Article Impact Level: HIGH Data Quality: STRONG Summary of JACC: Advances https://doi.org/10.1016/j.jacadv.2025.102162 Dr. Olga Mineeva et al.
Points
- Researchers developed and validated 10-year residual risk scores (RRS16, RRS24) for cardiovascular death in ASCVD patients.
- RRS16, using 16 factors, achieved C statistics of 0.752 (UKB) and 0.750 (MGB), outperforming the 2018 AHA guideline model.
- The 2018 AHA model had C statistics of 0.658 (UKB) and 0.580 (MGB), indicating lower discriminatory power.
- RRS24, with 24 factors including biomarkers, achieved a higher C statistic of 0.784 in the UKB cohort.
- Both RRS16 and RRS24 are well-calibrated and clinically applicable, offering personalized risk estimates superior to current guidelines.
Summary
This prospective observational cohort study developed and validated novel 10-year residual risk scores (RRS16 and RRS24) for cardiovascular death in patients with established atherosclerotic cardiovascular disease (ASCVD), addressing a critical clinical need for personalized secondary prevention tools. The models were developed and validated using the U.K. Biobank (UKB) cohort (32,994 participants, mean age 61; 35.5% women; 2,660 [8.0%] cardiovascular deaths over a median 10-year follow-up) and externally validated in the Mass General Brigham (MGB) cohort (54,969 patients, mean age 71; 41.4% women; 6,927 [12.6%] cardiovascular deaths over a median 9.4-year follow-up).
Two residual risk scores were developed: RRS16, incorporating 16 routinely available clinical factors, and RRS24, which additionally included self-reported health and other biomarkers. RRS16 achieved C statistics of 0.752 (95% CI: 0.736-0.768) in UKB and 0.750 (0.744-0.756) in MGB, demonstrating superior performance compared to the 2018 American Heart Association (AHA) guideline model, which yielded C statistics of 0.658 (0.642-0.674) in UKB and 0.580 (0.574-0.586) in MGB. RRS24 further improved discrimination, achieving a C statistic of 0.784 (0.768-0.800) in UKB. Both RRS16 and RRS24 were well-calibrated (P > 0.1), providing personalized absolute risk estimates unlike existing guideline models.
The RRS16 and RRS24 models significantly outperformed the 2018 AHA guideline model in accurately estimating the residual risk of cardiovascular death in patients with established ASCVD. The 2018 AHA guideline, which lacks sex specificity and provides only categorical risk stratification, has limitations in personalization and clinical applicability. The novel RRS models offer clinically applicable tools for improved individualized risk stratification, although further validation in diverse populations is warranted to ensure broad utility.
Link to the article: https://www.jacc.org/doi/10.1016/j.jacadv.2025.102162
References
Mineeva, O., Li, C., Giulianini, F., Häfliger, S., Bubes, V., Raetsch, G., Mora, S., & Demler, O. V. (2025). Development and validation of novel residual risk scores for patients with ascvd. JACC: Advances, 4(11), 102162. https://doi.org/10.1016/j.jacadv.2025.102162
