Evaluation of clonal hematopoiesis and mosaic loss of Y chromosome in cardiovascular risk: An analysis in prospective studies

(a) Targeted sequencing panel used in the laboratory of Hematology of the University Hospital of Bordeaux for the diagnosis and follow-up of myeloid hematological malignancies and used in this study. (b) Characteristics of the identified mutations according to the degree of certainty of their pathogenicity (deleterious, possibly deleterious, or variant of undetermined significance). Exceptions: ASXL1/ASXL2/TET2: only variants resulting in a truncated protein were retained as deleterious variants (A). For TET2, missense mutations were retained only when they affected CD1 or CD2 domain ANKRD26: non-coding region 5’-UTR was retained. TP53: database IARC (https://p53.iarc.fr/) was used for the classification. * Only variants classified as A or B are retained as clonal hematopoiesis of indeterminate potential (CHIP) in the study. (c) Mutational profile of CHIP(+) MI(+) subjects. (d) Mutational profile of CHIP(+) MI(-) subjects. (e) Comparison of characteristics of MI(+) subjects depending on their CHIP and mosaic loss of Y chromosome (mLOY) status. (f) comparison of characteristics of MI(-) subjects depending on their CHIP and mLOY status. For statistical analysis, logistical regression (adjusted on age and sex) and/or Fisher’s test were used to compare qualitative variables, and linear regression (adjusted on age and sex) and/or ANOVA were used to compare quantitative variables. Blood counts were not available for MI(-) subjects. (g) CHIP associated with DNMT3A or TET2 mutations do not present differential effect on inflammation or atherosclerotic burden. Data are expressed as numbers and frequency or median, first, and third quartiles. For quantitative values, comparisons were made by linear regression of log values adjusted for age and sex. For qualitative parameters, comparisons were made by the fisher test. (h) Important clones of CHIP and mLOY are not associated with increased inflammation, atherosclerosis, or CVE. Data are expressed as numbers and frequency or median, first, and third quartiles. For quantitative values, comparisons were made by linear regression of log values adjusted for age and sex. For qualitative parameters, comparisons were made by the Fisher test and logistic regression. For each variable, results are expressed among patients with available values. (i) mLOY do not impact the atherosclerotic burden in the presence of CHIP. Data are expressed as numbers and frequency or median, first and third quartiles. For quantitative values, comparisons were made by linear regression of log values adjusted for age and sex. For qualitative parameters, comparisons were made by the Fisher test. For each variable, results are expressed among patients with available values. (j) Characteristics of MI(-) patients at the time of inclusion depending on whether they presented a myocardial Infarction (MI) during follow-up or not. Data are expressed as numbers and frequency or median, first and third quartiles. For quantitative values, comparisons were made by linear regression of log values adjusted for age and sex. For qualitative parameters, comparisons were made by the Fisher test and logistic regression. For each variable, results are expressed among patients with available values. (k) CHIP may accelerate the incidence MI in the absence of mLOY in male subjects. Data are expressed as numbers and frequency or median, first and third quartiles. For the ‘time to MI’ in MI(-) subjects, comparisons were performed by the Mann-Whitney test for CHIP and mLOY separately and the Kruskall-Wallis test for combinations of CHIP +/- mLOY. For qualitative parameters, comparisons were made by the Fisher test. For each variable, results are expressed among patients with available values.