ACTB hypermethylation in blood is a potential biomarker as predictor to the risk of coronary heart disease.

Potential biomarkers that can assess the risk of coronary heart disease (CHD) and facilitate its preclinical detection are urgently needed. We aimed to explore the association between blood-based ACTB methylation and future CHD risk in a nested case-control study in the Chinese population. The methylation level of ACTB was quantitatively determined by mass spectrometry in 171 subclinical CHD cases and 356 controls. Logistic regression was used to examine the association between ACTB methylation and future CHD risk. We observed a significant association between hypermethylation of ACTB in peripheral blood and an increased risk of future CHD, particularly among individuals ≥ 60 years old and male subjects. Additionally, hypermethylation of ACTB was associated with the risk of future CHD in subjects with elevated TC and LDL-C levels. Furthermore, compared to using traditional risk factors alone, the model incorporating altered ACTB methylation demonstrated improved discriminative value, especially in individuals ≥ 60 years old and among males (area under curve = 0.79 and 0.81, respectively). Our findings demonstrated a strong association between ACTB hypermethylation in peripheral blood and increased future CHD risk, offering promise for improving risk assessment and early detection strategies.