We found a significant association between hypermethylation of ACTB in peripheral blood and increased risk of CHD (odds ratios (ORs) per +10% methylation: 1.19–1.45, p < 0.013 for nine out of thirteen CpG sites), especially in male subjects and heart failure (HF) patients (ORs per +10% methylation: 1.20–1.43, 1.38–1.46; p < 0.030, 1.52 × 10−4, respectively). Here, ACTB is linked to coronary artery disorder.