Chinese Medical Sciences Journal ›› 2021, Vol. 36 ›› Issue (1): 17-26.doi: 10.24920/003866
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,*()
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
Bin Wu1,Jianghua Zhou1,2,Wenxin Wang1,2,Huilin Yang2,3,Meng Xia2,Binghong Zhang4,Zhigang She1,2,Hongliang Li1,2,3,5,*()
Received:
2021-02-09
Accepted:
2021-03-05
Published:
2021-03-17
Online:
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。
Bin Wu,Jianghua Zhou,Wenxin Wang,Huilin Yang,Meng Xia,Binghong Zhang,Zhigang She,Hongliang Li. Association Analysis of Hyperlipidemia with the 28-Day All-Cause Mortality of COVID-19 in Hospitalized Patients[J].Chinese Medical Sciences Journal, 2021, 36(1): 17-26.
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Characteristics | Study cohort | Cohort after matching (1:1)b | |||||
---|---|---|---|---|---|---|---|
Hyperlipidemia a (n=6309) | Normal (n=3513) | SD | Hyperlipidemia a (n=3506) | Normal (n=3506) | SD | ||
Age [years, median (IQR)] | 59(48-68) | 59(45-68) | 0.083 | 58(47-67) | 59(45-68) | -0.001 | |
Gender-male [n (%)] | 3387(53.69) | 1450(41.28) | 0.250 | 1597(45.55) | 1450(41.36) | 0.085 | |
Heart rate [bpm, median (IQR)] | 85(78-97) | 84(78-96) | 0.049 | 85(78-96) | 84(78-96) | 0.005 | |
Respiratory [bpm, median(IQR)] | 20(19-21) | 20(19-21) | 0.104 | 20(19-21) | 20(19-21) | -0.018 | |
SBP [mmHg, median (IQR)] | 129(120-141) | 128(118-139) | 0.087 | 128(119-140) | 128(118-139) | 0.025 | |
DBP [mmHg, median (IQR)] | 80(72-88) | 79(72-86) | 0.101 | 79(72-87) | 79(72-86) | 0.038 | |
SpO2 [%, median(IQR)] | 97(95-98) | 97(96-98) | -0.06 | 98(96-98) | 97(96-98) | 0.024 | |
Comorbidities on admission [n (%)] | |||||||
Chronic obstructive pulmonary disease | 67(1.06) | 47(1.34) | -0.025 | 45(1.28) | 45(1.28) | 0.000 | |
Diabetes | 1095(17.36) | 408(11.61) | 0.164 | 386(11.01) | 408(11.64) | -0.020 | |
Heart failure | 40(0.63) | 23(0.65) | -0.003 | 20(0.57) | 23(0.66) | -0.011 | |
Coronary heart disease | 603(9.56) | 195(5.55) | 0.152 | 204(5.82) | 195(5.56) | 0.011 | |
Cerebrovascular diseases | 196(3.11) | 81(2.31) | 0.049 | 89(2.54) | 81(2.31) | 0.015 | |
Chronic liver disease | 151(2.39) | 76(2.16) | 0.015 | 75(2.14) | 76(2.17) | -0.002 | |
Chronic renal diseases | 266(4.22) | 103(2.93) | 0.002 | 112(3.19) | 103(2.94) | 0.015 | |
Medications [n (%)] | |||||||
Insulin | 975(15.45) | 320(9.11) | 0.194 | 332(9.47) | 320(9.13) | 0.012 | |
Oral hypoglycemic drugs | 1352(21.43) | 456(12.98) | 0.225 | 474(13.52) | 456(13.01) | 0.015 | |
non-ACEI/ARB antihypertensive drug | 1907(30.23) | 873(24.85) | 0.121 | 814(23.22) | 872(24.87) | -0.039 | |
ACEI/ARB | 628(9.95) | 233(6.63) | 0.121 | 215(6.13) | 233(6.65) | -0.021 | |
Antiplatelet | 533(8.45) | 110(3.13) | 0.229 | 89(2.54) | 110(3.14) | -0.036 | |
Chest CT on admission [n (%)] | |||||||
Bilateral lesions | 5154(87.05) | 2808(83.60) | 0.098 | 2718(83.35) | 2807(83.74) | -0.011 | |
Lab tests on admission [n (%), or median(IQR)] | |||||||
Leukocyte count > 9.5×109/L | 697(11.08) | 270(7.71) | 0.116 | 313(8.98) | 270(7.73) | 0.045 | |
Neutrophil count > 6.3×109/L | 1062(16.89) | 412(11.77) | 0.146 | 455(13.05) | 412(11.80) | 0.038 | |
Lymphocyte< 1.1×109/L | 2595(41.26) | 1400(40.00) | 0.026 | 1405(40.28) | 1394(39.91) | 0.008 | |
RBC < 3.5×1012/L (female) or 4.0×1012/L (male) | 2568(40.83) | 1579(45.14) | -0.087 | 1441(41.32) | 1574(45.09) | -0.076 | |
CRP > ULN c | 2103(52.65) | 821(46.10) | 0.131 | 1257(51.52) | 819(46.11) | 0.108 | |
PCT > ULN c | 2479(45.06) | 1021(34.95) | 0.207 | 954(31.39) | 1020(34.99) | -0.076 | |
ALT > 40 U/L | 1679(26.63) | 640(18.23) | 0.202 | 611(17.45) | 640(18.27) | -0.021 | |
eGFR value (mL/min) | 103.57 (87.61-120.50) | 105.30 (89.21-122.61) | -0.073 | 107.34 (91.14-125.22) | 105.29 (89.21-122.55) | 0.043 | |
D-dimer > ULN c | 3024(52.06) | 1351(42.26) | 0.197 | 1479(46.88) | 1351(42.32) | 0.092 | |
cTnI > ULN c | 446(10.96) | 160(7.35) | 0.125 | 153(7.65) | 160(7.36) | 0.013 |
"
Categories | Number of patients (n) | Deaths (n) | Adjusted HR (95% CI) | P value a |
---|---|---|---|---|
All patients of matched cohort b | ||||
Hyperlipidemia group vs. non-hyperlipidemia group | 3506 vs. 3506 | 231 vs. 193 | 1.17 (0.95, 1.44) | 0.151 |
TG ≥1.7 mmol/L group vs. TG<1.7 mmol/L group | 2409 vs. 2409 | 180 vs. 137 | 1.23 (0.98, 1.55) | 0.075 |
LDL-C ≥3 mmol/L group vs. LDL-C<3 mmol/L group | 2083 vs. 2083 | 67 vs. 95 | 0.78 (0.57, 1.07) | 0.123 |
HDL-C <1.0 mmol/L group vs. HDL-C ≥1.0 mmol/L group | 2855 vs. 2855 | 213 vs. 157 | 1.12 (0.90, 1.39) | 0.299 |
Male patients in matched cohort c | ||||
Hyperlipidemia group vs. non-hyperlipidemia group | 1449 vs. 1449 | 135 vs. 112 | 1.24 (0.91, 1.70) | 0.176 |
TG ≥1.7 mmol/L group vs. TG<1.7 mmol/L group | 1145 vs. 1145 | 114 vs. 81 | 1.23 (0.92, 1.66) | 0.170 |
LDL-C ≥3 mmol/L group vs. LDL-C<3 mmol/L group | 988 vs. 988 | 43 vs. 46 | 1.00 (0.65, 1.52) | 0.983 |
HDL-C <1.0 mmol/L group vs. HDL-C ≥1.0 mmol/L group | 1499 vs. 1499 | 131 vs. 86 | 1.27 (0.94, 1.72) | 0.113 |
Female patients in matched cohort d | ||||
Hyperlipidemia group vs. non-hyperlipidemia group | 2014 vs. 2014 | 92 vs. 81 | 0.91 (0.66, 1.25) | 0.547 |
TG ≥1.7 mmol/L group vs. TG<1.7 mmol/L group | 1233 vs. 1233 | 62 vs. 50 | 1.14 (0.78, 1.66) | 0.509 |
LDL-C ≥3 mmol/L group vs. LDL-C<3 mmol/L group | 1099 vs. 1099 | 24 vs. 33 | 0.82 (0.48, 1.39) | 0.456 |
HDL-C <1.0 mmol/L group vs. HDL-C ≥1.0 mmol/L group | 1326 vs. 1326 | 79 vs. 66 | 1.00 (0.71, 1.40) | 0.993 |
"
Categories | Number of Patients (n) | Deaths (n) | Adjusted HR (95% CI) | P value a |
---|---|---|---|---|
Cardiovascular diseases b | ||||
Hyperlipidemia group vs. non-hyperlipidemia group | 1242 vs. 1242 | 128 vs. 114 | 0.96 (0.73,1.26) | 0.765 |
TG ≥1.7 mmol/L group vs. TG<1.7 mmol/L group | 1004 vs. 1004 | 115 vs. 81 | 1.19 (0.88,1.60) | 0.253 |
LDL-C ≥3 mmol/L group vs. LDL-C<3 mmol/L group | 814 vs. 814 | 42 vs. 59 | 0.78 (0.52,1.17) | 0.235 |
HDL-C <1.0 mmol/L group vs. HDL-C ≥1.0 mmol/L group | 1131 vs. 1131 | 124 vs. 90 | 1.00 (0.75,1.33) | 0.991 |
Type 2 diabetes c | ||||
Hyperlipidemia group vs. non-hyperlipidemia group | 473 vs. 473 | 52 vs. 54 | 0.74 (0.49,1.13) | 0.164 |
TG ≥1.7 mmol/L group vs. TG<1.7 mmol/L group | 515 vs. 515 | 56 vs. 40 | 1.07 (0.70,1.64) | 0.752 |
LDL-C ≥3 mmol/L group vs. LDL-C<3 mmol/L group | 364 vs. 364 | 20 vs. 29 | 0.72 (0.40,1.30) | 0.279 |
HDL-C <1.0 mmol/L group vs. HDL-C ≥1.0 mmol/L group | 492 vs. 492 | 56 vs. 43 | 1.17 (0.76,1.81) | 0.468 |
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