DeConne Theodore M, Buzkova Petra, Pewowaruk Ryan, Delaney Joseph A, Psaty Bruce M, Tracy Russell P, Doyle Margaret F, Sitlani Colleen M, Landay Alan L, Huber Sally A, Hughes Timothy M, Bertoni Alain G, Gepner Adam D, Olson Nels C, Ding Jingzhong
Gerontology and Geriatric Medicine, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC.
Department of Biostatistics, University of Washington, Seattle, WA, USA.
medRxiv. 2024 Jul 31:2024.07.29.24311196. doi: 10.1101/2024.07.29.24311196.
Arterial stiffness measured by total pulse wave velocity (T-PWV) is associated with 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 associated with arterial remodeling, blood pressure, and arterial stiffness in humans and animals; however, it is unknown whether T-cells are related to S-PWV or LD-PWV. Therefore, we evaluated the cross-sectional associations of peripheral T-cell subpopulations with T-PWV, S-PWV, and LD-PWV stiffness.
Peripheral blood T-cells were characterized using flow cytometry and the carotid artery was measured using B-mode ultrasound to calculate T-PWV at the baseline examination in a 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 twenty-five exploratory (p-significance<0.05) immune cell subpopulations, per 1-SD increment, and arterial stiffness measures were assessed using adjusted, linear regressions.
For the primary analysis, higher CD4CD28CD57 T-cells were associated with higher LD-PWV (β=0.04 m/s, p<0.01) after adjusting for co-variates. For the exploratory analysis, T-cell subpopulations that commonly shift with aging towards memory and differentiated/immunosenescent phenotypes were associated with greater T-PWV, S-PWV, and LD-PWV after adjusting for co-variates.
In this cross-sectional study, several T-cell subpopulations commonly associated with aging were related with measures of arterial stiffness. Longitudinal studies that examine changes in T-cell subpopulations and measures of arterial stiffness are warranted.
通过总脉搏波速度(T-PWV)测量的动脉僵硬度与多种年龄相关疾病风险增加相关。T-PWV可由结构性(S-PWV)和负荷依赖性(LD-PWV)动脉僵硬度来描述。在人类和动物中,T细胞与动脉重塑、血压及动脉僵硬度相关;然而,T细胞是否与S-PWV或LD-PWV有关尚不清楚。因此,我们评估了外周血T细胞亚群与T-PWV、S-PWV和LD-PWV僵硬度之间的横断面关联。
在动脉粥样硬化多族裔研究(MESA,n = 1984)的一个子集中,于基线检查时使用流式细胞术对外周血T细胞进行特征分析,并使用B型超声测量颈动脉以计算T-PWV。基于弹性模量和血压梯度,使用参与者特异性指数模型计算S-PWV和LD-PWV。使用校正后的线性回归评估每增加1个标准差的5个主要(p值<0.01)和25个探索性(p值<0.05)免疫细胞亚群与动脉僵硬度测量值之间的关联。
在进行协变量校正后,对于主要分析,较高的CD4CD28CD57 T细胞与较高的LD-PWV相关(β = 0.04 m/s,p < 0.01)。对于探索性分析,在进行协变量校正后,通常随衰老向记忆及分化/免疫衰老表型转变的T细胞亚群与更高的T-PWV、S-PWV和LD-PWV相关。
在这项横断面研究中,几个通常与衰老相关的T细胞亚群与动脉僵硬度测量值有关。有必要开展纵向研究以检查T细胞亚群的变化及动脉僵硬度测量值。