Table 1.
Summary of studies showing associations between clonal hematopoiesis and cardiovascular disease
| Source | Population | Seq method | Findings |
|---|---|---|---|
| Jaiswal et al 2017 | 4,726 CHD patients 3,529 controls | Whole exome sequence | CHIP was associated with a greater risk of CHD (HR 2.0) and early-onset MI (HR 4.0). |
| Bick et al, 2020 | 35,416 individuals without prevalent CVD | Whole exome sequence | CHIP (DNMT3A, TET2) was associated with increased risk of incident CVD. Genetically reduced IL-6 signaling was associated with an attenuated CVD risk in CHIP. |
| Nachun et al, 2021 | 5,522 individuals | Whole genome sequence DNA methylation array |
CHIP and age acceleration were associated with increased risk of all-cause mortality (HR 2.9) and CHD (HR 3.2). |
| Saiki et al, 2021 | 11,234 individuals | Targeted sequence of 23 CH genes Array-based CNAs detection |
Co-occurrence of SNVs/indels and CNAs (DNMT3A, TET2, JAK2, and TP53) was associated with higher CVD mortality. |
| Yu et al, 2021 | 56,597 individuals without HF and hematological malignancy | Whole exome sequence Whole genome sequence |
Mutations in TET2, ASXL1, and JAK2 were prospectively associated with a 25% increased risk of HF. |
| Bhattacharya et al, 2021 | 7426 incident stroke cases 78752 controls | Whole exome sequence Whole genome sequence |
CHIP was associated with an increased risk of total stroke (HR 1.14). |
| Dorsheimer et al, 2019 | 200 patients undergoing autologous BMT for AMI | Error-corrected targeted exome sequencing | CH (DNMT3A, TET2) was associated with significantly worse long-term clinical outcomes, including mortality and mortality combined with re-hospitalization for HF. |
| Assmus et al, 2021 | 419 patients with chronic HF | Error-corrected targeted exome sequencing | CH (DNMT3A and TET2) was an independent predictor of mortality in HF patients Optimized VAF for TET2 and DNMT3A were 0.73% and 1.13%, respectively. |
| Cremer et al, 2020 | 419 patients with chronic HF | Error-corrected targeted exome sequencing | CH (DNMT3A, TET2, PHF6, SMC1A, PPM1D, EZH2, CEBPA, SRSF2, SETBP) was an independent predictor of mortality in patients with chronic HF. |
| Pascual-Figal et al, 2021 | 62 patients with HF (EF < 45%) | Error collected targeted-exome sequencing for 54 genes | CHIP in either DNMT3A or TET2 exhibited accelerated HF progression irrespective of ischemic/nonischemic etiology. |
CHD: coronary heart disease, MI: myocardial infarction, CVD: cardiovascular disease, CNAs: copy number alterations, BMT: bone marrow transplantation