Characteristics and impact of CHIP among individuals with established cardiovascular disease
| Cohort name . | Recruitment period . | Geographical region . | No. of participants . | Age, y . | Female, % . | Prevalence of CHIP . | Most common CHIP loci (% distribution) . | Follow-up duration . | Impact of CHIP (VAF of ≥2%, unless otherwise specified)∗ . | ||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Recurrent events . | All-cause mortality . | Other . | |||||||||
| ASCVD | |||||||||||
| UK Biobank42 | 2006-2010 | United Kingdom | 13 129 | 63 (median) | 24.4 | 665 (5.1%) | DNMT3A: 50.6 ASXL1: 21.2 TET2: 13.8 PPM1D: 6.1 SF3B1: 4.5 | 10.8 y | Recurrent ASCVD: HR, 1.3; 95% CI, 1.2-1.5 VAF ≥10%: HR, 1.5; 95% CI, 1.3-1.7 | HR, 1.5; 95% CI, 1.3-1.8 VAF ≥10%: HR, 1.7; 95% CI, 1.4-2.0 | NR |
| Acute coronary syndrome | |||||||||||
| CULPRIT-SHOCK46 | April 2013-April 2017 | Global | 446 | 69 (median) | 24.4 | 129 (28.9%) | DNMT3A: 47 TET2: 36 ASXL1: 13 JAK2: 2% | 1 y | Recurrent myocardial infarction: 1.6% vs 1.3%; P > .99 (unadjusted) Repeat revascularization: 10.9% vs 14.8%; P = .27 (unadjusted) | OR at 30 d: 1.67; 95% CI, 1.0-2.9; P = .07† OR at 1 y: 1.52; 95% CI, 0.87-2.63 | NR |
| Wang et al46 | January 2017-September 2019 | China | 485 | 61.8 y (mean) | 27.4 | 60 (12.4%) | DNMT3A: 42.1 TET2: 27.5 ASXL1: 12.7 SF3B1: 4.9 PPM1D: 2.9 | 3.0 y | Recurrent nonfatal MI or stroke: HR, 2.6; 95% CI, 1.3-5.1 | HR, 2.0; 95% CI, 1.1-3.5 | NR |
| AIS | |||||||||||
| PROSCIS-B and BeLOVE44 | March 2010-May 2013 | Berlin, Germany | 581 | 68 (median) | 55.1 | 236 (40.6%) with VAF ≥ 1% | DNMT3A: 50.4 TET2: 30.9 ASXL1: 10.6 PPM1D: 4.7 | 36.2 mo | No difference in time to recurrent vascular event between VAF of ≥10% vs <1% (P = .55) | Shorter survival time among VAF of ≥10% vs <1% (P = .0021) | NR |
| Lee et al47 | May 2016-January 2021 | South Korea | 380 | 67.2 (mean) | 41.3 | 110 (29.0%) with VAF ≥ 1.5% | DNMT3A: 57.1 TET2: 19.4 PPM1D: 3.1 | 90 d | NR | NR | Mean NIHSS at presentation: 8.1 vs 5.6 (adjusted β coefficient 1.67; P = .022) Hemorrhagic transformation: aOR, 5.6; 95% CI, 3.2-9.8 Modified Rankin score at 90 d: 2.5 vs 1.4; P < .001 |
| VTE | |||||||||||
| EDITH48 | May 2000-December 2004 | France | 394 first-episode unprovoked proximal DVT and PE | 67.4 (mean) | 58.5 | 4 (1.0%) with JAK2 V617F ≥1% and no MPN | JAK2 V617F: 100. Allele burden ≥10%: 50% | Up to 40 mo | No recurrent events | 2 (50%) | 1 (25%) episode of fatal anticoagulant-associated intracranial hemorrhage |
| Haque et al49 | 2017-2020 | Ohio, United States | 167 patients (81% unprovoked; 14% cancer associated) | 60.3 (median) | 55.5 | 22 (13.2%) | DNMT3A: 46 TET2: 13 PPM1D: 10 | 400 d | No difference (rates NR) | NR | Clinically relevant bleeds: 23% vs 10%; P = .14 |
| Cohort name . | Recruitment period . | Geographical region . | No. of participants . | Age, y . | Female, % . | Prevalence of CHIP . | Most common CHIP loci (% distribution) . | Follow-up duration . | Impact of CHIP (VAF of ≥2%, unless otherwise specified)∗ . | ||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Recurrent events . | All-cause mortality . | Other . | |||||||||
| ASCVD | |||||||||||
| UK Biobank42 | 2006-2010 | United Kingdom | 13 129 | 63 (median) | 24.4 | 665 (5.1%) | DNMT3A: 50.6 ASXL1: 21.2 TET2: 13.8 PPM1D: 6.1 SF3B1: 4.5 | 10.8 y | Recurrent ASCVD: HR, 1.3; 95% CI, 1.2-1.5 VAF ≥10%: HR, 1.5; 95% CI, 1.3-1.7 | HR, 1.5; 95% CI, 1.3-1.8 VAF ≥10%: HR, 1.7; 95% CI, 1.4-2.0 | NR |
| Acute coronary syndrome | |||||||||||
| CULPRIT-SHOCK46 | April 2013-April 2017 | Global | 446 | 69 (median) | 24.4 | 129 (28.9%) | DNMT3A: 47 TET2: 36 ASXL1: 13 JAK2: 2% | 1 y | Recurrent myocardial infarction: 1.6% vs 1.3%; P > .99 (unadjusted) Repeat revascularization: 10.9% vs 14.8%; P = .27 (unadjusted) | OR at 30 d: 1.67; 95% CI, 1.0-2.9; P = .07† OR at 1 y: 1.52; 95% CI, 0.87-2.63 | NR |
| Wang et al46 | January 2017-September 2019 | China | 485 | 61.8 y (mean) | 27.4 | 60 (12.4%) | DNMT3A: 42.1 TET2: 27.5 ASXL1: 12.7 SF3B1: 4.9 PPM1D: 2.9 | 3.0 y | Recurrent nonfatal MI or stroke: HR, 2.6; 95% CI, 1.3-5.1 | HR, 2.0; 95% CI, 1.1-3.5 | NR |
| AIS | |||||||||||
| PROSCIS-B and BeLOVE44 | March 2010-May 2013 | Berlin, Germany | 581 | 68 (median) | 55.1 | 236 (40.6%) with VAF ≥ 1% | DNMT3A: 50.4 TET2: 30.9 ASXL1: 10.6 PPM1D: 4.7 | 36.2 mo | No difference in time to recurrent vascular event between VAF of ≥10% vs <1% (P = .55) | Shorter survival time among VAF of ≥10% vs <1% (P = .0021) | NR |
| Lee et al47 | May 2016-January 2021 | South Korea | 380 | 67.2 (mean) | 41.3 | 110 (29.0%) with VAF ≥ 1.5% | DNMT3A: 57.1 TET2: 19.4 PPM1D: 3.1 | 90 d | NR | NR | Mean NIHSS at presentation: 8.1 vs 5.6 (adjusted β coefficient 1.67; P = .022) Hemorrhagic transformation: aOR, 5.6; 95% CI, 3.2-9.8 Modified Rankin score at 90 d: 2.5 vs 1.4; P < .001 |
| VTE | |||||||||||
| EDITH48 | May 2000-December 2004 | France | 394 first-episode unprovoked proximal DVT and PE | 67.4 (mean) | 58.5 | 4 (1.0%) with JAK2 V617F ≥1% and no MPN | JAK2 V617F: 100. Allele burden ≥10%: 50% | Up to 40 mo | No recurrent events | 2 (50%) | 1 (25%) episode of fatal anticoagulant-associated intracranial hemorrhage |
| Haque et al49 | 2017-2020 | Ohio, United States | 167 patients (81% unprovoked; 14% cancer associated) | 60.3 (median) | 55.5 | 22 (13.2%) | DNMT3A: 46 TET2: 13 PPM1D: 10 | 400 d | No difference (rates NR) | NR | Clinically relevant bleeds: 23% vs 10%; P = .14 |
DVT, deep vein thrombosis; MI, myocardial infarction; MPN, myeloproliferative neoplasm; NIHSS, National Institutes of Health stroke scale; NR, not reported.
Unless specified, comparative statistics reported are adjusted for baseline covariates.
Both 95% CIs and P values are reported in situations in which upper or lower bound of CI involves 1.0.