You are here

  • Home
  • Archive
  • Volume 15, Issue 4
  • Association of hyperuricaemia and hyperglycaemia with risk of in-hospital mortality in acute aortic dissection: a multicentre cohort study in the Han Chinese population

Article Text

Article menu

Download PDFPDF

Epidemiology
Original research
Association of hyperuricaemia and hyperglycaemia with risk of in-hospital mortality in acute aortic dissection: a multicentre cohort study in the Han Chinese population
  1. Qu Zhao1,2,
  2. Wenhua Wang3,
  3. Abudunaibi Balati2,
  4. Baoquan Zhang4,
  5. Chunwen Li5,
  6. Suping Guo3,
  7. Dan Yu2,6,
  8. Peng Chen1,2
  1. 1Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorder, Wuhan, China
  2. 2Division of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
  3. 3Department of Cardiac Intensive Care Unit, Central China Fuwai Hospital of Zhengzhou University (Fuwai Central China Cardiovascular Hospital), Zhengzhou, China
  4. 4Department of Critical Care Medicine, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, China
  5. 5Department of Emergency Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
  6. 6Department of Cardiac Intensive Care Unit, People’s Hospital of Zhengzhou University (Henan Provincial People’s Hospital), Zhengzhou, China
  1. Correspondence to Dr Peng Chen; chenpeng_088{at}126.com

Abstract

Objective The objective is to investigate the association of hyperuricaemia and hyperglycaemia with an increased risk of mortality in acute aortic dissection (AAD).

Design Retrospective multicentre cohort study.

Setting De-identified information of patients was collected from electronic medical records between 2010 and 2021 across five hospitals in China.

Participants A total of 2603 AAD patients from 5337 patients who underwent arterial aortic computed tomographic angiography were selected after three rounds of screening.

Main outcome measure All-cause in-hospital mortality.

Results Of the 2603 patients, 20.3% were women, and the mean age was 54 years old. In-hospital mortality risk escalated linearly with increased levels of uric acid (P non-linearity=0.1699) and serum glucose (P non-linearity=0.2423). The per SD of increment in uric acid was associated with 40% (1.40, 1.22 to 1.60) in HR and 95% CI of AAD all-cause in-hospital mortality and 39% (1.39, 1.22 to 1.58) in serum glucose after full adjustment. Patients with a decrease in uric acid and/or serum glucose within the 7 days preceding admission showed significantly lower in-hospital mortality compared with those without a decrease. Notably, patients exhibiting both hyperuricaemia and serum glucose>180.2 mg/dL faced over double mortality risk (2.21, 1.58 to 3.10) compared with those with normal uric acid and normal serum glucose levels.

Conclusions Hyperuricaemia and hyperglycaemia are significantly associated with an increased risk of mortality among AAD patients in the Han Chinese population. These findings suggest the importance of monitoring and managing uric acid and glucose levels in AAD patients to potentially improve outcomes.

  • Cardiovascular Disease
  • China
  • EPIDEMIOLOGY
  • Vascular medicine

Data availability statement

Data are available on reasonable request.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bmjopen-2024-094857

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    STRENGTHS AND LIMITATIONS OF THIS STUDY

    • This multicentre, retrospective cohort study used data from hospitalised acute aortic dissection (AAD) patients across five hospitals in China, thereby improving representativeness and generalisability.

    • This study examined the impact of hyperglycaemia and hyperuricaemia, two prevalent and modifiable metabolic factors, on in-hospital mortality in AAD patients, with a focus on the cumulative risk posed by these metabolic factors.

    • This study was limited to all-cause mortality, precluding an assessment of cause-specific mortality. Long-term follow-up data were lacking to evaluate prognostic outcomes.

    • This study lacked data on glycated haemoglobin or long-term serum glucose dynamics, and further evaluation was needed in the future.

    Introduction

    Acute aortic dissection (AAD) is a severe and potentially life-threatening condition characterised by a high mortality rate and limited treatment options.1 2 Data from the International Registry of Acute Aortic Dissection indicate an overall mortality of 27.4% in the 2010s.3 Hypertension is widely recognised as a major risk factor for the adverse outcomes in AAD.4 Other identified risk factors include previous AAD, known aortic aneurysm, previous cardiac surgery, cigarette smoking, anatomical and haemodynamic considerations, atherosclerosis and various clinical biomarkers.1 3 5 Given their ease of detection and potential for targeted intervention, clinical biomarkers serve as crucial indicators for assessing the mortality risk in AAD patients.

    The role of metabolic factors in cardiovascular disease (CVD) has garnered increasing attention.6 Recent studies have demonstrated that metabolites can play a regulatory role in the pathological process of CVD.7 As an important CVD, AAD is also associated with metabolic factors. A number of metabolites have been found to be significantly altered in patients with aortic aneurysm or dissection.8–10 Uric acid and serum glucose, as the most commonly used clinical metabolic biomarkers, have been linked to aortic aneurysm or dissection in some studies.11–13 However, there are no relevant studies on the relationship between uric acid or serum glucose and mortality in AAD in the Chinese population. Furthermore, numerous studies have identified significant correlations between elevated uric acid and increased serum glucose or the onset of metabolic syndrome.14–16 Therefore, it is crucial to investigate whether the concurrent elevation of uric acid and blood glucose signifies more severe metabolic dysfunction. It is also important to explore their potential association with mortality risk from AAD.

    This study aims to investigate the relationship between uric acid, serum glucose and the risk of mortality in AAD, testing the hypothesis that elevated levels of these metabolic factors contribute to an increased risk of mortality. Additionally, we aim to examine the potential interaction between uric acid and serum glucose in influencing mortality risk in the Han Chinese population.

    Methods

    Study population and data collection

    This multicentre retrospective cohort study collected electronic medical records (EMRs) from August 2010 to October 2021 from five hospitals: Tongji Hospital Tongji Medical College of Huazhong University of Science and Technology, People’s Hospital of Zhengzhou University, Central China Fuwai Hospital of Zhengzhou University, the Third Affiliated Hospital of Xinxiang Medical University and the Second Affiliated Hospital of Chongqing Medical University, respectively. The data obtained were de-identified and collected from the hospitals’ anonymised medical record system built for clinical research purposes.

    All patients diagnosed with AAD through aortic CT angiography (CTA) were enrolled in the research. Exclusion criteria were: (1) unavailable EMRs, (2) under 18 years old, (3) aortic dissection in pregnancy, (4) non-Han patients, (5) with an overall absence of laboratory test results and (6) onset greater than 14 days or vague records of onset time. To prevent potential interference from high serum glucose levels on long-term patient outcomes, individuals with self-reported diabetes mellitus (DM) were omitted from the study.17 18 Data on demographics, medical history, initial vital signs, laboratory examination and CTA-based anatomical classification were gathered as baseline information during hospitalisation.

    Study variables

    The primary outcome of this study was AAD all-cause in-hospital mortality associated with study baseline variable. The variables of demographics, medical history, initial vital signs, laboratory examination, CTA and the outcome of the patient were identified based on the EMRs from the five hospitals. All blood samples were collected and tested within 2 hours of admission. The anatomical classification, based on the DeBakey system19 and the category of isolated abdominal AAD,20 was independently judged by a skilled clinician using aortic CTA. The aetiology of AAD was classified as hereditary, traumatic, congenital, vascular inflammation, infection or sporadic, depending on the patient’s medical history.

    As uric acid varies between different sexes, we defined hyperuricaemia according to the test standard of the clinical lab of the hospital, which was >7.0 mg/dL in men and >5.7 mg/dL in women. Serum glucose for the patients was classified as ≤109.9 mg/dL, 109.9–140.6 mg/dL, 140.6–180.2 mg/dL, >180.2 mg/dL, according to Diabetes Care in the Hospital: Standards of Medical Care in Diabetes—2022.21

    Statistical analysis

    The characteristics of the patients in our study were grouped according to their mortality outcomes. Categorical variables were presented as number and percentages, normally distributed continuous variables were presented as means and SD, and skewed distributed variables as median (IQR). Missing values were not interpolated. To compare these baseline characteristics, the χ2 test was used for categorical variables and the Mann-Whitney U test was used for continuous variables. Multivariate Cox proportional hazard regression models were used to calculate HRs and 95% CIs to investigate the relationship between uric acid levels, serum glucose levels and all-cause in-hospital mortality. General additive model (GAM) and contour map were used to visualise the synergistic effects of uric acid and serum glucose.

    Analyses were conducted using SAS V.9.4 and R software (the R Foundation, http://www.r-project.org, V.4.0.2) with a two-sided significance threshold of p<0.05. Plotting was conducted using R software (the R Foundation, http://www.r-project.org, V.4.0.2) and GraphPad Prism V.10.0.0 for Windows (GraphPad Software, www.graphpad.com, Boston, Massachusetts, USA).

    Patient and public involvement

    None.

    Results

    The population of AAD patients

    After three rounds of screening, we selected a total of 2603 patients from 5337 who underwent arterial CTA at the five hospitals between August 2010 and December 2021 (figure 1), with a mean age of 54 (IQR 46–62) years old and women accounted for 20.3%. There were 599 cases of all-cause in-hospital mortality, with an incidence rate of 23.01%. These patients had a significant difference in anatomical classification, smoking history, hypertension history, stroke or coma history, procedure of operation, onset time and hospital centres, compared with the in-hospital survived patients (online supplemental table 1).

    Figure 1
    Figure 1

    Flowchart of the study. AAD, acute aortic dissection; EMRs, electronic medical records.

    Association between uric acid and serum glucose with the risk of AAD all-cause in-hospital mortality

    Cox regression analyses were conducted using uric acid and serum glucose as continuous variables to fit smoothing splines that represent the dose–response relationship between these two variables and the risk of mortality. The adjusted risk of all-cause in-hospital mortality was positively associated with increasing uric acid and increasing serum glucose. The test for non-linearity for AAD all-cause in-hospital mortality was not statistically significant for uric acid (P non-linearity=0.170) and serum glucose (P non-linearity=0.243) (figure 2A,B). Therefore, we converted uric acid and serum glucose into categorical variables. Uric acid was delivered as normal uric acid and hyperuricaemia based on different sexes, and serum glucose was delivered into four groups. Baseline characteristics of patients in different uric acid and serum glucose groups are shown in tables 1 and 2 and online supplemental tables 2 and 3.

    Figure 2
    Figure 2

    HRs and 95% CIs of uric acid (A) and serum glucose (B), adjusted for smoking history, hypertension history, aortic valve replacement history, anatomical classification, procedure of operation and onset time and hospital centres.

    View this table:
    Table 1

    Baseline characteristics of patients in different uric acid groups

    View this table:
    Table 2

    Baseline characteristics of patients in different serum glucose groups

    The unadjusted Kaplan-Meier survival curve showed a significant difference between the groups of patients with different levels of uric acid (figure 3A,B) and serum glucose (figure 3C,D) (p<0.0001, log-rank test) in both 7 days after admission and 28 days after admission. Patients with hyperuricaemia developed a higher all-cause in-hospital mortality HR of 1.47 (1.24–1.75) versus patients with normal uric acid as reference (online supplemental table 4). In comparison to patients in group 1 (serum glucose≤109.9 mg/dL) as reference, patients in group 4 (serum glucose>180.2 mg/dL) had a higher all-cause in-hospital mortality HR of 1.60 (1.22–2.09) while no significant difference in HR was found between patients in group 2 (serum glucose 109.9–140.6 mg/dL) and group 3 (serum glucose 140.6–180.2 mg/dL) when compared with the reference (online supplemental table 5). Adjusted models using stepwise Cox regression analyses were shown in table 3. When uric acid and serum glucose were considered as continuous variables, per SD of increment in uric acid was associated with 40% (1.40, 1.22 to 1.60) in HR and 95% CI of AAD all-cause in-hospital mortality and 39% (1.39, 1.22 to 1.58) in serum glucose in model 3. The HRs and 95% CIs of normal uric acid and hyperuricaemia for all-cause in-hospital mortality were 1.00 (reference) and 1.52 (1.26 to 1.84), respectively, in the crude model, while in the full adjusted model (model 3) were 1.00 (reference) and 1.45 (1.07 to 1.96). The HRs and 95% CI of different serum glucose levels for all-cause in-hospital mortality were 1.00 (reference), 1.42 (1.12 to 1.82), 1.71 (1.31 to 2.24) and 3.30 (2.46 to 4.41), respectively, in the crude model from the lowest level to the highest one, while in the full adjusted model (model 3) were 1.00 (reference), 1.15 (0.90 to 1.48), 1.34 (1.02 to 1.77) and 2.30 (1.70 to 3.10), respectively.

    Figure 3
    Figure 3

    Kaplan-Meier survival curve of acute aortic dissection in-hospital mortality showing that outcomes significantly varied among the groups of patients with the different levels of uric acid (A,B) and serum glucose (C,D) (p<0.001, log-rank test) in 7 days after admission and 28 days after admission.

    View this table:
    Table 3

    Associations of serum glucose and uric acid level with risk of in-hospital mortality

    Association of uric acid, serum glucose and AAD all-cause in-hospital mortality

    Combined analysis of uric acid, serum glucose and AAD all-cause in-hospital mortality showed more than double risk (2.21, 1.58–3.10) was observed in patients with hyperuricaemia and serum glucose>180.2 mg/dL, compared with those with normal uric acid and serum glucose≤109.9 mg/dL. The two variables showed were used statistically significant interaction (p=0.005) when they were used as continuous variables. Then the GAM and contour map were used to visualise the synergistic effects of uric acid and serum glucose (figure 4), indicating the value of hyperuricaemia and hyperglycaemia combining to estimate the in-hospital modality risk of AAD patients.

    Figure 4
    Figure 4

    Contour map based on general additive model showed the association between uric acid, serum glucose and HR of in-hospital mortality.

    Dynamic change of uric acid and serum glucose and AAD all-cause in-hospital mortality

    Since patients experience dynamic fluctuations in uric acid and serum glucose levels, we investigated the association between dynamic change of uric acid and serum glucose during the first 7 days post admission and all-cause in-hospital mortality among AAD patients. Repeated measures analysis of variance showed that AAD patients who died in the hospital exhibited significantly elevated uric acid and serum glucose levels compared with those who did not (p<0.001). Mann-Whitney U test showed that there were significant differences between them on all 7 days post admission (online supplemental figure 1). The all-cause in-hospital mortality was significantly higher (p<0.001) in patients who did not experience a decrease in uric acid levels within the 7 days preceding admission, compared with those who exhibited a decrease during the same timeframe. The similar result was found in dynamic changes of serum glucose (table 4).

    View this table:
    Table 4

    All-cause in-hospital mortality in patients with or without decrease in uric acid/serum glucose

    Sensitivity analysis

    We performed stratified analyses by sex, age, onset time, anatomical classification, operation type and medical centre (online supplemental tables 6 and 7). It was found that the associations between uric acid and serum glucose and AAD all-cause in-hospital mortality showed no statistically significant differences across sex and age groups.

    Discussion

    This study aimed to explore the association between uric acid, serum glucose levels and all-cause in-hospital mortality among AAD patients, focusing on the cumulative risk posed by these metabolic factors. Our findings confirm that both hyperglycaemia and hyperuricaemia significantly increase the risk of mortality in this patient population and that combined elevations in these markers further exacerbate mortality risk.

    Our findings align with those from the Specific Health Check and Guidance study in Japan,22 reinforcing the significant impact of hyperuricaemia on increasing mortality in AAD patients. Similarly, Li et al23 highlighted that elevated uric acid levels are strongly associated with a higher risk of both all-cause and cardiovascular mortality. The HR and CIs were 1.08 (1.05 to 1.11) and 1.05 (1.03 to 1.06), respectively. Yang et al24 also found that elevated uric acid levels were significantly associated with an increased risk of cardiovascular or all-cause mortality, coronary artery disease and major adverse cardiovascular events in patients with hypertension. Elevated serum uric acid levels have been associated with an increased risk of both short-term or mid/long-term mortality and major adverse cardiovascular events in patients experiencing acute myocardial infarction.25 Recent research26 found the direct impact of lowering uric acid levels to improve mortality in Beta-aminopropionitrile (BAPN)-induced thoracic aortic aneurysms and dissection (TAAD) mice. These reports further substantiate our findings. In animal models of hyperuricaemia, the proliferation of vascular smooth muscle cells and subsequent luminal narrowing have been observed, underscoring the detrimental impact of elevated uric acid levels on vascular health.27 Such findings offer a plausible explanation for the observed increase in AAD all-cause in-hospital mortality linked to hyperuricaemia, potentially due to endothelial dysfunction and overactivation of local inflammation, adversely affecting vascular remodelling and recovery processes.27–29 Our hypothesis is further substantiated by clinical evidence indicating a significant correlation between hyperuricaemia and both stroke morbidity and mortality,30 31 as well as its association with the incidence of atherosclerosis.32

    Regarding serum glucose, our study identified an association between hyperglycaemia and in-hospital mortality in AAD patients, which contrasts with the findings from the Union Hospital of Fujian Medical University.33 Their study showed no significant association between hyperglycaemia and in-hospital mortality in patients with acute type A aortic dissection (20.3% vs 23.2%, p>0.05) when compared with patients with normal serum glucose. However, in fact, previous studies have yielded some evidence regarding the detrimental effects of hyperglycaemia. Some large-scale prospective studies34 35 have already demonstrated the tissue damage caused by hyperglycaemia. Sodium-glucose cotransporter-2 inhibitors, classified as hypoglycaemic agents, have also demonstrated cardiovascular benefits.36 Hyperglycaemia can cause vascular injury through multiple pathways.37 In AAD patients, elevated serum glucose may further aggravate arterial injury through the aforementioned mechanisms, impairing vascular repair and increasing susceptibility to aortic dissection expansion or rupture, ultimately leading to higher in-hospital mortality.

    In the sensitivity analysis, we observed that the association between uric acid levels and serum glucose and all-cause in-hospital mortality remained unaffected by demographic variables such as age and sex (online supplemental tables 6 and 7). However, the mortality risk in AAD patients is influenced by a range of factors, including age, sex, onset time, anatomical classification, operation type and the quality of medical care.3 This may contribute to the observed variability in the effects of uric acid and serum glucose within the subgroups defined by anatomical classification, surgical approach, onset time and medical centre.

    The novelty of this study lies in the identification of a synergistic effect between uric acid and serum glucose on AAD all-cause in-hospital mortality. Our analysis reveals that hyperuricaemia significantly elevates the risk of mortality in AAD patients, particularly when accompanied by elevated serum glucose levels. We postulate that the simultaneous elevation of uric acid and glucose may exacerbate metabolic dysregulation and increase the burden on vascular repair mechanisms, thereby leading to higher rates of in-hospital mortality. This finding highlights the combined impact of elevated uric acid and glucose levels in AAD patients, which is comparable to the various metabolic abnormalities observed in metabolic syndrome. Consequently, clinical management for AAD patients should not only focus on controlling blood pressure and directly addressing aortic dissection, but also consider the patients’ metabolic status. The concurrent presence of hyperuricaemia and hyperglycaemia may predispose patients to an increased risk of cardiovascular events even after the acute phase, indicating the need for in-hospital and extended health management.

    This retrospective observational study presents not only valuable insights but also has several limitations that merit careful consideration. First, the results cannot establish causality due to the nature of observational studies. Second, the measurement of uric acid and serum glucose levels was conducted at a single point in time or the first 7 days after admission, which may not accurately represent fluctuations in these levels throughout the hospital stay. Moreover, to mitigate the potential confounding effects of DM on the study outcomes, patients with a known history of DM were excluded. However, due to the absence of glycosylated haemoglobin (HbA1c) test results, there may be undiagnosed DM cases among patients without a self-reported history. As a result, a subset of undiagnosed DM cases may have been excluded from the analysis, which could impact the generalisability and accuracy of our findings. Future prospective cohort studies may explore the potential association between diabetes/HbA1c levels and in-hospital mortality in patients with AAD. Fourth, although the Han Chinese population can represent East Asians to some extent, this study included only Han individuals due to the very small non-Han sample and genetic background differences. It may limit the generalisability of the results to other ethnic groups.

    Despite these limitations, we believe that this study offers valuable support for clinicians in identifying AAD patients at higher risk of mortality.

    Conclusion

    This multicentre retrospective cohort study highlights the significant association between hyperuricaemia, hyperglycaemia and increased mortality risk in patients hospitalised with AAD. The findings show that the presence of either hyperuricaemia or hyperglycaemia elevates the risk of AAD all-cause in-hospital mortality, with this risk being notably amplified when both conditions coexist. These insights highlight the critical need for clinicians to closely monitor and manage these metabolic factors in AAD patients, aiming to enhance patient prognosis and survival outcomes.

    Data availability statement

    Data are available on reasonable request.

    Ethics statements

    Patient consent for publication

    Ethics approval

    This study involves human participants. This study has received approval from the research ethics commissions of Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology (TJ-IRB20211102), People’s Hospital of Zhengzhou University (2021-190), Central China Fuwai Hospital of Zhengzhou University (2021-38), the Third Affiliated Hospital of Xinxiang Medical University (K2021-039-01) and the Second Affiliated Hospital of Chongqing Medical University (2022-15). Informed consent was waived by the respective ethics commissions. The authors had access to information which might identify individual patients during or after data collection. As this is a retrospective study using de-identified data, the institutional review board did not require patient consent.

    Acknowledgments

    We thank all medical staff including physicians and nurses for their efforts in the five medical centres.

    References

    1. ↵
      1. Erbel R,
      2. Aboyans V,
      3. Boileau C, et al
      . 2014 ESC Guidelines on the diagnosis and treatment of aortic diseases: Document covering acute and chronic aortic diseases of the thoracic and abdominal aorta of the adult. The Task Force for the Diagnosis and Treatment of Aortic Diseases of the European Society of Cardiology (ESC). Eur Heart J 2014;35:2873–926. doi:10.1093/eurheartj/ehu281
      OpenUrlCrossRefPubMedWeb of Science
    2. ↵
      1. Rylski B,
      2. Schilling O,
      3. Czerny M
      . Acute aortic dissection: evidence, uncertainties, and future therapies. Eur Heart J 2023;44:813–21. doi:10.1093/eurheartj/ehac757
      OpenUrlPubMed
    3. ↵
      1. Evangelista A,
      2. Isselbacher EM,
      3. Bossone E, et al
      . Insights From the International Registry of Acute Aortic Dissection: A 20-Year Experience of Collaborative Clinical Research. Circulation 2018;137:1846–60. doi:10.1161/CIRCULATIONAHA.117.031264
      OpenUrlAbstract/FREE Full Text
    4. ↵
      1. Hibino M,
      2. Otaki Y,
      3. Kobeissi E, et al
      . Blood Pressure, Hypertension, and the Risk of Aortic Dissection Incidence and Mortality: Results From the J-SCH Study, the UK Biobank Study, and a Meta-Analysis of Cohort Studies. Circulation 2022;145:633–44. doi:10.1161/CIRCULATIONAHA.121.056546
      OpenUrlCrossRefPubMed
    5. ↵
      1. Nienaber CA,
      2. Clough RE
      . Management of acute aortic dissection. Lancet 2015;385:800–11. doi:10.1016/S0140-6736(14)61005-9
      OpenUrlCrossRefPubMed
    6. ↵
      1. Joseph JJ,
      2. Deedwania P,
      3. Acharya T, et al
      . Comprehensive Management of Cardiovascular Risk Factors for Adults With Type 2 Diabetes: A Scientific Statement From the American Heart Association. Circulation 2022;145:e722–59. doi:10.1161/CIR.0000000000001040
      OpenUrlCrossRefPubMed
    7. ↵
      1. Jin L,
      2. Shi X,
      3. Yang J, et al
      . Gut microbes in cardiovascular diseases and their potential therapeutic applications. Protein Cell 2021;12:346–59. doi:10.1007/s13238-020-00785-9
      OpenUrl
    8. ↵
      1. Yang H,
      2. Yang F,
      3. Luo M, et al
      . Metabolomic Profile Reveals That Ceramide Metabolic Disturbance Plays an Important Role in Thoracic Aortic Dissection. Front Cardiovasc Med 2022;9:826861. doi:10.3389/fcvm.2022.826861
    9. ↵
      1. Gu J,
      2. Hu J,
      3. Qian H, et al
      . Intestinal Barrier Dysfunction: A Novel Therapeutic Target for Inflammatory Response in Acute Stanford Type A Aortic Dissection. J Cardiovasc Pharmacol Ther 2016;21:64–9. doi:10.1177/1074248415581176
      OpenUrlCrossRefPubMed
    10. ↵
      1. Wong YYE,
      2. Golledge J,
      3. Flicker L, et al
      . Plasma total homocysteine is associated with abdominal aortic aneurysm and aortic diameter in older men. J Vasc Surg 2013;58:364–70. doi:10.1016/j.jvs.2013.01.046
      OpenUrl
    11. ↵
      1. Tsai CL,
      2. Lin CL,
      3. Wu YY, et al
      . Advanced complicated diabetes mellitus is associated with a reduced risk of thoracic and abdominal aortic aneurysm rupture: a population-based cohort study. Diabetes Metab Res Rev 2015;31:190–7. doi:10.1002/dmrr.2585
      OpenUrlCrossRefPubMed
    12. ↵
      1. Takagi H,
      2. Umemoto T, ALICE (All-Literature Investigation of Cardiovascular Evidence) Group
      . Negative Association of Diabetes With Thoracic Aortic Dissection and Aneurysm. Angiol Open Access 2017;68:216–24. doi:10.1177/0003319716647626
      OpenUrl
    13. ↵
      1. Li WF,
      2. Huang YQ,
      3. Feng YQ
      . Serum uric acid concentration is associated with ascending aortic dilatation in newly diagnosed nondiabetic hypertensive patients. Clin Exp Hypertens 2020;42:75–80. doi:10.1080/10641963.2019.1571602
      OpenUrl
    14. ↵
      1. Lee MJ,
      2. Khang AR,
      3. Kang YH, et al
      . Synergistic Interaction between Hyperuricemia and Abdominal Obesity as a Risk Factor for Metabolic Syndrome Components in Korean Population. Diabetes Metab J 2022;46:756–66. doi:10.4093/dmj.2021.0166
      OpenUrl
    15. ↵
      1. Tu YC,
      2. Liu YH,
      3. Chen SC, et al
      . Metabolic Syndrome and Its Components Are Associated with New-Onset Hyperuricemia in a Large Taiwanese Population Follow-Up Study. Nutrients 2023;15:1083. doi:10.3390/nu15051083
    16. ↵
      1. Babio N,
      2. Martínez-González MA,
      3. Estruch R, et al
      . Associations between serum uric acid concentrations and metabolic syndrome and its components in the PREDIMED study. Nutr Metab Cardiovasc Dis 2015;25:173–80. doi:10.1016/j.numecd.2014.10.006
      OpenUrlCrossRefPubMed
    17. ↵
      1. Holman RR,
      2. Paul SK,
      3. Bethel MA, et al
      . 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008;359:1577–89. doi:10.1056/NEJMoa0806470
      OpenUrlCrossRefPubMedWeb of Science
    18. ↵
      1. Doehner W,
      2. Schoene N,
      3. Rauchhaus M, et al
      . Effects of xanthine oxidase inhibition with allopurinol on endothelial function and peripheral blood flow in hyperuricemic patients with chronic heart failure: results from 2 placebo-controlled studies. Circulation 2002;105:2619–24. doi:10.1161/01.cir.0000017502.58595.ed
      OpenUrlAbstract/FREE Full Text
    19. ↵
      1. Nienaber CA,
      2. Clough RE,
      3. Sakalihasan N, et al
      . Aortic dissection. Nat Rev Dis Primers 2016;2:16053. doi:10.1038/nrdp.2016.53
      OpenUrl
    20. ↵
      1. Liu Y,
      2. Han M,
      3. Zhao J, et al
      . Systematic Review and Meta-analysis of Current Literature on Isolated Abdominal Aortic Dissection. Eur J Vasc Endovasc Surg 2020;59:545–56. doi:10.1016/j.ejvs.2019.05.013
      OpenUrl
    21. ↵
      1. American Diabetes Association Professional Practice Committee
      . 16. Diabetes Care in the Hospital: Standards of Medical Care in Diabetes-2022. Diabetes Care 2022;45:S244–53. doi:10.2337/dc22-S016
      OpenUrlCrossRefPubMed
    22. ↵
      1. Otaki Y,
      2. Watanabe T,
      3. Konta T, et al
      . Impact of hyperuricemia on mortality related to aortic diseases: a 3.8-year nationwide community-based cohort study. Sci Rep 2020;10:14281. doi:10.1038/s41598-020-71301-6
    23. ↵
      1. Li B,
      2. Chen L,
      3. Hu X, et al
      . Association of Serum Uric Acid With All-Cause and Cardiovascular Mortality in Diabetes. Diabetes Care 2023;46:425–33. doi:10.2337/dc22-1339
      OpenUrlCrossRefPubMed
    24. ↵
      1. Yang Y,
      2. Zhang X,
      3. Jin Z, et al
      . Association of serum uric acid with mortality and cardiovascular outcomes in patients with hypertension: a meta-analysis. J Thromb Thrombolysis 2021;52:1084–93. doi:10.1007/s11239-021-02453-z
      OpenUrl
    25. ↵
      1. Xu Q,
      2. Zhang M,
      3. Abeysekera IR, et al
      . High serum uric acid levels may increase mortality and major adverse cardiovascular events in patients with acute myocardial infarction. Saudi Med J 2017;38:577–85. doi:10.15537/smj.2017.6.17190
      OpenUrlAbstract/FREE Full Text
    26. ↵
      1. Yang L,
      2. Wu H,
      3. Luo C, et al
      . Urate-Lowering Therapy Inhibits Thoracic Aortic Aneurysm and Dissection Formation in Mice. Arterioscler Thromb Vasc Biol 2023;43:e172–89. doi:10.1161/ATVBAHA.122.318788
      OpenUrl
    27. ↵
      1. Kang D-H,
      2. Nakagawa T,
      3. Feng L, et al
      . A role for uric acid in the progression of renal disease. J Am Soc Nephrol 2002;13:2888–97. doi:10.1097/01.asn.0000034910.58454.fd
      OpenUrlAbstract/FREE Full Text
    28. ↵
      1. Sul OJ,
      2. Ra SW
      . Quercetin Prevents LPS-Induced Oxidative Stress and Inflammation by Modulating NOX2/ROS/NF-kB in Lung Epithelial Cells. Molecules 2021;26:6949. doi:10.3390/molecules26226949
    29. ↵
      1. Mittal M,
      2. Siddiqui MR,
      3. Tran K, et al
      . Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal 2014;20:1126–67. doi:10.1089/ars.2012.5149
      OpenUrlCrossRefPubMedWeb of Science
    30. ↵
      1. Kim SY,
      2. Guevara JP,
      3. Kim KM, et al
      . Hyperuricemia and risk of stroke: a systematic review and meta-analysis. Arthritis Rheum 2009;61:885–92. doi:10.1002/art.24612
      OpenUrlCrossRefPubMedWeb of Science
    31. ↵
      1. Li M,
      2. Hou W,
      3. Zhang X, et al
      . Hyperuricemia and risk of stroke: a systematic review and meta-analysis of prospective studies. Atherosclerosis 2014;232:265–70. doi:10.1016/j.atherosclerosis.2013.11.051
      OpenUrl
    32. ↵
      1. Ji X,
      2. Leng X-Y,
      3. Dong Y, et al
      . Modifiable risk factors for carotid atherosclerosis: a meta-analysis and systematic review. Ann Transl Med 2019;7:632. doi:10.21037/atm.2019.10.115
    33. ↵
      1. Lin L,
      2. Lin Y,
      3. Peng Y, et al
      . Admission Hyperglycemia in Acute Type A Aortic Dissection Predicts for a Prolonged Duration of Mechanical Ventilation. Int Heart J 2022;63:106–12. doi:10.1536/ihj.21-485
      OpenUrl
    34. ↵
      Effect of intensive diabetes treatment on the development and progression of long-term complications in adolescents with insulin-dependent diabetes mellitus: Diabetes Control and Complications Trial. Diabetes Control and Complications Trial Research Group. J Pediatr 1994;125:177–88. doi:10.1016/s0022-3476(94)70190-3
      OpenUrlCrossRefPubMedWeb of Science
    35. ↵
      Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:837–53.
      OpenUrlCrossRefPubMedWeb of Science
    36. ↵
      1. Heerspink HJL,
      2. Perkins BA,
      3. Fitchett DH, et al
      . Sodium Glucose Cotransporter 2 Inhibitors in the Treatment of Diabetes Mellitus: Cardiovascular and Kidney Effects, Potential Mechanisms, and Clinical Applications. Circulation 2016;134:752–72. doi:10.1161/CIRCULATIONAHA.116.021887
      OpenUrlAbstract/FREE Full Text
    37. ↵
      1. Giacco F,
      2. Brownlee M
      . Oxidative stress and diabetic complications. Circ Res 2010;107:1058–70. doi:10.1161/CIRCRESAHA.110.223545
      OpenUrlAbstract/FREE Full Text
      1. Koba A,
      2. Yamagishi K,
      3. Sairenchi T, et al
      . Risk Factors for Mortality From Aortic Aneurysm and Dissection: Results From a 26-Year Follow-Up of a Community-Based Population. J Am Heart Assoc 2023;12:e027045. doi:10.1161/JAHA.122.027045
      1. Vrsalović M,
      2. Vrsalović Presečki A
      . Admission C-reactive protein and outcomes in acute aortic dissection: a systematic review. Croat Med J 2019;60:309–15. doi:10.3325/cmj.2019.60.309
      OpenUrl
      1. Wei X-B,
      2. Wang Y,
      3. Luo J-F, et al
      . Utility of age, creatinine, and ejection fraction score in patients with type B aortic dissection undergoing thoracic endovascular aortic repair. Int J Cardiol 2020;303:69–73. doi:10.1016/j.ijcard.2019.09.076
      OpenUrl

    Footnotes

    • QZ and WW contributed equally.

    • Contributors All authors contributed substantially to this study. SG, DY and PC supervised and designed the study. DY, WW, BZ and CL helped to collect the data. QZ and AB analysed the data. QZ wrote the article. PC is the guarantor.

    • Funding This study was supported in part by the National Natural Science Foundation of China (No. 82100510).

    • Competing interests None declared.

    • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.