Atherosclerosis forms the pathological basis for the development of cardiovascular disease. Since pathological processes initially develop without clinically relevant symptoms, the identification of early markers in the subclinical stage plays an important role for initiating early interventions. There is evidence that regulatory T cells (Tregs) are involved in the development of atherosclerosis. Therefore, the present study aimed to identify and investigate associations with Tregs and their subsets in a cohort of healthy elderly individuals with and without subclinical atherosclerotic plaques (SAP). In addition, various lifestyle and risk factors, such as cardiorespiratory fitness, were investigated as associated signatures. A cross-sectional study was performed in 79 participants (male: = 50; age = 63.6 ± 3.7 years; body mass index = 24.9 ± 3.1 kg/m²; mean ± SD) who had no previous diagnosis of chronic disease and were not taking medication. Ultrasound of the carotids to identify SAP, cardiovascular function measurement for vascular assessment and a cardiorespiratory fitness test to determine peak oxygen uptake were performed. Additionally, tests were conducted to assess blood lipids and determine glucose levels. Immunophenotyping of Tregs and their subtypes (resting (rTregs) and effector/memory (mTregs)) was performed by 8-chanel flow cytometry. Participants were categorized according to atherosclerotic plaque status. Linear and logistic regression models were used to analyze associations between parameters. SAP was detected in a total of 29 participants. The participants with plaque were older (64.8 ± 3.6 years 62.9 ± 3.5 years) and had higher peripheral systolic blood pressure (133.8 ± 14.7 mmHg . 125.8 ± 10.9 mmHg). The participants with SAP were characterized by a lower percentage of rTregs (28.8% ± 10.7% . 34.6% ± 10.7%) and a higher percentage of mTregs (40.3% ± 14.7% . 30.0% ± 11.9%). Multiple logistic regression identified age (odds ratio (OR) = 1.20 (95% confidence interval (95%CI): 1.01–1.42)) and mTregs (OR = 1.05 (95%CI: 1.02–1.10)) as independent risk factors for SAP. Stepwise linear regression could reveal an association of peak oxygen uptake ( = 0.441), low-density lipoprotein (LDL) ( = –0.096), and SAP ( = 6.733) with mTregs and LDL ( = 0.104) with rTregs. While at an early stage of SAP, the total proportion of Tregs gives no indication of vascular changes, this is indicated by a shift in the Treg subgroups. Factors such as serum LDL or cardiopulmonary fitness may be associated with this shift and may also be additional diagnostic indicators. This could be used to initiate lifestyle-based preventive measures at an early stage, which may have a protective effect against disease progression.

中文翻译：

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调节性 T 细胞亚群与亚临床动脉粥样硬化斑块、低密度脂蛋白水平和老年人心肺健康相关

动脉粥样硬化是心血管疾病发生的病理基础。由于病理过程最初发展时没有临床相关症状，因此亚临床阶段早期标志物的识别对于启动早期干预措施起着重要作用。有证据表明调节性 T 细胞 (Treg) 参与动脉粥样硬化的发展。因此，本研究旨在识别和研究一组患有或不患有亚临床动脉粥样硬化斑块 (SAP) 的健康老年人中与 Tregs 及其亚群的关联。此外，各种生活方式和风险因素（例如心肺健康）也作为相关特征进行了研究。对 79 名参与者（男性：= 50；年龄 = 63.6 ± 3.7 岁；体重指数 = 24.9 ± 3.1 kg/m²；平均值 ± SD）进行了一项横断面研究，这些参与者之前没有慢性病诊断，并且没有服用药物。进行颈动脉超声检查以识别 SAP，进行心血管功能测量以进行血管评估，并进行心肺健康测试以确定峰值摄氧量。此外，还进行了测试来评估血脂并确定血糖水平。通过 8 通道流式细胞术对 Tregs 及其亚型（静息 (rTregs) 和效应/记忆 (mTregs)）进行免疫表型分析。根据动脉粥样硬化斑块状态对参与者进行分类。使用线性和逻辑回归模型来分析参数之间的关联。共有 29 名参与者检测到 SAP。有斑块的参与者年龄较大（64.8 ± 3.6 岁 62.9 ± 3.5 岁），外周收缩压较高（133.8 ± 14.7 mmHg . 125.8 ± 10.9 mmHg）。 SAP 参与者的特征是 rTreg 百分比较低 (28.8% ± 10.7% . 34.6% ± 10.7%) 和 mTreg 百分比较高 (40.3% ± 14.7% . 30.0% ± 11.9%)。多元逻辑回归将年龄（优势比 (OR) = 1.20（95% 置信区间 (95%CI)：1.01–1.42））和 mTregs（OR = 1.05（95%CI：1.02–1.10））确定为独立危险因素树液。逐步线性回归可以揭示峰值摄氧量 (= 0.441)、低密度脂蛋白 (LDL) (= –0.096) 和 SAP (= 6.733) 与 mTreg 的关联，以及 LDL (= 0.104) 与 rTreg 的关联。虽然在 SAP 的早期阶段，Treg 的总比例没有显示出血管变化的迹象，但 Treg 亚群的变化表明了这一点。血清低密度脂蛋白或心肺健康等因素可能与这种转变有关，也可能是额外的诊断指标。这可用于在早期阶段启动基于生活方式的预防措施，这可能对疾病进展具有保护作用。