Risk Factors And Epigenetic Markers Of Left Ventricular Diastolic Dysfunction With Preserved Ejection Fraction In A Community-Based Elderly Chinese Population

PURPOSE: 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.