Blood-Based DNA Methylation Biomarkers to Identify Risk and Progression of Cardiovascular Disease

Non-communicable diseases (NCDs) are the leading cause of death worldwide, with cardiovascular disease (CVD) accounting for half of all NCD-related deaths. The biological onset of CVD may occur long before the development of clinical symptoms, hence the urgent need to understand the molecular alterations underpinning CVD, which would facilitate intervention strategies to prevent or delay the onset of the disease. There is evidence to suggest that CVD develops through a complex interplay between genetic, lifestyle, and environmental factors. Epigenetic modifications, including DNA methylation, serve as proxies linking genetics and the environment to phenotypes and diseases. In the past decade, a growing list of studies has implicated DNA methylation in the early events of CVD pathogenesis. In this regard, screening for these epigenetic marks in asymptomatic individuals may assist in the early detection of CVD and serve to predict the response to therapeutic interventions. This review discusses the current literature on the relationship between blood-based DNA methylation alterations and CVD in humans. We highlight a set of differentially methylated genes that show promise as candidates for diagnostic and prognostic CVD biomarkers, which should be prioritized and replicated in future studies across additional populations. Finally, we discuss key limitations in DNA methylation studies, including genetic diversity, interpatient variability, cellular heterogeneity, study confounders, different methodological approaches used to isolate and measure DNA methylation, sample sizes, and cross-sectional study design.