OBJECTIVE CD4+CD28null T cells have been shown to be associated with recurrent coronary events and suggested as potential biomarker and therapeutic target. It is unknown whether CD4+CD28null T cells associate with first-time cardiovascular events. We examined CD4+CD28null T cells in a prospective population-based cohort and in patients with advanced atherosclerosis. Approach and Results: CD4+CD28null T cells were quantified in 272 individuals experiencing a first-time coronary event during up to 17 years of follow-up and 272 age- and sex-matched controls in a case-control study, nested within the population-based Malmö Diet and Cancer study. The highest tertile of CD4+CD28null T cells was associated with a lower incidence of first-time coronary events compared with the lowest tertile (odds ratio, 0.48 [95% CI, 0.29-0.79], P=0.004) when adjusting for Framingham risk factors. This association remained significant for events recorded after >9 years of follow-up, when most coronary events occurred, but not during the first 9 years of follow-up, despite similar odds ratio. Additionally, we analyzed CD4+CD28null T cells in 201 patients with advanced atherosclerosis undergoing carotid endarterectomy. The adjusted hazard ratio for cardiovascular events in patients with advanced atherosclerosis was 2.11 (95% CI, 1.10-4.05, P=0.024), comparing the highest with the lowest CD4+CD28null T-cell tertile. CONCLUSIONS Our findings reveal complex associations between CD4+CD28null T cells and cardiovascular disease. Although we confirm the reported positive associations with an adverse prognosis in patients with already established disease, the opposite associations with first-time coronary events in the population-based cohort may limit the clinical use of CD4+CD28null T cells.

中文翻译：

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基线水平低的CD4 + CD28null T细胞与基于人群的前瞻性病例对照队列中的首次冠状动脉事件相关。

目的CD4 + CD28null T细胞已被证明与复发性冠状动脉事件相关，并被建议作为潜在的生物标志物和治疗靶标。尚不清楚CD4 + CD28null T细胞是否与首次心血管事件相关。我们在前瞻性人群研究和晚期动脉粥样硬化患者中检查了CD4 + CD28null T细胞。方法和结果：在病例对照研究中，对多达17年的随访中272名经历首次冠状动脉事件的个体和272名年龄和性别匹配的对照进行了定量的CD4 + CD28null T细胞嵌套在人群中基于马尔默的饮食与癌症研究。与最低的三分位数相比，CD4 + CD28null T细胞的最高三分位数与首次冠状动脉事件的发生率较低相关（比值比为0.48 [95％CI，0.29-0.79]，P = 0。004）在调整Framingham危险因素时。尽管随访的比值比相似，但对于≥9年的随访记录的事件（大多数冠心病发生），但在随访的前9年没有记录，这种关联仍然很显着。此外，我们分析了201例接受颈动脉内膜切除术的晚期动脉粥样硬化患者的CD4 + CD28null T细胞。晚期动脉粥样硬化患者心血管事件的调整后风险比为2.11（95％CI，1.10-4.05，P = 0.024），最高和最低的CD4 + CD28null T细胞三分位数相比较。结论我们的发现揭示了CD4 + CD28null T细胞与心血管疾病之间的复杂联系。尽管我们确认已报告的疾病与已确诊患者的不良预后呈正相关，