{"doi":"10.1016/j.jacadv.2025.102162","title":"Development and Validation of Novel Residual Risk Scores for Patients With ASCVD","abstract":"BACKGROUND: Despite clinical need, personalized risk scores for established atherosclerotic cardiovascular disease (ASCVD) are scarce. OBJECTIVES: The objective of the study was to develop and validate 10-year residual risk scores for cardiovascular death in patients with established ASCVD. METHODS: Prospective observational cohort study. Models developed and validated in U.K. Biobank (UKB) (baseline 2006-2010; follow-up through 2021) and externally validated in Mass General Brigham cohort (MGB) (baseline 2007; follow-up through 2018). Analyzed on October 2022-February 2024. Eligible participants had established ASCVD. Guideline-based clinical factors plus additional biomarkers and self-reported health ratings. PRIMARY OUTCOME: 10-year cardiovascular death. Elastic-net Cox and gradient-boosted tree models. C statistics and goodness-of-fit assessed in holdout set. RESULTS: UKB: 32,994 participants (mean age 61; 11,727 [35.5%] women; 2,660 [8.0%] cardiovascular deaths), with 9,899 (30%) randomly selected as a holdout validation set. MGB: 54,969 patients (mean age 71; 22,738 [41.4%] women; 6,927 [12.6%] cardiovascular deaths). Median follow-up: 10 years (IQR 10-10) in UKB; 9.4 years (5-10) in MGB. We developed 2 residual risk scores, RRS16 and RRS24, incorporating 16 and 24 algorithmically selected factors. RRS16 used routinely available factors; RRS24 also included self-reported health and additional 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, outperforming the 2018 the American Heart Association (AHA) guideline model (0.658 [0.642-0.674] in UKB, 0.580 [0.574-0.586] in MGB). RRS24 achieved 0.784 (0.768-0.800) in UKB. Both models well calibrated (P > 0.1). RRS16 calculator: https://mora.bwh.harvard.edu/rrs16/. CONCLUSIONS: RRS16 and RRS24 outperformed AHA guideline model in estimating the residual risk in patients with established ASCVD. Both are clinically applicable but require further validation in diverse populations.","journal":"JACC Advances","year":2025,"id":532992,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.5493,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":399815,"name":"Chunying Li","orcid":"0000-0002-2558-6971","position":1,"is_corresponding":false},{"id":243636,"name":"Franco Giulianini","orcid":null,"position":2,"is_corresponding":false},{"id":1414954,"name":"Simeon Häfliger","orcid":null,"position":3,"is_corresponding":false},{"id":239408,"name":"Vadim Bubes","orcid":null,"position":4,"is_corresponding":false},{"id":41879,"name":"Gunnar Raetsch","orcid":null,"position":5,"is_corresponding":false},{"id":351263,"name":"Samia Mora","orcid":"0000-0001-6283-0980","position":6,"is_corresponding":false},{"id":69363,"name":"Olga Demler","orcid":"0000-0003-3355-3210","position":7,"is_corresponding":false},{"id":1414501,"name":"Olga Mineeva","orcid":"0000-0002-5669-3497","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:51:27.893975Z","pmid":"41061571","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}