{"doi":"10.1001/jamanetworkopen.2023.51927","title":"Clonal Hematopoiesis Risk Score and All-Cause and Cardiovascular Mortality in Older Adults","abstract":"Importance: Clonal hematopoiesis (CH) with acquired pathogenic variants in myeloid leukemia driver genes is common in older adults but of unknown prognostic value. Objective: To investigate the prevalence of CH and the utility of the CH risk score (CHRS) in estimating all-cause and disease-specific mortality in older adults with CH. Design, Setting, and Participants: This population-based prospective cohort study involved community-dwelling older adults (aged 67-90 years) without hematologic malignant neoplasms (HMs) who were participants in the Atherosclerosis Risk in Communities Visit 5 at 4 US centers: Forsyth County, North Carolina; Jackson, Mississippi; Minneapolis, Minnesota; and Washington County, Maryland. Samples were collected from 2011 to 2013, sequencing was performed in 2022, and data analysis was completed in 2023. Exposure: The exposure was a diagnosis of CH. CHRS scores (calculated using 8 demographic, complete blood cell count, and molecular factors) were used to categorize individuals with CH into low-risk (CHRS ≤9.5), intermediate-risk (CHRS >9.5 to <12.5), and high-risk (CHRS ≥12.5) groups. Main Outcomes and Measures: The primary outcome was all-cause mortality, and secondary outcomes were HM mortality, cardiovascular disease mortality, and death from other causes. Results: Among 3871 participants without a history of HM (mean [SD] age, 75.7 [5.2] years; 2264 [58.5%] female individuals; 895 [23.1%] Black individuals; 2976 White individuals [76.9%]), 938 (24.2%) had CH. According to the CHRS, 562 (59.9%) were low risk, 318 (33.9%) were intermediate risk, and 58 (6.2%) were high risk. During a median (IQR) follow-up of 7.13 (5.63-7.78) years, 570 participants without CH (19.4%) and 254 participants with CH (27.1%) died. Mortality by CHRS risk group was 128 deaths (22.8%) for low risk, 93 (29.2%) for intermediate risk, and 33 (56.9%) for high risk. By use of multivariable competing risk regression, subdistribution hazard ratios (sHRs) for all-cause mortality were 1.08 (95% CI, 0.89-1.31; P = .42) for low-risk CH, 1.12 (95% CI, 0.89-1.41; P = .31) for intermediate-risk CH, and 2.52 (95% CI, 1.72-3.70; P < .001) for high-risk CH compared with no CH. Among individuals in the high-risk CH group, the sHR of death from HM (6 deaths [10.3%]) was 25.58 (95% CI, 7.55-86.71; P < .001) and that of cardiovascular death (12 deaths [20.7%]) was 2.91 (95% CI, 1.55-5.47; P < .001). Conclusions and Relevance: In this cohort study, the CHRS was associated with all-cause, HM-related, and cardiovascular disease mortality in older adults with CH and may be useful in shared decision-making to guide clinical management and identify appropriate candidates for clinical trials.","journal":"JAMA Network Open","year":2024,"id":419185,"datarank":0.5641800173540344,"base_score":3.7612001156935624,"endowment":3.7612001156935624,"self_citation_contribution":0.5641800173540344,"citation_network_contribution":0.0,"self_endowment_contribution":0.5641800173540344,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":42,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9344,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":561964,"name":"Md Mesbah Uddin","orcid":"0000-0003-1846-0411","position":1,"is_corresponding":false},{"id":667669,"name":"Lachelle D. Weeks","orcid":"0000-0001-8726-6212","position":2,"is_corresponding":false},{"id":218531,"name":"Abhishek Niroula","orcid":"0000-0002-5904-0635","position":3,"is_corresponding":false},{"id":971892,"name":"Meng Ru","orcid":"0000-0002-1439-6451","position":4,"is_corresponding":false},{"id":108815,"name":"Koichi Takahashi","orcid":"0000-0002-8027-9659","position":5,"is_corresponding":false},{"id":320776,"name":"Lukasz P. Gondek","orcid":"0000-0002-1551-3496","position":6,"is_corresponding":false},{"id":51217,"name":"Bing Yu","orcid":"0000-0003-4818-1077","position":7,"is_corresponding":false},{"id":27378,"name":"Alexander G. Bick","orcid":"0000-0001-5824-9595","position":8,"is_corresponding":false},{"id":16672,"name":"Benjamin L. Ebert","orcid":"0000-0003-0197-5451","position":9,"is_corresponding":false},{"id":218634,"name":"Elizabeth A. Platz","orcid":"0000-0003-3676-8954","position":10,"is_corresponding":false},{"id":24665,"name":"Pradeep Natarajan","orcid":"0000-0001-8402-7435","position":11,"is_corresponding":false},{"id":233725,"name":"Christie M. Ballantyne","orcid":"0000-0002-6432-1730","position":12,"is_corresponding":false},{"id":683350,"name":"Seyedmohammad Saadatagah","orcid":"0000-0003-4950-8334","position":0,"is_corresponding":true}],"reference_count":10,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:57:14.586331Z","pmid":"38231513","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":[]}