弗雷明汉卒中高风险增加新型冠状病毒病患者的炎症反应及不良预后

doi:10.3969/j.issn.1673-5765.2020.11.003

摘要/Abstract

摘要：

目的探讨弗雷明汉卒中危险因素负荷对2019冠状病毒病（coronavirus disease 2019，COVID-19）患者循环炎症反应及预后的影响。方法本研究为单中心回顾性研究，分析了158例就诊于武汉大学中南医院隔离病区的COVID-19患者。根据弗雷明汉10年卒中风险评分，将所有受试者分为卒中低危组（风险＜10%）、中危组（风险 10%～20%）和高危组（风险＞20%）。收集患者住院后每周的血清炎症指标检查结果，包括CRP、IL-6 和降钙素原（procalcitonin，PCT），连续4周。预后指标定义为病程4周内死亡、病程4周时仍需住院治疗和痊愈。比较3组间预后和不同时间点的炎症指标差异，采用多元Logistic回归分析弗雷明汉卒中风险与COVID-19患者4周预后的关系。结果发病第1周内的炎症指标在3组之间无显著的差异，第2周、第3周和第4周血清I L-6和PCT 水平在3组间有显著差异，第2周和3周的血清CRP水平也有显著的差异。低危组患者的血清CRP 和IL-6自第2周开始逐渐降低，PCT水平相对平稳，而高危组患者的IL-6和PCT水平在第4周明显上升。多元Logi sti c回归分析结果显示，与弗雷明汉卒中高危组相比，低危组的死亡风险降低（OR 0.062，95%CI 0.004～0.772，P =0.031），低危组（OR 0.117，95%CI 0.031～0.396，P =0.001）与中危组（OR 0.108，95%CI 0.025～0.501，P =0.004）患者病程第4周仍需要住院治疗的风险也均降低。中介效应模型分析显示当纳入第2周IL-6水平为协变量时，弗雷明汉卒中低危组与死亡和第4周仍需住院治疗之间的回归系数显著下降（死亡：β下降13.7%，OR 0.071，95%CI 0.005～0.815；仍需治疗：β下降 19.1%，OR 0.128，95%CI 0.034～0.452）。结论与弗雷明汉卒中高风险相比，卒中低、中风险COVID-19患者的炎症反应水平较低，不良预后的风险较低。

文章导读： 本研究对COVID-19患者进行了弗雷明汉卒中风险评分，发现10年低卒中风险患者的短期预后优于高风险患者，患者体内的炎症反应可能与卒中危险因素通过协同作用共同影响患者的预后。

关键词: 2019冠状病毒病; 弗雷明汉10年卒中风险; 炎症反应; 预后

Abstract:

Objective To investigate the effects of Framingham stroke risk on the circulating inflammation and prognosis in coronavirus disease 2019 (COVID-19) patients. Methods This was a single-center retrospective study which enrolled 158 COVID-19 patients. According to Framingham score for 10-year stroke risk, all subjects were divided into low-risk group (10-year stroke risk <10%), medium-risk group (10%-20%) and high-risk group (>20%). The levels of serum inflammation biomarkers including CRP, IL-6 and procalcitonin (PCT) in all patients were collected once a week for four consecutive weeks. The prognosis was defined as death within 4 weeks, hospitalization at 4 weeks and recovery. The prognosis and inflammation biomarkers level at different time point among three groups were compared, and multivariate logistic regression analysis was used to determine the relationship between Framingham stroke risk and the prognosis at 4 weeks. Results There was no statistical difference in inflammation biomarkers level among three groups at the first week. The serum IL-6 and PCT levels at the second, third and fourth week were significantly different among three groups, and serum CRP level at the second, third week was also significantly different among three groups. The serum CRP and IL-6 levels gradually decreased after the second week in low-risk group, while the PCT level was relatively stable. The IL-6 and PCT levels began to increase obviously at the fourth week in high-risk group. Compared with the high-risk group, the low-risk group had a lower risk of death (OR 0.062, 95%CI 0.004-0.772, P =0.031), the low-risk group (OR 0.117, 95%CI 0.031-0.396, P =0.001) and medium-risk group (OR 0.108, 95%CI 0.025- 0.501, P =0.004) had a lower risk of hospitalization. The mediation effect model showed that the higher level of serum IL-6 can partly explain the relationship between Framingham stroke risk and the poor prognosis of COVID-19 patients (death: β decreased by 13.7%, OR 0.071, 95%CI 0.005-0.815; hospitalization: β decreased by 19.1%, OR 0.128, 95%CI 0.034-0.452). Conclusions Higher Framingham stroke risk increased circulatory inflammatory response and poor prognosis in COVID-19 patients.

Key words: COVID-19; Framingham stroke risk; Inflammatory response; Prognosis

刘明珠，孙冬，李华钢，李曾，梅斌，刘煜敏. 弗雷明汉卒中高风险增加新型冠状病毒病患者的炎症反应及不良预后[J]. 中国卒中杂志, 2020, 15(11): 1162-1167.

LIU Ming-Zhu, SUN Dong, LI Huang-Gang, LI Zeng, MEI Bin, LIU Yu-Min. Higher Framingham Stroke Risk Increased Inflammatory Response and Adverse Prognosis in Patients with Coronavirus Disease 2019[J]. Chinese Journal of Stroke, 2020, 15(11): 1162-1167.

参考文献

[1] MEHTA P，MCAULEY D F，BROWN M，et al.

COVID-19：consider cytokine storm syndromes and

immunosuppression[J]. Lancet，2020，395（10229）：

1033-1034.

[2] GUO W N，LI M Y，DONG Y L，et al. Diabetes

is a risk factor for the progression and prognosis

of COVID-19[J/OL]. Diabetes Metab Res Rev，

2020：e3319[2020-07-01]. https：//doi.org/10.1002/

dmrr.3319.

[3] AKBARI M，HASSAN-ZADEH V. IL-6 signalling

pathways and the development of type 2 diabetes[J].

Inflammopharmacology，2018，26（3）：685-698.

[4] YANG S，CHEN D D，CHEN F，et al. Deletion

of protein kinase B2 preserves cardiac function by

blocking interleukin-6-mediated injury and restores

blood pressure during angiotensin Ⅱ/high-salt-dietinduced

hypertension[J]. J Hypertens，2018，36（4）：

834-846.

[5] CAPURON L，POITOU C，MACHAUX-THOLLIEZ D，et al. Relationship between adiposity，

emotional status and eating behaviour in obese

women：role of inflammation[J]. Psychol Med，2011，

41（7）：1517-1528.

[6] SUNYER J，FORASTIERE F，PEKKANEN J，et al.

Interaction between smoking and the interleukin-6

gene affects systemic levels of inflammatory

biomarkers[J]. Nicotine Tob Res，2009，11（11）：

1347-1353.

[7] MIWA K，TANAKA M，OKAZAKI S，et al.

Association between interleukin-6 levels and firstever

cerebrovascular events in patients with vascular

risk factors[J]. Arterioscler Thromb Vasc Biol，2013，

33（2）：400-405.

[8] 中华人民共和国国家卫生健康委员会办公厅与国家

中医药管理局办公室. 新型冠状病毒肺炎诊疗方案

（试行第七版）[J]. 中国医药，2020，15（6）：801-805.

[9] WOLF P A，D'AGOSTINO R B，BELANGER A

J，et al. Probability of stroke：a risk profile from the

Framingham Study[J]. Stroke，1991，22（3）：312-

318.

[10] KAUR S，BANSAL Y，KUMAR R，et al. A

panoramic review of IL-6：structure，pathophysiological

roles and inhibitors[J/OL]. Bioorg Med Chem，

2020，28（5）：115327[2020-07-01]. https：//doi.

org/10.1016/j.bmc.2020.115327.

[11] CHEN G，WU D，GUO W，et al. Clinical and

immunological features of severe and moderate

coronavirus disease 2019[J]. J Clin invest，2020，130

（5）：2620-2629.

[12] LUO P，LIU Y，QIU L，et al. Tocilizumab treatment

in COVID-19：a single center experience[J]. J Med

Virol，2020，92（7）：814-818.

[13] LODIGIANI C，IAPICHINO G，CARENZO

L，et al. Venous and arterial thromboembolic

complications in COVID-19 patients admitted to an

academic hospital in Milan，Italy[J/OL]. Thromb Res，

2020，191：9-14[2020-07-01]. https：//doi.org/10.

1016/j.thromres.2020.04.024.

[14] MAO L，JIN H J，WANG M D，et al. Neurologic

manifestations of hospitalized patients with

coronavirus disease 2019 in Wuhan，China[J].

JAMA Neurol，2020，77（6）：683-690.

[15] HESS D C，ELDAHSHAN W，RUTKOWSKI E.

COVID-19-related stroke[J]. Transl Stroke Res，

2020，11（3）：322-325.

[16] CHOI J Y，LEE H K，PARK J H，et al. Altered

COVID-19 receptor ACE2 expression in a higher

risk group for cerebrovascular disease and ischemic

stroke[J]. Biochem Biophys Res Commun，2020，528

（3）：413-419.