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

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:

• left ventricular diastolic dysfunction
• DNA methylation
• risk factor

Acknowledgments

This work was supported by the National Natural Science Foundation of China (grant no. 81872720) and Shanghai Municipal Commission of Health and Family Planning (grant no. 201840066) to Dr Lijuan Zhang. The National Natural Science Foundation of China (grant no. 81471402) to Jue Li and the National Natural Science Foundation of China (grant no. 81501203) to Jie Zhang. The abstract of this paper was presented at the Pulse of Asia 2019 Shanghai Conference name “Risk factors and epigenetic markers of left ventricular diastolic dysfunction with preserved ejection fraction in a community-based elderly Chinese population” as a poster presentation with interim findings. The poster’s abstract was published in “Poster Abstracts” in Pulse: DOI: 10.1159/000499586.

Data Sharing Statement

Individual deidentified participant data underlying the results reported in this study and other study-related documents will not be accessible since the Northern Shanghai Study is an on-going prospective community-based study. The follow-up study is still in the process and new enrolment is also conducted at the same time.

Author Contributions

All authors contributed to the conception and design, data analysis, drafting and critically revising the article, gave final approval of the version to be published, and agreed to be accountable for all aspects of the work.

Disclosure

The authors declare no conflicts of interest in this work.