett C, Skinner M, Vargas HM, Wisialowski T, Pugsley MK. The Challenges of Predicting Drug-Induced QTc Prolongation in Humans. Toxicol Sci 2022; 187:3-24. [PMID: 35148401 PMCID: PMC9041548 DOI: 10.1093/toxsci/kfac013] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
The content of this article derives from a Health and Environmental Sciences Institute (HESI) consortium with a focus to improve cardiac safety during drug development. A detailed literature review was conducted to evaluate the concordance between nonclinical repolarization assays and the clinical thorough QT (TQT) study. Food and Drug Administration and HESI developed a joint database of nonclinical and clinical data, and a retrospective analysis of 150 anonymized drug candidates was reviewed to compare the performance of 3 standard nonclinical assays with clinical TQT study findings as well as investigate mechanism(s) potentially responsible for apparent discrepancies identified. The nonclinical assays were functional (IKr) current block (Human ether-a-go-go related gene), action potential duration, and corrected QT interval in animals (in vivo corrected QT). Although these nonclinical assays demonstrated good specificity for predicting negative clinical QT prolongation, they had relatively poor sensitivity for predicting positive clinical QT prolongation. After review, 28 discordant TQT-positive drugs were identified. This article provides an overview of direct and indirect mechanisms responsible for QT prolongation and theoretical reasons for lack of concordance between clinical TQT studies and nonclinical assays. We examine 6 specific and discordant TQT-positive drugs as case examples. These were derived from the unique HESI/Food and Drug Administration database. We would like to emphasize some reasons for discordant data including, insufficient or inadequate nonclinical data, effects of the drug on other cardiac ion channels, and indirect and/or nonelectrophysiological effects of drugs, including altered heart rate. We also outline best practices that were developed based upon our evaluation.
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Affiliation(s)
- Jean-Pierre Valentin
- Department of Investigative Toxicology, UCB Biopharma SRL, Braine-l’Alleud B-1420, Belgium
| | | | | | - John Koerner
- Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland 20993, USA
| | - Jennifer Pierson
- Health and Environmental Sciences Institute, Washington, District of Columbia 20005, USA
| | | | - James Willard
- Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland 20993, USA
| | - Christine Garnett
- Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland 20993, USA
| | | | - Hugo M Vargas
- Department of Safety Pharmacology & Animal Research Center, Amgen, Thousand Oaks, California 91320, USA
| | - Todd Wisialowski
- Department of Safety Pharmacology, Pfizer, Groton, Connecticut 06340, USA
| | - Michael K Pugsley
- Department of Toxicology, Cytokinetics, South San Francisco, California 94080, USA
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Abstract
BACKGROUND Adult patients diagnosed with type 1 diabetes mellitus are at risk for ventricular arrhythmias and sudden cardiac death. AIM The objective of our study is to evaluate the electrocardiographic data of children diagnosed with type 1 diabetes mellitus and to determine the possibility of arrhythmia in order to prevent sudden death. METHODS Electrocardiographic data of 60 patients diagnosed with type 1 diabetes mellitus and 86 controls, who were compatible with the patient group in terms of age and gender, were compared. RESULTS The duration of diabetes in our patients with type 1 diabetes mellitus was 5.23 ± 1.76 years, and the haemoglobin A1c levels were 9.63% ± 1.75%. The heart rate, QRS, QT maximum, QT dispersion, QTc minimum, QTc maximum, QTc dispersion, Tp-e maximum, Tp-e maximum/QTc maximum and the JTc were significantly higher compared to the control group. There was no significant correlation between the duration of type 1 diabetes mellitus and HbA1c levels and the electrocardiographic data. CONCLUSION We attributed the lack of a significant correlation between the duration of type 1 diabetes mellitus and the haemoglobin A1c levels and the electrocardiographic data to the fact that the duration of diabetes was short, since our patients were children. We believe that patients with type 1 diabetes mellitus should be followed up closely in terms of sudden death, as they have electrocardiographic changes that may cause arrhythmias compared to the control group. However, more studies with longer follow-up periods are necessary to support our data.
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Lu CF, Ge XQ, Wang Y, Su JB, Wang XQ, Zhang DM, Xu F, Liu WS, Su M. The relationship between adenosine deaminase and heart rate-corrected QT interval in type 2 diabetic patients. Endocr Connect 2021; 10:894-901. [PMID: 34261041 PMCID: PMC8346184 DOI: 10.1530/ec-21-0199] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Accepted: 07/14/2021] [Indexed: 12/25/2022]
Abstract
BACKGROUND Prolonged heart rate-corrected QT (QTc) interval may reflect poor prognosis of patients with type 2 diabetes (T2D). Serum adenosine deaminase (ADA) levels are related to hyperglycemia, insulin resistance (IR) and inflammation, which may participate in diabetic complications. We investigated the association of serum ADA levels with prolonged QTc interval in a large-scale sample of patients with T2D. METHODS In this cross-sectional study, a total of 492 patients with T2D were recruited. Serum ADA levels were determined by venous blood during fasting. QTc interval was estimated from resting 12-lead ECGs, and prolonged QTc interval was defined as QTc > 440 ms. RESULTS In this study, the prevalence of prolonged QTc interval was 22.8%. Serum ADA levels were positively associated with QTc interval (r = 0.324, P < 0.0001). The proportion of participants with prolonged QTc interval increased significantly from 9.2% in the first tertile (T1) to 24.7% in the second tertile (T2) and 39.0% in the third tertile (T3) of ADA (P for trend < 0.001). After adjusting for other possible risk factors by multiple linear regression analysis, serum ADA level was still significantly associated with QTc interval (β = 0.217, t = 3.400, P < 0.01). Multivariate logistic regression analysis showed that female (OR 5.084, CI 2.379-10.864, P < 0.001), insulin-sensitizers treatment (OR 4.229, CI 1.290-13.860, P = 0.017) and ADA (OR 1.212, CI 1.094-1.343, P < 0.001) were independent contributors to prolonged QTc interval. CONCLUSIONS Serum ADA levels were independently associated with prolonged QTc interval in patients with T2D.
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Affiliation(s)
- Chun-feng Lu
- Department of Endocrinology, Affiliated Hospital 2 of Nantong University and First People’s Hospital of Nantong City, Nantong, China
| | - Xiao-qin Ge
- Department of Endocrinology, Affiliated Hospital 2 of Nantong University and First People’s Hospital of Nantong City, Nantong, China
| | - Yan Wang
- Department of Geriatrics, Affiliated Hospital 2 of Nantong University and First People’s Hospital of Nantong City, Nantong, China
| | - Jian-bin Su
- Department of Endocrinology, Affiliated Hospital 2 of Nantong University and First People’s Hospital of Nantong City, Nantong, China
- Correspondence should be addressed to J Su or X Wang: or
| | - Xue-qin Wang
- Department of Endocrinology, Affiliated Hospital 2 of Nantong University and First People’s Hospital of Nantong City, Nantong, China
- Correspondence should be addressed to J Su or X Wang: or
| | - Dong-mei Zhang
- Clinical Medicine Research Center, Affiliated Hospital 2 of Nantong University and First People’s Hospital of Nantong City, Nantong, China
| | - Feng Xu
- Department of Endocrinology, Affiliated Hospital 2 of Nantong University and First People’s Hospital of Nantong City, Nantong, China
| | - Wang-shu Liu
- Department of Endocrinology, Affiliated Hospital 2 of Nantong University and First People’s Hospital of Nantong City, Nantong, China
| | - Min Su
- Department of Endocrinology, Nantong Hospital of Traditional Chinese Medicine, Nantong Hospital Affiliated to Nanjing University of Chinese Medicine, Nantong, China
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18
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Hong J, Liu WY, Hu X, Jiang FF, Xu ZR, Li F, Shen FX, Zhu H. Association between heart rate-corrected QT interval and severe peripheral arterial disease in patients with type 2 diabetes and foot ulcers. Endocr Connect 2021; 10:845-851. [PMID: 34223825 PMCID: PMC8346192 DOI: 10.1530/ec-21-0140] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Accepted: 07/05/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND A prolonged heart rate-corrected QT interval (QTc) has been associated with peripheral artery disease (PAD) in the general population. However, no study to date has identified a link between prolonged QTc and the severity of PAD in patients with diabetes mellitus and foot ulcers (DFUs). This study aimed to investigate this relationship. METHODS This multicenter study enrolled 281 patients with DFUs. The severity of PAD was classified into no severe PAD group (without stenosis or occlusion) and severe PAD group (with stenosis or occlusion) based on duplex ultrasonography. The association of prolonged QTc with severe PAD was evaluated in a multivariable mixed-effect logistic regression model, with the hospital as a random effect. Directed acyclic graphs were used to drive the selection of variables to fit the regression model. RESULTS Patients with severe PAD had longer QTc than those without. Based on the multivariable mixed-effect logistic regression model, a prolonged QTc was positively associated with severe PAD (odds ratio (OR) = 2.61; 95% CI: 1.07-6.35) and severe DFUs (Wagner grade score ≥ 3) (OR = 2.87; 95% CI: 1.42-5.81). CONCLUSIONS A prolonged QTc was associated with severe PAD in patients with DFUs. Further research is required to ascertain whether the association is causal.
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Affiliation(s)
- Jing Hong
- Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Wen-Yue Liu
- Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Xiang Hu
- Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Fei-Fei Jiang
- Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Ze-Ru Xu
- Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Fang Li
- Department of Endocrinology, Ruian Traditional Chinese Medicine Hospital, Wenzhou, China
| | - Fei-Xia Shen
- Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Hong Zhu
- Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Correspondence should be addressed to H Zhu:
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Andersen A, Bagger JI, Baldassarre MPA, Christensen MB, Abelin KU, Faber J, Pedersen-Bjergaard U, Holst JJ, Lindhardt TB, Gislason G, Knop FK, Vilsbøll T. Acute hypoglycemia and risk of cardiac arrhythmias in insulin-treated type 2 diabetes and controls. Eur J Endocrinol 2021; 185:343-353. [PMID: 34085953 PMCID: PMC8345897 DOI: 10.1530/eje-21-0232] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Accepted: 06/03/2021] [Indexed: 12/04/2022]
Abstract
OBJECTIVE Hypoglycemia is associated with an increased risk of cardiovascular disease including cardiac arrhythmias. We investigated the effect of hypoglycemia in the setting of acute glycemic fluctuations on cardiac rhythm and cardiac repolarization in insulin-treated patients with type 2 diabetes compared with matched controls without diabetes. DESIGN A non-randomized, mechanistic intervention study. METHODS Insulin-treated patients with type 2 diabetes (n = 21, age (mean ± s.d.): 62.8 ± 6.5 years, BMI: 29.0 ± 4.2 kg/m2, HbA1c: 6.8 ± 0.5% (51.0 ± 5.4 mmol/mol)) and matched controls (n = 21, age: 62.2 ± 8.3 years, BMI 29.2 ± 3.5 kg/m2, HbA1c: 5.3 ± 0.3% (34.3 ± 3.3 mmol/mol)) underwent a sequential hyperglycemic and hypoglycemic clamp with three steady-states of plasma glucose: (i) fasting plasma glucose, (ii) hyperglycemia (fasting plasma glucose +10 mmol/L) and (iii) hyperinsulinemic hypoglycemia (plasma glucose < 3.0 mmol/L). Participants underwent continuous ECG monitoring and blood samples for counterregulatory hormones and plasma potassium were obtained. RESULTS Both groups experienced progressively increasing heart rate corrected QT (Fridericia's formula) interval prolongations during hypoglycemia ((∆mean (95% CI): 31 ms (16, 45) and 39 ms (24, 53) in the group of patients with type 2 diabetes and controls, respectively) with similar increases from baseline at the end of the hypoglycemic phase (P = 0.43). The incidence of ventricular premature beats increased significantly in both groups during hypoglycemia (P = 0.033 and P < 0.0001, respectively). One patient with type 2 diabetes developed atrial fibrillation during recovery from hypoglycemia. CONCLUSIONS In insulin-treated patients with type 2 diabetes and controls without diabetes, hypoglycemia causes clinically significant and similar increases in cardiac repolarization that might increase vulnerability for serious cardiac arrhythmias and sudden cardiac death.
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Affiliation(s)
- Andreas Andersen
- Steno Diabetes Center Copenhagen, Gentofte Hospital, Hellerup, Denmark
- Center for Clinical Metabolic Research, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
| | - Jonatan I Bagger
- Steno Diabetes Center Copenhagen, Gentofte Hospital, Hellerup, Denmark
- Center for Clinical Metabolic Research, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
| | - Maria P A Baldassarre
- Center for Clinical Metabolic Research, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
- Department of Medicine and Aging Sciences, G. d’Annunzio University, Chieti, Italy
| | - Mikkel B Christensen
- Center for Clinical Metabolic Research, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
- Department of Clinical Pharmacology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Kirsten U Abelin
- Steno Diabetes Center Copenhagen, Gentofte Hospital, Hellerup, Denmark
- Center for Clinical Metabolic Research, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
| | - Jens Faber
- Department of Medicine, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Ulrik Pedersen-Bjergaard
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Endocrinology and Nephrology, Nordsjællands Hospital Hillerød, University of Copenhagen, Hillerød, Denmark
| | - Jens J Holst
- Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Tommi B Lindhardt
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Cardiology, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
| | - Gunnar Gislason
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Cardiology, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
- The Danish Heart Foundation, Copenhagen, Denmark
| | - Filip K Knop
- Steno Diabetes Center Copenhagen, Gentofte Hospital, Hellerup, Denmark
- Center for Clinical Metabolic Research, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Tina Vilsbøll
- Steno Diabetes Center Copenhagen, Gentofte Hospital, Hellerup, Denmark
- Center for Clinical Metabolic Research, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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20
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Gallego M, Zayas-Arrabal J, Alquiza A, Apellaniz B, Casis O. Electrical Features of the Diabetic Myocardium. Arrhythmic and Cardiovascular Safety Considerations in Diabetes. Front Pharmacol 2021; 12:687256. [PMID: 34305599 PMCID: PMC8295895 DOI: 10.3389/fphar.2021.687256] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 06/15/2021] [Indexed: 12/20/2022] Open
Abstract
Diabetes is a chronic metabolic disease characterized by hyperglycemia in the absence of treatment. Among the diabetes-associated complications, cardiovascular disease is the major cause of mortality and morbidity in diabetic patients. Diabetes causes a complex myocardial dysfunction, referred as diabetic cardiomyopathy, which even in the absence of other cardiac risk factors results in abnormal diastolic and systolic function. Besides mechanical abnormalities, altered electrical function is another major feature of the diabetic myocardium. Both type 1 and type 2 diabetic patients often show cardiac electrical remodeling, mainly a prolonged ventricular repolarization visible in the electrocardiogram as a lengthening of the QT interval duration. The underlying mechanisms at the cellular level involve alterations on the expression and activity of several cardiac ion channels and their associated regulatory proteins. Consequent changes in sodium, calcium and potassium currents collectively lead to a delay in repolarization that can increase the risk of developing life-threatening ventricular arrhythmias and sudden death. QT duration correlates strongly with the risk of developing torsade de pointes, a form of ventricular tachycardia that can degenerate into ventricular fibrillation. Therefore, QT prolongation is a qualitative marker of proarrhythmic risk, and analysis of ventricular repolarization is therefore required for the approval of new drugs. To that end, the Thorough QT/QTc analysis evaluates QT interval prolongation to assess potential proarrhythmic effects. In addition, since diabetic patients have a higher risk to die from cardiovascular causes than individuals without diabetes, cardiovascular safety of the new antidiabetic drugs must be carefully evaluated in type 2 diabetic patients. These cardiovascular outcome trials reveal that some glucose-lowering drugs actually reduce cardiovascular risk. The mechanism of cardioprotection might involve a reduction of the risk of developing arrhythmia.
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Affiliation(s)
- Mónica Gallego
- Department of Physiology, Faculty of Pharmacy, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain
| | - Julián Zayas-Arrabal
- Department of Physiology, Faculty of Pharmacy, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain
| | - Amaia Alquiza
- Department of Physiology, Faculty of Pharmacy, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain
| | - Beatriz Apellaniz
- Department of Physiology, Faculty of Pharmacy, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain
| | - Oscar Casis
- Department of Physiology, Faculty of Pharmacy, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain
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21
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Duque A, Mediano MFF, De Lorenzo A, Rodrigues Jr LF. Cardiovascular autonomic neuropathy in diabetes: Pathophysiology, clinical assessment and implications. World J Diabetes 2021; 12:855-867. [PMID: 34168733 PMCID: PMC8192252 DOI: 10.4239/wjd.v12.i6.855] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 04/05/2021] [Accepted: 05/20/2021] [Indexed: 02/06/2023] Open
Abstract
Cardiovascular autonomic neuropathy (CAN) is a debilitating condition that mainly occurs in long-standing type 2 diabetes patients but can manifest earlier, even before diabetes is diagnosed. CAN is a microvascular complication that results from lesions of the sympathetic and parasympathetic nerve fibers, which innervate the heart and blood vessels and promote alterations in cardiovascular autonomic control. The entire mechanism is still not elucidated, but several aspects of the pathophysiology of CAN have already been described, such as the production of advanced glycation end products, reactive oxygen species, nuclear factor kappa B, and pro-inflammatory cytokines. This microvascular complication is an important risk factor for silent myocardial ischemia, chronic kidney disease, myocardial dysfunction, major cardiovascular events, cardiac arrhythmias, and sudden death. It has also been suggested that, compared to other traditional cardiovascular risk factors, CAN progression may have a greater impact on cardiovascular disease development. However, CAN might be subclinical for several years, and a late diagnosis increases the mortality risk. The duration of the transition period from the subclinical to clinical stage remains unknown, but the progression of CAN is associated with a poor prognosis. Several tests can be used for CAN diagnosis, such as heart rate variability (HRV), cardiovascular autonomic reflex tests, and myocardial scintigraphy. Currently, it has already been described that CAN could be detected even during the subclinical stage through a reduction in HRV, which is a non-invasive test with a lower operating cost. Therefore, considering that diabetes mellitus is a global epidemic and that diabetic neuropathy is the most common chronic complication of diabetes, the early identification and treatment of CAN could be a key point to mitigate the morbidity and mortality associated with this long-lasting condition.
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Affiliation(s)
- Alice Duque
- Education and Research Department, Instituto Nacional de Cardiologia, Rio de Janeiro 22240006, RJ, Brazil
| | - Mauro Felippe Felix Mediano
- Education and Research Department, Instituto Nacional de Cardiologia, Rio de Janeiro 22240006, RJ, Brazil
- Laboratory of Clinical Research on Chagas Disease, Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro 21040360, RJ, Brazil
| | - Andrea De Lorenzo
- Education and Research Department, Instituto Nacional de Cardiologia, Rio de Janeiro 22240006, RJ, Brazil
| | - Luiz Fernando Rodrigues Jr
- Education and Research Department, Instituto Nacional de Cardiologia, Rio de Janeiro 22240006, RJ, Brazil
- Department of Physiological Sciences, Biomedical Institute, Federal University of the State of Rio de Janeiro, Rio de Janeiro 22240006, RJ, Brazil
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22
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Zhang S, Zhuang X, Lv Q, Du Z, Zhou H, Zhong X, Sun X, Xiong Z, Hu X, Yang D, Zhang M, Liao X. Six-Year Change in QT Interval Duration and Risk of Incident Heart Failure - A Secondary Analysis of the Atherosclerosis Risk in Communities Study. Circ J 2021; 85:640-646. [PMID: 33268658 DOI: 10.1253/circj.cj-20-0719] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
BACKGROUND Few studies have investigated the association between temporal change in QT interval and incident heart failure (HF). The aim of this study is to examine this association in the Atherosclerosis Risk in Communities (ARIC) study. METHODS AND RESULTS A secondary analysis was performed for the ARIC study. Overall, 10,274 participants (age 60.0±5.7 years, 45.7% male and 19.5% black) who obtained a 12-lead electrocardiography (ECG) at both Visit 1 (1987-1989) and Visit 3 (1993-1995) in the ARIC study were included. QT interval duration was corrected by using Bazett's formula (QTc). The change in corrected QT interval duration (∆QTc) was calculated by subtracting QTc at Visit 3 from Visit 1. The main outcome measure was incident HF. Multivariable Cox regression models were used to assess the association between ∆QTc and incident HF. During a median follow up of 19.5 years, 1,833 cases (17.8%) of incident HF occurred. ∆QTc was positively associated with incident HF (HR: 1.06, 95% CI 1.03, 1.08, per 10 ms increase, P<0.001; HR 1.22, 95% CI 1.08, 1.36, T3 vs. T1, P=0.002), after adjusting for traditional cardiovascular risk factor, QTc and QRS duration. CONCLUSIONS Temporal increases in QTc are independently associated with increased risk of HF.
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Affiliation(s)
- Shaozhao Zhang
- Cardiology Department, First Affiliated Hospital of Sun Yat-Sen University
- NHC Key Laboratory of Assisted Circulation (Sun Yat-Sen University)
| | - Xiaodong Zhuang
- Cardiology Department, First Affiliated Hospital of Sun Yat-Sen University
- NHC Key Laboratory of Assisted Circulation (Sun Yat-Sen University)
| | - Qiyuan Lv
- School of Nursing, Sun Yat-Sen University
| | - Zhimin Du
- Cardiology Department, First Affiliated Hospital of Sun Yat-Sen University
- NHC Key Laboratory of Assisted Circulation (Sun Yat-Sen University)
| | - Huimin Zhou
- Cardiology Department, First Affiliated Hospital of Sun Yat-Sen University
- NHC Key Laboratory of Assisted Circulation (Sun Yat-Sen University)
| | - Xiangbin Zhong
- Cardiology Department, First Affiliated Hospital of Sun Yat-Sen University
- NHC Key Laboratory of Assisted Circulation (Sun Yat-Sen University)
| | - Xiuting Sun
- Cardiology Department, First Affiliated Hospital of Sun Yat-Sen University
- NHC Key Laboratory of Assisted Circulation (Sun Yat-Sen University)
| | - Zhenyu Xiong
- Cardiology Department, First Affiliated Hospital of Sun Yat-Sen University
- NHC Key Laboratory of Assisted Circulation (Sun Yat-Sen University)
| | - Xun Hu
- Cardiology Department, First Affiliated Hospital of Sun Yat-Sen University
- NHC Key Laboratory of Assisted Circulation (Sun Yat-Sen University)
| | - Daya Yang
- Cardiology Department, First Affiliated Hospital of Sun Yat-Sen University
- NHC Key Laboratory of Assisted Circulation (Sun Yat-Sen University)
| | | | - Xinxue Liao
- Cardiology Department, First Affiliated Hospital of Sun Yat-Sen University
- NHC Key Laboratory of Assisted Circulation (Sun Yat-Sen University)
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23
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Harms PP, van der Heijden AA, Rutters F, Tan HL, Beulens JWJ, Nijpels G, Elders P. Prevalence of ECG abnormalities in people with type 2 diabetes: The Hoorn Diabetes Care System cohort. J Diabetes Complications 2021; 35:107810. [PMID: 33280986 DOI: 10.1016/j.jdiacomp.2020.107810] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Revised: 10/26/2020] [Accepted: 11/01/2020] [Indexed: 10/22/2022]
Abstract
AIMS The American Diabetes Association, and the joint European Society of Cardiology and European Association for the Study of Diabetes guidelines recommend a resting ECG in people with type 2 diabetes with hypertension or suspected cardiovascular disease (CVD). However, knowledge on the prevalence of ECG abnormalities is incomplete. We aimed to analyse the prevalence of ECG abnormalities and their cross-sectional associations with cardiovascular risk factors in people with type 2 diabetes. METHODS We used data of the Diabetes Care System cohort obtained in 2018. ECG abnormalities were defined using the Minnesota Classification and categorised into types of abnormalities. The prevalence was calculated for the total population (n = 8068) and the subgroup of people without a history of CVD (n = 6494). Logistic regression models were used to asses cross-sectional associations. RESULTS Approximately one-third of the total population had minor (16.0%) or major (13.1%) ECG abnormalities. Of the participants without a CVD history, approximately one-quarter had minor (14.9%) or major (9.1%) ECG abnormalities, and for those with hypertension or very high CVD risk, the prevalence was 27.5% and 39.6%, respectively. ECG abnormalities were significantly and consistently associated with established CVD risk factors. CONCLUSIONS Resting ECG abnormalities are common in all people with type 2 diabetes (29.1%), including those without a history of CVD (24.0%), and their prevalence is related to traditional cardiovascular risk factors such as older age, male sex, hypertension, lower HDL cholesterol, higher BMI, and smoking behaviour.
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Affiliation(s)
- Peter P Harms
- Amsterdam UMC, Vrije Universiteit Amsterdam, Department of General Practice Medicine, Amsterdam Public Health Research Institute, De Boelelaan 1117, Amsterdam, the Netherlands.
| | - Amber A van der Heijden
- Amsterdam UMC, Vrije Universiteit Amsterdam, Department of General Practice Medicine, Amsterdam Public Health Research Institute, De Boelelaan 1117, Amsterdam, the Netherlands
| | - Femke Rutters
- Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, De Boelelaan 1117, Amsterdam, the Netherlands
| | - Hanno L Tan
- Amsterdam UMC, University of Amsterdam, Heart Center, Department of Experimental and Clinical Cardiology, Amsterdam Cardiovascular Sciences Research Institute, Meibergdreef 9, Amsterdam, the Netherlands; Netherlands Heart Institute, Utrecht, the Netherlands
| | - Joline W J Beulens
- Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, De Boelelaan 1117, Amsterdam, the Netherlands; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Giel Nijpels
- Amsterdam UMC, Vrije Universiteit Amsterdam, Department of General Practice Medicine, Amsterdam Public Health Research Institute, De Boelelaan 1117, Amsterdam, the Netherlands
| | - Petra Elders
- Amsterdam UMC, Vrije Universiteit Amsterdam, Department of General Practice Medicine, Amsterdam Public Health Research Institute, De Boelelaan 1117, Amsterdam, the Netherlands
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24
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Liu H, Zhao Y, Xie A, Kim TY, Terentyeva R, Liu M, Shi G, Feng F, Choi BR, Terentyev D, Hamilton S, Dudley SC. Interleukin-1β, Oxidative Stress, and Abnormal Calcium Handling Mediate Diabetic Arrhythmic Risk. ACTA ACUST UNITED AC 2021; 6:42-52. [PMID: 33532665 PMCID: PMC7838050 DOI: 10.1016/j.jacbts.2020.11.002] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Revised: 11/03/2020] [Accepted: 11/03/2020] [Indexed: 12/14/2022]
Abstract
Diabetes-induced arrhythmic risk involved activation of innate immunity, elevation of IL-1β, mitochondrial oxidative stress, SR calcium release channel oxidation, and QT prolongation. Diabetes-induced arrhythmic risk could be inhibited by IL-1β antagonism, mitoROS scavenging, and SR calcium release stabilization. The relationship of inflammation and arrhythmic risk may account for increased susceptibility of diabetic patients to the effects of COVID-19. Diabetes mellitus (DM) is associated with increased arrhythmia. Type 2 DM (T2DM) mice showed prolonged QT interval and increased ventricular arrhythmic inducibility, accompanied by elevated cardiac interleukin (IL)-1β, increased mitochondrial reactive oxygen species (mitoROS), and oxidation of the sarcoplasmic reticulum (SR) Ca2+ release channel (ryanodine receptor 2 [RyR2]). Inhibiting IL-1β and mitoROS reduced RyR2 oxidation and the ventricular arrhythmia in DM. Inhibiting SR Ca2+ leak by stabilizing the oxidized RyR2 channel reversed the diabetic arrhythmic risk. In conclusion, cardiac IL-1β mediated the DM-associated arrhythmia through mitoROS generation that enhances SR Ca2+ leak. The mechanistic link between inflammation and arrhythmias provides new therapeutic options.
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Key Words
- APD, action potential duration
- DM, diabetes mellitus
- EAD, early afterdepolarization
- IL, interleukin
- IL-1RA, interleukin-1 receptor antagonist
- Ito, transient outward potassium current
- RyR2, ryanodine receptor
- SR, sarcoplasmic reticulum
- T1DM, type 1 diabetes mellitus
- T2DM, type 2 diabetes mellitus
- VT, ventricular tachycardia
- calcium handling
- inflammation
- mitoROS, mitochondrial reactive oxygen species
- mitochondria
- oxidation
- sudden cardiac death
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Affiliation(s)
- Hong Liu
- Division of Cardiology, Department of Medicine, Lillehei Heart Institute, University of Minnesota Twin Cities, Minneapolis, Minnesota, USA
| | - Yang Zhao
- Division of Cardiology, Lanzhou University Second Hospital, Lanzhou University, Lanzhou, China
| | - An Xie
- Division of Cardiology, Department of Medicine, Lillehei Heart Institute, University of Minnesota Twin Cities, Minneapolis, Minnesota, USA
| | - Tae-Yun Kim
- Division of Cardiology, Cardiovascular Research Center, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA
| | - Radmila Terentyeva
- Division of Cardiology, Cardiovascular Research Center, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA.,Department of Physiology and Cell Biology, The Ohio State University, Columbus, Ohio, USA
| | - Man Liu
- Division of Cardiology, Department of Medicine, Lillehei Heart Institute, University of Minnesota Twin Cities, Minneapolis, Minnesota, USA
| | - Guangbin Shi
- Division of Cardiology, Cardiovascular Research Center, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA
| | - Feng Feng
- Division of Cardiology, Department of Medicine, Lillehei Heart Institute, University of Minnesota Twin Cities, Minneapolis, Minnesota, USA
| | - Bum-Rak Choi
- Division of Cardiology, Cardiovascular Research Center, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA
| | - Dmitry Terentyev
- Division of Cardiology, Cardiovascular Research Center, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA.,Department of Physiology and Cell Biology, The Ohio State University, Columbus, Ohio, USA
| | - Shanna Hamilton
- Department of Physiology and Cell Biology, The Ohio State University, Columbus, Ohio, USA
| | - Samuel C Dudley
- Division of Cardiology, Department of Medicine, Lillehei Heart Institute, University of Minnesota Twin Cities, Minneapolis, Minnesota, USA
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25
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Kobayashi S, Nagao M, Fukuda I, Oikawa S, Sugihara H. Multiple daily insulin injections ameliorate QT interval by lowering blood glucose levels in patients with type 2 diabetes. Ther Adv Endocrinol Metab 2021; 12:20420188211010057. [PMID: 34104393 PMCID: PMC8072833 DOI: 10.1177/20420188211010057] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Accepted: 03/24/2021] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND A prolonged QT interval plays a causal role in fatal arrhythmia and is known to be a risk factor for sudden cardiac death. Although diabetic patients with microvascular complications tend to have a longer QT interval, the therapeutic effect of diabetes on the QT interval remains unclear. Here, we assessed the changes in QT interval in patients with type 2 diabetes (T2D) who received multiple daily insulin injections. MATERIALS AND METHODS Patients with T2D (n = 34) who were admitted to our hospital and initiated multiple daily insulin injections for glycemic control were enrolled in this study. Clinical measurements, including electrocardiogram, were taken on admission and discharge. The QT interval was measured manually in lead II on the electrocardiogram, and corrected QT interval (QTc) was calculated using Bazett's formula. The change in QTc (ΔQTc) during hospitalization (median, 15 days) and clinical parameters affecting ΔQTc were investigated. RESULTS QTc was shortened from 439 ± 24 to 427 ± 26 ms during hospitalization (p < 0.0001). ΔQTc was positively correlated with the changes in fasting plasma glucose (ΔFPG, r = 0.55, p = 0.0008) and glycated albumin (r = 0.38, p = 0.026) following insulin therapy, but not with the final dose of insulin (r = -0.20, p = 0.26). The multiple regression analyses revealed that ΔFPG was independently associated with ΔQTc. CONCLUSIONS Multiple daily insulin injections can ameliorate QT interval by lowering the blood glucose levels in T2D, suggesting that glycemic control is important for preventing patients with T2D from sudden cardiac death.
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Affiliation(s)
- Shunsuke Kobayashi
- Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | | | - Izumi Fukuda
- Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Shinichi Oikawa
- Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Hitoshi Sugihara
- Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
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26
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Liu P, Wang L, Han D, Sun C, Xue X, Li G. Acquired long QT syndrome in chronic kidney disease patients. Ren Fail 2020; 42:54-65. [PMID: 31878817 PMCID: PMC6968512 DOI: 10.1080/0886022x.2019.1707098] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Revised: 11/30/2019] [Accepted: 12/01/2019] [Indexed: 12/19/2022] Open
Abstract
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in chronic kidney disease (CKD) patients. QT interval prolongation is a congenital or acquired condition that is associated with an increased risk of torsade de pointes (TdP), sudden cardiac death (SCD), and all-cause mortality in the general population. The prevalence of acquired long QT syndrome (aLQTS) is high, and various acquired conditions contribute to the prolonged QT interval in patients with CKD. More notably, the prolonged QT interval in CKD is an independent risk factor for SCD and all-cause mortality. In this review, we focus on the epidemiological characteristics, risk factors, underlying mechanisms and treatments of aLQTS in CKD, promoting the management of aLQTS in CKD patients.
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Affiliation(s)
- Peng Liu
- Department of Cardiovascular Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, P.R. China;
| | - Lu Wang
- Department of Cardiovascular Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, P.R. China;
- Department of Endocrinology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, P.R. China
| | - Dan Han
- Department of Cardiovascular Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, P.R. China;
| | - Chaofeng Sun
- Department of Cardiovascular Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, P.R. China;
| | - Xiaolin Xue
- Department of Cardiovascular Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, P.R. China;
| | - Guoliang Li
- Department of Cardiovascular Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, P.R. China;
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27
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Shi H, Jiang X. Correlation Between QTc Prolongation and Obstructive Sleep Apnea in Patients with Type 2 Diabetes Mellitus. Med Sci Monit 2020; 26:e926954. [PMID: 32853184 PMCID: PMC7478427 DOI: 10.12659/msm.926954] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND Obstructive sleep apnea (OSA) plays an important role in the progression of cardiovascular disease (CVD), and is a common symptom in patients with type 2 diabetes mellitus (T2DM). Prolongation of corrected QT interval (QTc) reflects ventricular arrhythmias and CVD. The aim of this study was to explore the relationship between OSA and QTc in T2DM patients and to evaluate the potential application of QTc in clinical practice. MATERIAL AND METHODS A total of 358 T2DM patients were involved in this study. OSA was diagnosed with apnea-hypopnea index ≥5 by full-night polysomnography and QTc was measured by a 12-lead electrocardiogram (ECG). Patients were grouped into 2 groups based on median QTc, and clinical data were studied. Logistic regression analysis was used to investigate the association between OSA and QTc with adjusted age, sex, body mass index (BMI), hypertension, total bilirubin (TBL), and smoking history. RESULTS Among 358 T2DM patients, 59.2% had OSA. Compared to those in the QTc <418 ms group, older patients, females, patients with higher BMI, and OSA patients in the QTc ≥418 ms group were more likely to have OSA (p<0.05). Correlation analysis suggested that OSA was associated with longer QTc (OR: 2.355, 95% CI: 1.529-3.626, p<0.001). For T2DM patients with QTc ≥418 ms, older patients (OR: 1.042, 95% CI: 1.042-1.064, p<0.001), females (OR: 2.36, 95% CI: 1.371-4.063, p<0.01), and patients with higher BMI (OR: 1.113, 95% CI: 1.037-1.195, p<0.01) were significantly more likely to have OSA. CONCLUSIONS In this cross-sectional study, we found that the presence and severity of OSA was associated with QTc prolongation in 358 patients with T2DM, and age, female sex, and BMI appear to be independent risk factors for OSA and CVD.
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Affiliation(s)
- Huan Shi
- Department of Endocrinology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China (mainland)
| | - Xiaohong Jiang
- Department of Endocrinology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China (mainland)
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28
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Farré N, Mojón D, Llagostera M, Belarte-Tornero LC, Calvo-Fernández A, Vallés E, Negrete A, García-Guimaraes M, Bartolomé Y, Fernández C, García-Duran AB, Marrugat J, Vaquerizo B. Prolonged QT Interval in SARS-CoV-2 Infection: Prevalence and Prognosis. J Clin Med 2020; 9:E2712. [PMID: 32839385 PMCID: PMC7563186 DOI: 10.3390/jcm9092712] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Revised: 08/13/2020] [Accepted: 08/20/2020] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND The prognostic value of a prolonged QT interval in SARS-Cov2 infection is not well known. OBJECTIVE To determine whether the presence of a prolonged QT on admission is an independent factor for mortality in SARS-Cov2 hospitalized patients. METHODS Single-center cohort of 623 consecutive patients with positive polymerase-chain-reaction test (PCR) to SARS Cov2, recruited from 27 February to 7 April 2020. An electrocardiogram was taken on these patients within the first 48 h after diagnosis and before the administration of any medication with a known effect on QT interval. A prolonged QT interval was defined as a corrected QT (QTc) interval >480 milliseconds. Patients were followed up with until 10 May 2020. RESULTS Sixty-one patients (9.8%) had prolonged QTc and only 3.2% had a baseline QTc > 500 milliseconds. Patients with prolonged QTc were older, had more comorbidities, and higher levels of immune-inflammatory markers. There were no episodes of ventricular tachycardia or ventricular fibrillation during hospitalization. All-cause death was higher in patients with prolonged QTc (41.0% vs. 8.7%, p < 0.001, multivariable HR 2.68 (1.58-4.55), p < 0.001). CONCLUSIONS Almost 10% of patients with COVID-19 infection have a prolonged QTc interval on admission. A prolonged QTc was independently associated with a higher mortality even after adjustment for age, comorbidities, and treatment with hydroxychloroquine and azithromycin. An electrocardiogram should be included on admission to identify high-risk SARS-CoV-2 patients.
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Affiliation(s)
- Núria Farré
- Department of Cardiology, Hospital del Mar, 08003 Barcelona, Spain; (D.M.); (M.L.); (L.C.B.-T.); (A.C.-F.); (E.V.); (A.N.); (M.G.-G.); (Y.B.); (C.F.); (A.B.G.-D.); (B.V.)
- Department of Medicine, School of Medicine, Univ Autonoma de Barcelona, 08003 Barcelona, Spain
- Heart Diseases Biomedical Research Group (GREC), IMIM (Hospital del Mar Medical Research Institute), 08003 Barcelona, Spain
| | - Diana Mojón
- Department of Cardiology, Hospital del Mar, 08003 Barcelona, Spain; (D.M.); (M.L.); (L.C.B.-T.); (A.C.-F.); (E.V.); (A.N.); (M.G.-G.); (Y.B.); (C.F.); (A.B.G.-D.); (B.V.)
| | - Marc Llagostera
- Department of Cardiology, Hospital del Mar, 08003 Barcelona, Spain; (D.M.); (M.L.); (L.C.B.-T.); (A.C.-F.); (E.V.); (A.N.); (M.G.-G.); (Y.B.); (C.F.); (A.B.G.-D.); (B.V.)
| | - Laia C. Belarte-Tornero
- Department of Cardiology, Hospital del Mar, 08003 Barcelona, Spain; (D.M.); (M.L.); (L.C.B.-T.); (A.C.-F.); (E.V.); (A.N.); (M.G.-G.); (Y.B.); (C.F.); (A.B.G.-D.); (B.V.)
- Department of Medicine, School of Medicine, Univ Autonoma de Barcelona, 08003 Barcelona, Spain
- Heart Diseases Biomedical Research Group (GREC), IMIM (Hospital del Mar Medical Research Institute), 08003 Barcelona, Spain
| | - Alicia Calvo-Fernández
- Department of Cardiology, Hospital del Mar, 08003 Barcelona, Spain; (D.M.); (M.L.); (L.C.B.-T.); (A.C.-F.); (E.V.); (A.N.); (M.G.-G.); (Y.B.); (C.F.); (A.B.G.-D.); (B.V.)
- Department of Medicine, School of Medicine, Univ Autonoma de Barcelona, 08003 Barcelona, Spain
| | - Ermengol Vallés
- Department of Cardiology, Hospital del Mar, 08003 Barcelona, Spain; (D.M.); (M.L.); (L.C.B.-T.); (A.C.-F.); (E.V.); (A.N.); (M.G.-G.); (Y.B.); (C.F.); (A.B.G.-D.); (B.V.)
- Department of Medicine, School of Medicine, Univ Autonoma de Barcelona, 08003 Barcelona, Spain
- Heart Diseases Biomedical Research Group (GREC), IMIM (Hospital del Mar Medical Research Institute), 08003 Barcelona, Spain
| | - Alejandro Negrete
- Department of Cardiology, Hospital del Mar, 08003 Barcelona, Spain; (D.M.); (M.L.); (L.C.B.-T.); (A.C.-F.); (E.V.); (A.N.); (M.G.-G.); (Y.B.); (C.F.); (A.B.G.-D.); (B.V.)
| | - Marcos García-Guimaraes
- Department of Cardiology, Hospital del Mar, 08003 Barcelona, Spain; (D.M.); (M.L.); (L.C.B.-T.); (A.C.-F.); (E.V.); (A.N.); (M.G.-G.); (Y.B.); (C.F.); (A.B.G.-D.); (B.V.)
| | - Yolanda Bartolomé
- Department of Cardiology, Hospital del Mar, 08003 Barcelona, Spain; (D.M.); (M.L.); (L.C.B.-T.); (A.C.-F.); (E.V.); (A.N.); (M.G.-G.); (Y.B.); (C.F.); (A.B.G.-D.); (B.V.)
| | - Camino Fernández
- Department of Cardiology, Hospital del Mar, 08003 Barcelona, Spain; (D.M.); (M.L.); (L.C.B.-T.); (A.C.-F.); (E.V.); (A.N.); (M.G.-G.); (Y.B.); (C.F.); (A.B.G.-D.); (B.V.)
| | - Ana B. García-Duran
- Department of Cardiology, Hospital del Mar, 08003 Barcelona, Spain; (D.M.); (M.L.); (L.C.B.-T.); (A.C.-F.); (E.V.); (A.N.); (M.G.-G.); (Y.B.); (C.F.); (A.B.G.-D.); (B.V.)
| | - Jaume Marrugat
- REGICOR (Registre Gironí del Cor) Study Group, IMIM (Hospital del Mar Medical Research Institute), 08003 Barcelona, Spain;
- CIBER (Centro de Investigación Biomédica en Red) of Cardiovascular Diseases (CIBERCV), Instituto de Salud Carlos III (ISCIII), 08003 Barcelona, Spain
| | - Beatriz Vaquerizo
- Department of Cardiology, Hospital del Mar, 08003 Barcelona, Spain; (D.M.); (M.L.); (L.C.B.-T.); (A.C.-F.); (E.V.); (A.N.); (M.G.-G.); (Y.B.); (C.F.); (A.B.G.-D.); (B.V.)
- Department of Medicine, School of Medicine, Univ Autonoma de Barcelona, 08003 Barcelona, Spain
- Heart Diseases Biomedical Research Group (GREC), IMIM (Hospital del Mar Medical Research Institute), 08003 Barcelona, Spain
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Elhakeem RF, Lutfi MF, Ali ABM, Sukkar MY. Can short-term heart rate variability predict coronary artery disease in patients undergoing elective coronary angiography due to typical chest pain? J Clin Transl Res 2020; 6:66-70. [PMID: 33426355 PMCID: PMC7787221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2020] [Revised: 07/05/2020] [Accepted: 07/27/2020] [Indexed: 11/11/2022] Open
Abstract
BACKGROUND Presence of typical chest pain and normal coronary angiography suggests the possibility of microvascular ischemia of the myocardium as well as other non-cardiac causes that are also likely to decrease heart rate variability (HRV). This raises a question of whether poor HRV can predict abnormal elective coronary angiography (ECA). AIM The aim of this study was to compare HRV in patients with typical chest pain when they are classified according to ECA outcomes. METHODS The study enrolled 150 patients planned for ECA in the cardiac center of AlShaab Teaching Hospital, Khartoum, Sudan, due to typical chest pain. Following assessment of medical history and clinical examination, the Bluetooth electrocardiography (ECG) transmitter and receiver were used for ECG recording and evaluation of time and frequency domains HRV. ECA confirmed the diagnosis of coronary artery disease (CAD) in 108 patients, who were considered as the test group. The other 42 subjects were considered as a control group after the exclusion of CAD. RESULTS The Mean±SD of Ln(pNN10), Ln(pNN20), LnLF, and LnHF was significantly higher in subjects with normal angiography compared with CAD patients. However, these statistically significant differences disappeared when the comparison was adjusted for age, gender, BMI, and HR of the studied groups. CONCLUSION HRV is comparable in patients with typical chest pain regardless of ECA outcomes. RELEVANCE FOR PATIENTS The HRV differences between patients with normal and abnormal ECA are likely to be biased by CAD risk factors such as old age, male gender, and tachycardia that are known to disturb HRV. The possibility of microvascular ischemia in patients with normal ECA may have attenuated HRV in this group and make it comparable to those suffering from macrovascular ischemia due to CAD.
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Affiliation(s)
| | - Mohamed Faisal Lutfi
- 1College of Medicine, Qassim University, KSA,2Nile College of Medicine, Khartoum, Sudan,
Corresponding author: Mohamed Faisal Lutfi College of Medicine, Qassim University, KSA and Nile College of Medicine, Khartoum, Sudan Tel.: +249912257731 Fax: +2499183797836 Mailbox: 12702 - Code: 11121
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Andersen A, Jørgensen PG, Knop FK, Vilsbøll T. Hypoglycaemia and cardiac arrhythmias in diabetes. Ther Adv Endocrinol Metab 2020; 11:2042018820911803. [PMID: 32489579 PMCID: PMC7238305 DOI: 10.1177/2042018820911803] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Accepted: 01/30/2020] [Indexed: 01/11/2023] Open
Abstract
Hypoglycaemia remains an inevitable risk in insulin-treated type 1 diabetes and type 2 diabetes and has been associated with multiple adverse outcomes. Whether hypoglycaemia is a cause of fatal cardiac arrhythmias in diabetes, or merely a marker of vulnerability, is still unknown. Since a pivotal report in 1991, hypoglycaemia has been suspected to induce cardiac arrhythmias in patients with type 1 diabetes, the so-called 'dead-in-bed syndrome'. This suspicion has subsequently been supported by the coexistence of an increased mortality and a three-fold increase in severe hypoglycaemia in patients with type 2 diabetes receiving intensive glucose-lowering treatment in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Studies have investigated the association between hypoglycaemia-induced cardiac arrhythmias. In a rat-model, severe hypoglycaemia resulted in a specific pattern of cardiac arrhythmias including QT-prolongation, ventricular tachycardia, second- and third-degree AV block and ultimately cardiorespiratory arrest. In clinical studies of experimentally induced hypoglycaemia, QTc-prolongation, a risk factor of ventricular arrhythmias, is an almost consistent finding. The extent of QT-prolongation seems to be modified by several factors, including antecedent hypoglycaemia, diabetes duration and cardiac autonomic neuropathy. Observational studies indicate diurnal differences in the pattern of electrocardiographic alterations during hypoglycaemia with larger QTc-prolongations during daytime, whereas the risk of bradyarrhythmias may be increased during sleep. Daytime periods of hypoglycaemia are characterized by shorter duration, increased awareness and a larger increase in catecholamines. The counterregulatory response is reduced during nightly episodes of hypoglycaemia, resulting in prolonged periods of hypoglycaemia with multiple nadirs. An initial sympathetic activity at plasma glucose nadir is replaced by increased vagal activity, which results in bradycardia. Here, we provide an overview of the existing literature exploring potential mechanisms for hypoglycaemia-induced cardiac arrhythmias and studies linking hypoglycaemia to cardiac arrhythmias in patients with diabetes.
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Affiliation(s)
- Andreas Andersen
- Steno Diabetes Center Copenhagen, Gentofte
Hospital, Hellerup, Denmark
- Center for Clinical Metabolic Research, Herlev
and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
| | - Peter G. Jørgensen
- Department of Cardiology, Herlev and Gentofte
Hospital, University of Copenhagen, Hellerup, Denmark
| | - Filip K. Knop
- Center for Clinical Metabolic Research, Herlev
and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
- Steno Diabetes Center Copenhagen, Gentofte
Hospital, Hellerup, Denmark
- Department of Clinical Medicine, Faculty of
Health and Medical Sciences, University of Copenhagen, Copenhagen,
Denmark
- Novo Nordisk Foundation Center for Basic
Metabolic Research, Faculty of Health and Medical Sciences, University of
Copenhagen, Copenhagen, Denmark
| | - Tina Vilsbøll
- Steno Diabetes Centre Copenhagen, Gentofte
Hospital, Kildegårdsvej 28, Hellerup, 2900, Denmark
- Center for Clinical Metabolic Research, Herlev
and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
- Department of Clinical Medicine, Faculty of
Health and Medical Sciences, University of Copenhagen, Copenhagen,
Denmark
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Inanır M, Gunes Y, Sincer I, Erdal E. Evaluation of Electrocardiographic Ventricular Depolarization and Repolarization Variables in Type 1 Diabetes Mellitus. Arq Bras Cardiol 2020; 114:275-280. [PMID: 32215498 PMCID: PMC7077569 DOI: 10.36660/abc.20180343] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2018] [Accepted: 03/10/2019] [Indexed: 12/14/2022] Open
Abstract
Background The risk of cardiovascular events and sudden death increases with type 1 diabetes mellitus (T1DM). Objective To evaluate electrocardiographic markers of arrhythmias in T1DM patients. Methods Electrocardiographic parameters reflecting ventricular depolarization and repolarization, namely, QT, QTc, QTd, QTdc, Tp-e, JT, and JTc intervals and Tp-e/QT and Tp-e/QTc ratios, of 46 patients diagnosed with T1DM were retrospectively analyzed and compared with 46 healthy age-, sex-, and body mass-matched controls. Correlations between T1DM duration, hemoglobin A1c (HbA1c), and ventricular repolarization variables were analyzed. P values lower than 0.05 were considered statistically significant. Results Diabetes duration was 16.6 ± 7.1 years, and HbA1c was 10.81% ± 3.27% in the T1DM group. In comparison with the control group, heart rate, QTc, QTd, QTdc, Tp-e and JTc intervals, Tp-e/QT ratio (p < 0.001), and Tp-e/QTc ratio (p = 0.007) were significantly higher in T1DM patients. T1DM duration and HbA1c levels were significantly correlated with QTc, QTd, QTdc, Tp-e, and JTc intervals and Tp-e/QT and Tp-e/QTc ratios. Conclusions In T1DM patients, potential electrocardiographic repolarization predictors were significantly increased in correlation with disease duration and HbA1c levels. These findings may contribute to the understanding of sudden cardiac death in patients with T1DM.
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Affiliation(s)
- Mehmet Inanır
- Abant Izzet Baysal University Hospital, Bolu - Turkey
| | - Yilmaz Gunes
- Abant Izzet Baysal University Hospital, Bolu - Turkey
| | - Isa Sincer
- Abant Izzet Baysal University Hospital, Bolu - Turkey
| | - Emrah Erdal
- Abant Izzet Baysal University Hospital, Bolu - Turkey
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Association of QTc Interval with Risk of Cardiovascular Diseases and Related Vascular Traits: A Prospective and Longitudinal Analysis. Glob Heart 2020; 15:13. [PMID: 32489786 PMCID: PMC7218767 DOI: 10.5334/gh.533] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Background: Prolonged heart rate corrected QT (QTc) interval was reported to be associated with cardiovascular diseases (CVDs). Objective: There exists little data on the association between QTc interval and cardiovascular risk in Asian populations. We prospectively investigated the association of QTc interval with CVDs and vascular traits in a large cohort of Chinese adults. Methods: A total of 7,605 participants aged 40 years or older from a well-defined community without CVDs at baseline were included and followed up for an average of 4.5 years. Association of baseline QTc interval with incident CVDs was evaluated using Cox regression analysis. Associations of QTc interval with brachial-ankle pulse wave velocity (baPWV), carotid intima-media thickness (CIMT), and risk of microalbuminuria and peripheral arterial diseases (PAD) were secondarily examined. Results: Prolonged QTc interval (≥460 ms in women and ≥450 ms in men) was associated with 51% higher risk of total major CVDs (hazard ratio [HR] = 1.51, 95% confidence interval [CI] [1.20, 1.90]), particularly, 48% increased risk of stroke (95% CI [1.16, 1.88]). Prolonged QTc interval was positively associated with baPWV (β = 38.10 cm/s, standard error [SE] = 8.04, P < 0.0001) and CIMT (β = 0.01 mm, SE = 0.01, P = 0.04). Prolonged QTc interval was associated with increased risk of incident microalbuminuria (odds ratio [OR] = 1.65, 95% CI [1.21, 2.24]) and PAD (2.49, 95% CI [1.35, 4.59]). Conclusions: Prolonged QTc interval is positively and significantly associated with increased risk of CVDs and related vascular traits in Chinese population.
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Singleton MJ, German C, Hari KJ, Saylor G, Herrington DM, Soliman EZ, Freedman BI, Bowden DW, Bhave PD, Yeboah J. QRS duration is associated with all-cause mortality in type 2 diabetes: The diabetes heart study. J Electrocardiol 2020; 58:150-154. [DOI: 10.1016/j.jelectrocard.2019.11.053] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Revised: 11/09/2019] [Accepted: 11/27/2019] [Indexed: 01/12/2023]
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Massardo T, Araya AV, Prat H, Alarcón L, Berrocal I, Pino A, Cordero F, Jaimovich R, Fernández R, Herrera E, Carmona J, Castro A. Factors associated with silent myocardial ischemia, autonomic or peripheral neuropathies, and survival in diabetes mellitus type 2 patients without cardiovascular symptoms. Int J Diabetes Dev Ctries 2019. [DOI: 10.1007/s13410-019-00758-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/26/2022] Open
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Carvalho NNC, de Oliveira Junior FA, da Silva G, Baccin Martins VJ, Braga VDA, da Costa-Silva JH, Fernandes Pimenta FC, de Brito Alves JL. Impact of arterial hypertension and type 2 diabetes on cardiac autonomic modulation in obese individuals with recommendation for bariatric surgery. Diabetes Metab Syndr Obes 2019; 12:1503-1511. [PMID: 31686874 PMCID: PMC6709514 DOI: 10.2147/dmso.s204414] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2019] [Accepted: 07/13/2019] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND AND AIM Obese individuals with recommendation for bariatric surgery (BS) exhibit increased cardiovascular risk. The association of obesity with comorbidities, such as arterial hypertension (HTN) and type 2 diabetes mellitus (T2DM) can worsen cardiovascular dysfunction. This study aimed to investigate the effect of HTN on cardiac autonomic function and whether diabetes exacerbates HTN-related impairment of autonomic function in obese subjects. METHODS Samples (n=63) were allocated to three groups: Obese without HTN and T2DM (n=29), Obese with HTN (OHTN, n=17) and OHTN with T2DM (OHTN+T2DM, n=17), in which anthropometric measures, body composition, blood biochemical parameters, blood pressure (BP) and heart rate variability (HRV) were evaluated. RESULTS The age was higher in OHTN+T2DM and OHTN than in obese groups (p<0.05). OHTN+T2DM individuals had increased neck circumference and compromised glycemic profile when compared to obese and OHTN groups (p<0.05). Mean values for standard deviation of RR (SDRR), square root of the mean squared differences of successive RR interval (RMSSD) and number of pairs of successive normal-to-normal beat intervals that differed by 50 ms (pRR50) were significantly lower in OHTN+T2DM and OHTN groups when compared to patients with obesity alone (p<0.05). The low frequency (LF), low frequency/high frequency (LF/HF) ratio were higher in the OHTN+T2DM and OHTN than subjects with obesity alone (p<0.05). Nonlinear parameters SD2 and SD1 were also lower in the OHTN+T2DM when compared to the obese group (p<0.05). However, the SD2/SD1 ratio was higher in the OHTN+T2DM and OHTN groups than the obese group. CONCLUSION T2DM and/or HTN impair the cardiac autonomic function in obese patients. However, the presence of T2DM did not exacerbate the hypertension-related impairment of autonomic function.
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Affiliation(s)
- Nara Nóbrega Crispim Carvalho
- Department of Nutrition, Health Sciences Center, Federal University of Paraiba, João Pessoa, Brazil
- Department of Endocrinology, Lauro Wanderley University Hospital, Federal University of Paraiba, João Pessoa, Brazil
| | | | - Gitana da Silva
- Lauro Wanderley Hospital, Federal University of Paraiba, João Pessoa, Brazil
| | - Vinícius José Baccin Martins
- Department of Physiology and Pathology, Health Sciences Center, Federal University of Paraiba, João Pessoa, Brazil
| | - Valdir de Andrade Braga
- Department of Biotechnology, Center of Biotechnology, Federal University of Paraíba, João Pessoa, Brazil
| | - João Henrique da Costa-Silva
- Department of Physical Education and Sport Sciences, Federal University of Pernambuco, Vitória De Santo Antão, PE, Brazil
| | | | - José Luiz de Brito Alves
- Department of Nutrition, Health Sciences Center, Federal University of Paraiba, João Pessoa, Brazil
- Correspondence: José Luiz de Brito Alves; Nara Nóbrega Crispim CarvalhoDepartment of Nutrition, Federal University of Paraiba, Campus I – Jd. Cidade Universitária, João Pessoa, PBCEP: 58051-900, BrazilTel/fax +55 8 199 845 5485 Email ;
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Mahmud R, Gray A, Nabeebaccus A, Whyte MB. Incidence and outcomes of long QTc in acute medical admissions. Int J Clin Pract 2018; 72:e13250. [PMID: 30222237 PMCID: PMC6220840 DOI: 10.1111/ijcp.13250] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2018] [Revised: 07/04/2018] [Accepted: 07/31/2018] [Indexed: 11/27/2022] Open
Abstract
AIMS Prolonged QT interval on electrocardiogram (ECG) increases the risk of ventricular arrhythmia. Patients admitted to acute medical units (AMU) may be at risk of QT prolongation from multiple, recognised risk factors. Few data exist regarding incidence or outcomes of QT prolongation in acute general medical admissions. The aims were to determine the incidence of Bazett's-corrected QT (QTc) prolongation upon admission to AMU; the relationship between QTc and inpatient mortality, length of stay and readmission; proportion with prolonged QTc subsequently administered QT interval-prolonging drugs. METHODS Retrospective, observational study of 1000 consecutive patients admitted to an AMU in a large urban hospital. EXCLUSION CRITERIA age <18 years, ventricular pacing, poor quality/absent ECG. QTc determined manually from ECG obtained within 4-hours of admission. QTc prolongation considered ≥470 milliseconds (males) and ≥480 milliseconds (females). In both genders, >500 milliseconds was considered severe. Study end-points, (a) incidence of QTc prolongation at admission; (b) inpatient mortality, length of stay and readmission rates; (c) proportion with QTc prolongation subsequently administered QT interval-prolonging drugs. RESULTS Of 1000 patients, 288 patients were excluded, therefore final sample was n = 712. Patient age (mean ± SD) was 63.1 ± 19.4 years; females 49%. QTc prolongation was present in n = 50 (7%) at admission; 1.7% had QTc interval >500 ms. Of the 50 patients admitted with prolonged QTc, 6 (12%) were subsequently administered QT interval-prolonging drugs. QTc prolongation was not associated with worse inpatient mortality or readmission rate. Length of stay was greater in those with prolonged QTc, 7.2 (IQR 2.4-13.2) days vs 3.3 (IQR 1.3-10.0; P = 0.004), however, in a regression model, presence of QTc did not independently affect length of stay. CONCLUSIONS QTc interval prolongation is frequent among patients admitted to AMU. QT interval-prolonging drugs are commonly prescribed to patients presenting with prolonged QTc but whether this affects clinical outcomes is uncertain.
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Affiliation(s)
- Rahel Mahmud
- Department of Acute MedicineKing's College Hospital NHS Foundation TrustLondonUK
| | - Adam Gray
- Department of Acute MedicineKing's College Hospital NHS Foundation TrustLondonUK
| | - Adam Nabeebaccus
- Department of CardiologyKing's College Hospital NHS Foundation TrustLondonUK
| | - Martin Brunel Whyte
- Department of Acute MedicineKing's College Hospital NHS Foundation TrustLondonUK
- Department of Clinical & Experimental MedicineUniversity of SurreyGuildfordUK
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Moon KA, Zhang Y, Guallar E, Francesconi KA, Goessler W, Umans JG, Best LG, Howard BV, Devereux RB, Okin PM, Navas-Acien A. Association of low-moderate urine arsenic and QT interval: Cross-sectional and longitudinal evidence from the Strong Heart Study. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2018; 240:894-902. [PMID: 29793197 PMCID: PMC6339816 DOI: 10.1016/j.envpol.2018.04.129] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/07/2017] [Revised: 04/17/2018] [Accepted: 04/27/2018] [Indexed: 05/06/2023]
Abstract
Epidemiologic studies suggest that chronic exposure to arsenic is related to cardiovascular disease (CVD), but the pathophysiological link remains uncertain. We evaluated the association of chronic low-moderate arsenic exposure and arsenic metabolism with baseline difference and annual change in ECG measures (QT interval, JT interval, PR interval, QRS duration, and QT dispersion) using linear mixed models in the Strong Heart Study main cohort (N = 1174, median age 55 years) and family study (N = 1695 diabetes-free, median age 36 years). At baseline, arsenic exposure was measured as the sum of inorganic and methylated species in urine (ΣAs) and arsenic metabolism was measured as the relative percentage of arsenic species. Median ΣAs and Bazett heart rate-corrected QT interval (QTc) were 8.6 μg/g creatinine and 424 ms in the main cohort and 4.3 μg/g and 414 ms in the family study, respectively. In the main cohort, a comparison of the highest to lowest ΣAs quartile (>14.4 vs. <5.2 μg/g creatinine) was associated with a 5.3 (95% CI: 1.2, 9.5) ms higher mean baseline QTc interval but no difference in annual change in QTc interval. In the family study, a comparison of the highest to lowest quartile (>7.1 vs. <2.9 μg/g creatinine) was associated with a 3.2 (95% CI: 0.6, 5.7) ms higher baseline QTc interval and a 0.6 (95% CI: 0.04, 1.2) ms larger annual increase in QTc interval. Associations with JTc interval were similar but stronger in magnitude compared to QTc interval. Arsenic exposure was largely not associated with PR interval, QRS duration or QT dispersion. Similar to arsenic exposure, a pattern of lower %MMA and higher %DMA was associated with longer baseline QTc interval in both cohorts and with a larger annual change in QTc interval in the family study. Chronic low-moderate arsenic exposure and arsenic metabolism were associated with prolonged ventricular repolarization.
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Affiliation(s)
- Katherine A Moon
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
| | - Yiyi Zhang
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Eliseo Guallar
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Kevin A Francesconi
- Institute for Chemistry-Analytical Chemistry, University of Graz, Graz, Austria
| | - Walter Goessler
- Institute for Chemistry-Analytical Chemistry, University of Graz, Graz, Austria
| | - Jason G Umans
- MedStar Health Research Institute, Hyattsville, MD, USA
| | - Lyle G Best
- Missouri Breaks Industries Research, Timber Lake, SD, USA
| | | | | | | | - Ana Navas-Acien
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY, USA
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Tahata Y, Sakamori R, Urabe A, Morishita N, Yamada R, Yakushijin T, Hiramatsu N, Doi Y, Kaneko A, Hagiwara H, Yamada Y, Hijioka T, Inada M, Tamura S, Imai Y, Furuta K, Kodama T, Hikita H, Tatsumi T, Takehara T. Liver Fibrosis Is Associated With Corrected QT Prolongation During Ledipasvir/Sofosbuvir Treatment for Patients With Chronic Hepatitis C. Hepatol Commun 2018; 2:884-892. [PMID: 30094400 PMCID: PMC6078212 DOI: 10.1002/hep4.1206] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2018] [Revised: 05/14/2018] [Accepted: 05/15/2018] [Indexed: 12/15/2022] Open
Abstract
Combination treatment of ledipasvir and sofosbuvir (LDV/SOF) is first-line treatment for patients with chronic hepatitis C genotype 1 in the United States, Europe, and Japan. However, the influence of LDV/SOF on the cardiovascular system is poorly characterized. A total of 470 chronic hepatitis C patients who started LDV/SOF treatment between September 2015 and February 2016 at nine hospitals in Japan were prospectively enrolled in this study. Corrected QT (QTc) prolongation was defined as a QTc interval ≥450 milliseconds. The sustained virologic response rate was 96.0% (451/470), and the discontinuance rate due to adverse effects was 0.9% (4/470). Among 395 patients whose electrocardiogram was evaluated over time and compared with baseline, the QTc interval was significantly prolonged during treatment and returned to baseline levels 12 weeks after the end of treatment. Twenty-four of 376 patients with baseline QTc intervals <450 milliseconds experienced on-treatment QTc prolongation. Higher aspartate aminotransferase-to-platelet ratio index scores (≥0.76; odds ratio, 4.375; P = 0.005) and longer QTc intervals (≥416 milliseconds; odds ratio, 4.823; P = 0.003) at baseline were significantly associated with on-treatment QTc prolongation on multivariate analysis. Patients with cirrhosis showed significantly longer QTc intervals than those without cirrhosis during treatment but not at baseline, and they developed on-treatment QTc prolongation at a higher rate than patients without cirrhosis. No cardiovascular events occurred, except for 1 patient who developed paroxysmal supraventricular tachycardia. Conclusion: Newly developed QTc prolongation was observed in 6.4% of Japanese patients during treatment and was associated with more advanced fibrosis. (Hepatology Communications 2018; 00:000-000).
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Affiliation(s)
- Yuki Tahata
- Department of Gastroenterology and HepatologyOsaka University Graduate School of MedicineSuitaJapan
| | - Ryotaro Sakamori
- Department of Gastroenterology and HepatologyOsaka University Graduate School of MedicineSuitaJapan
| | - Ayako Urabe
- Department of Gastroenterology and HepatologyOsaka University Graduate School of MedicineSuitaJapan
| | - Naoki Morishita
- Department of Gastroenterology and HepatologyOsaka University Graduate School of MedicineSuitaJapan
| | - Ryoko Yamada
- Department of Gastroenterology and HepatologyOsaka University Graduate School of MedicineSuitaJapan
| | - Takayuki Yakushijin
- Department of Gastroenterology and HepatologyOsaka University Graduate School of MedicineSuitaJapan
| | - Naoki Hiramatsu
- Department of Gastroenterology and HepatologyOsaka University Graduate School of MedicineSuitaJapan
| | | | | | | | | | - Taizo Hijioka
- National Hospital Organization Osaka Minami Medical CenterKawachinaganoJapan
| | | | | | | | - Kunimaro Furuta
- Department of Gastroenterology and HepatologyOsaka University Graduate School of MedicineSuitaJapan
| | - Takahiro Kodama
- Department of Gastroenterology and HepatologyOsaka University Graduate School of MedicineSuitaJapan
| | - Hayato Hikita
- Department of Gastroenterology and HepatologyOsaka University Graduate School of MedicineSuitaJapan
| | - Tomohide Tatsumi
- Department of Gastroenterology and HepatologyOsaka University Graduate School of MedicineSuitaJapan
| | - Tetsuo Takehara
- Department of Gastroenterology and HepatologyOsaka University Graduate School of MedicineSuitaJapan
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Kuzu F. The effect of type 2 diabetes on electrocardiographic markers of significant cardiac events. Pak J Med Sci 2018; 34:626-632. [PMID: 30034428 PMCID: PMC6041533 DOI: 10.12669/pjms.343.14562] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/04/2022] Open
Abstract
Background & Objectives: In diabetics, cardiac microvascular circulation disorder increases the risk of arrhythmia and sudden cardiac death. Tpeak-Tend (Tp-e) interval, Tp-e dispersion, and Tp-e/QT and Tp-e/QTc ratios measured by surface electrocardiogram (ECG) are new parameters used to evaluate ventricular arrhythmogenity. We aimed to compare QT dispersion (QTd), corrected QT dispersion (QTcd), P dispersion (Pd), Tp-e interval, Tp-e dispersion, and Tp-e/QT and Tp-e/QTc ratios in patients with type- 2 diabetes (T2D) with healthy population. Methods: Electrocardiographic parameters of a total of 100 patients diagnosed with T2D were retrospectively analyzed and compared with the ECG results of 100 healthy age-, sex-, and body weight and height-matched controls. Results: The Pd, QT interval, QTc interval, QTd, QTcd, Tp-e/QT, Tp-e/QT ratios were higher in the patients. A statistically significant correlation was found only between hemoglobin A1c and Tp-e dispersion, QTd, QTcd, Pd, Tp-e/QT and Tp-e/QTc parameters, in linear regression analysis. There was also a statistically significant positive correlation between the values of low-density lipoprotein, systolic blood pressure, and Tp-e dispersion. Conclusion: The risk of arrhythmia can be predicted by evaluating Tp-e interval, Tp-e dispersion, Tp-e/QT, and Tp-e/QTc ratio, suggesting heterogeneity of ventricular repolarization and P wave and Pd showing heterogeneity of atrial repolarization in diabetic patients.
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Affiliation(s)
- Fatih Kuzu
- Fatih Kuzu, MD. Department of Endocrinology and Metabolism, Dumlupinar University, Evliya Celebi Training and Research Hospital, Kutahya, Turkey
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Wang S, He Y, Xu L, Zhang S, Gu X, Gu J, Shi J, Shen Y, Tang Z. Association between QTc interval prolongation and outcomes of diabetic foot ulcers: Data from a 4-year follow-up study in China. Diabetes Res Clin Pract 2018; 138:26-34. [PMID: 29382590 DOI: 10.1016/j.diabres.2018.01.021] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2017] [Revised: 12/30/2017] [Accepted: 01/23/2018] [Indexed: 11/19/2022]
Abstract
OBJECTIVES To examine whether QTc interval prolongation is an independent risk factor of outcomes in patients with diabetic foot ulcers (DFU). RESEARCH DESIGN AND METHODS 331 patients with type 2 diabetes and DFU hospitalized in a Chinese tertiary hospital were recruited. ECG was done at baseline and QTc interval was calculated through Bazett's formula. Participants were classified into 2 groups according to the QTc interval as prolonged (≥440 ms) or not (<440 ms). These patients were followed-up for an average of 48 months to observe the outcomes, including ulcer healing, ulcer recurrence, nonfatal cerebral or cardiovascular events (NCCVE), cerebral cardiovascular death, cardiac death and all-cause death. The associations between the risk of outcomes and QTc interval prolongation, as well as per 1-SD increase in QTc interval were analyzed by Cox proportional-hazards models. RESULTS In terms of the univariate Cox proportional hazard models, patients with QTc interval prolongation had a higher all-cause mortality (HR = 1.621, 95%CI: 1.040-2.526, P = .013), higher cardiac mortality (HR = 2.011 95%CI: 1.106-3.657, P = .019), higher cerebral cardiovascular mortality (HR = 1.525, 95%CI: 0.8151-2.852, P = .045). The multivariate analysis showed that QTc prolongation was an independent risk factor for cardiac death (HR = 5.465, 95%CI: 2.818-8.112, P = .039). Similar results were obtained when QTc interval was used as a continue variable, a 1-SD increase in QTc interval was associated with an 5.883 times risk for cardiac mortality (HR = 6.883, 95%CI: 4.153-9.613, P = .012). The association between QTc interval prolongation with ulcer healing, recurrence and NCCVE were not observed either in univariate or multivariate analysis (P > .05). CONCLUSION QTc interval prolongation was a plausible predictor for cardiac death in DFU patients, but it cannot accurately predict ulcer healing or recurrence.
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Affiliation(s)
- Shumin Wang
- Shanghai Clinical Center for Endocrine and Metabolism Diseases, Yuanyang Subdivision for Diabetic Foot Disease, Shanghai Institute of Endocrine and Metabolism Disease, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
| | - Yang He
- Shanghai Clinical Center for Endocrine and Metabolism Diseases, Yuanyang Subdivision for Diabetic Foot Disease, Shanghai Institute of Endocrine and Metabolism Disease, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
| | - Lei Xu
- Shanghai Clinical Center for Endocrine and Metabolism Diseases, Yuanyang Subdivision for Diabetic Foot Disease, Shanghai Institute of Endocrine and Metabolism Disease, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
| | - Shanshan Zhang
- Shanghai Clinical Center for Endocrine and Metabolism Diseases, Yuanyang Subdivision for Diabetic Foot Disease, Shanghai Institute of Endocrine and Metabolism Disease, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
| | - Xueming Gu
- Department of Internal Medicine, Shanghai Yuanyang Hospital, Shanghai 200031, China
| | - Junyi Gu
- Department of Internal Medicine, Shanghai Yuanyang Hospital, Shanghai 200031, China
| | - Jianyuan Shi
- Department of Internal Medicine, Shanghai Yuanyang Hospital, Shanghai 200031, China
| | - Yaping Shen
- Department of Internal Medicine, Shanghai Yuanyang Hospital, Shanghai 200031, China
| | - Zhengyi Tang
- Shanghai Clinical Center for Endocrine and Metabolism Diseases, Yuanyang Subdivision for Diabetic Foot Disease, Shanghai Institute of Endocrine and Metabolism Disease, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200025, China; Department of Internal Medicine, Shanghai Yuanyang Hospital, Shanghai 200031, China.
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Nguyen T, Waits G, Soliman EZ. The Role of Resting Electrocardiogram in Screening for Primary Prevention of Cardiovascular Diseases in High-Risk Groups. CURRENT CARDIOVASCULAR RISK REPORTS 2018. [DOI: 10.1007/s12170-018-0572-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Prasada S, Oswalt C, Yeboah P, Saylor G, Bowden D, Yeboah J. Heart rate is an independent predictor of all-cause mortality in individuals with type 2 diabetes: The diabetes heart study. World J Diabetes 2018; 9:33-39. [PMID: 29359027 PMCID: PMC5763038 DOI: 10.4239/wjd.v9.i1.33] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2017] [Revised: 08/25/2017] [Accepted: 11/27/2017] [Indexed: 02/05/2023] Open
Abstract
AIM To assess the association of resting heart rate with all-cause and cardiovascular disease (CVD) mortality in the Diabetes Heart Study (DHS).
METHODS Out of a total of 1443 participants recruited into the DHS, 1315 participants with type 2 diabetes who were free of atrial fibrillation and supraventricular tachycardia during the baseline exam were included in this analysis. Heart rate was collected from baseline resting electrocardiogram and mortality (all-cause and CVD) was obtained from state and national death registry. Kaplan-Meier (K-M) and Cox proportional hazard analyses were used to assess the association.
RESULTS The mean age, body mass index (BMI) and systolic blood pressure (SBP) of the cohort were 61.4 ± 9.2 years, 32.0 ± 6.6 kg/m2, and 139.4 ± 19.4 mmHg respectively. Fifty-six percent were females, 85% were whites, 15% were blacks, 18% were smokers. The mean ± SD heart rate was 69.8 (11.9) beats per minute (bpm). After a median follow-up time of 8.5 years (maximum follow-up time is 14.0 years), 258 participants were deceased. In K-M analysis, participants with heart rate above the median had a significantly higher event rate compared with those below the median (log-rank P = 0.0223). A one standard deviation increase in heart rate was associated with all-cause mortality in unadjusted (hazard ratio 1.16, 95%CI: 1.03-1.31) and adjusted (hazard ratio 1.20, 95%CI: 1.05-1.37) models. Similar results were obtained with CVD mortality as the outcome of interest.
CONCLUSION Heart rate is an independent predictor of all-cause mortality in this population with type 2 diabetes. In this study, a 1-SD increase in heart rate was associated with a 20% increase in risk suggesting that additional prognostic information may be gleaned from this ubiquitously collected vital sign.
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Affiliation(s)
- Sameer Prasada
- Department of Medical School (Medical students), Wake Forest University, Winston Salem, NC 27157, United States
| | - Cameron Oswalt
- Department of Medical School (Medical students), Wake Forest University, Winston Salem, NC 27157, United States
| | - Phyllis Yeboah
- Department of Internal Medicine, Wake Forest Baptist Health, Winston Salem, NC 27157, United States
| | - Georgia Saylor
- Department of Heart and Vascular Center of Excellence, Wake Forest Baptist Health, Winston Salem, NC 27157, United States
| | - Donald Bowden
- Department of Biochemistry, Genomics and Personalized Medicine Research, Wake Forest University, Winston Salem, NC 27157, United States
| | - Joseph Yeboah
- Department of Heart and Vascular Center of Excellence, Wake Forest Baptist Health, Winston Salem, NC 27157, United States
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Howarth FC, Qureshi MA, Jayaprakash P, Parekh K, Oz M, Dobrzynski H, Adrian TE. The Pattern of mRNA Expression Is Changed in Sinoatrial Node from Goto-Kakizaki Type 2 Diabetic Rat Heart. J Diabetes Res 2018; 2018:8454078. [PMID: 30246030 PMCID: PMC6139199 DOI: 10.1155/2018/8454078] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2018] [Revised: 07/16/2018] [Accepted: 08/12/2018] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND In vivo experiments in Goto-Kakizaki (GK) type 2 diabetic rats have demonstrated reductions in heart rate from a young age. The expression of genes encoding more than 70 proteins that are associated with the generation and conduction of electrical activity in the GK sinoatrial node (SAN) have been evaluated to further clarify the molecular basis of the low heart rate. MATERIALS AND METHODS Heart rate and expression of genes were evaluated with an extracellular electrode and real-time RT-PCR, respectively. Rats aged 12-13 months were employed in these experiments. RESULTS Isolated spontaneous heart rate was reduced in GK heart (161 ± 12 bpm) compared to controls (229 ± 11 bpm). There were many differences in expression of mRNA, and some of these differences were of particular interest. Compared to control SAN, expression of some genes were downregulated in GK-SAN: gap junction, Gja1 (Cx43), Gja5 (Cx40), Gjc1 (Cx45), and Gjd3 (Cx31.9); cell membrane transport, Trpc1 (TRPC1) and Trpc6 (TRPC6); hyperpolarization-activated cyclic nucleotide-gated channels, Hcn1 (HCN1) and Hcn4 (HCN4); calcium channels, Cacna1d (Cav1.3), Cacna1g (Cav3.1), Cacna1h (Cav3.2), Cacna2d1 (Cavα2δ1), Cacna2d3 (Cavα2δ3), and Cacng4 (Cav γ 4); and potassium channels, Kcna2 (Kv1.2), Kcna4 (Kv1.4), Kcna5 (Kv1.5), Kcnb1 (Kv2.1), Kcnd3 (Kv4.3), Kcnj2 (Kir2.1), Kcnk1 (TWIK1), Kcnk5 (K2P5.1), Kcnk6 (TWIK2), and Kcnn2 (SK2) whilst others were upregulated in GK-SAN: Ryr2 (RYR2) and Nppb (BNP). CONCLUSIONS This study provides new insight into the changing expression of genes in the sinoatrial node of diabetic heart.
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MESH Headings
- Action Potentials
- Animals
- Arrhythmias, Cardiac/etiology
- Arrhythmias, Cardiac/genetics
- Arrhythmias, Cardiac/metabolism
- Arrhythmias, Cardiac/physiopathology
- Diabetes Mellitus, Type 2/complications
- Diabetes Mellitus, Type 2/genetics
- Diabetes Mellitus, Type 2/metabolism
- Diabetic Cardiomyopathies/etiology
- Diabetic Cardiomyopathies/genetics
- Diabetic Cardiomyopathies/metabolism
- Diabetic Cardiomyopathies/physiopathology
- Disease Models, Animal
- Gene Expression Regulation
- Heart Rate/genetics
- Isolated Heart Preparation
- Male
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Rats, Wistar
- Sinoatrial Node/metabolism
- Sinoatrial Node/physiopathology
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Affiliation(s)
- F. C. Howarth
- Department of Physiology, College of Medicine & Health Sciences, UAE University, Al Ain, UAE
| | - M. A. Qureshi
- Department of Physiology, College of Medicine & Health Sciences, UAE University, Al Ain, UAE
| | - P. Jayaprakash
- Department of Pharmacology, College of Medicine & Health Sciences, UAE University, Al Ain, UAE
| | - K. Parekh
- Department of Physiology, College of Medicine & Health Sciences, UAE University, Al Ain, UAE
| | - M. Oz
- Department of Pharmacology, College of Medicine & Health Sciences, UAE University, Al Ain, UAE
| | - H. Dobrzynski
- Cardiovascular Sciences, University of Manchester, Manchester, UK
| | - T. E. Adrian
- Department of Basic Medical Sciences, Mohammed Bin Rashid University of Medicine & Health Sciences, Dubai, UAE
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Kobayashi S, Nagao M, Asai A, Fukuda I, Oikawa S, Sugihara H. Severity and multiplicity of microvascular complications are associated with QT interval prolongation in patients with type 2 diabetes. J Diabetes Investig 2017; 9:946-951. [PMID: 29095573 PMCID: PMC6031516 DOI: 10.1111/jdi.12772] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2017] [Revised: 10/19/2017] [Accepted: 10/27/2017] [Indexed: 01/08/2023] Open
Abstract
Aims/Introduction A prolonged QT interval plays a causal role in life‐threatening arrhythmia, and becomes a risk factor for sudden cardiac death. Here, we assessed the association between microvascular complications and the QT interval in patients with type 2 diabetes. Materials and Methods Patients with type 2 diabetes (n = 219) admitted to Nippon Medical School Hospital (Tokyo, Japan) for glycemic control were enrolled. QT interval was measured manually in lead II on the electrocardiogram, and corrected for heart rate using Bazett's formula (QTc). Diabetic neuropathy, retinopathy and nephropathy were assessed by neuropathic symptoms or Achilles tendon reflex, ophthalmoscopy and urinary albumin excretion, respectively. Results In univariate analyses, female sex (P = 0.025), duration of type 2 diabetes (P = 0.041), body mass index (P = 0.0008), systolic blood pressure (P = 0.0011) and receiving insulin therapy (P < 0.0001) were positively associated with QTc. Patients with each of the three microvascular complications had longer QTc than those without: neuropathy (P = 0.0005), retinopathy (P = 0.0019) and nephropathy (P = 0.0001). As retinopathy or nephropathy progressed, QTc became longer (P < 0.001 and P < 0.001 for trend in retinopathy and nephropathy, respectively). Furthermore, QTc was prolonged with the multiplicity of the microvascular complications (P < 0.001 for trend). Multiple regression analyses showed that neuropathy, nephropathy and the multiplicity of the microvascular complications were independently associated with QTc. Conclusions Patients with type 2 diabetes with severe microvascular complications might be at high risk for life‐threatening arrhythmia associated with QT interval prolongation.
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Affiliation(s)
- Shunsuke Kobayashi
- Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Mototsugu Nagao
- Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Akira Asai
- Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.,Food and Health Science Research Unit, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
| | - Izumi Fukuda
- Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Shinichi Oikawa
- Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.,Diabetes and Lifestyle-related Disease Center, Japan Anti-Tuberculosis Association, Fukujuji Hospital, Tokyo, Japan
| | - Hitoshi Sugihara
- Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
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Su JB, Yang XH, Zhang XL, Cai HL, Huang HY, Zhao LH, Xu F, Chen T, Cheng XB, Wang XQ, Lu Y. The association of long-term glycaemic variability versus sustained chronic hyperglycaemia with heart rate-corrected QT interval in patients with type 2 diabetes. PLoS One 2017; 12:e0183055. [PMID: 28846720 PMCID: PMC5573287 DOI: 10.1371/journal.pone.0183055] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2017] [Accepted: 07/30/2017] [Indexed: 01/24/2023] Open
Abstract
Objectives Prolonged heart rate-corrected QT(QTc) interval is related to ventricular arrhythmia and cardiovascular mortality, with considerably high prevalence of type 2 diabetes. Additionally, long-term glycaemic variability could be a significant risk factor for diabetic complications in addition to chronic hyperglycaemia. We compared the associations of long-term glycaemic variability versus sustained chronic hyperglycaemia with the QTc interval among type 2 diabetes patients. Methods In this cross-sectional study, 2904 type 2 diabetes patients were recruited who had undergone at least four fasting plasma glucose (FPG) and 2-hour postprandial plasma glucose (PPG) measurements (at least once for every 3 months, respectively) during the preceding year. Long-term glycaemic variabilities of FPG and 2-hour PPG were assessed by their standard deviations (SD-FPG and SD-PPG, respectively), and chronic fasting and postprandial hyperglycaemia were assessed by their means (M-FPG and M-PPG, respectively). HbA1c was also determined upon enrolment to assess current overall glycaemic control. QTc interval was estimated from resting 12-lead electrocardiograms, and more than 440 ms was considered abnormally prolonged. Results Patients with prolonged QTc interval (≥440 ms) had greater M-FPG, M-PPG, SD-PPG and HbA1c than those with normal QTc interval but comparable SD-FPG. QTc interval was correlated with M-FPG, M-PPG, SD-PPG and HbA1c (r = 0.133, 0.153, 0.245 and 0.207, respectively, p = 0.000) but not with SD-FPG (r = 0.024, p = 0.189). After adjusting for metabolic risk factors via multiple linear regression analysis, SD-PPG, M-PPG and HbA1c (t = 12.16, 2.69 and 10.16, respectively, p = 0.000) were the major independent contributors to the increased QTc interval. The proportion of prolonged QTc interval increased significantly from 10.9% to 14.2% to 26.6% for the first (T1) to second (T2) to third (T3) tertiles of SD-PPG. After adjusting via multiple logistic regression analysis, the odd ratios of prolonged QTc interval of the T2 and T3 versus the T1 of SD-PPG were 1.15 (95% CI, 0.82–1.60) and 2.62 (1.92–3.57), respectively. Conclusions Increased long-term variability of PPG is a strong independent risk factor for prolonged QTc interval in type 2 diabetes patients, in addition to long-term postprandial hyperglycaemia and current HbA1c.
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Affiliation(s)
- Jian-Bin Su
- Department of Endocrinology, The First Affiliated Hospital of Soochow University, Suzhou, China.,Department of Endocrinology, The Second Affiliated Hospital of Nantong University, Nantong, China
| | - Xiao-Hua Yang
- Department of Endocrinology, The First Affiliated Hospital of Soochow University, Suzhou, China.,Department of Endocrinology, The Affiliated Haian Hospital of Nantong University, Haian, China
| | - Xiu-Lin Zhang
- Department of Clinical Laboratory, The Second Affiliated Hospital of Nantong University, Nantong, China
| | - Hong-Li Cai
- Department of Geriatrics, The Second Affiliated Hospital of Nantong University, Nantong, China
| | - Hai-Yan Huang
- Department of Endocrinology, The Second Affiliated Hospital of Nantong University, Nantong, China
| | - Li-Hua Zhao
- Department of Endocrinology, The Second Affiliated Hospital of Nantong University, Nantong, China
| | - Feng Xu
- Department of Endocrinology, The Second Affiliated Hospital of Nantong University, Nantong, China
| | - Tong Chen
- Department of Clinical Laboratory, The Second Affiliated Hospital of Nantong University, Nantong, China
| | - Xing-Bo Cheng
- Department of Endocrinology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Xue-Qin Wang
- Department of Endocrinology, The Second Affiliated Hospital of Nantong University, Nantong, China
| | - Yan Lu
- Department of Endocrinology, The First Affiliated Hospital of Soochow University, Suzhou, China
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Lu Z, Lense L, Sharma M, Shah A, Luu Y, Cardinal L, Faro J, Kaell A. Prevalence of QT prolongation and associated LVEF changes in diabetic patients over a four-year retrospective time period. J Community Hosp Intern Med Perspect 2017. [PMID: 28638571 PMCID: PMC5473188 DOI: 10.1080/20009666.2017.1320203] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Aim: To evaluate the prevalence and longitudinal changes of prolonged QTc in DM patients admitted to our community hospital, and to determine, if any, its correlation with changes of left ventricular ejection fraction (LVEF). Methods: A retrospective chart review of patients with Type 1 (T1DM) and Type 2 (T2DM) with at least two admissions during a four-year period was performed to identify QTc interval, and LVEF, as measured on transthoracic echocardiogram. Changes in QTc and LVEF between patient hospital admissions were compared. Results: A prolonged QTc interval was found in 66.7% (n = 24) of type 1 and 51.3% (n = 154) type 2 diabetic patients. The QTc interval is progressively increased in both type 1 and type 2 diabetes during follow-up, although it did not reach statistical significance. A total of 62% patients (23 out 37 patients) had a reduction of LVEF during follow-up. Conclusion and Discussion: High prevalence of QTc prolongation was confirmed in hospitalized patients with in both T1DM and T2DM. Significant reduction of LVEF correlated with QTc prolongation over a mean of 17.3 months in T2DM patients, and may have implications for interventions. Abbreviations CHF: Congestive heart failure LVEF: Left ventricular ejection fraction
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Affiliation(s)
- Zhongju Lu
- Department of Internal Medicine, John T. Mather Memorial Hospital, Port Jefferson, NY, USA
| | - Lloyd Lense
- Division of Cardiology, Stony Brook University Hospital, Stony Brook, NY, USA
| | - Mohit Sharma
- Department of Internal Medicine, John T. Mather Memorial Hospital, Port Jefferson, NY, USA
| | - Ankit Shah
- Department of Internal Medicine, John T. Mather Memorial Hospital, Port Jefferson, NY, USA
| | - Ying Luu
- Department of Internal Medicine, John T. Mather Memorial Hospital, Port Jefferson, NY, USA
| | - Lucien Cardinal
- Department of Internal Medicine, John T. Mather Memorial Hospital, Port Jefferson, NY, USA
| | - Joan Faro
- Department of Internal Medicine, John T. Mather Memorial Hospital, Port Jefferson, NY, USA
| | - Alan Kaell
- Department of Internal Medicine, John T. Mather Memorial Hospital, Port Jefferson, NY, USA
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Hu Y, Jiang S, Lu S, Xu R, Huang Y, Zhao Z, Qu Y. Echocardiography and Electrocardiography Variables Correlate With the New York Heart Association classification: An Observational Study of Ischemic Cardiomyopathy Patients. Medicine (Baltimore) 2017; 96:e7071. [PMID: 28658100 PMCID: PMC5500022 DOI: 10.1097/md.0000000000007071] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
The aim of our study was to determine whether combinations of ultrasound echocardiography (UCG) and electrocardiography (EKG) parameters correlated with the functional status of ischemic cardiomyopathy (ICM) patients according to the New York Heart Association (NYHA) classification system.We assessed 536 elderly Chinese ICM patients according to the NYHA criteria, which included 196 patients with type 2 diabetes mellitus (T2DM). All of the patients underwent UCG. Transmural dispersion of ventricular repolarization was examined using EKG. Cumulative odds logistic regression was performed to evaluate associations between NYHA class and the demographic, clinical, UCG, and EKG variables based on the odds ratio (OR) and 95% confidence interval (CI). A Pearson analysis was also performed to examine correlations between the NYHA classification and the UCG and EKG variables.Based on the NYHA assessment, 140, 147, 138, and 111 patients were identified as class I, II, III and IV, respectively. A comparison of UCG and EKG variables based on T2DM status showed that CO and Tp-e differed significantly between all NYHA classes (P < .05 for all), with values of each increasing with increasing NYHA class regardless of T2DM status. Multivariate logistic regression analysis showed that the disease course (OR: 1.30; 95% CI: 1.20-1.40), heart rate (OR: 1.16; 95% CI: 1.12-1.21), T wave peak to endpoint (Tp-e; OR: 1.22; 95% CI: 1.18-1.27), dispersion of the QT interval (OR: 0.98; 95% CI: 0.95-1.22), left ventricular fractional shortening (OR: 0.82; 95% CI: 0.78-0.87), cardiac output (CO; OR: 5.58; 95% CI: 3.08-10.13) were significantly associated with the NYHA class (P < .0001 for all). A Pearson correlation analysis showed that Tp-e (r = 0.75982, P < .0001), CO (r = 0.56072, P < .0001), and stroke volume (r = -0.14839, P = .0006) significantly correlated with the NYHA class.An index consisting of Tp-e and CO will be useful for corroborating the results of the NYHA assessment of ICM patients.
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Affiliation(s)
- Ying Hu
- Department of Geriatrics, Xuhui District Central Hospital
| | - Shifeng Jiang
- Department of Geriatrics, Qingpu Branch of Zhongshan Hospital, Fudan University
| | - Siyuan Lu
- Department of Geriatrics, Xuhui District Central Hospital
| | - Rong Xu
- Department of Geriatrics, Xuhui District Central Hospital
| | - Yunping Huang
- Department of Geriatrics, Xuhui District Central Hospital
| | - Zongliang Zhao
- Geriatric Nursing Services, Xuhui District Tianlin Street Community Health Service Center General, Shanghai, China
| | - Yi Qu
- Department of Geriatrics, Xuhui District Central Hospital
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Chow E, Bernjak A, Walkinshaw E, Lubina-Solomon A, Freeman J, Macdonald IA, Sheridan PJ, Heller SR. Cardiac Autonomic Regulation and Repolarization During Acute Experimental Hypoglycemia in Type 2 Diabetes. Diabetes 2017; 66:1322-1333. [PMID: 28137792 PMCID: PMC5860266 DOI: 10.2337/db16-1310] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2016] [Accepted: 01/25/2017] [Indexed: 02/03/2023]
Abstract
Hypoglycemia is associated with increased cardiovascular mortality in trials of intensive therapy in type 2 diabetes mellitus (T2DM). We previously observed an increase in arrhythmias during spontaneous prolonged hypoglycemia in patients with T2DM. We examined changes in cardiac autonomic function and repolarization during sustained experimental hypoglycemia. Twelve adults with T2DM and 11 age- and BMI-matched control participants without diabetes underwent paired hyperinsulinemic clamps separated by 4 weeks. Glucose was maintained at euglycemia (6.0 mmol/L) or hypoglycemia (2.5 mmol/L) for 1 h. Heart rate, blood pressure, and heart rate variability were assessed every 30 min and corrected QT intervals and T-wave morphology every 60 min. Heart rate initially increased in participants with T2DM but then fell toward baseline despite maintained hypoglycemia at 1 h accompanied by reactivation of vagal tone. In control participants, vagal tone remained depressed during sustained hypoglycemia. Participants with T2DM exhibited greater heterogeneity of repolarization during hypoglycemia as demonstrated by T-wave symmetry and principal component analysis ratio compared with control participants. Epinephrine levels during hypoglycemia were similar between groups. Cardiac autonomic regulation during hypoglycemia appears to be time dependent. Individuals with T2DM demonstrate greater repolarization abnormalities for a given hypoglycemic stimulus despite comparable sympathoadrenal responses. These mechanisms could contribute to arrhythmias during clinical hypoglycemic episodes.
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Affiliation(s)
- Elaine Chow
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, U.K
| | - Alan Bernjak
- INSIGNEO Institute for In Silico Medicine, University of Sheffield, Sheffield, U.K
- Department of Oncology and Metabolism, University of Sheffield, Sheffield, U.K
| | - Emma Walkinshaw
- Department of Oncology and Metabolism, University of Sheffield, Sheffield, U.K
| | | | - Jenny Freeman
- Leeds Institute of Health Sciences, University of Leeds, Leeds, U.K
| | - Ian A Macdonald
- School of Life Sciences, University of Nottingham, Nottingham, U.K
| | - Paul J Sheridan
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, U.K
| | - Simon R Heller
- Department of Oncology and Metabolism, University of Sheffield, Sheffield, U.K.
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Guo X, Li Z, Guo L, Yu S, Yang H, Zheng L, Pan G, Zhang Y, Sun Y, Pletcher MJ. Effects of Metabolically Healthy and Unhealthy Obesity on Prolongation of Corrected QT Interval. Am J Cardiol 2017; 119:1199-1204. [PMID: 28209348 DOI: 10.1016/j.amjcard.2016.12.033] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2016] [Revised: 12/22/2016] [Accepted: 12/22/2016] [Indexed: 10/20/2022]
Abstract
Although obesity and the metabolic syndrome (MS) often co-occur, many obese (OB) subjects have a favorable metabolic profile. It is unclear whether these factors independently influence cardiac electrophysiology including prolongation of the QT interval. We examined associations among obesity, MS, and prolonged corrected QT (QTc) interval in a large sample of Chinese research participants aged ≥35 years recruited from rural areas of Liaoning Province during 2012 to 2013. Of the 11,209 participants, 6,364 (56.8%) were nonobese and metabolically healthy (OB-/MS-), 2,853 (25.5%) were OB-/MS+, 493 (4.4%) were OB+/MS-, and 1,499 (13.4%) were OB+/MS+. Mean (±SD) QTc intervals were higher in OB-/MS+ (436.3 ± 24.3) and OB+/MS+ (436.6 ± 25.9) participants but not OB+/MS- participants (425.4 ± 24.0) than in OB-/MS- participants (426.8 ± 21.5, p <0.001), and the prevalence of QTc prolongation was higher in OB-/MS+ and OB+/MS+ participants (adjusted odds ratios [aOR] 1.68, 95% confidence interval [CI] 1.52 to 1.85; aOR 1.92, 95% CI 1.69 to 2.17, respectively) compared with OB-/MS- group but not in OB+/MS- participants (aOR 0.92, 95% CI 0.73 to 1.15). Prevalence increased with each MS component (aOR 1.27, 95% CI 1.22 to 1.32) but not with body mass index (aOR 1.01, 95% CI 0.99 to 1.02). In conclusion, prolonged QTc interval is associated with the MS and not independently associated with obesity.
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Dimova R, Tankova T, Chakarova N, Grozeva G, Dakovska L. Cardio-metabolic profile of subjects with early stages of glucose intolerance and cardiovascular autonomic dysfunction. Diabetes Res Clin Pract 2017; 126:115-121. [PMID: 28242436 DOI: 10.1016/j.diabres.2017.02.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2016] [Accepted: 02/02/2017] [Indexed: 01/25/2023]
Abstract
AIMS The present study evaluates the cardio-metabolic profile of subjects with early stages of glucose intolerance and presence of cardiovascular autonomic dysfunction (CAD). MATERIALS AND METHODS 478 subjects, of mean age 49.3±13.7years and mean BMI 31.0±6.2kg/m2, divided according to glucose tolerance: 130 with normal glucose tolerance, 227 with prediabetes, and 121 with newly-diagnosed type 2 diabetes, were enrolled. Glucose tolerance was studied during OGTT applying 2006 WHO criteria. Anthropometric indices, blood pressure, HbA1c, serum lipids, hsCRP, and albumin-to-creatinine ratio (ACR) were measured. Body fat distribution was estimated by a bioimpedance method (InBody720, BioSpace). Tissue AGEs accumulation was assessed by skin autofluorescence (AGE-Reader-DiagnOptics™). CAD was assessed by ANX-3.0 method. RESULTS CAD was found in 24.1% of subjects with any disorder of glucose tolerance in comparison to 12.3% in NGT, OR 2.0 (95% CI: 1.2-3.2), p=0.005. Sympathetic and parasympathetic tone declined with the progression of glucose intolerance. Age, waist circumference, visceral fat area, fasting and 120-min plasma glucose, HbA1c, AGEs, ACR and QTc interval were higher in subjects with CAD, p<0.05. In a logistic regression analysis the panel of age >53years (76% sensitivity, 61% specificity), HbA1c >6.0% (66% sensitivity, 60% specificity), QTc interval >423ms (65% sensitivity, 61% specificity) and presence of arterial hypertension (83% sensitivity, 55% specificity) was related to the presence of CAD - AUC 0.778 (95% CI: 0.73-0.83), p<0.001. CONCLUSION Our results demonstrate a high prevalence of CAD in early stages of glucose dysmetabolism. Age, HbA1c, QTc interval and presence of arterial hypertension are related to the presence of CAD in this population.
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Affiliation(s)
- Rumyana Dimova
- Department of Diabetology, Clinical Center of Endocrinology, Medical University Sofia, 2, Zdrave Str., Sofia 1431, Bulgaria.
| | - Tsvetalina Tankova
- Department of Diabetology, Clinical Center of Endocrinology, Medical University Sofia, 2, Zdrave Str., Sofia 1431, Bulgaria
| | - Nevena Chakarova
- Department of Diabetology, Clinical Center of Endocrinology, Medical University Sofia, 2, Zdrave Str., Sofia 1431, Bulgaria
| | - Greta Grozeva
- Department of Diabetology, Clinical Center of Endocrinology, Medical University Sofia, 2, Zdrave Str., Sofia 1431, Bulgaria
| | - Lilia Dakovska
- Department of Diabetology, Clinical Center of Endocrinology, Medical University Sofia, 2, Zdrave Str., Sofia 1431, Bulgaria
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