Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.
Department of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
PLoS Med. 2020 May 7;17(5):e1003115. doi: 10.1371/journal.pmed.1003115. eCollection 2020 May.
Atherosclerotic cardiovascular disease (ASCVD) is driven by multifaceted contributions of the immune system. However, the dysregulation of immune cells that leads to ASCVD is poorly understood. We determined the association of components of innate and adaptive immunity longitudinally with ASCVD, and assessed whether arterial calcifications play a role in this association.
Granulocyte (innate immunity) and lymphocyte (adaptive immunity) counts were determined 3 times (2002-2008, mean age 65.2 years; 2009-2013, mean age 69.0 years; and 2014-2015, mean age 78.5 years) in participants of the population-based Rotterdam Study without ASCVD at baseline. Participants were followed-up for ASCVD or death until 1 January 2015. A random sample of 2,366 underwent computed tomography at baseline to quantify arterial calcification volume in 4 vessel beds. We studied the association between immunity components with risk of ASCVD and assessed whether immunity components were related to arterial calcifications at baseline. Of 7,730 participants (59.4% women), 801 developed ASCVD during a median follow-up of 8.1 years. Having an increased granulocyte count increased ASCVD risk (adjusted hazard ratio for doubled granulocyte count [95% CI] = 1.78 [1.34-2.37], P < 0.001). Higher granulocyte counts were related to larger calcification volumes in all vessels, most prominently in the coronary arteries (mean difference in calcium volume [mm3] per SD increase in granulocyte count [95% CI] = 32.3 [9.9-54.7], P < 0.001). Respectively, the association between granulocyte count and incident coronary heart disease and stroke was partly mediated by coronary artery calcification (overall proportion mediated [95% CI] = 19.0% [-10% to 32.3%], P = 0.08) and intracranial artery calcification (14.9% [-10.9% to 19.1%], P = 0.05). A limitation of our study is that studying the etiology of ASCVD remains difficult within an epidemiological setting due to the limited availability of surrogates for innate and especially adaptive immunity.
In this study, we found that an increased granulocyte count was associated with a higher risk of ASCVD in the general population. Moreover, higher levels of granulocytes were associated with larger volumes of arterial calcification. Arterial calcifications may explain a proportion of the link between granulocytes and ASCVD.
动脉粥样硬化性心血管疾病（ASCVD）是由免疫系统多方面的贡献驱动的。然而，导致 ASCVD 的免疫细胞失调仍知之甚少。我们确定了固有免疫和适应性免疫的成分与 ASCVD 的纵向关联，并评估了动脉钙化是否在这种关联中起作用。
在基线时无 ASCVD 的人群为基础的鹿特丹研究参与者中，3 次（2002-2008 年，平均年龄 65.2 岁；2009-2013 年，平均年龄 69.0 岁；2014-2015 年，平均年龄 78.5 岁）测定粒细胞（固有免疫）和淋巴细胞（适应性免疫）计数。参与者随访 ASCVD 或死亡至 2015 年 1 月 1 日。随机抽取 2366 名参与者在基线时进行计算机断层扫描，以量化 4 个血管床的动脉钙化体积。我们研究了免疫成分与 ASCVD 风险之间的关联，并评估了免疫成分与基线时的动脉钙化是否有关。在 7730 名参与者（59.4%为女性）中，801 名在中位随访 8.1 年内发生 ASCVD。粒细胞计数增加与 ASCVD 风险增加相关（双倍粒细胞计数[95%CI]的调整后的危险比[1.78（1.34-2.37）]，P<0.001）。在所有血管中，较高的粒细胞计数与较大的钙化体积相关，在冠状动脉中最为明显（每增加一个标准偏差的粒细胞计数[95%CI]的钙体积差异[mm3]=32.3[9.9-54.7]，P<0.001）。分别地，粒细胞计数与冠心病和中风的发生之间的关联部分通过冠状动脉钙化（总体介导比例[95%CI]=19.0%[-10%至 32.3%]，P=0.08）和颅内动脉钙化（14.9%[-10.9%至 19.1%]，P=0.05）介导。本研究的一个局限性是，由于先天和特别是适应性免疫的替代物的有限可用性，在流行病学环境中研究 ASCVD 的病因仍然很困难。
在这项研究中，我们发现粒细胞计数增加与普通人群中 ASCVD 的风险增加相关。此外，较高的粒细胞水平与较大的动脉钙化体积有关。动脉钙化可能解释了粒细胞与 ASCVD 之间联系的一部分。
