Clinical Interventions in Aging (Oct 2019)
Risk Factors And Epigenetic Markers Of Left Ventricular Diastolic Dysfunction With Preserved Ejection Fraction In A Community-Based Elderly Chinese Population
Abstract
Wei Wang,1,2 Yi Zhang,3 Runzi Wang,1,2 Yeshaswi Shrestha,1,2 Yawei Xu,3 Luying Peng,1,4,5 Jie Zhang,1,2 Jue Li,1,2 Lijuan Zhang1,2 1Key Laboratory of Arrhythmias of the Ministry of Education, Tongji University School of Medicine, Shanghai 200092, People’s Republic of China; 2Institute of Clinical Epidemiology and Evidence-Based Medicine, Tongji University School of Medicine, Shanghai 200092, People’s Republic of China; 3Department of Cardiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, People’s Republic of China; 4Department of Pathology and Pathophysiology, Tongji University School of Medicine, Shanghai 200092, People’s Republic of China; 5Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, People’s Republic of ChinaCorrespondence: Jue Li; Lijuan ZhangKey Laboratory of Arrhythmias of the Ministry of Education, Tongji University School of Medicine, Shanghai 200092, People’s Republic of ChinaTel/fax +86 21 65985195Email [email protected]; [email protected]: Left ventricular diastolic dysfunction with preserved ejection fraction (LVDD-PEF) is an early-stage manifestation but poorly understood in the process of heart failure. This study was designed to investigate risk factors and epigenetic markers for predicting LVDD-PEF.Patients and methods: A community-based study in 1568 residents over 65 years was conducted in Shanghai, People’s Republic of China, from June 2014 to August 2015. Echocardiography was performed to diagnose LVDD-PEF. DNA methylation by whole-genome bisulfite sequencing was used to determine those potential epigenetic markers contributing to LVDD-PEF.Results: A total of 177 participants (11.3%) were diagnosed with LVDD-PEF, and higher prevalence in females than in males (15.0% vs 6.5%, P<0.001). Multivariate logistic regression analysis indicated that female sex (OR 2.46, 95% CI 1.47–4.13), body mass index (BMI) (OR 1.09, 95% CI 1.04–1.14), pulse pressure (PP) (OR 1.03, 95% CI 1.01–1.05) and carotid intima-media thickness (CIMT) (OR 4.20, 95% CI 1.40–12.55) showed a significant association with LVDD-PEF. Overall, 638 CpG sites were differentially methylated in LVDD-PEF group compared to non-LVDD-PEF group (P<0.001); 242 sites were significantly hypermethylated (covering 238 genes) and 396 sites were significantly hypomethylated (covering 265 genes).Conclusion: Our findings found female, BMI, PP, and CIMT were independent predictors for LVDD-PEF in the community-dwelling elderly population. Regulation of DNA methylation might play a crucial role for LVDD-PEF.Keywords: left ventricular diastolic dysfunction, DNA methylation, risk factor
