Chinese Medical Sciences Journal ›› 2021, Vol. 36 ›› Issue (1): 17-26.doi: 10.24920/003866

• 论著 • 上一篇    下一篇

高脂血症与新型冠状病毒肺炎住院患者28天全因死亡率的关系

吴斌1,周江华1,2,汪文鑫1,2,杨慧琳2,3,夏盟2,张丙宏4,折志刚1,2,李红良1,2,3,5,*()   

  1. 1武汉大学人民医院心内科,武汉430071,中国
    2武汉大学模式动物研究所,武汉430071,中国
    3武汉大学基础医学院,武汉430071,中国
    4武汉大学人民医院新生儿科,武汉430072,中国
    5武汉大学中南医院,医学科学研究中心,武汉430071,中国
  • 收稿日期:2021-02-09 接受日期:2021-03-05 出版日期:2021-03-17 发布日期:2021-03-17
  • 通讯作者: 李红良 E-mail:lihl@whu.edu.cn

Association Analysis of Hyperlipidemia with the 28-Day All-Cause Mortality of COVID-19 in Hospitalized Patients

Bin Wu1,Jianghua Zhou1,2,Wenxin Wang1,2,Huilin Yang2,3,Meng Xia2,Binghong Zhang4,Zhigang She1,2,Hongliang Li1,2,3,5,*()   

  1. 1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430071, China
    2Institute of Model Animal, Wuhan University, Wuhan 430071, China
    3Basic Medical School, Wuhan University, Wuhan 430071, China
    4Department of Neonatology, Renmin Hospital of Wuhan University, Wuhan 430072, China
    5Medical Science Research Center, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
  • Received:2021-02-09 Accepted:2021-03-05 Online:2021-03-17 Published:2021-03-17
  • Contact: Hongliang Li E-mail:lihl@whu.edu.cn

摘要:

目的 本研究旨在确定高脂血症与COVID-19住院患者的临床终点之间的关联,尤其是那些伴随心血管疾病(cardiovascular diseases, CVDs)和糖尿病的COVID-19患者。

方法 这项多中心回顾性队列研究搜集2019年12月31日至2020年4月21日期间中国湖北省21家医院全部确诊COVID-19的住院患者。 我们排除了年龄<18岁或≥85岁、处于妊娠期间、患有急性致死性器官损伤(如急性心肌梗塞,严重的急性胰腺炎或急性中风)、甲状腺功能减退、恶性疾病、严重的营养不良以及因服用降脂药物(如他汀类,烟酸,非诺贝特或吉非贝齐,依泽替米贝)而血脂正常的患者。采用1:1倾向性评分匹配(Propensity score matching,PSM)控制高脂血症组和非高脂血症组的患者的基线特征差异,并以相同的PSM策略对不同高脂血症参数亚组进行匹配, 包括甘油三酸酯(triglyceride,TG)升高组,低密度脂蛋白胆固醇(low-density lipoprotein cholesterol, LDL-C)升高组和高密度脂蛋白胆固醇(high-density lipoprotein cholesterol, HDL-C)降低组。采取混合效应Cox模型分析总体以及各亚组内高脂血症与COVID-19患者28天全因死亡率之间的相关性,并分别在男性、女性、伴有CVDs及伴有2型糖尿病患者的亚组中对结果进行验证分析。

结果 在10 945例住院的COVID-19患者中,共9822例纳入研究,包括6309例(64.2%)血脂升高患者和3513例(35.8%)血脂正常患者。按1:1的倾向性评分匹配后经混合效应Cox模型分析显示,与血脂正常组相比,高脂血症不显著增加或减少COVID-19患者28天全因死亡风险(HR=1.17, 95% CI,0.95~1.44, P=0.151)。COVID-19患者预后与血脂各参数异常亦无显著关联,包括TG升高(HR=1.23,95% CI,0.98~1.55,P=0.075),LDL-C升高(HR=0.78;95% CI,0.57~1.07,P=0.123),以及HDL-C降低(HR=1.12,95% CI,0.90~1.39,P=0.299)。在伴有心血管疾病、伴有糖尿病的COVID-19患者亚组中,以及在男性或女性COVID-19患者亚组中,高脂血症与COVID-19全因死亡率均无显著相关性。

结论 我们的研究表明,即使在伴有心血管疾病和伴有糖尿病的患者中,脂质分布失衡与COVID-19的28天全因死亡率也无显着相关性。分别对TG,HDL-C及LDL-C脂质参数的高脂血症亚组分析也获得了相似的结果。因此,脂质失衡可能不是导致与心血管代谢性疾病相关的COVID-19不良预后的主要原因。该结果为COVID-19流行期间住院患者的干预提供了参考。

关键词: 新型冠状病毒肺炎, 血脂异常, 死亡率, 心血管疾病, 糖尿病

Abstract:

Objective This study aimed to determine the association of hyperlipidemia with clinical endpoints among hospitalized patients with COVID-19, especially those with pre-existing cardiovascular diseases (CVDs) and diabetes.

Methods This multicenter retrospective cohort study included all patients who were hospitalized due to COVID-19 from 21 hospitals in Hubei province, China between December 31, 2019 and April 21, 2020. Patients who were aged < 18 or ≥ 85 years old, in pregnancy, with acute lethal organ injury (e.g., acute myocardial infarction, severe acute pancreatitis, acute stroke), hypothyroidism, malignant diseases, severe malnutrition, and those with normal lipid profile under lipid-lowering medicines (e.g., statin, niacin, fenofibrate, gemfibrozil, and ezetimibe) were excluded. Propensity score matching (PSM) analysis at 1:1 ratio was performed to minimize baseline differences between patient groups of hyperlipidemia and non-hyperlipidemia. PSM analyses with the same strategies were further conducted for the parameters of hyperlipidemia in patients with increased triglyceride (TG), increased low-density lipoprotein cholesterol (LDL-C), and decreased high-density lipoprotein cholesterol (HDL-C). Mixed-effect Cox model analysis was performed to investigate the associations of the 28-days all-cause deaths of COVID-19 patients with hyperlipidemia and the abnormalities of lipid parameters. The results were verified in male, female patients, and in patients with pre-existing CVDs and type 2 diabetes.

Results Of 10 945 inpatients confirmed as COVID-19, there were 9822 inpatients included in the study, comprising 3513 (35.8%) cases without hyperlipidemia and 6309 (64.2%) cases with hyperlipidemia. Based on a mixed-effect Cox model after PSM at 1:1 ratio, hyperlipidemia was not associated with increased or decreased 28-day all-cause death [adjusted hazard ratio (HR), 1.17 (95% CI, 0.95-1.44), P =0.151]. We found that the parameters of hyperlipidemia were not associated with the risk of 28-day all-cause mortality [adjusted HR, 1.23 (95% CI, 0.98-1.55), P = 0.075 in TG increase group; 0.78 (95% CI, 0.57-1.07), P = 0.123 in LDL-C increase group; and 1.12 (95% CI, 0.9-1.39), P = 0.299 in HDL-C decrease group, respectively]. Hyperlipidemia was also not significantly associated with the increased mortality of COVID-19 in patients accompanied with CVDs or type 2 diabetes, and in both male and female cohorts.

Conclusion Our study support that the imbalanced lipid profile is not significantly associated with the 28-day all-cause mortality of COVID-19 patients, even in those accompanied with CVDs or diabetes. Similar results were also obtained in subgroup analyses of abnormal lipid parameters. Therefore, hyperlipidemia might be not a major causative factor for poor outcome of COVID-19, which provides guidance for the intervention of inpatients during the epidemic of COVID-19.

Key words: coronavirus disease 2019 (COVID-19), lipid disorder, mortality, cardiovascular diseases, diabetes

基金资助: 国家重点研发计划重大科学仪器设备开发重点专项2016年度项目基金(2016YFF0101500);国家自然科学基金。(81970364);国家自然科学基金。(81770053)

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