Prevention & lipidsCohort study

Genetic Interleukin 6 Signaling Deficiency Attenuates Cardiovascular Risk in Clonal Hematopoiesis

CirculationPublished

  • Genetic association cohort study
  • UK Biobank
  • exome sequencing

Authors' conclusion

CHIP is associated with increased risk of incident CVD. Among carriers of large CHIP clones, genetically reduced IL-6 signaling abrogated this risk.

Study context

Population
UK Biobank individuals without prevalent cardiovascular disease (CVD)
Participants
35,416 individuals
Exposure
Clonal hematopoiesis of indeterminate potential (CHIP) vs no CHIP; modification by IL6R p.Asp358Ala
  • CHIPn = 1,079
  • Large CHIP clonesn = 432
Outcome
Incident CVD events:
  • MI
  • Coronary revascularization
  • Stroke
  • Death
Follow-up
6.9-year median

Main finding

As reported in the abstract

Incident CVD events
Each group vs no CHIPHazard ratio (95% CI)P value
CHIP
1.27(1.04–1.56)
P = 0.019
Large CHIP clones
1.59(1.21–2.09)
P < 0.001
IL6R p.Asp358Alaamong large CHIP clones
0.46(0.29–0.73)
P < 0.001
IL6R p.Asp358Alawithout CHIP
0.95(0.89–1.01)
P = 0.08

Observational data: associations, not effects.

Further findings

MI by CHIP status, modified by IL6R p.Asp358Ala (independent sample, n=9951)

Association of CHIP with MI similarly varied by IL6R p.Asp358Ala
P for interaction = 0.036

Original publication

Genetic Interleukin 6 Signaling Deficiency Attenuates Cardiovascular Risk in Clonal Hematopoiesis. Circulation. Published 11 November 2019. doi:10.1161/circulationaha.119.044362

Summarised from the published abstract; every number is checked against it