BACKGROUND: The relationship between coronary artery calcium (CAC) and progression of diastolic dysfunction (DD) during longitudinal follow-up is uncertain. This study aimed to investigate the prevalence and progression of DD according to severity of CAC and understand their synergistic effect on mortality. METHODS: This was a population-based cohort study. All 15,193 adults who underwent a health screening exam with simultaneous echocardiography and CAC scan were enrolled. Definite DD (≥ 3/4 abnormal parameters for DD [e', E/e', tricuspid regurgitation velocity, and left atrial volume index]) and definite or probable DD (≥ 2/4) were defined. All-cause mortality was assessed based on the CAC and DD. RESULTS: Among the population, 7995 participants (52.6%) had CAC = 0
4661 (30.7%) had 0 <
CAC <
100
and 2537 (16.7%) had CAC ≥ 100. The prevalence ratios for definite (adjusted ratio: 1.72, 95% CI: 1.23-2.22) and definite or probable DD (adjusted ratio: 1.83, 95% CI: 1.31-2.36) were significantly higher in individuals with CAC ≥ 100 than in those with CAC = 0. There was significant linear association of CAC with E/e' (adjusted p for linearity = 0.002). Compared with CAC <
100 without definite DD, the adjusted HRs with 95% CI for mortality of CAC ≥ 100 without definite DD, CAC <
100 with definite DD, and CAC ≥ 100 with definite DD were 2.56 (95% CI: 1.67-3.94), 3.08 (95% CI: 1.28-7.39), and 3.91 (95% CI: 1.68-9.10). Among participants without DD at CAC measurement who had at least two echocardiographic measurements, the presence of significant CAC (≥ 100) was significantly associated with accelerated progression in definite DD over time (adjusted HR: 1.46, 95% CI: 1.13-1.88), with more rapid elevation of E/e' during follow-up (difference: 0.06, 95% CI: 0.02-0.10, p = 0.003). CONCLUSIONS: In the general population, there was a significant relationship between CAC and prevalence of DD, and both subclinical parameters were associated with increased mortality. Moreover, CAC ≥ 100 significantly affects the progression of DD independently of other clinical factors.