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

Clin Interv Aging. 2019 Oct 4:14:1719-1728. doi: 10.2147/CIA.S219748. eCollection 2019.

Abstract

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.

Keywords: DNA methylation; left ventricular diastolic dysfunction; risk factor.

MeSH terms

  • Aged
  • Carotid Intima-Media Thickness / statistics & numerical data*
  • China / epidemiology
  • DNA Methylation*
  • Echocardiography
  • Epigenesis, Genetic*
  • Female
  • Humans
  • Male
  • Prevalence
  • Risk Factors
  • Stroke Volume / physiology*
  • Ventricular Dysfunction, Left / diagnosis*
  • Ventricular Dysfunction, Left / diagnostic imaging
  • Ventricular Dysfunction, Left / genetics
  • Ventricular Function, Left