Modifiable influencing factors and their joint effects on early- and late-onset coronary heart disease

Over the past decade, the previously declining trend in coronary heart disease burden has reversed, particularly among younger adults. Using an exposure-wide association study with data from 394,579 UK Biobank participants, we examined the relationship between 213 modifiable factors across eight domains and coronary heart disease. Weighted domain scores were calculated to assess the combined effects of these factors and their interactions with genetic risk. We identified 155 modifiable factors associated with coronary heart disease, 31 of which showed evidence of causality. The major contributors are health and medical history (15.75%), including diabetes mellitus; blood assays (13.87%), including cystatin C; lifestyle factors (10.01%), including time spent watching television; and physical measures (8.70%), including systolic blood pressure. We estimate that 40% to 62% of cases could be prevented by modifying these factors, which have a stronger effect on younger populations. These findings underscore the importance of early and comprehensive prevention strategies.