CHIP in Health and Disease

Clonal hematopoiesis (CH), including clonal hematopoiesis of indeterminate potential (CHIP), is an age-associated condition characterized by the expansion of hematopoietic stem and progenitor cell clones carrying acquired somatic mutations. Although CH is associated with an increased risk of hematologic malignancies, its greater public health impact derives from its strong association with cardiovascular diseases, including coronary artery disease and stroke. Emerging evidence suggests that CH-associated mutations promote chronic inflammatory signaling in myeloid immune cells, thereby contributing to atherosclerosis and adverse cardiovascular remodeling. This observational translational study aims to characterize the biological spectrum of clonal hematopoiesis across different stages of disease risk and manifestation. Using state-of-the-art single-cell and multi-omics approaches, the study will compare inflammatory pathways, immune cell states, and mutation-associated molecular programs among healthy individuals without CH, individuals with high-risk CH, and patients with CH-associated hematologic or cardiovascular disease. The ultimate goal is to identify shared and disease-specific mechanisms linking clonal hematopoiesis to adverse clinical outcomes and to generate insights for future preventive, anti-clonal, and anti-inflammatory therapeutic strategies.

Inclusion Criteria: Participants must be ≥18 years of age and meet at least one of the following criteria: * Written informed consent has been obtained for participation in the study "Deconvolution of Clonal Hematopoiesis-Associated Inflammation in Health and Disease"; OR * Participant is enrolled in the Inn.Health study and has provided written informed consent; OR * Participant is enrolled in the study "Clonal Hematopoiesis of Indeterminate Potential and Infarct Severity in ST-Elevation Myocardial Infarction" and has provided written informed consent. Group A: Control Group (n=20) * Age ≥60 years * No detectable somatic variant identified by peripheral blood next-generation sequencing (NGS) * No history of stroke or myocardial infarction * No surgery within the previous 3 months * No diagnosis of a WHO-defined neoplasm * No cytopenia at study enrollment Group B: Low-Risk Clonal Hematopoiesis Risk Score (CHRS) Group (n=20) * Age ≥60 years * Somatic variant in DNMT3A, TET2, ASXL1, or JAK2 with variant allele frequency (VAF) ≥2% in peripheral blood * No history of stroke or myocardial infarction * No surgery within the previous 3 months * No diagnosis of a WHO-defined neoplasm * No cytopenia at study enrollment * Low-risk CHRS (\9.5 points) Group D: Clonal Cytopenia of Undetermined Significance (CCUS) Group (n=20) * Age ≥60 years * Somatic variant in DNMT3A, TET2, ASXL1, or JAK2 with VAF ≥2% in peripheral blood * No history of stroke or myocardial infarction * No surgery within the previous 3 months * No diagnosis of a WHO-defined neoplasm * Untreated, unexplained cytopenia present for ≥4 months * Hemoglobin \