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Elevated circulating PCSK9 level is associated with 28-day mortality in patients with sepsis: a prospective cohort study

BMC Emergency Medicine volume 23, Article number: 127 (2023) Cite this article

Abstract

Objectives

Pro-protein convertase subtilisin/kexin 9 (PCSK9) decreases the clearance of the pathogenic lipids, supporting the potential role of PCSK9 in the prognosis of sepsis.

Methods

In this prospective cohort study, patients with sepsis were consecutively recruited from 1 to 2020 to 30 September 2021 at the First People’s Hospital of Huaihua, China. All the eligible patients were categorized into low-PCSK9 and high-PCSK9 groups, based on their PCSK9 levels at admission. Time-dependent receiver operating characteristic curves and Cox proportional hazards regression were used to evaluate the association between PCSK9 level and 28-day mortality of sepsis.

Results

Of the 203 enrolled patients, 56 (27.59%) died during the 28-day follow-up. The PCSK9 level was positively related to the C-reactive protein level. The cut-off point of PCSK9 levels for 28-day mortality risk was 370 ng/ml. Through comparison between high-PCSK9 (> 370 ng/ml) with low-PCSK9 (≤ 370 ng/ml) groups, the adjusted HR for mortality was 2.56 (95% CI: 1.25–5.23, p = 0.01).

Conclusions

The 28-day mortality of sepsis increased significantly as the baseline circulating PCSK9 level exceeded 370 ng/ml, indicating circulating PCSK9 levels may be a potential biomarker to predict the prognosis of sepsis.

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Introduction

Sepsis, a life-threatening organ dysfunction syndrome, arises as the host response to infection is dysregulated. Despite emerging treatments for sepsis, mortality remains high in the intensive care unit [1, 2]. Extensive studies have confirmed that cholesterol and pathogenic lipids are closely involved in the pathogenesis of sepsis.

Cholesterol and pathogenic lipids trigger the inflammatory process via signaling Toll-like receptors, which then augment the production of cytokines [3]. Increasing the clearance of circulating cholesterol and pathogenic lipids may improve patient’s clinical outcomes [4]. Hepatic low-density lipoprotein receptor (LDLR) plays a key role in determining the level of plasma cholesterol by mediating its clearance from circulation [5]. LDLR also represses the inflammatory response through clearing pathogenic lipids [5, 6].

Proprotein convertase subtilisin/kexin type-9 (PCSK9), a circulating protein, binds to LDLR on hepatocytes’ surface and targets it for lysosomal degradation [7]. Due to this capability, PCSK9 has become a promising cholesterol-lowering candidate [8]. Furthermore, a low density of hepatic LDLR may hinder the clearance of cholesterol and pathogenic lipids from circulation [9]. Evidence has also demonstrated that PCSK9 is closely related to inflammation, with a serum level increasing significantly during sepsis [9, 10].

Nowadays, genetic and clinical trials have explored whether circulating PCSK9 is a prognosis biomarker of sepsis [10,11,12,13,14]. Unfortunately, their results are inconsistent, and can’t reach a clear-out conclusion. Here conducted a study on Chinese patients to identify the relationship between the circulating PCSK9 level and the 28-day mortality of sepsis.

Materials and methods

Study design and participants

This study was a prospective single-center, observational cohort study conducted at the First People’s Hospital of Huaihua, a treatment center for critically ill patients in Huaihua, China. The study was conducted in January 2020. Participants were recruited from 1 to 2020 to 30 September 2021. Patients aged 18 years or older and meeting the clinical criteria for Sepsis 3.0 within 24 h before any time point during their stay in the hospital were enrolled [15]. The exclusion criteria were as follows: (i) more than 24 h had passed since the patient was defined as meeting inclusion criteria; (ii) the patient was in a terminal state or died within 48 h; (iii) the patient showed inability or refusal to sign informed consent.

Follow-up time was defined as the period from the establishment of diagnosis to the onset of death, loss to follow-up, or the end of follow-up (28 days).

The study was approved by the research ethics committee of the First People’s Hospital of Huaihua (No. KY-2,019,082,203). Informed consent was obtained from all study participants. The study was carried out in accordance with relevant guidelines and regulations (e.g. Declaration of Helsinki). The study protocol was available at http://www.chictr.org.cn (ChiCTR1900026452).

Data collection and PCSK9 detection

Within 24 h after admission, demographic and clinical characteristics of the patients, including age, sex, and underlying diseases, were collected by researchers. The data collection of laboratory results were defined using the first-time examination at admission (within 6 h after admission).

Venous blood samples were collected in sterile Ethylene Diamine Tetraacetic Acid (EDTA)-coated tubes within 1 h after diagnosis, during which any drug use was avoided. Plasma was collected by centrifugation at 1000 g for 15 min at room temperature, pipetted into Eppendorf tubes, and stored at − 80 °C. PCSK9 was measured using a colorimetric enzyme-linked immunosorbent assay (ELISA) according to the manufacturer’s instructions (Cusabio, Wuhan, China).

Statistical analysis

Continuous variables were presented as the median and interquartile range (IQR), and categorical variables as numbers and percentages. Continuous variables were compared using the Wilcoxon rank-sum test and categorical using the chi-square test. Cross-sectional associations between PCSK9 levels and other characteristics were analyzed using Pearson correlation coefficients.

Time-dependent receiver operating characteristic (ROC) curve analysis determined the optimum threshold value of PCSK9. Cumulative event survival curves for 28-day mortality were compared across dichotomous categories of PCSK9 using the log-rank test. Cox proportional-hazards regression models were used to calculate covariate-adjusted hazard ratios (HRs) of PCSK9 for predicting the risk of 28-day mortality.

The p-value was 2-sided, and an alpha level of 0.05 was used to define statistical significance. All analyses were conducted using R software (version R 3.6.3; https://cran.r-project.org/).

Result

Patient characteristics

Figure 1 shows the flowchart of patient recruitment. The demographic and clinical characteristics of the 203 patients are summarized in Table 1. The median age was 63.00 years (IQR, 51.50–72.50), and 123 (60.59%) patients were male. The median PCSK9 level was 381.60 (IQR 223.50-655.80) ng/ml. During the 28-day follow-up, 56 (27.59%) patients died. The PCKS9 levels in those who died than in those who still survived (median [IQR]: 568.30 [345.80, 756.00] ng/ml vs. 343.50 [202.90, 602.20] ng/ml).

Table 1 Baseline characteristics of study patients
Full size table
Fig. 1
figure 1

Study flowchart

Full size image

Correlation between circulating PCSK9 and infection with lipid indexes

Pearson correlation analysis did not observe significant correlations of circulating PCSK9 level with white blood cells (WBC) (correlation coefficient R = -0.10, p = 0.16) and procalcitonin (PCT) (correlation coefficient R = 0.11, p = 0.13). However, the circulating PCSK9 level was positively correlated with C-reactive protein (CRP) (correlation coefficient R = 0.29, p < 0.001) (Fig. 2). Moreover, no significant association was found between PCSK9 and lipid indexes (Additional file 1: Fig. S1).

Fig. 2
figure 2

Associations between PCSK9 and WBC (A), PCT (B), and CRP (C) levels. The association was calculated using Pearson’s correlation coefficient (R). The grey area shows the 95% confidence interval (CI).

Full size image

Association between circulating PCSK9 and 28-day mortality of sepsis

Figure 3 shows the ROC curve for PCSK9 with overall survival at 28 days after the start of follow-up based on time-dependent ROC analysis. The optimal PCSK9 cut-off value was determined to be 370 ng/ml based on the Youden index. The Kaplan-Meier analysis of 28-day overall survival showed a significant difference between high- and low-PCSK9 groups (p < 0.001, Fig. 4).

Fig. 3
figure 3

Time-dependent ROC curve of PCSK9 for overall survival at 28 days after the start of follow-up. The area under the ROC curve was 0.66. At a cut-off value of 370 ng/ml, PCSK9 achieved a sensitivity of 68.17% and a specificity of 61.97% in predicting sepsis survival, according to the Youden index

Full size image
Fig. 4
figure 4

Cumulative overall survival curves stratified by PCSK9. Cumulative overall survival rates at 7, 14, 21, and 28 days were 94.35%, 94.35%, 79.94%, and 73.27% in patients with a low-PCSK9 group (≤ 370 ng/ml) and 89.03%, 76.85%, 59.34%, and 41.72% in a high-PCSK9 group (> 370 ng/ml) (p < 0.001, log-rank test)

Full size image

The Cox proportional-hazards model revealed that the high-PCSK9 group represented a higher risk of 28-day mortality than the low-PCSK9 group, HR was 2.69 with 95% CI (1.49–4.87) in model 1 (unadjusted), 2.58 with 95% CI (1.37–4.84) in model 2 (after adjusted for age, sex, and comorbidities), and 2.56 with 95% CI (1.25–5.23) in model 3 (after adjusted for age, sex, comorbidities, SOFA, ALT, creatinine, BUN, hemoglobin, lactate, and TG) (Table 2).

Table 2 Associations between PCSK9 levels and 28-day all-cause mortality in patients with sepsis
Full size table

Discussion

This study, for the first time, found that circulating PCSK9 has a high prognostic value in Chinese sepsis patients. The cut-off value of serum PCSK9 level for predicting 28-day mortality was 370 ng/ml. According to this value, the high-PCSK9 group presented a much higher risk of 28-day mortality.

Causal relationships between PCSK9 level and the severity of sepsis are supported by clinical, experimental, and genetic studies. Pathogenic lipids (e.g. lipopolysaccharide, LPS) stimulate PCSK9 expression via SREBP2 pathways [16]. In a mouse model [17], PCSK9 overexpression aggravated LPS-induced sepsis, while knockout alleviated it [18]. Epidemiological data also confirm that levels of PCSK9 are elevated in patients with inflammatory diseases, particularly those with sepsis [19]. Moreover, in septic patients with coronavirus disease 2019 (COVID-19) with a more severe inflammatory response, PCSK9 levels are further elevated [20]. WBC, PCT, and CRP are commonly used diagnostic and prognostic biomarkers for sepsis [19, 21]. Consistent with our findings, it has been observed in a sepsis cohort that includes COVID-19 that there is a positive correlation between PCSK9 and CRP, but not with WBC and PCT [20]. This correlation was also observed in bacteremia patients [10]. However, this is at odds with the results of the study involving stable coronary heart disease patients who were naïve to lipid-lowering therapy [22], they reported a positive correlation between PCSK9 and WBC, which might be due to the difference existing in the study population.

Previous studies have revealed that serum triglyceride levels in septic patients were elevated but the cholesterol levels were decreased [23]. Importantly, decreased cholesterol levels may be associated with increased mortality in sepsis [24]. In the current study, it was found that triglyceride levels were higher in the survival group than in the death group, but the differences in cholesterol levels between the two groups were not significant, these results were consistent with previous studies [25]. Furthermore, though some studies reported positive correlations between circulating PCSK9 and lipid levels in healthy populations and cardiovascular patients [26, 27], these relationships were not significant in septic patients. Lipid metabolism was complex under an inflammatory state, inflammatory factors play an important role in the regulation of lipid metabolism, and serum lipid levels are shared largely variations in patients with inflammatory disease [28]. A study demonstrated that the serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) were decreased in autoimmune rheumatic disease, and then increased after anti-inflammatory therapies [29].

A genetic study has demonstrated that patients carrying loss-of-function (LOF) alleles exhibit a higher rate of LPS clearance [30]. Experimental studies using genetic mouse models also showed similar results [31]. These results support that PCSK9 may play a central role in the pathogenesis or progression of sepsis. Theoretically, PCSK9 may predict the prognostic prediction of sepsis. Time-dependent ROC analysis showed the cut-off value of circulating PCSK9 level was 370 ng/ml. A previous study has found that the risk of multiple organ failure increases significantly in patients with PCSK9 levels > 370 ng/ml [9]. The multi-organ dysfunction is a major cause of death in septic patients. Therefore, the cut-off value set in the present study is sure of great clinical significance. Using the cut-off value to divide the patients into high- and low-PCSK9 groups, the high-PCSK9 group presented a much higher risk of 28-day mortality. After adjusting for potential confounders, this association remained evident. Although different studies of different populations have harvested inconsistent results, this study adds strong evidence to define the prognostic value of PCSK9 for mortality in sepsis patients.

This study has several limitations. First, some biases might remain in this single-center cohort study, although the data quality was controlled seriously. Second, the sample size was relatively small. However, the sample size might be sufficient according to a previous study calculation [12]. Moreover, gender, age, and cardiovascular disease may be confounding factors in observational studies, but these potential confounders exhibit no significant differences between the two groups. Finally, similar to previous studies, this study did not assess the association between longitudinal PCSK9 changes and prognosis, despite that PCSK9 changes during sepsis have been reported in several studies [9, 11].

Conclusions

This study demonstrated that PCSK9 levels at or above 370 ng/ml significantly increase the risk of 28-day mortality in sepsis, providing evidence to evaluate the potential clinical significance of circulating PCSK9 in assessing the prognosis of septic.

Data Availability

The data that support the findings of this study are available from the corresponding author (Chengfeng Qiu) but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of the corresponding author (Chengfeng Qiu).

Abbreviations

ALT:

alanine aminotransferase

AST:

aspartate aminotransferase

BUN:

blood urea nitrogen

CHD:

coronary heart disease

CKD:

chronic kidney disease

CRP:

C-reactive protein

HDL-C:

high-density lipoprotein cholesterol

HRs:

hazard ratios

IQR:

interquartile range

LDL-C:

low-density lipoprotein cholesterol

LDLR:

low-density lipoprotein receptor

LOF:

loss-of-function

LPS:

lipopolysaccharide

PCSK9:

proprotein convertase subtilisin/kexin type-9

PCT:

procalcitonin

RBC:

red blood cell

ROC:

receiver operating characteristic

SOFA:

Sequential Organ Failure Assessment

TC:

total cholesterol

TG:

triglyceride

UA:

uric acid

WBC:

white blood cells

References

  1. Motzkus CA, Chrysanthopoulou SA, Luckmann R, Rincon TA, Lapane KL, Lilly CM. ICU admission source as a predictor of mortality for patients with Sepsis. J Intensive Care Med. 2018;33(9):510–6.

    Article  PubMed  Google Scholar 

  2. van Vught LA, Klein Klouwenberg PM, Spitoni C, Scicluna BP, Wiewel MA, Horn J, et al. Incidence, risk factors, and Attributable Mortality of Secondary Infections in the Intensive Care Unit after Admission for Sepsis. JAMA. 2016;315(14):1469–79.

    Article  PubMed  Google Scholar 

  3. Momtazi AA, Banach M, Sahebkar A. PCSK9 inhibitors in sepsis: a new potential indication? Expert Opin Investig Drugs. 2017;26(2):137–9.

    Article  CAS  PubMed  Google Scholar 

  4. Yuan Y, Wu W, Sun S, Zhang Y, Chen Z. PCSK9: a potential therapeutic target for Sepsis. J Immunol Res. 2020;2020:2687692.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Topchiy E, Cirstea M, Kong HJ, Boyd JH, Wang Y, Russell JA, et al. Lipopolysaccharide is cleared from the circulation by Hepatocytes via the Low Density Lipoprotein Receptor. PLoS ONE. 2016;11(5):e0155030.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Leung AKK, Genga KR, Topchiy E, Cirstea M, Shimada T, Fjell C, et al. Reduced Proprotein convertase subtilisin/kexin 9 (PCSK9) function increases lipoteichoic acid clearance and improves outcomes in Gram positive septic shock patients. Sci Rep. 2019;9(1):10588.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Zhang DW, Lagace TA, Garuti R, Zhao Z, McDonald M, Horton JD, et al. Binding of proprotein convertase subtilisin/kexin type 9 to epidermal growth factor-like repeat a of low density lipoprotein receptor decreases receptor recycling and increases degradation. J Biol Chem. 2007;282(25):18602–12.

    Article  CAS  PubMed  Google Scholar 

  8. Stein EA, Mellis S, Yancopoulos GD, Stahl N, Logan D, Smith WB, et al. Effect of a monoclonal antibody to PCSK9 on LDL cholesterol. N Engl J Med. 2012;366(12):1108–18.

    Article  CAS  PubMed  Google Scholar 

  9. Boyd JH, Fjell CD, Russell JA, Sirounis D, Cirstea MS, Walley KR. Increased plasma PCSK9 levels are Associated with reduced endotoxin clearance and the development of Acute Organ failures during Sepsis. J Innate Immun. 2016;8(2):211–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Rannikko J, Jacome Sanz D, Ortutay Z, Seiskari T, Aittoniemi J, Huttunen R, et al. Reduced plasma PCSK9 response in patients with bacteraemia is associated with mortality. J Intern Med. 2019;286(5):553–61.

    Article  CAS  PubMed  Google Scholar 

  11. Vecchié A, Bonaventura A, Meessen J, Novelli D, Minetti S, Elia E, et al. PCSK9 is associated with mortality in patients with septic shock: data from the ALBIOS study. J Intern Med. 2021;289(2):179–92.

    Article  PubMed  Google Scholar 

  12. Innocenti F, Gori AM, Giusti B, Tozzi C, Donnini C, Meo F, et al. Plasma PCSK9 levels and sepsis severity: an early assessment in the emergency department. Clin Experimental Med. 2021;21(1):101–7.

    Article  CAS  Google Scholar 

  13. Genga KR, Lo C, Cirstea MS, Leitao Filho FS, Walley KR, Russell JA, et al. Impact of PCSK9 loss-of-function genotype on 1-year mortality and recurrent Infection in sepsis survivors. EBioMedicine. 2018;38:257–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Atreya MR, Whitacre BE, Cvijanovich NZ, Bigham MT, Thomas NJ, Schwarz AJ, et al. Proprotein Convertase Subtilisin/Kexin type 9 loss-of-function is detrimental to the juvenile host with septic shock. Crit Care Med. 2020;48(10):1513–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The Third International Consensus definitions for Sepsis and septic shock (Sepsis-3). JAMA. 2016;315(8):801–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Stein EA, Raal FJ. Insights into PCSK9, low-density lipoprotein receptor, and low-density lipoprotein cholesterol metabolism: of mice and man. Circulation. 2013;127(24):2372–4.

    Article  PubMed  Google Scholar 

  17. Dwivedi DJ, Grin PM, Khan M, Prat A, Zhou J, Fox-Robichaud AE, et al. Differential expression of PCSK9 modulates Infection, inflammation, and Coagulation in a murine model of Sepsis. Shock (Augusta Ga). 2016;46(6):672–80.

    Article  CAS  PubMed  Google Scholar 

  18. Muady GF, Bitterman H, Laor A, Vardi M, Urin V, Ghanem-Zoubi N. Hemoglobin levels and blood transfusion in patients with sepsis in Internal Medicine Departments. BMC Infect Dis. 2016;16(1):569.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Sproston NR, Ashworth JJ. Role of C-Reactive protein at sites of inflammation and Infection. Front Immunol. 2018;9:754.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Mester P, Amend P, Schmid S, Müller M, Buechler C, Pavel V. Plasma Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) as a possible biomarker for severe COVID-19. Viruses. 2023;15(7):1511.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Arora S, Singh P, Singh PM, Trikha A. Procalcitonin levels in survivors and nonsurvivors of Sepsis: systematic review and Meta-analysis. Shock (Augusta Ga). 2015;43(3):212–21.

    Article  CAS  PubMed  Google Scholar 

  22. Li S, Guo YL, Xu RX, Zhang Y, Zhu CG, Sun J, et al. Association of plasma PCSK9 levels with white blood cell count and its subsets in patients with stable coronary artery Disease. Atherosclerosis. 2014;234(2):441–5.

    Article  CAS  PubMed  Google Scholar 

  23. Pirillo A, Catapano AL, Norata GD. HDL in infectious Diseases and sepsis. Handb Exp Pharmacol. 2015;224:483–508.

    Article  CAS  PubMed  Google Scholar 

  24. Hofmaenner DA, Arina P, Kleyman A, Page Black L, Salomao R, Tanaka S, et al. Association between Hypocholesterolemia and Mortality in critically Ill patients with Sepsis: a systematic review and Meta-analysis. Crit Care Explor. 2023;5(2):e0860.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Lee SH, Park MS, Park BH, Jung WJ, Lee IS, Kim SY, et al. Prognostic implications of serum lipid metabolism over Time during Sepsis. Biomed Res Int. 2015;2015:789298.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Peng J, Liu MM, Jin JL, Cao YX, Guo YL, Wu NQ, et al. Association of circulating PCSK9 concentration with cardiovascular metabolic markers and outcomes in stable coronary artery Disease patients with or without Diabetes: a prospective, observational cohort study. Cardiovasc Diabetol. 2020;19(1):167.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Wu Y, Shi J, Su Q, Yang Z, Qin L. Correlation between circulating PCSK9 levels and gestational Diabetes Mellitus in a Chinese Population. Front Endocrinol (Lausanne). 2022;13:826757.

    Article  PubMed  Google Scholar 

  28. Zhang C, Wang K, Yang L, Liu R, Chu Y, Qin X, et al. Lipid metabolism in inflammation-related Diseases. Analyst. 2018;143(19):4526–36.

    Article  CAS  PubMed  Google Scholar 

  29. Robinson G, Pineda-Torra I, Ciurtin C, Jury EC. Lipid metabolism in autoimmune rheumatic Disease: implications for modern and conventional therapies. J Clin Invest. 2022;132(2):e148552.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Feng Q, Wei WQ, Chaugai S, Carranza Leon BG, Kawai V, Carranza Leon DA, et al. A genetic Approach to the Association between PCSK9 and Sepsis. JAMA Netw open. 2019;2(9):e1911130.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Walley KR, Thain KR, Russell JA, Reilly MP, Meyer NJ, Ferguson JF, et al. PCSK9 is a critical regulator of the innate immune response and septic shock outcome. Sci Transl Med. 2014;6(258):258ra143.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

None.

Funding

This research was funded by the National Natural Science Foundation of China [grant numbers 82160075]; the Natural Science Foundation of Hunan Province, CN [grant numbers 2019JJ40230, 2020JJ4072, 2021JJ30534]; the Health Commission Program of Hunan province, CN [grant numbers B2019034, B2019035, B202303018485, 202113011165]; the Science and Technology Plan Project of the Huaihua city, CN [grant numbers 2021R3114, 2021R3115]; the School-level Scientific Research Project of Jishou University, CN [grant numbers Jdzd21041].

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Author notes

  1. Yuanlu Shu, Ziwei Deng and Ye Deng these authors contributed equally to this work.

Authors and Affiliations

  1. Evidence-based Medicine and Clinical Center, The First People’s Hospital of Huaihua, Huaihua, 418000, P.R. China

    Yuanlu Shu, Xiang Zhao & Chengfeng Qiu

  2. Clinical Pharmacy Department, The First People’s Hospital of Huaihua, Huaihua, 418000, P.R. China

    Ziwei Deng, Ye Deng, Zhihua Shi & Chengfeng Qiu

  3. Emergency Department, The First People’s Hospital of Huaihua, Huaihua, 418000, P.R. China

    Jianliang Zhou, Jin Wang, Zhenxing Duan & Tao Jiang

  4. School of Basic Medical Sciences, University of South China, Hengyang, 421000, P.R. China

    Chengfeng Qiu

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Contributions

Conceptualization: CQ, YS, Z(i)D, and YD; Methodology: JZ, JW, Z(h)D, TJ, XZ, and ZS; Data Curation, YS, and Z(i)D; Formal Analysis, YS, and CQ; Writing – Original Draft Preparation, YS, Z(i)D and YD; Writing – Review & Editing, CQ. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Chengfeng Qiu.

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Ethics approval and consent to participate

The study was approved by the research ethics committee of the First People’s Hospital of Huaihua (No. KY-2019082203). Informed consent was obtained from all study participants and the study was carried out in accordance with relevant guidelines and regulations (e.g. Declaration of Helsinki).

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Not applicable.

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Shu, Y., Deng, Z., Deng, Y. et al. Elevated circulating PCSK9 level is associated with 28-day mortality in patients with sepsis: a prospective cohort study. BMC Emerg Med 23, 127 (2023). https://0-doi-org.brum.beds.ac.uk/10.1186/s12873-023-00896-6

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BMC Emergency Medicine

ISSN: 1471-227X

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