glucagon-like-peptide-1 and Atrial-Fibrillation

Atrial fibrillation (AF) is the most common clinically significant arrhythmia, and it increases stroke risk. A preventive approach to AF is needed because virtually all treatments such as cardioversion, antiarrhythmic drugs, ablation, and anticoagulation are associated with high cost and carry significant risk. A systematic review was performed to identify effective lifestyle-based strategies for reducing primary and secondary AF. A PubMed search was performed using articles up to March 1, 2021. Search terms included atrial fibrillation, atrial flutter, exercise, diet, metabolic syndrome, type 2 diabetes mellitus, obesity, hypertension, stress, tobacco smoking, alcohol, Mediterranean diet, sodium, and omega-3 fatty acids. Additional articles were identified from the bibliographies of retrieved articles. The control of hypertension, ideally with a renin-angiotensin-aldosterone system inhibitor, is effective for preventing primary AF and recurrence. Obstructive sleep apnea is a common cause of AF, and treating it effectively reduces AF episodes. Alcohol increases the risk of AF in a dose-dependent manner, and abstinence reduces risk of recurrence. Sedentary behavior and chronic high-intensity endurance exercise are both risk factors for AF; however, moderate physical activity is associated with lower risk of AF. Recently, sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 agonists have been associated with reduced risk of AF. Among overweight/obese patients, weight loss of ≥10% is associated with reduced AF risk. Lifestyle changes and risk factor modification are highly effective for preventing AF.

Topics: Alcohol Drinking; Atrial Fibrillation; Bariatric Surgery; Diabetes Mellitus, Type 2; Diet Therapy; Diet, Mediterranean; Dietary Fats, Unsaturated; Endurance Training; Exercise; Fatty Acids, Omega-3; Glucagon-Like Peptide 1; Humans; Metabolic Syndrome; Obesity; Overweight; Risk Reduction Behavior; Sedentary Behavior; Sleep Apnea, Obstructive; Smoking; Smoking Cessation; Sodium-Glucose Transporter 2 Inhibitors; Weight Loss

There are limited data on head-to-head comparative risk of stroke between sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA). We compared risk of stroke with its subtypes and incident atrial fibrillation (AF) between them.. A population-based, retrospective cohort of patients with type 2 diabetes between 2008 and 2020 were identified from the electronic health records of Hong Kong Hospital Authority. Patients who received SGLT2i or GLP-1RA were matched pairwise by propensity score. Risks of stroke and AF were evaluated by hazard ratios (HRs) from the Cox proportional hazard regression models.. A total of 5840 patients (2920 SGLT2i users; 2920 GLP-1RA users) were included (mean age 55.5 years, 56.1% men, mean HbA1c 8.9% and duration of diabetes 13.7 years). Upon median follow-up of 17 months, there were 111 (1.9%) events of stroke (SGLT2i: 62, 2.1%; GLP-1RA: 49 1.7%). SGLT2i users had comparable risk of all stroke as GLP-1RA users (HR 1.46, 95% CI 0.99-2.17, p = 0.058). SGLT2i users had higher risk of ischemic stroke (HR 1.53, 95% CI 1.01-2.33, p = 0.044) but similar risk of hemorrhagic stroke compared to GLP-1RA users. Although SGLT2i was associated with lower risk of incident AF (HR 0.43, 95% CI 0.23-0.79, p = 0.006), risk of cardioembolic stroke was similar.. Our real-world study demonstrated that GLP-1RA use was associated with lower risk of ischemic stroke, despite the association between SGLT2i use and lower risk of incident AF. There was no significant difference in hemorrhagic stroke risk. GLP-1RA may be the preferred agent for patients with type 2 diabetes at risk of ischemic stroke.

Topics: Atrial Fibrillation; Cohort Studies; Diabetes Mellitus, Type 2; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Glucose; Hemorrhagic Stroke; Hong Kong; Humans; Hypoglycemic Agents; Ischemic Stroke; Male; Middle Aged; Retrospective Studies; Sodium; Sodium-Glucose Transporter 2 Inhibitors

Glucagon-like peptide-1 receptor (GLP-1R) agonists reduce the rates of major cardiovascular events, including myocardial infarction in people with type 2 diabetes, and decrease infarct size while preserving ventricular function in preclinical studies. Nevertheless, the precise cellular sites of GLP-1R expression that mediate the cardioprotective actions of GLP-1 in the setting of ischemic cardiac injury are uncertain.. Publicly available single cell RNA sequencing (scRNA-seq) datasets on mouse and human heart cells were analyzed for Glp1r/GLP1R expression. Fluorescent activated cell sorting was used to localize Glp1r expression in cell populations from the mouse heart. The importance of endothelial and hematopoietic cells for the cardioprotective response to liraglutide in the setting of acute myocardial infarction (MI) was determined by inactivating the Glp1r in Tie2+ cell populations. Cardiac gene expression profiles regulated by liraglutide were examined using RNA-seq to interrogate mouse atria and both infarcted and non-infarcted ventricular tissue after acute coronary artery ligation.. In mice, cardiac Glp1r mRNA transcripts were exclusively detected in endocardial cells by scRNA-seq. In contrast, analysis of human heart by scRNA-seq localized GLP1R mRNA transcripts to populations of atrial and ventricular cardiomyocytes. Moreover, very low levels of GIPR, GCGR and GLP2R mRNA transcripts were detected in the human heart. Cell sorting and RNA analyses detected cardiac Glp1r expression in endothelial cells (ECs) within the atria and ventricle in the ischemic and non-ischemic mouse heart. Transcriptional responses to liraglutide administration were not evident in wild type mouse ventricles following acute MI, however liraglutide differentially regulated genes important for inflammation, cardiac repair, cell proliferation, and angiogenesis in the left atrium, while reducing circulating levels of IL-6 and KC/GRO within hours of acute MI. Inactivation of the Glp1r within the Tie2+ cell expression domain encompassing ECs revealed normal cardiac structure and function, glucose homeostasis and body weight in Glp1r. These findings identify the importance of the murine Tie2+ endothelial cell GLP-1R as a target for the cardioprotective actions of GLP-1R agonists and support the importance of the atrial and ventricular endocardial GLP-1R as key sites of GLP-1 action in the ischemic mouse heart. Hitherto unexplored species-specific differences in cardiac GLP-1R expression challenge the exclusive use of mouse models for understanding the mechanisms of GLP-1 action in the normal and ischemic human heart.

Topics: Animals; Atrial Fibrillation; Diabetes Mellitus, Type 2; Disease Models, Animal; Endothelial Cells; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Liraglutide; Mice; Myocardial Infarction; Receptor, TIE-2; RNA, Messenger

Topics: Atrial Fibrillation; Cardiovascular System; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Female; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Insulin; Male; Metformin; Middle Aged; Risk Assessment; Sulfonylurea Compounds