INTRODUCTION Inflammation plays a pivotal role across all stadia of the cardiovascular disease (CVD) continuum, i.e. non-obstructive coronary artery disease (CAD), myocardial infarction (MI), and ischemic heart failure (iHF). However, inflammation across CVD continuum has not been studied yet within one population. Therefore, we mapped leukocyte profiles across the continuum within the UK Biobank. METHODS The UK Biobank cohort study includes >500,000 participants aged 40 to 70 years who were recruited from 22 assessment centers across the United Kingdom from 2006 to 2010. A total of 333,218 individuals with available laboratory measurements at baseline were included in this study. These consisted of controls and individuals who had progression of CVD during follow-up (i.e. who developed CAD, MI, or iHF during follow-up). We investigated whether leukocytes and subtypes of leukocytes at baseline differed among the CVD continuum. Furthermore, we studied the possible interactions between sex and CVD on leukocytes. RESULTS Of 333,218 individuals, 325,054 (97.5%) individuals were categorized as controls, and 8164 (2.5%) individuals had progression of CVD during follow-up. Of those 8164 individuals, 4552 (1.4%) developed CAD during follow-up, 2839 (0.9%) MI, and 773 (0.2%) in iHF. Compared to controls, mean leukocyte levels at baseline increased across the CVD continuum from 6.8·109 cells/L (SD 1.7·109 cells/L) to 7.7·109 cells/L (SD 1.9·109 cells/L) (Ptrend = 2.19·10-132) in individuals who developed iHF. This increase mainly depended on an increase in neutrophils. Furthermore, controls with leukocyte levels in the highest quartile at baseline had a 1.44 higher chance of being diagnosed with CAD during follow-up compared with individuals with leukocyte levels in lower quartiles (OR 1.44, 95% CI 1.34-1.56 P = 9.63·10-21). A similar increased change was observed for neutrophils, lymphocytes, monocytes, and eosinophils. There was a significant interaction between sex and CVD continuum on lymphocytes (P = 8.49·10-5). CONCLUSION Overall leukocyte count increased across the CVD continuum, which mainly depended on the increase in neutrophil count. High leukocytes in individuals not having CAD at baseline were predictive for the development of CAD during follow-up. Women had a greater increase of lymphocytes across the CVD continuum compared to men. Understanding which cells are key players in which stadium, could serve as a starting point for the identification of new potential therapeutic targets in CVD.

中文翻译：

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整个心血管疾病连续统中的白细胞概况：一项基于人群的队列研究。

引言炎症在心血管疾病（CVD）连续体的所有静止状态（即非阻塞性冠状动脉疾病（CAD），心肌梗塞（MI）和缺血性心力衰竭（iHF））中都起着关键作用。但是，尚未在一个人群中研究整个CVD连续体的炎症。因此，我们绘制了英国生物库内整个连续体的白细胞分布图。方法英国生物库队列研究包括从2006年至2010年从英国22个评估中心招募的500,000名年龄在40至70岁之间的参与者。该研究共纳入333,218名基线时可用的实验室测量值。这些对象包括在随访期间发生CVD进展的对照组和个体（即在随访期间出现CAD，MI或iHF的患者）。我们调查了CVD连续体之间基线时白细胞和白细胞亚型是否不同。此外，我们研究了性别与CVD在白细胞之间的可能相互作用。结果在333,218个人中，有325,054（97.5％）个人被归为对照组，在随访期间有8164（2.5％）个人有CVD进展。在这8164名个体中，有4552名（1.4％）在随访期间发生了CAD，2839名（0.9％）的心梗和773名（0.2％）的iHF患者发生了冠心病。与对照组相比，整个CVD连续性基线的平均白细胞水平从6.8·109细胞/ L（SD 1.7·109细胞/ L）增加到7.7·109细胞/ L（SD 1.9·109细胞/ L）（趋势= 2.19 ·10-132）在发生iHF的个体中。这种增加主要取决于嗜中性粒细胞的增加。此外，基线时四分位数最高的白细胞水平的对照组为1。与较低四分位数的白细胞水平患者相比，在随访期间被诊断为CAD的几率高出44（OR 1.44，95％CI 1.34-1.56 P = 9.63·10-21）。对于嗜中性粒细胞，淋巴细胞，单核细胞和嗜酸性粒细胞，观察到类似的增加变化。淋巴细胞的性别与CVD连续体之间存在显着的相互作用（P = 8.49·10-5）。结论整个CVD连续体中白细胞总数增加，这主要取决于嗜中性粒细胞数的增加。基线时没有CAD的个体中的高白细胞可预测随访期间CAD的发展。与男性相比，女性在整个CVD连续体中的淋巴细胞增加更多。了解哪个单元是哪个体育场的关键参与者，