Associations of circulating T-cell subsets with carotid artery stiffness: the multiethnic study of atherosclerosis

Abstract

Arterial stiffness measured by total pulse wave velocity (T-PWV) is associated with an increased risk of multiple age-related diseases. T-PWV can be described by structural (S-PWV) and load-dependent (LD-PWV) arterial stiffening. T-cells have been implicated in arterial remodeling, arterial stiffness, and hypertension in humans and animals; however, it is unknown whether T-cells are risk factors for T-PWV or its components. Therefore, we evaluated the cross-sectional associations of peripheral T-cell subpopulations with T-PWV, S-PWV, and LD-PWV. Peripheral blood T-cells were characterized using flow cytometry, and carotid artery stiffness was measured using B-mode ultrasound to calculate T-PWV at the baseline examination in a participant subset of the Multi-Ethnic Study of Atherosclerosis (MESA, n = 1,984). A participant-specific exponential model was used to calculate S-PWV and LD-PWV based on elastic modulus and blood pressure gradients. The associations between five primary (P-significance < 0.01) and 25 exploratory (P-significance < 0.05) immune cell subpopulations, per 1-SD increment, and arterial stiffness measures were assessed using adjusted linear regression models. For the primary analysis, higher CD4⁺CD28^-CD57⁺, but not CD8⁺CD28^-CD57⁺, T-cells were associated with higher LD-PWV (β = 0.04 m/s, P < 0.01) after adjusting for covariates. None of the remaining T-cell subpopulations in the primary analysis were associated with T-PWV or S-PWV. For the exploratory analysis, several memory and differentiated/senescence-associated CD4⁺ and CD8⁺ T-cell subpopulations were associated with greater T-PWV, S-PWV, and LD-PWV after adjusting for covariates. In conclusion, we highlight novel associations in humans between CD4⁺ and CD8⁺ memory and differentiated/senescence-associated T-cell subpopulations and measures of arterial stiffness in MESA. These results warrant longitudinal, prospective studies that examine changes in T-cell subpopulations and arterial stiffness in humans.NEW & NOTEWORTHY We investigated associations between T-cells and novel measures of structural and load-dependent arterial stiffness in a large multiethnic cohort. The primary analysis revealed that pro-inflammatory, senescence-associated CD4⁺CD28^-CD57⁺ T-cells were associated with higher load-dependent arterial stiffness. An exploratory analysis revealed that multiple pro-inflammatory CD4⁺ and CD8⁺ T-cell subpopulations were associated with both higher structural and load-dependent arterial stiffness. These results suggest that pro-inflammatory T-cells may contribute to arterial stiffness through both arterial remodeling and elevated blood pressure.

Keywords: T-cells; aging; arterial stiffness; epidemiology; risk factors.