Fig. 2: Longitudinal assessment of the effects of CH on de novo femoral atherosclerosis development.

We investigated the association between CH at baseline and de novo development of femoral atherosclerosis ∼3 years and ∼6 years after enrollment among PESA participants who initially lacked detectable atherosclerosis in this region. 3DVUS imaging was used to determine the presence of femoral atherosclerosis. a, Summary of study design. b, Representative images from femoral atherosclerosis burden, assessed by 3DVUS, in an individual exhibiting de novo femoral atherosclerosis development (that is, absence of detectable atherosclerosis at the baseline evaluation (left) and plaque development at follow-up (right); scale bar, 5 mm). c,d, Incidence of de novo femoral atherosclerosis development at the 3-year follow-up (c, n = 2,347) or the 6-year follow-up (d, n = 2,214) in individuals free of CH (no CH) and in individuals exhibiting CH with VAF 0.2–2% or ≥2%. Incidence of de novo femoral atherosclerosis is also shown for myeloid CH (CHIP) or CH driven by specific CHIP genes. Statistical significance in the analyses of CH and CHIP was evaluated using univariate logistic regression models (P for trends are shown). In gene-specific analyses, statistical significance was examined through proportion tests relative to the non-CHIP carriers group (*P < 0.05, **P ≤ 0.01, ***P ≤ 0.001). e,f, The association between CH or CHIP and de novo femoral atherosclerosis development at the 3-year follow-up (e, n = 2,347) and 6-year follow-up (f, n = 2,214) based on multivariate logistic regression analyses. Statistical models were adjusted for age, sex, smoking, lipid-lowering treatment and the AUC of SBP, fasting glucose, LDL-C, BMI, CACS and global atherosclerotic plaque volume assessed by 3DVUS imaging; the bars indicate 95% confidence intervals centered in the mean value (square).