Vth Department of Medicine (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
European Center for Angioscience ECAS, Medical Faculty Mannheim of the University Heidelberg, Mannheim, Germany.
Nicotine Tob Res. 2021 Jun 8;23(7):1191-1198. doi: 10.1093/ntr/ntab011.
Elevated leukocyte counts are associated with cardiovascular disease. Smoking induces inflammation and alters levels of leukocyte subtypes.
Our aim was to investigate the effect of smoking on circulating immune cells and their association with mortality. Lymphocyte subtypes were identified by flow cytometry of fluorescent-labeled cells. We analyzed the association of leukocytes with mortality using Cox regression and assessed their effect on risk prediction based on principle components (PCs) using area under the receiver operating characteristic curve and net-reclassification in 2173 participants from the Ludwigshafen Risk and Cardiovascular Health Study, a prospective case-control study in patients who underwent coronary angiography.
The numbers of T cells, monocytes, and neutrophils were higher and natural killer cells were lower in smokers compared with never-smokers. In never-smokers, lymphocyte counts were inversely associated with mortality while a positive association was observed for neutrophils. The neutrophil-to-lymphocyte ratio (NLR) had the strongest association in never-smokers with a hazard ratio (95% confidence interval) of 1.43 (1.26-1.61). No associations were found in smokers. Adding the first five PCs or the NLR to a risk prediction model based on conventional risk factors did not improve risk prediction in smokers, but significantly increased the area under the curve from 0.777 to 0.801 and 0.791, respectively, in never-smokers.
Lymphocyte counts were inversely associated with mortality in never-smokers but not in active smokers. Markers of innate immunity, namely total neutrophils and CD11b+/CD18+ and CD31+/CD40- granulocytes, were directly associated with mortality. Adding markers of immune function like PCs or the NLR to basic risk models improved risk prediction in never-smokers only.
Total leukocyte counts were higher in active smokers as compared to never-smokers due to elevated counts of neutrophils and monocytes but declined in ex-smokers with increasing time since quitting. In the never-smokers but not in smokers, lymphocyte counts were inversely associated with mortality while there was a direct association with neutrophils, even after adjustment for conventional cardiovascular risk factors. Adding markers of immune function to basic risk models improved risk prediction in never-smokers only. Our data indicate that smoking status has an important impact on the ability of leukocyte counts to predict long-term cardiovascular outcomes.
白细胞计数升高与心血管疾病有关。吸烟会引起炎症，并改变白细胞亚型的水平。
我们的目的是研究吸烟对循环免疫细胞的影响及其与死亡率的关系。通过荧光标记细胞的流式细胞术鉴定淋巴细胞亚型。我们使用 Cox 回归分析白细胞与死亡率的关系，并根据原理成分（PC）评估它们对 2173 名接受冠状动脉造影的患者前瞻性病例对照研究 Ludwigshafen 风险和心血管健康研究中患者的风险预测的影响。
与从不吸烟者相比，吸烟者的 T 细胞、单核细胞和中性粒细胞数量较高，自然杀伤细胞数量较低。在从不吸烟者中，淋巴细胞计数与死亡率呈负相关，而中性粒细胞则呈正相关。中性粒细胞与淋巴细胞比值（NLR）在从不吸烟者中与危险比（95%置信区间）的相关性最强，为 1.43（1.26-1.61）。在吸烟者中未发现相关性。在基于传统危险因素的风险预测模型中添加前五个 PC 或 NLR 并不能提高吸烟者的风险预测，但在从不吸烟者中，曲线下面积分别从 0.777 增加到 0.801 和 0.791。
在从不吸烟者中，淋巴细胞计数与死亡率呈负相关，但在活跃吸烟者中则没有。先天免疫标志物，即总中性粒细胞和 CD11b+/CD18+和 CD31+/CD40-粒细胞，与死亡率直接相关。在从不吸烟者中，仅在从不吸烟者中添加免疫功能标志物（如 PC 或 NLR）可以提高风险预测。
与从不吸烟者相比，活跃吸烟者的总白细胞计数因中性粒细胞和单核细胞计数升高而升高，但在戒烟时间增加后，白细胞计数会下降。在从不吸烟者中，淋巴细胞计数与死亡率呈负相关，但与中性粒细胞直接相关，即使在调整了传统心血管危险因素后也是如此。在从不吸烟者中，仅在从不吸烟者中添加免疫功能标志物可以提高基本风险模型的风险预测。我们的数据表明，吸烟状况对白细胞计数预测长期心血管结局的能力有重要影响。
