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The vicious cycle of clonal haematopoiesis and CVD - Driver mutations in middle aged patients and their role as independent risk factor

2023; Elsevier BV; Volume: 379; Linguagem: Inglês

10.1016/j.atherosclerosis.2023.06.792

1879-1484

Carolin A. Ehlert, Tsai-Sang Dederichs, Heiko Becker, Christoph Bode, Dennis Wolf, Klaus Kaier, Dirk Westermann, Ingo Hilgendorf,

Hemoglobinopathies and Related Disorders

Background and Aims: CHIP is a mutation-driven clonal hematopoiesis in the absence of overt hematologic disease. In the general population CHIP-carriers are twice as likely to suffer from CHD as non-carriers (Jaiswal et al.). However prevalence of CHIP and its association with risk factors and extent CAD in patients undergoing coronary-angiography are unknown. Aim: To determine whether CHIP mutations are associated with the extend of CAD independent of comorbidities and to investigate possible associations. Methods: 178 out of 815 screened patients undergoing coronary angiography proved eligible. CHIP-status was determined by whole-blood genome sequencing and correlated with the patients’ medical-history, laboratory and coronary-angiography-findings. Results: 30% of patients carried CHIP mutations, 75% in the DNMT3A and/or TET2-gen. The median age was 69 years, with mutation-carriers being significantly older then non-carriers (72.5 versus 67.1 years, p=0.001). CHIP-carriers showed elevated RDW levels in blood (CHIP positive: 13.3 +/- 0.14, CHIP negative: 13.0 +/- 0.08, p=0.030) with no other laboratory-findings being significantly associated. Among DNMT3A and TET2 mutation carriers, those below median age showed elevated Gensini scores (CHIP positive: 40.1 +/- 10.8, CHIP negative: 16.3 +/- 2.4, p=0.044). In a multivariate-approach, this finding proved to be independent of common cardiovascular risk factors. Conclusions: Prevalence of CHIP is three times higher in our preselected patient-population compared to the general-population. DNMT3A/TET2-mutations associate with severe CAD particularly in younger patients in which genetic traits are highly-relevant. Given the widely described link between inflammation and CHD as well as hematopoiesis, we recognize this process as a vicious-cycle and will conduct further research in this field.