Cardiovascular health assessed by Life's Essential 8 score, genetic risk, colonoscopy status, and risk of colorectal cancer: an analysis of UK Biobank.

High LE8 scores were associated with a 26% reduced colorectal cancer risk compared with low LE8 scores.

• 291,177 UK Biobank participants were included in the analysis.
• During a median follow-up of 12.97 years, 3,791 incident CRC cases were identified.
• Cox proportional hazards models were used for analysis.
• HR: 0.74; 95% CI 0.64 to 0.86 for high vs. low LE8 scores.

High LE8 scores were associated with a 27% lower CRC risk in individuals with high genetic risk.

• HR: 0.73; 95% CI 0.56 to 0.94 for high LE8 in individuals with high genetic risk.
• This finding suggests that better cardiovascular health can reduce CRC risk even among those genetically predisposed.
• Genetic risk was examined as a modifying factor in the association between LE8 score and CRC.

High LE8 scores were associated with a 35% reduction in CRC risk in individuals without a history of colonoscopy screening.

• HR: 0.65; 95% CI 0.54 to 0.78 for high LE8 in those without prior colonoscopy.
• Colonoscopy screening status was examined as a modifying factor in the LE8-CRC association.
• The protective association of high LE8 was stronger in unscreened individuals than the overall population.

Joint analysis of high LE8 and low genetic risk showed a 78% lower CRC risk compared to the reference group.

• HR: 0.22; 95% CI 0.15 to 0.34 for individuals with both high LE8 scores and low genetic risk.
• This represents the most favorable combination of modifiable cardiovascular health and genetic predisposition.
• The joint analysis highlights the combined benefit of optimal cardiovascular health and low genetic susceptibility on CRC risk.

The LE8 score comprises eight cardiovascular health indicators used to assess cardiovascular health in relation to CRC risk.

• The eight LE8 indicators are: diet, physical activity, nicotine exposure, sleep health, body mass index, blood lipids, blood glucose, and blood pressure.
• CRC and cardiovascular disease share common risk factors, providing the rationale for using LE8 to study CRC risk.
• Participants were categorized into low, moderate, and high LE8 score groups for analysis.