INTRODUCTION: Atrial fibrillation (AF) is the most common form of arrhythmia in humans and is associated with substantial morbidity and mortality. Obesity and diabetes have been linked to myocardial lipotoxicity - a condition where the heart accumulates and produces toxic lipid species. We hypothesized that obesity and diabetes were involved in the pathophysiology of AF by means of promoting a lipotoxic phenotype in atrial muscle, and that AF predicts mortality in cardiac care patients. METHODS: Our study consists of two parts. The first part is a registry study based on prospective data obtained through the Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (RIKS-HIA) from hospitals in western Sweden. All consecutive patients between 2006 and 2011 admitted to coronary care unit (CCU) with sinus rhythm (SR) or AF were included in the analysis. Multivariate logistic regression and Cox proportional-hazards regression were used to test whether diabetes and obesity were independent predictors of AF at admission to CCU and whether AF was associated with increased one-year mortality. In the second part we obtained atrial biopsies from 54 patients undergoing cardiac surgery and performed lipidomic analysis for a detailed qualitative and quantitative analysis of lipid species including triglycerides (TAG), ceramides (CER), phosphatidylcholine (PC), lysophosphatidylcholine (LPC), phosphatidylethanolamine (PE), sphyngomyelins (SM), free cholesterol (FC), cholesterol esters (CEs) and diacylglycerols (DAGs). RESULTS: Between 2006 and 2011, 35232 patients were admitted to CCUs in western Sweden, mostly due to ischemic heart disease, heart failure, arrhythmia, syncope and chest pain. The mean age was 66years and 58.7% were male. There was a high prevalence of obesity (20.3%) and diabetes (16.8%). Obesity (OR 1.35, 95% CI 1.17-1.56, P<0.001) and severe obesity (1.6, 95% CI 1.29-1.99, P<0.001) were independent predictors of AF but diabetes was not (OR=0.92, 95% CI=0.82-1.04). AF increased one-year mortality (HR 1.32, 95% CI 1.16-1.50, P<0.001). Lipidomic analysis revealed that atrial TAG content was substantially lower in the AF patients (P<0.05). No quantitative difference was found in the content of CER, PC, LPC, PE, SM, FC, CE and DAG, between the patients who had AF or sinus rhythm at admission to the CCU. AF patients had greater proportion of polyunsaturated DAG (P<0.05) while no difference was found in saturated DAG. CONCLUSION: Obesity but not diabetes is an independent predictor of AF and AF is associated with increased one-year mortality in this CCU population. AF is associated with quantitative and qualitative alterations in atrial lipid content but not with lipotoxicity.
INTRODUCTION:Atrial fibrillation (AF) is the most common form of arrhythmia in humans and is associated with substantial morbidity and mortality. Obesity and diabetes have been linked to myocardial lipotoxicity - a condition where the heart accumulates and produces toxic lipid species. We hypothesized that obesity and diabetes were involved in the pathophysiology of AF by means of promoting a lipotoxic phenotype in atrial muscle, and that AF predicts mortality in cardiac care patients. METHODS: Our study consists of two parts. The first part is a registry study based on prospective data obtained through the Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (RIKS-HIA) from hospitals in western Sweden. All consecutive patients between 2006 and 2011 admitted to coronary care unit (CCU) with sinus rhythm (SR) or AF were included in the analysis. Multivariate logistic regression and Cox proportional-hazards regression were used to test whether diabetes and obesity were independent predictors of AF at admission to CCU and whether AF was associated with increased one-year mortality. In the second part we obtained atrial biopsies from 54 patients undergoing cardiac surgery and performed lipidomic analysis for a detailed qualitative and quantitative analysis of lipid species including triglycerides (TAG), ceramides (CER), phosphatidylcholine (PC), lysophosphatidylcholine (LPC), phosphatidylethanolamine (PE), sphyngomyelins (SM), free cholesterol (FC), cholesterol esters (CEs) and diacylglycerols (DAGs). RESULTS: Between 2006 and 2011, 35232 patients were admitted to CCUs in western Sweden, mostly due to ischemic heart disease, heart failure, arrhythmia, syncope and chest pain. The mean age was 66years and 58.7% were male. There was a high prevalence of obesity (20.3%) and diabetes (16.8%). Obesity (OR 1.35, 95% CI 1.17-1.56, P<0.001) and severe obesity (1.6, 95% CI 1.29-1.99, P<0.001) were independent predictors of AF but diabetes was not (OR=0.92, 95% CI=0.82-1.04). AF increased one-year mortality (HR 1.32, 95% CI 1.16-1.50, P<0.001). Lipidomic analysis revealed that atrial TAG content was substantially lower in the AFpatients (P<0.05). No quantitative difference was found in the content of CER, PC, LPC, PE, SM, FC, CE and DAG, between the patients who had AF or sinus rhythm at admission to the CCU. AFpatients had greater proportion of polyunsaturated DAG (P<0.05) while no difference was found in saturated DAG. CONCLUSION:Obesity but not diabetes is an independent predictor of AF and AF is associated with increased one-year mortality in this CCU population. AF is associated with quantitative and qualitative alterations in atrial lipid content but not with lipotoxicity.
Authors: Michelle L Meyer; Andrea Jaensch; Ute Mons; Lutz P Breitling; Harry Hahmann; Wolfgang Koenig; Hermann Brenner; Dietrich Rothenbacher Journal: Int J Cardiol Date: 2015-11-17 Impact factor: 4.164