Aging-related immune phenotypes are associated with subclinical coronary atherosclerosis in a middle-aged population: a subcohort of the Swedish CArdioPulmonary bioImage Study

Abstract Aging-related immune perturbations, including lower proportions of regulatory T (T reg ) cells, shifts in naïve/memory T cells, and elevated monocyte and neutrophil counts, are well documented in patients with manifest coronary artery disease (CAD). In a cross-sectional study, we investigated whether these changes are present in subclinical coronary atherosclerosis. A total of 1078 participants aged 50–64 (49% female) were consecutively recruited from the Swedish CArdioPulmonary bioImage Study (SCAPIS) cohort at Linköping University Hospital. Immune composition (25 subsets) was analyzed in fresh whole blood using flow cytometry. Atherosclerotic burden was assessed by coronary computed tomography angiography (CCTA) and coronary artery calcification (CAC) scoring. Subjects with a prior history of CAD ( n = 11), active inflammation ( n = 20), poor CCTA data ( n = 19), missing CCTA data ( n = 5), CT not performed ( n = 5) or CCTA not performed ( n = 51) were excluded. Individuals with CCTA-detected coronary atherosclerosis ( n = 327) showed higher levels of monocytes and central memory (CM) CD4 + T cells, and lower levels of naïve T reg and naïve CD8 + T cells, compared to those without atherosclerosis ( n = 640). Moreover, those with significant stenosis (≥50%, n = 40) had lower levels of naïve CD4 + T and CD56 bright NK cells. After adjustment for age and sex, increases in CM CD4 + T cells and reductions in effector memory (EM) CD4 + T, naïve T reg , and CD56 bright NK cells remained associated with ≥50% stenosis. After exploratory adjustment for other covariates and type 1 errors, changes in the proportions of CM and EM CD4 + T cells and naïve T reg cells continued to show significant associations with subclinical atherosclerosis when subjects with ≥50% stenosis and those without were compared. No associations were observed between any immune cell subsets and CAC scores. To conclude, immune perturbations, mainly related to an imbalance in naïve/memory CD4 + T cells and a reduction of naïve T reg cells, are present already during the asymptomatic stage of CAD. The findings highlight the potential role of aging-related T cell phenotypes in the pathogenesis of atherosclerosis.