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 9 822 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
Footnotes
published online March 17, 2021.
This work was supported by grants from National Key R&D Program of China (2016YFF0101500) and the National Natural Science Foundation of China (81970364, 81770053).
References
- 1.Zhang P, Zhu L, Cai J. Association of inpatient use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers with mortality among patients with hypertension hospitalized with COVID-19. Circ Res. 2020;126(12):1671–1681. doi: 10.1161/CIRCRESAHA.120.317134. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Zhu L, She ZG, Cheng X. Association of blood glucose control and outcomes in patients with COVID-19 and pre-existing type 2 diabetes. Cell Metab. 2020;31(6):1068. doi: 10.1016/j.cmet.2020.04.021. 77.e3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Guo T, Fan Y, Chen M. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19) JAMA Cardiol. 2020;5(7):811–818. doi: 10.1001/jamacardio.2020.1017. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Bornstein SR, Rubino F, Khunti K. Practical recommendations for the management of diabetes in patients with COVID-19. Lancet Diabetes Endocrinol. 2020;8(6):546–550. doi: 10.1016/S2213-8587(20)30152-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Ni WQ, Liu XL, Zhuo ZP. Serum lipids and associated factors of dyslipidemia in the adult population in Shenzhen. Lipids Health Dis. 2015;14(1):1–11. doi: 10.1186/s12944-015-0073-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Palaiodimos L, Kokkinidis DG, Li W. Severe obesity is associated with higher in-hospital mortality in a cohort of patients with COVID-19 in the Bronx, New York. Metabolism. 2020;108 doi: 10.1016/j.metabol.2020.154262. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Abu-Farha M, Thanaraj TA, Qaddoumi MG. The role of lipid metabolism in COVID-19 virus infection and as a drug target. Int J Mol Sci. 2020;21(10) doi: 10.3390/ijms21103544. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Tanaka S, Labreuche J, Drumez E. Low HDL levels in sepsis versus trauma patients in intensive care unit. Ann Intensive Care. 2017;7(1):4–11. doi: 10.1186/s13613-017-0284-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Peñarrubia L, Ruiz M, Porco R. Multiple assays in a real-time RT-PCR SARS-CoV-2 panel can mitigate the risk of loss of sensitivity by new genomic variants during the COVID-19 outbreak. Int J Infect Dis. 2020;97:225–229. doi: 10.1016/j.ijid.2020.06.027. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Official website of the National Health Commission of People’s Republic of China The prevention and control guideline for novel coronavirus pneumonia. http://www.nhc.gov.cn/xcs/zhengcwj/202002/a5d6f7b8c48c451c87dba14889b30147.shtml (5th edition) Released February 21, 2020.
- 11.Joint committee issued Chinese guideline for the management of dyslipidemia 2016 Chinese guideline for the management of dyslipidemia in adults. Zhonghua Xin Xue Guan Bing Za Zhi. 2016;44(10):833–853. doi: 10.3760/cma.j.issn.0253-3758.2016.10.005. Chinese. [DOI] [PubMed] [Google Scholar]
- 12.Mach F, Baigent C, Catapano AL. 2019 ESC/EAS guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk. Atherosclerosis. 2019;290:140–205. doi: 10.1016/j.atherosclerosis.2019.08.014. [DOI] [PubMed] [Google Scholar]
- 13.Chinese Diabetes Society; National Office for Primary Diabetes Care National guidelines for the prevention and control of diabetes in primary care(2018) Zhonghua nei ke za zhi. 2018;57(12):885–893. doi: 10.3760/cma.j.issn.0578-1426.2018.12.003. Chinese. [DOI] [PubMed] [Google Scholar]
- 14.Jakubowski KP, Cundiff JM, Matthews KA. Cumulative childhood adversity and adult cardiometabolic disease: A meta-analysis. Heal Psychol. 2018;37(8):701–715. doi: 10.1037/hea0000637. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Tay MZ, Poh CM, Rénia L. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol. 2020;20(6):363–374. doi: 10.1038/s41577-020-0311-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Cao X. COVID-19: immunopathology and its implications for therapy. Nat Rev Immunol. 2020;20(5):269–270. doi: 10.1038/S41577-020-0308-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Touyz RM, Li H, Delles C. ACE2 the Janus-faced protein-from cardiovascular protection to severe acute respiratory syndrome-coronavirus and COVID-19. Clin Sci. 2020;134(7):747–750. doi: 10.1042/CS20200363. [DOI] [PubMed] [Google Scholar]
- 18.Chen T, Wu D, Chen H. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: Retrospective study. BMJ. 2020;368(ml091):1–14. doi: 10.1136/bmj.m1091. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Richardson S, Hirsch JS, Narasimhan M. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York city area. JAMA. 2020;323(20):2052–2059. doi: 10.1001/jama.2020.6775. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Shao B, Heinecke JW. HDL, lipid peroxidation, and atherosclerosis. J Lipid Res. 2009;50(4):599–601. doi: 10.1194/jlr.E900001-JLR200. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2005;352(16):1685–1695. doi: 10.1056/NEJMra043430. [DOI] [PubMed] [Google Scholar]
- 22.Steinberg D. An interpretive history of the cholesterol controversy, part III: Mechanistically defining the role of hyperlipidemia. J Lipid Res. 2005;46(10):2037–2051. doi: 10.1194/jlr.R500010-JLR200. [DOI] [PubMed] [Google Scholar]
- 23.Zhou F, Yu T, Du R. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054–1062. doi: 10.1016/S0140-6736(20)30566-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Yang X, Yu Y, Xu J. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020;8(5):475–481. doi: 10.1016/S2213-2600(20)30079-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Criner GJ, Connett JE, Aaron SD. Simvastatin for the prevention of exacerbations in moderate-to-severe COPD. N Engl J Med. 2014;370(23):2201–2210. doi: 10.1056/nejmoa1403086. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Truwit JD, Bernard GR, Steingrub J. Rosuvas-tatin for sepsis-associated acute respiratory distress syndrome. N Engl J Med. 2014;370(23):2191–2200. doi: 10.1056/NEJMoa1401520. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Zhang XJ, Qin JJ, Cheng X. In-hospital use of statins is associated with a reduced risk of mortality among individuals with COVID-19. Cell Metab. 2020;32(2):176. doi: 10.1016/j.cmet.2020.06.015. 87.e4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Liu G, Zhang S, Mao Z. Clinical significance of nutritional risk screening for older adult patients with COVID-19. Eur J Clin Nutr. 2020;74(6):876–883. doi: 10.1038/s41430-020-0659-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Deniz O, Gumus S, Yaman H. Serum total cholesterol, HDL-C and LDL-C concentrations significantly correlate with the radiological extent of disease and the degree of smear positivity in patients with pulmonary tuberculosis. Clin Biochem. 2007;40(3-4):162–166. doi: 10.1016/j.clinbiochem.2006.10.015. [DOI] [PubMed] [Google Scholar]
- 30.Ishiyama Y, Gallagher PE, Averill DB. Upregulation of angiotensin-converting enzyme 2 after myocardial infarction by blockade of angiotensin II receptors. Hypertension. 2004;43(5):970–976. doi: 10.1161/01.HYP.0000124667.34652.1a. [DOI] [PubMed] [Google Scholar]
- 31.Dijkman R, Jebbink MF, Deijs M. Replication-dependent downregulation of cellular angiotensin-converting enzyme 2 protein expression by human coronavirus NL63. J Gen Virol. 2012;93(Pt 9):1924–1929. doi: 10.1099/vir.0.043919-0. [DOI] [PubMed] [Google Scholar]
- 32.Putnam K, Shoemaker R, Yiannikouris F. The renin-angiotensin system: A target of and contributor to dyslipidemias, altered glucose homeostasis, and hypertension of the metabolic syndrome. Am J Physiol Hear Circ Physiol. 2012;302(6):H1219–H1230. doi: 10.1152/ajpheart.00796.2011. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Cholesterol Treatment Trialists’ Collaboration Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomised controlled trials. Lancet. 2019;393(10170):407–415. doi: 10.1016/S0140-6736(18)31942-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Lemmers RFH, van Hoek M, Lieverse AG. The anti-inflammatory function of high-density lipoprotein in type II diabetes: A systematic review. J Clin Lipidol. 2017;11(3):712–724. doi: 10.1016/j.jacl.2017.03.013. [DOI] [PubMed] [Google Scholar]
- 35.Hui N, Barter PJ, Ong KL. Altered HDL metabolism in metabolic disorders: Insights into the therapeutic potential of HDL. Clin Sci. 2019;133(21):2221–2235. doi: 10.1042/CS20190873. [DOI] [PubMed] [Google Scholar]
- 36.Wei X, Zeng W, Su J. Hypolipidemia is associated with the severity of COVID-19. J Clin Lipidol. 2020;14(3):297–304. doi: 10.1016/j.jacl.2020.04.008. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37.Guirgis FW, Donnelly JP, Dodani S. Cholesterol levels and long-term rates of community-acquired sepsis. Crit Care. 2016;20(1):1–12. doi: 10.1186/s13054-016-1579-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38.Cirstea M, Walley KR, Russell JA. Decreased high-density lipoprotein cholesterol level is an early prognostic marker for organ dysfunction and death in patients with suspected sepsis. J Crit Care. 2017;38:289–294. doi: 10.1016/j.jcrc.2016.11.041. [DOI] [PubMed] [Google Scholar]