Association of serum complement C3 with central pulmonary embolism in patients with acute pulmonary embolism: a cross-sectional study in Jilin Province, China

Association of serum complement C3 with central pulmonary embolism in patients with acute pulmonary embolism: a cross-sectional study in Jilin Province, China | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Association of serum complement C3 with central pulmonary embolism in patients with acute pulmonary embolism: a cross-sectional study in Jilin Province, China Baoguo Wang, Jian Zhang, Liping Zhang, Bo Li, Ming Lu, Hongjun Zhang, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9369379/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract Background Acute pulmonary embolism (PE) is a major cause of cardiovascular mortality. The complement system is implicated in inflammatory and thrombotic processes. This study aimed to explore the association between serum complement C3 levels and the presence of central PE in patients with acute PE. Methods This cross-sectional study enrolled 416 acute PE patients from the First Hospital of Jilin University. Acute PE was diagnosed based on computed tomographic pulmonary angiography. Logistic regression models and subgroup analyses were used to evaluate the association between serum complement C3 and central PE. Restricted cubic spline (RCS) analysis was conducted to investigate potential non-linear relationships. The discriminatory ability of serum complement C3 for central PE was assessed using receiver operating characteristic (ROC) curve analysis. Results Among the 416 patients, 270 (64.9%) were diagnosed with central PE. In fully adjusted models, higher serum complement C3 was significantly associated with a higher likelihood of central PE (highest vs. lowest quartile: OR = 4.21, 95% CI: 2.05–8.66, P < 0.001). Subgroup analyses according to gender, age, hypertension, and diabetes status showed consistent trends without significant interaction. RCS analysis indicated a linear dose-response relationship. ROC curve analysis demonstrated that serum complement C3 had moderate discriminative ability for central PE, with an area under the curve (AUC) of 0.641. Conclusion This study demonstrated a significant association between serum complement C3 levels and central PE in Chinese patients with acute PE. Specifically, higher serum complement C3 levels were associated with a higher prevalence of central PE. Further prospective longitudinal studies are needed to validate these findings. serum complement C3 central pulmonary embolism cross-sectional study thromboinflammation Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Acute pulmonary embolism (PE), a life-threatening condition caused by thromboembolic obstruction of the pulmonary vasculature, remains a major contributor to global cardiovascular morbidity and mortality[ 1 – 3 ]. Central PE, defined as the presence of a thrombus in the main pulmonary artery or its left or right main branches, is often associated with more severe hemodynamic compromise and a higher risk of early mortality compared to peripheral PE[ 4 – 6 ]. In recent years, the interplay between thrombosis and the innate immune system, particularly the complement system—termed “thromboinflammation”—has emerged as a major focus of research in cardiovascular disease[ 7 , 8 ]. Complement component 3 (C3), the convergence point of all activation pathways, is central to this process. Upon activation, C3 cleavage yields bioactive fragments like the anaphylatoxin C3a, which promotes inflammation, endothelial dysfunction, and thrombosis[ 9 – 14 ]. A self-amplifying C3/C3a circuit has been implicated in vascular injury models[ 15 ], and C3 deposition on neutrophil extracellular traps can localize and exacerbate vascular damage[ 12 ]. These mechanisms position the complement system as a potential link between systemic inflammation and thrombotic events. A large-scale population-based cohort study showed that higher baseline levels of complement C3 in individuals without venous thromboembolism (VTE) were significantly associated with an increased risk of developing VTE, including deep vein thrombosis (DVT) and PE[ 16 ]. Another clinical study involving 109 normotensive, non-cancer white adults with acute PE found an increase in the proportion of central PE across rising tertiles of complement C3 levels and C3a levels were independently associated with right ventricular dysfunction (RVD) and the severity of PE[ 17 ]. Other studies found higher C3 levels predicted poorer outcomes after ischemic stroke[ 18 , 19 ]. Although the relationship between complement system and thrombosis is established, the association between serum complement C3 levels and the presence of central PE among acute PE patients remains limited. Therefore, this cross-sectional study aimed to investigate the potential association between serum complement C3 levels and the presence of central PE among acute PE patients in China. Materials and methods Study population This a single-center, retrospective, cross-sectional study consecutively enrolled 1089 acute PE patients at the First Hospital of Jilin University between April 1, 2023 and December 1, 2025. Inclusion criteria were as follows: (1) Age ≥ 18 years; (2) Diagnosis of acute PE was based on computed tomographic pulmonary angiography (CTPA); (3) Time from symptom onset to hospital admission ≤ 14 days. Exclusion criteria included: (1) missing complement C3 data; (2) missing CTPA images; (3) missing echocardiography data; (4) history of trauma or surgery within 1 month; (5) active malignancy, chronic thromboembolic pulmonary hypertension (CTEPH), liver cirrhosis, severe pneumonia, systemic lupus erythematosus (SLE) at admission. The final analytic sample comprised 416 acute PE patients. The detailed selection process is illustrated in Fig. 1 . The study protocol was approved by the Ethics Committee of First Hospital of Jilin University (Approval No. 2026-117). The requirement for informed consent was waived as the study utilized only anonymized retrospective data. Diagnostic Criteria Central PE was defined as the presence of a thrombus in the main pulmonary artery, or the left or right main pulmonary artery and peripheral PE in the lobar, segmental, or subsegmental arteries on CTPA[20]. RVD was defined by transthoracic echocardiographic parameters, including enlarged right ventricle on parasternal long axis view, basal right ventricle (RV)/ left ventricle (LV) ratio >1.0 on four chamber view and decreased tricuspid annular plane systolic excursion (TAPSE) measured with M-Mode (<16 mm), which was performed in strict accordance with the 2019 ESC Guidelines for the Diagnosis and Management of Acute Pulmonary Embolism Developed in Collaboration with the European Respiratory Society (ERS)[21]. Chronic heart failure was diagnosed in accordance with the European Society of Cardiology (ESC) guidelines[22]. Chronic pulmonary disease included asthma or chronic obstructive pulmonary disease (COPD). Statistical analysis Continuous variables were presented as means ± standard deviations, while group comparisons were performed using the T-test or Mann -Whitney U test. Categorical variables were displayed as numbers and percentages, while group comparisons were performed via the chi-square test or Fisher's exact test. Logistic regression analyses were performed in crude and adjusted models to investigate the associations between serum complement C3 levels and the presence of central PE. In model I, no adjustments for covariates were applied. Model II was adjusted for variables including age and gender. Model III was additionally adjusted for heart rate, systolic pressure, hypertension, diabetes, chronic pulmonary disease, chronic heart failure, atrial fibrillation, history of VTE, smoking history, alcohol consumption history. Model IV was additionally adjusted for serum creatinine, high-sensitive C-reactive protein (hs-CRP), DVT. Restricted cubic splines (RCS) were used to examine the dose-response relationship between serum complement C3 levels and the presence of central PE. The discriminatory ability of complement C3 for central PE was evaluated using receiver operating characteristic (ROC) curve analysis. To assess the robustness of the association, we performed a pre-specified subgroup analysis. In the subgroup analysis, we examined the relationship between serum complement C3 levels and the presence of central PE according to age (≤65 years vs.>65 years), gender (male vs. female), hypertension (no vs. yes), and diabetes (no vs. yes). Interactions between subgroups were assessed using the likelihood ratio test. The percentages of missing values were lower than 15%. We imputed missing data of the covariates by using multiple imputations. Five datasets were created and analysed together. All the analyses were performed with the statistical software packages R (http://www.R-project.org, The R Foundation) and Free Statistics software versions 2.4.0. Statistical significance was defined as P < 0.05. Results Participant Baseline Characteristics After applying the eligibility criteria, 416 participants were enrolled to investigate the relationship between serum complement C3 levels and the presence of central PE. The mean age was 64.3 years; 50% were men, indicating a balanced sex distribution. Overall, 270 participants (64.9%) had central PE. Table 1 presents the baseline characteristics of the study participants categorized according to the type of PE. Statistically significant differences (p<0.05) were observed for heart rate, alcohol consumption history, globulin, γ‑glutamyl transferase, hs-CRP, total cholesterol, low-density lipoprotein cholesterol (LDL-C), serum uric acid, partial pressure of arterial oxygen (PaO₂), partial pressure of arterial carbon dioxide (PaCO₂), lactate, soluble suppression of tumorigenicity 2 (sST2), serum complements C3 and C4, as well as the proportions of patients with increased B-type natriuretic peptide/N-terminal pro-B-type natriuretic peptide (BNP/NT-proBNP), increased cardiac troponin I (cTnI), RVD, DVT, and those receiving mechanical thrombectomy or systemic thrombolysis. Compared with patients with peripheral PE, those with central PE exhibited higher inflammatory and metabolic markers (e.g., hs-CRP, sST2, serum uric acid), more pronounced abnormalities in blood gas parameters (lower PaO₂ and PaCO₂), and a greater prevalence of indicators associated with disease severity (RVD) and the need for more invasive interventions. Table 1. Baseline characteristics of the study participants Variable Total (n = 416) Peripheral PE (n = 146) Central PE (n = 270) P * Age(years) 64.3 ± 13.0 64.5 ± 12.0 64.3 ± 13.6 0.893 Male, n(%) 208 (50.0) 71 (48.6) 137 (50.7) 0.681 * Heart rate(beat/min) 85.8 ± 17.6 82.0 ± 15.5 87.9 ± 18.4 0.001 * Systolic pressure(mmHg) 129.1 ± 21.4 130.6 ± 22.1 128.2 ± 21.1 0.277 Hypertension, n(%) 190 (45.7) 65 (44.5) 125 (46.3) 0.729 Diabetes, n(%) 67 (16.1) 19 (13) 48 (17.8) 0.207 Chronic pulmonary disease, n(%) 28 ( 6.7) 9 (6.2) 19 (7) 0.735 Chronic heart failure, n(%) 20 ( 4.8) 10 (6.8) 10 (3.7) 0.152 Atrial fibrillation, n(%) 28 ( 6.7) 10 (6.8) 18 (6.7) 0.943 History of VTE, n(%) 11 ( 2.6) 1 (0.7) 10 (3.7) 0.106 Smoking history, n (%) 67 (16.1) 20 (13.7) 47 (17.4) 0.326 Alcohol consumption history, n(%) 55 (13.2) 12 (8.2) 43 (15.9) 0.027 * White blood cell count(10 9 /L) 10.0 ± 5.3 9.5 ± 6.3 10.2 ± 4.7 0.189 * Absolute neutrophil count(10 9 /L) 6.9 ± 3.7 6.4 ± 4.0 7.2 ± 3.6 0.058 # Absolute lymphocyte count(10 9 /L) 1.8 (1.2, 2.3) 1.7 (1.2, 2.2) 1.8 (1.3, 2.4) 0.074 * Red blood cell count(10 12 /L) 5.0 ± 2.2 4.7 ± 1.9 5.1 ± 2.3 0.086 * Platelets(10 9 /L) 238.6 ± 142.8 244.1 ± 131.1 235.6 ± 149.0 0.579 # hs-CRP(mg/L) 21.2 (6.9, 60.0) 13.4 (2.6, 42.7) 25.5 (10.4, 63.9) < 0.001 * Prothrombin time(seconds) 12.0 ± 1.6 12.0 ± 1.5 12.0 ± 1.6 0.669 * APTT(seconds) 26.9 ± 4.1 26.9 ± 3.8 26.9 ± 4.3 0.914 * Albumin(g/L) 36.0 ± 4.2 36.1 ± 4.0 36.0 ± 4.3 0.946 * Globulin(g/L) 28.0 ± 4.5 27.4 ± 3.9 28.4 ± 4.8 0.041 # γ‑Glutamyl transferase(U/L) 40.5 (24.5, 73.1) 30.4 (19.1, 67.4) 41.7 (31.0, 74.9) 0.004 # Alanine aminotransferase(U/L) 19.9 (13.1, 34.1) 19.8 (12.6, 31.8) 20.1 (13.5, 35.5) 0.399 # Aspartate aminotransferase(U/L) 22.0 (17.1, 31.2) 22.1 (17.3, 31.1) 21.8 (17.0, 31.2) 0.947 # Direct bilirubin(μmol/L) 2.7 (2.0, 4.0) 2.6 (2.0, 3.5) 2.9 (2.1, 4.1) 0.223 * Indirect bilirubin (μmol/L) 13.2 ± 6.9 12.8 ± 7.1 13.5 ± 6.8 0.332 * Total bilirubin(μmol/L) 16.9 ± 9.5 16.5 ± 10.2 17.2 ± 9.2 0.516 * Total cholesterol(mmol/L) 4.8 ± 1.2 4.6 ± 1.0 4.9 ± 1.2 0.028 * LDL-C(mmol/L) 3.1 ± 0.8 2.9 ± 0.8 3.1 ± 0.9 0.005 * Triglyceride(mmol/L) 1.6 ± 1.0 1.5 ± 0.9 1.6 ± 1.0 0.069 * HDL-C(mmol/L) 1.1 ± 0.3 1.1 ± 0.3 1.1 ± 0.3 0.117 * Glucose(mmol/L) 6.2 ± 2.5 5.9 ± 2.1 6.4 ± 2.6 0.089 * Serum creatinine(umol/L) 77.1 ± 32.3 75.2 ± 29.7 78.1 ± 33.6 0.412 * Serum uric acid(umol/L) 386.8 ± 140.9 350.7 ± 109.6 406.3 ± 151.8 < 0.001 * PaO 2 (mmHg) 84.4 ± 25.8 91.4 ± 31.6 80.8 ± 21.6 < 0.001 * PaCO 2 (mmHg) 32.8 ± 5.3 34.6 ± 5.2 31.9 ± 5.2 < 0.001 * Lactate(mmol/L) 1.6 ± 1.1 1.4 ± 0.7 1.8 ± 1.2 0.002 # sST2(ng/mL) 20.0 (11.9, 36.4) 14.5 (9.9, 26.4) 23.7 (13.4, 37.9) < 0.001 Table 1 Continued # Homocysteine(umol/L) 13.0 (9.9, 17.6) 12.8 (10.0, 16.0) 13.3 (9.9, 18.7) 0.258 * serum complement C3(g/L) 1.4 ± 0.3 1.3 ± 0.3 1.4 ± 0.3 < 0.001 * serum complement C4(g/L) 0.4 ± 0.1 0.4 ± 0.1 0.4 ± 0.1 < 0.001 BNP/NT-proBNP increase, n(%) 263 (63.2) 72 (49.3) 191 (70.7) < 0.001 cTnI increase, n (%) 169 (40.6) 42 (28.8) 127 (47) < 0.001 Right ventricular dysfunction, n (%) 201 (48.3) 38 (26) 163 (60.4) < 0.001 DVT, n (%) 331 (79.6) 102 (69.9) 229 (84.8) < 0.001 Mechanical thrombectomy, n (%) 29 ( 7.0) 1 (0.7) 28 (10.4) < 0.001 Systemic thrombolysis, n (%) 51 (12.3) 5 (3.4) 46 (17) < 0.001 For categorical variables, Fisher's Exact Test and the Chi-Square Test of Independence were employed, whereas for continuous variables, the Mann -Whitney U Test ( # Median [IQR]) and the T - Test ( * Mean ± SD) were utilized. Abbreviations: PE, pulmonary embolism; VTE, venous thromboembolism; hs-CRP, high-sensitive C-reactive protein; APTT, activated partial thromboplastin time; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; PaO 2 , partial pressure of arterial oxygen; PaCO 2 , partial pressure of arterial carbon dioxide; sST2, soluble suppression of tumorigenicity 2; BNP/NT-proBNP, B-type natriuretic peptide/N-terminal pro-B-type natriuretic peptide; cTnI, cardiac troponin I; DVT, deep vein thrombosis. Association between serum complement C3 and central PE. We first evaluated the association between serum complement C3 levels and the presence of central PE in the overall study population of acute PE patients ( Table 2 ). In the fully adjusted logistic regression model (Model IV), each unit increase in serum complement C3 was associated with significantly higher odds of central PE (OR = 7.83, 95% CI: 3.02–20.30, P < 0.001). Similarly, when complement C3 was analyzed as a categorical variable by quartiles, participants in the highest quartile (Q4) had over fourfold increased odds of central PE compared to those in the lowest quartile (Q1) (Model IV: OR = 4.21, 95% CI: 2.05–8.66, P < 0.001). A significant positive trend was observed across increasing quartiles in all models ( P for trend < 0.001). In the unadjusted model (Model I), complement C3 as a continuous variable was also strongly associated with central PE (OR = 6.12, 95% CI: 2.80–13.39, P < 0.001), and this association remained consistent across progressively adjusted models. RCS analysis, after full adjustment for covariates, revealed a significant overall association between serum complement C3 levels and central PE ( P for overall < 0.001), with limited evidence of nonlinearity ( P for nonlinearity = 0.076), supporting a generally monotonic positive relationship ( Fig. 2 ). Table 2. Multivariable logistic regression models examining the association between serum complement C3 levels and the presence of central PE in acute PE patients. Variables Model I Model II Model III Model IV OR (95%CI) P OR (95%CI) P OR (95%CI) P OR (95%CI) P complementC3 6.12 (2.8~13.39) <0.001 7.14 (3.15~16.16) <0.001 8.51 (3.46~20.91) <0.001 7.83 (3.02~20.3) <0.001 complementC3 quantile Q1 1.00 (Reference) 1.00 (Reference) 1.00 (Reference) 1.00 (Reference) Q2 1.71 (0.98~2.97) 0.058 1.79 (1.02~3.12) 0.042 1.57 (0.87~2.85) 0.134 1.47 (0.81~2.7) 0.208 Q3 2.26 (1.28~4.01) 0.005 2.43 (1.36~4.35) 0.003 2.40 (1.29~4.47) 0.006 2.21 (1.17~4.19) 0.015 Q4 3.64 (1.99~6.66) <0.001 4.05 (2.15~7.63) <0.001 4.43 (2.25~8.73) <0.001 4.21 (2.05~8.66) <0.001 P for trend <0.001 <0.001 <0.001 <0.001 Model I: unadjusted. Model II: adjusted for age and gender. Model III: adjusted for model II covariates + heart rate, systolic pressure, hypertension, diabetes mellitus, chronic pulmonary disease, chronic heart failure, atrial fibrillation, history of VTE, smoking history, alcohol consumption history. Model IV: adjusted for model III covariates + serum creatinine, hs-CRP, DVT. Subgroup Analysis To comprehensively evaluate the robustness of the association between serum complement C3 levels and the presence of central PE, multi-subgroup analyses with interaction tests were conducted, adjusted for Model IV covariates and visually summarized in the corresponding forest plot ( Fig. 3 ). In the diabetic subgroup, this correlation did not reach statistical significance as the 95%CI crossed 1, which might be attributed to the small sample size. Subgroup analysis indicated that the relationship between serum complement C3 and central PE remained consistent across patient subgroups stratified according to gender, age, hypertension, and diabetes. ( P values for interaction>0.05). ROC analysis ROC curve analysis was performed to evaluate the diagnostic performance of serum complement C3 for identifying central PE. The area under the ROC curve (ACU) was 0.641(95% CI: 0.585 – 0.698), indicating a moderate discriminatory ability of serum complement C3 for central PE. The optimal cut-off value was 1.305 g/L, corresponding to a sensitivity of 0.704 and a specificity of 0.521( Fig. 4 ). Discussion To the best of our knowledge, this is the first cross-sectional study to investigate the association between serum complement C3 levels and the presence of central PE in Chinese patients with acute PE. We found that elevated serum complement C3 levels were statistically significantly associated with an increased likelihood of central PE, irrespective of whether C3 was analyzed as a continuous or categorical variable. The statistically significant association remained after adjusting for potential confounders. Consistently, subgroup analyses further confirmed the robustness of this association across clinical subpopulations. The non-linear relationship between serum complement C3 levels and the presence of central PE was not statistically significant in RCS analysis. ROC analysis demonstrated a moderate discriminatory ability of serum complement C3 for central PE. This finding extends the understanding of complement’s role from other thrombotic and vascular disorders, such as intrahepatic thrombophlebitis[23] and preeclampsia[24-26], to a specific high-risk phenotype of acute PE. In recent years, the interplay between thrombosis and the innate immune system, particularly the complement system—termed “thromboinflammation”—has emerged as a major focus of research in cardiovascular disease[7, 8]. Complement C3, acting as the convergence point for all activation pathways (classical, lectin, and alternative), plays a pivotal role in both inflammation and thrombosis through its activation fragments[9, 10]. Upon activation, C3 cleavage releases potent fragments like the anaphylatoxin C3a, which, via its receptor (C3aR), drives a pro-inflammatory cascade involving immune cell recruitment, vascular dysfunction, and thrombosis[13, 14]. For example, in a Klebsiella pneumoniae liver abscess model, C3 deposited on neutrophil extracellular traps was found to mediate localized endothelial damage and thrombophlebitis[23]. Venous air embolism in a porcine model was found to induce selective activation of complement C3, thereby eliciting a robust thromboinflammatory response[27]. Moreover, genetic deletion of complement C3 attenuated the development of RVD and fibrosis in a murine model of right heart failure[28]. Collectively, these findings may indicate that the complement C3–thromboinflammation axis mediates the association between serum C3 levels and acute PE pathogenesis. Clinical studies found that elevated baseline serum complement C3 levels were associated with an increased risk of adverse clinical outcomes at 3 months after ischemic stroke and each standard deviation increment in log‑transformed complement C3 was associated with a 13% higher risk of the primary outcome (95% CI: 2%–25%)[18, 19]. A large-scale population-based cohort study showed that higher baseline levels of complement C3 in individuals without VTE were significantly associated with an increased risk of developing VTE, including DVT and PE. Furthermore, the multivariable-adjusted hazard ratio for VTE per 1 g/L increase in complement C3 was 2.43 (95% CI = 1.74–3.40)[16]. Another clinical study involving 109 normotensive, non-cancer white adults with acute PE reported an increase in the proportion of central PE across rising tertiles of complement C3 levels, although this trend did not reach statistical significance. However, this study found that C3a levels were independently associated with the RVD and each tertile increase in C3a was associated with an approximately 1.9-fold higher risk of RVD. Furthermore, C3a levels were positively correlated with clot lysis time, indicating formation of denser and poorly lysable clots in subjects with elevated C3a[17]. Our study revealed that serum complement C3 levels were positively correlated with the presence of central PE and the difference was statistically significant. This discrepancy with our findings may be explained by the fact that the aforementioned study excluded high-risk PE patients and was conducted exclusively in a White adult population. Therefore, integrating evidence from previous research and the current study, the collective findings demonstrate that elevated serum C3 levels are associated with an increased propensity for intravascular thrombogenesis. This pro-thrombotic state may provide a plausible biological link to the more extensive and proximally located thrombus burden characteristic of acute PE. This study has several limitations. First, this is a cross-sectional study with a small sample size, so the causal relationship between serum complement C3 levels and the presence of central PE cannot be deduced. Second, the single-center, retrospective design might introduce selection bias, though we employed consecutive enrollment to minimize this potential. Third, although measuring activation fragments such as C3a may directly reflect complement activity, such assays are not routinely accessible in our clinical practice. Therefore, we cannot verify the relationship between complement C3a and central PE. Future research should address these limitations by employing multicenter, prospective study designs to enhance external validity and by including more ethnically diverse populations. And future research should conduct mechanistic studies to elucidate the specific role of complement C3 in the initiation, localization, and progression of acute PE, and explore the therapeutic potential of targeting the complement pathway as a novel strategy for acute PE. Conclusion This study identified a statistically significant association between serum complement C3 levels and the presence of central PE in Chinese patients with acute PE. Future research should validate these findings through well-designed longitudinal and multiethnic cohort studies to strengthen the robustness and generalizability of the conclusions. Abbreviations PE: Pulmonary embolism OR: Odds ratio CI: Confidence interval. RCS: Restricted cubic spline ROC: Receiver operating characteristic CTPA: Computed tomographic pulmonary angiography CTEPH: Chronic thromboembolic pulmonary hypertension SLE: Systemic lupus erythematosus VTE: Venous thromboembolism hs-CRP: high-sensitive C-reactive protein APTT: Activated partial thromboplastin time LDL-C: Low-density lipoprotein cholesterol HDL-C: High-density lipoprotein cholesterol PaO2: Partial pressure of arterial oxygen PaCO2: Partial pressure of arterial carbon dioxide sST2: soluble suppression of tumorigenicity 2 BNP/NT-proBNP: B-type natriuretic peptide/N-terminal pro-B-type natriuretic peptide cTnI: cardiac troponin I DVT: deep vein thrombosis Q1: The first quartile Q2: The second quartile Q3: The third quartile Q4: The fourth quartile Declarations Acknowledgements None. Authors’ contributions BW: Writing – original draft. JZ: Writing – review & editing. LZ: Writing – review & editing, Data curation. BL: Formal analysis,Writing – review & editing. ML: Formal analysis, Writing – review & editing. HZ: Visualization, Writing – review & editing. XY: Visualization, Writing – review & editing. WZ: Project administration, Writing – review & editing. QT: Project administration, Writing – review & editing, Funding acquisition. Data availability Data supporting the findings of this study are available from the corresponding author upon request. Ethics statement The studies involving humans were approved by Ethics Committee of First Hospital of Jilin University (Approval No. 2026-117). The studies were conducted in accordance with the local legislation and institutional requirements. Given that the research was retrospective and based solely on the analysis of anonymized data, the committee granted an exemption from obtaining informed consent. Clinical trial number Not applicable Funding This work was supported by the Medical and Health Talents Special Program of Jilin Province (JLSRCZX2025-002). 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Konstantinides SV, Meyer G, Becattini C, Bueno H, Geersing GJ, Harjola VP, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020;41(4):543–603. McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;42(36):3599–726. Wang H, Chen L, Wang C, Chang Z. Neutrophil extracellular trap-borne C3-driven endothelial dysfunction in Klebsiella pneumoniae liver abscess. Virulence. 2025;16(1):2580104. Lokki AI, Kaartokallio T, Holmberg V, Onkamo P, Koskinen LLE, Saavalainen P, et al. Analysis of Complement C3 Gene Reveals Susceptibility to Severe Preeclampsia. Front Immunol. 2017;8:589. Zhu S, Chen S, Ge Y, Zhou F, Su K, Xu C, et al. High-fat diet induces pre-eclampsia through dampening cell-autonomous C3 in trophoblasts. Commun Biol. 2025;8(1):879. Wang W, Irani RA, Zhang Y, Ramin SM, Blackwell SC, Tao L, et al. Autoantibody-mediated complement C3a receptor activation contributes to the pathogenesis of preeclampsia. Hypertension. 2012;60(3):712–21. Storm BS, Ludviksen JK, Christiansen D, Fure H, Pettersen K, Landsem A, et al. Venous Air Embolism Activates Complement C3 Without Corresponding C5 Activation and Trigger Thromboinflammation in Pigs. Front Immunol. 2022;13:839632. Ito S, Hashimoto H, Yamakawa H, Kusumoto D, Akiba Y, Nakamura T, et al. The complement C3-complement factor D-C3a receptor signalling axis regulates cardiac remodelling in right ventricular failure. Nat Commun. 2022;13(1):5409. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 14 May, 2026 Reviews received at journal 08 May, 2026 Reviewers agreed at journal 07 May, 2026 Reviewers invited by journal 07 May, 2026 Editor invited by journal 14 Apr, 2026 Editor assigned by journal 14 Apr, 2026 Submission checks completed at journal 14 Apr, 2026 First submitted to journal 09 Apr, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9369379","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":641607831,"identity":"d863030d-f1fb-465d-9ad4-de8837df14f5","order_by":0,"name":"Baoguo Wang","email":"","orcid":"","institution":"The First Hospital of Jilin University","correspondingAuthor":false,"prefix":"","firstName":"Baoguo","middleName":"","lastName":"Wang","suffix":""},{"id":641607837,"identity":"905b79fa-7fbb-4355-a0a5-81db1446a1c9","order_by":1,"name":"Jian Zhang","email":"","orcid":"","institution":"The First Hospital of Jilin University","correspondingAuthor":false,"prefix":"","firstName":"Jian","middleName":"","lastName":"Zhang","suffix":""},{"id":641607842,"identity":"3b15dee3-6856-4cdb-a6c3-10d3d013d0f7","order_by":2,"name":"Liping Zhang","email":"","orcid":"","institution":"The First Hospital of Jilin University","correspondingAuthor":false,"prefix":"","firstName":"Liping","middleName":"","lastName":"Zhang","suffix":""},{"id":641607843,"identity":"a49e925f-0ad7-4b5e-80d3-a643f461e368","order_by":3,"name":"Bo Li","email":"","orcid":"","institution":"The First Hospital of Jilin University","correspondingAuthor":false,"prefix":"","firstName":"Bo","middleName":"","lastName":"Li","suffix":""},{"id":641607845,"identity":"131a4f2c-3b17-43b6-98f1-b967690c3c07","order_by":4,"name":"Ming Lu","email":"","orcid":"","institution":"The First Hospital of Jilin University","correspondingAuthor":false,"prefix":"","firstName":"Ming","middleName":"","lastName":"Lu","suffix":""},{"id":641607846,"identity":"d2653bf6-b357-4d90-af00-754d590b8633","order_by":5,"name":"Hongjun Zhang","email":"","orcid":"","institution":"The First Hospital of Jilin University","correspondingAuthor":false,"prefix":"","firstName":"Hongjun","middleName":"","lastName":"Zhang","suffix":""},{"id":641607852,"identity":"d2c41e9e-6b71-4c4d-b247-0021c0af180f","order_by":6,"name":"Xinyu Yang","email":"","orcid":"","institution":"The First Hospital of Jilin University","correspondingAuthor":false,"prefix":"","firstName":"Xinyu","middleName":"","lastName":"Yang","suffix":""},{"id":641607853,"identity":"2d7a3c89-8269-4cc5-9b52-56c66777360f","order_by":7,"name":"Weihua Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAw0lEQVRIiWNgGAWjYFACxjYgYcPMB2LzkKAljZmNBC0MIMWHGYjXYnC8ue0xT815djaJBMYHb9sY5M0JajlzsN2Y59htZqAWZsO5bQyGOxsIaDG7kdgmzcMG1sImzdvGkGBwgJCW+w+BWv6dA2lh/02clhuMbUDDD4BtYSZKi/2ZxDbJuX3JzGw8D5sl55yTMNxASItk+/FnEm++2SXzsycf/PCmzEaeoC0wkAyM0wYgLUGkeiCwI17pKBgFo2AUjDgAABpbN5uu1K3uAAAAAElFTkSuQmCC","orcid":"","institution":"The First Hospital of Jilin University","correspondingAuthor":true,"prefix":"","firstName":"Weihua","middleName":"","lastName":"Zhang","suffix":""},{"id":641607855,"identity":"1df65745-1a20-484e-8f36-14b5a8499d38","order_by":8,"name":"Qian Tong","email":"","orcid":"","institution":"The First Hospital of Jilin University","correspondingAuthor":false,"prefix":"","firstName":"Qian","middleName":"","lastName":"Tong","suffix":""}],"badges":[],"createdAt":"2026-04-09 13:40:04","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9369379/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9369379/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":109446150,"identity":"eaa98209-51e6-4fd5-a151-7c714fdace43","added_by":"auto","created_at":"2026-05-18 08:18:29","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":2409203,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart of participant selection.\u003c/p\u003e\n\u003cp\u003eAbbreviations: CTPA, computed tomographic pulmonary angiography; CTEPH, chronic thromboembolic pulmonary hypertension; SLE, systemic lupus erythematosus.\u003c/p\u003e","description":"","filename":"image1.png","url":"https://assets-eu.researchsquare.com/files/rs-9369379/v1/02becbebb53fe21c976633d1.png"},{"id":109760302,"identity":"56f1d841-8102-47f7-a6ad-d1bf26af3202","added_by":"auto","created_at":"2026-05-22 07:28:30","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":26113,"visible":true,"origin":"","legend":"\u003cp\u003eRCS curves show the relationship between serum complement C3 levels and the presence of central PE. The red line represents the adjusted odds ratio (OR) for central PE, with the shaded area indicating the 95% confidence interval (CI). The analysis was adjusted for Model IV covariates.\u003c/p\u003e","description":"","filename":"image2.png","url":"https://assets-eu.researchsquare.com/files/rs-9369379/v1/94bf429f90ad7a9e5dd2c278.png"},{"id":109446147,"identity":"a222c04e-e9de-4d54-97bb-fb4e7c97971f","added_by":"auto","created_at":"2026-05-18 08:18:29","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":69532,"visible":true,"origin":"","legend":"\u003cp\u003eForest plots of the OR and 95% CI for the association between serum complement C3 levels and the presence of central PE compared among different subgroups.\u003c/p\u003e\n\u003cp\u003eAbbreviations: OR: Odds Ratio; CI: Confidence Interval.\u003c/p\u003e","description":"","filename":"image3.png","url":"https://assets-eu.researchsquare.com/files/rs-9369379/v1/b7e79f7516d6d18d717134c6.png"},{"id":109446149,"identity":"c1caee9d-3f24-4993-b9fe-149bcccbd12f","added_by":"auto","created_at":"2026-05-18 08:18:29","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":40498,"visible":true,"origin":"","legend":"\u003cp\u003eROC curve analysis showed the discriminatory ability of complement C3 for central PE.\u003c/p\u003e","description":"","filename":"image4.png","url":"https://assets-eu.researchsquare.com/files/rs-9369379/v1/9ed827341ad44c3c3c84b85a.png"},{"id":109763895,"identity":"5f814a7c-d8b2-48a4-8c41-587b833e16b5","added_by":"auto","created_at":"2026-05-22 07:36:14","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":531858,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9369379/v1/f8125bd4-1648-4383-aaa5-a9f05d27d700.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Association of serum complement C3 with central pulmonary embolism in patients with acute pulmonary embolism: a cross-sectional study in Jilin Province, China","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAcute pulmonary embolism (PE), a life-threatening condition caused by thromboembolic obstruction of the pulmonary vasculature, remains a major contributor to global cardiovascular morbidity and mortality[\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Central PE, defined as the presence of a thrombus in the main pulmonary artery or its left or right main branches, is often associated with more severe hemodynamic compromise and a higher risk of early mortality compared to peripheral PE[\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In recent years, the interplay between thrombosis and the innate immune system, particularly the complement system\u0026mdash;termed \u0026ldquo;thromboinflammation\u0026rdquo;\u0026mdash;has emerged as a major focus of research in cardiovascular disease[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Complement component 3 (C3), the convergence point of all activation pathways, is central to this process. Upon activation, C3 cleavage yields bioactive fragments like the anaphylatoxin C3a, which promotes inflammation, endothelial dysfunction, and thrombosis[\u003cspan additionalcitationids=\"CR10 CR11 CR12 CR13\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. A self-amplifying C3/C3a circuit has been implicated in vascular injury models[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], and C3 deposition on neutrophil extracellular traps can localize and exacerbate vascular damage[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. These mechanisms position the complement system as a potential link between systemic inflammation and thrombotic events.\u003c/p\u003e \u003cp\u003eA large-scale population-based cohort study showed that higher baseline levels of complement C3 in individuals without venous thromboembolism (VTE) were significantly associated with an increased risk of developing VTE, including deep vein thrombosis (DVT) and PE[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Another clinical study involving 109 normotensive, non-cancer white adults with acute PE found an increase in the proportion of central PE across rising tertiles of complement C3 levels and C3a levels were independently associated with right ventricular dysfunction (RVD) and the severity of PE[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Other studies found higher C3 levels predicted poorer outcomes after ischemic stroke[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Although the relationship between complement system and thrombosis is established, the association between serum complement C3 levels and the presence of central PE among acute PE patients remains limited. Therefore, this cross-sectional study aimed to investigate the potential association between serum complement C3 levels and the presence of central PE among acute PE patients in China.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003e\u003cstrong\u003eStudy population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis a single-center, retrospective, cross-sectional study consecutively enrolled 1089 acute PE patients at the First Hospital of Jilin University between April 1, 2023 and December 1, 2025. Inclusion criteria were as follows: (1) Age \u0026ge; 18 years; (2) Diagnosis of acute PE was based on computed tomographic pulmonary angiography (CTPA); (3) Time from symptom onset to hospital admission \u0026le; 14 days. Exclusion criteria included: (1) missing complement C3 data; (2) missing CTPA images; (3) missing echocardiography data; (4) history of trauma or surgery within 1 month; (5) active malignancy, chronic thromboembolic pulmonary hypertension (CTEPH), liver cirrhosis, severe pneumonia, systemic lupus erythematosus (SLE) at admission. The final analytic sample comprised 416 acute PE patients. The detailed selection process is illustrated in\u003cstrong\u003e\u0026nbsp;Fig. 1\u003c/strong\u003e. The study protocol was approved by the Ethics Committee of First Hospital of Jilin University (Approval No. 2026-117). The requirement for informed consent was waived as the study utilized only anonymized retrospective data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiagnostic Criteria\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCentral PE was defined as the presence of a thrombus in the main pulmonary artery, or the left or right main pulmonary artery and peripheral PE in the lobar, segmental, or subsegmental arteries on CTPA[20]. RVD was defined by transthoracic echocardiographic parameters, including enlarged right ventricle on parasternal long axis view, basal right ventricle (RV)/ left ventricle (LV) ratio \u0026gt;1.0 on four chamber view and decreased tricuspid annular plane systolic excursion (TAPSE) measured with M-Mode (\u0026lt;16 mm), which was performed in strict accordance with the 2019 ESC Guidelines for the Diagnosis and Management of Acute Pulmonary Embolism Developed in Collaboration with the European Respiratory Society (ERS)[21]. Chronic heart failure was diagnosed in accordance with the European Society of Cardiology (ESC) guidelines[22]. Chronic pulmonary disease included asthma or chronic obstructive pulmonary disease (COPD).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eContinuous variables were presented as means \u0026plusmn; standard deviations, while group comparisons were performed using the T-test or Mann -Whitney U test. Categorical variables were displayed as numbers and percentages, while group comparisons were performed via the chi-square test or Fisher\u0026apos;s exact test. Logistic regression analyses were performed in crude and adjusted models to investigate the associations between serum complement C3 levels and the presence of central PE. In model I, no adjustments for covariates were applied. Model II was adjusted for variables including age and gender. Model III was additionally adjusted for heart rate, systolic pressure, hypertension, diabetes, chronic pulmonary disease, chronic heart failure, atrial fibrillation, history of VTE, smoking history, alcohol consumption history. Model IV was additionally adjusted for serum creatinine, high-sensitive C-reactive protein (hs-CRP), DVT. Restricted cubic splines (RCS) were used to examine the dose-response relationship between serum complement C3 levels and the presence of central PE. The discriminatory ability of complement C3 for central PE was evaluated using receiver operating characteristic (ROC) curve analysis. To assess the robustness of the association, we performed a pre-specified subgroup analysis. In the subgroup analysis, we examined the relationship between serum complement C3 levels and the presence of central PE according to age (\u0026le;65\u0026nbsp;years vs.\u0026gt;65\u0026nbsp;years), gender (male vs. female), hypertension (no vs. yes), and diabetes (no vs. yes). Interactions between subgroups were assessed using the likelihood ratio test. The percentages of missing values were lower than 15%. We imputed missing data of the covariates by using multiple imputations. Five datasets were created and analysed together.\u003c/p\u003e\n\u003cp\u003eAll the analyses were performed with the statistical software packages R (http://www.R-project.org, The R Foundation) and Free Statistics software versions 2.4.0. Statistical significance was defined as P \u0026lt; 0.05.\u0026nbsp;\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eParticipant Baseline Characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAfter applying the eligibility criteria, 416 participants were enrolled to investigate the relationship between serum complement C3 levels and the presence of central PE. The mean age was 64.3 years; 50% were men, indicating a balanced sex distribution. Overall, 270 participants (64.9%) had central PE. \u003cstrong\u003eTable 1\u003c/strong\u003e presents the baseline characteristics of the study participants categorized according to the type of PE. Statistically significant differences (p\u0026lt;0.05) were observed for heart rate, alcohol consumption history, globulin, \u0026gamma;‑glutamyl transferase, hs-CRP, total cholesterol, low-density lipoprotein cholesterol (LDL-C), serum uric acid, partial pressure of arterial oxygen (PaO₂), partial pressure of arterial carbon dioxide (PaCO₂), lactate, soluble suppression of tumorigenicity 2 (sST2), serum complements C3 and C4, as well as the proportions of patients with increased B-type natriuretic peptide/N-terminal pro-B-type natriuretic peptide (BNP/NT-proBNP), increased cardiac troponin I (cTnI), RVD, DVT, and those receiving mechanical thrombectomy or systemic thrombolysis. Compared with patients with peripheral PE, those with central PE exhibited higher inflammatory and metabolic markers (e.g., hs-CRP, sST2, serum uric acid), more pronounced abnormalities in blood gas parameters (lower PaO₂ and PaCO₂), and a greater prevalence of indicators associated with disease severity (RVD) and the need for more invasive interventions.\u003c/p\u003e\n\u003cp\u003eTable 1. Baseline characteristics of the study participants\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"579\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n = 416)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePeripheral PE\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n = 146)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCentral PE\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n = 270)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003e\u003csup\u003e*\u003c/sup\u003eAge(years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e64.3 \u0026plusmn; 13.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e64.5 \u0026plusmn; 12.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e64.3 \u0026plusmn; 13.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0.893\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003eMale, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e208 (50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e71 (48.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e137 (50.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0.681\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003e\u003csup\u003e*\u003c/sup\u003eHeart rate(beat/min)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e85.8 \u0026plusmn; 17.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e82.0 \u0026plusmn; 15.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e87.9 \u0026plusmn; 18.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003e\u003csup\u003e*\u003c/sup\u003eSystolic pressure(mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e129.1 \u0026plusmn; 21.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e130.6 \u0026plusmn; 22.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e128.2 \u0026plusmn; 21.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0.277\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003eHypertension, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e190 (45.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e65 (44.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e125 (46.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0.729\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003eDiabetes, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e67 (16.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e19 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e48 (17.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0.207\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003eChronic pulmonary disease, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e28 ( 6.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e9 (6.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e19 (7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0.735\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003eChronic heart failure, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e20 ( 4.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e10 (6.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e10 (3.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0.152\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003eAtrial fibrillation, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e28 ( 6.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e10 (6.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e18 (6.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0.943\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003eHistory of VTE, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e11 ( 2.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e1 (0.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e10 (3.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0.106\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003eSmoking history, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e67 (16.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e20 (13.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e47 (17.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0.326\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003eAlcohol consumption history, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e55 (13.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e12 (8.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e43 (15.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0.027\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003e\u003csup\u003e*\u003c/sup\u003eWhite blood cell count(10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e10.0 \u0026plusmn; 5.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e9.5 \u0026plusmn; 6.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e10.2 \u0026plusmn; 4.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0.189\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003e\u003csup\u003e*\u003c/sup\u003eAbsolute neutrophil count(10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e6.9 \u0026plusmn; 3.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e6.4 \u0026plusmn; 4.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e7.2 \u0026plusmn; 3.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0.058\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003e\u003csup\u003e#\u003c/sup\u003eAbsolute lymphocyte count(10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e1.8 (1.2, 2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e1.7 (1.2, 2.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e1.8 (1.3, 2.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0.074\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003e\u003csup\u003e*\u003c/sup\u003eRed blood cell count(10\u003csup\u003e12\u003c/sup\u003e/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e5.0 \u0026plusmn; 2.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e4.7 \u0026plusmn; 1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e5.1 \u0026plusmn; 2.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0.086\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003e\u003csup\u003e*\u003c/sup\u003ePlatelets(10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e238.6 \u0026plusmn; 142.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e244.1 \u0026plusmn; 131.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e235.6 \u0026plusmn; 149.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0.579\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003e\u003csup\u003e#\u003c/sup\u003ehs-CRP(mg/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e21.2 (6.9, 60.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e13.4 (2.6, 42.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e25.5 (10.4, 63.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003e\u003csup\u003e*\u003c/sup\u003eProthrombin time(seconds)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e12.0 \u0026plusmn; 1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e12.0 \u0026plusmn; 1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e12.0 \u0026plusmn; 1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0.669\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003e\u003csup\u003e*\u003c/sup\u003eAPTT(seconds)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e26.9 \u0026plusmn; 4.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e26.9 \u0026plusmn; 3.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e26.9 \u0026plusmn; 4.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0.914\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003e\u003csup\u003e*\u003c/sup\u003eAlbumin(g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e36.0 \u0026plusmn; 4.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e36.1 \u0026plusmn; 4.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e36.0 \u0026plusmn; 4.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0.946\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003e\u003csup\u003e*\u003c/sup\u003eGlobulin(g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e28.0 \u0026plusmn; 4.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e27.4 \u0026plusmn; 3.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e28.4 \u0026plusmn; 4.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0.041\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003e\u003csup\u003e#\u003c/sup\u003e\u0026gamma;‑Glutamyl transferase(U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e40.5 (24.5, 73.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e30.4 (19.1, 67.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e41.7 (31.0, 74.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003e\u003csup\u003e#\u003c/sup\u003eAlanine aminotransferase(U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e19.9 (13.1, 34.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e19.8 (12.6, 31.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e20.1 (13.5, 35.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0.399\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003e\u003csup\u003e#\u003c/sup\u003eAspartate aminotransferase(U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e22.0 (17.1, 31.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e22.1 (17.3, 31.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e21.8 (17.0, 31.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0.947\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003e\u003csup\u003e#\u003c/sup\u003eDirect bilirubin(\u0026mu;mol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e2.7 (2.0, 4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e2.6 (2.0, 3.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e2.9 (2.1, 4.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0.223\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003e\u003csup\u003e*\u003c/sup\u003eIndirect bilirubin (\u0026mu;mol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e13.2 \u0026plusmn; 6.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e12.8 \u0026plusmn; 7.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e13.5 \u0026plusmn; 6.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0.332\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003e\u003csup\u003e*\u003c/sup\u003eTotal bilirubin(\u0026mu;mol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e16.9 \u0026plusmn; 9.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e16.5 \u0026plusmn; 10.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e17.2 \u0026plusmn; 9.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0.516\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003e\u003csup\u003e*\u003c/sup\u003eTotal cholesterol(mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e4.8 \u0026plusmn; 1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e4.6 \u0026plusmn; 1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e4.9 \u0026plusmn; 1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0.028\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003e\u003csup\u003e*\u003c/sup\u003eLDL-C(mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e3.1 \u0026plusmn; 0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e2.9 \u0026plusmn; 0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e3.1 \u0026plusmn; 0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003e\u003csup\u003e*\u003c/sup\u003eTriglyceride(mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e1.6 \u0026plusmn; 1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e1.5 \u0026plusmn; 0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e1.6 \u0026plusmn; 1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0.069\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003e\u003csup\u003e*\u003c/sup\u003eHDL-C(mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e1.1 \u0026plusmn; 0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e1.1 \u0026plusmn; 0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e1.1 \u0026plusmn; 0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0.117\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003e\u003csup\u003e*\u003c/sup\u003eGlucose(mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e6.2 \u0026plusmn; 2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e5.9 \u0026plusmn; 2.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e6.4 \u0026plusmn; 2.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0.089\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003e\u003csup\u003e*\u003c/sup\u003eSerum creatinine(umol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e77.1 \u0026plusmn; 32.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e75.2 \u0026plusmn; 29.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e78.1 \u0026plusmn; 33.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0.412\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003e\u003csup\u003e*\u003c/sup\u003eSerum uric acid(umol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e386.8 \u0026plusmn; 140.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e350.7 \u0026plusmn; 109.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e406.3 \u0026plusmn; 151.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003e\u003csup\u003e*\u003c/sup\u003ePaO\u003csub\u003e2\u003c/sub\u003e(mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e84.4 \u0026plusmn; 25.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e91.4 \u0026plusmn; 31.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e80.8 \u0026plusmn; 21.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003e\u003csup\u003e*\u003c/sup\u003ePaCO\u003csub\u003e2\u003c/sub\u003e(mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e32.8 \u0026plusmn; 5.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e34.6 \u0026plusmn; 5.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e31.9 \u0026plusmn; 5.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003e\u003csup\u003e*\u003c/sup\u003eLactate(mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e1.6 \u0026plusmn; 1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e1.4 \u0026plusmn; 0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e1.8 \u0026plusmn; 1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003e\u003csup\u003e#\u003c/sup\u003esST2(ng/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e20.0 (11.9, 36.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e14.5 (9.9, 26.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e23.7 (13.4, 37.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003ctable cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd height=\"59\" style=\"width: 237px;\"\u003e\u0026nbsp;\u003ctable cellpadding=\"0\" cellspacing=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cdiv v:shape=\"文本框_x0020_8\"\u003e\n \u003cp\u003eTable 1 Continued\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\u0026nbsp;\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\u0026nbsp;\u003csup\u003e#\u003c/sup\u003eHomocysteine(umol/L)\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e13.0 (9.9, 17.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e12.8 (10.0, 16.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e13.3 (9.9, 18.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0.258\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003e\u003csup\u003e*\u003c/sup\u003eserum complement C3(g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e1.4 \u0026plusmn; 0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e1.3 \u0026plusmn; 0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e1.4 \u0026plusmn; 0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003e\u003csup\u003e*\u003c/sup\u003eserum complement C4(g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e0.4 \u0026plusmn; 0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e0.4 \u0026plusmn; 0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e0.4 \u0026plusmn; 0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003eBNP/NT-proBNP increase, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e263 (63.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e72 (49.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e191 (70.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003ecTnI increase, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e169 (40.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e42 (28.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e127 (47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003eRight ventricular dysfunction, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e201 (48.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e38 (26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e163 (60.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003eDVT, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e331 (79.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e102 (69.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e229 (84.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003eMechanical thrombectomy, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e29 ( 7.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e1 (0.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e28 (10.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 197px;\"\u003e\n \u003cp\u003eSystemic thrombolysis, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 117px;\"\u003e\n \u003cp\u003e51 (12.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 106px;\"\u003e\n \u003cp\u003e5 (3.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 100px;\"\u003e\n \u003cp\u003e46 (17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eFor categorical variables, Fisher\u0026apos;s Exact Test and the Chi-Square Test of Independence were employed, whereas for continuous variables, the Mann -Whitney U Test (\u003csup\u003e#\u003c/sup\u003eMedian [IQR]) and the T - Test (\u003csup\u003e*\u003c/sup\u003eMean \u0026plusmn; SD) were utilized.\u003c/p\u003e\n\u003cp\u003eAbbreviations: PE, pulmonary embolism; VTE, venous thromboembolism; hs-CRP, high-sensitive C-reactive protein; APTT, activated partial thromboplastin time; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; PaO\u003csub\u003e2\u003c/sub\u003e, partial pressure of arterial oxygen; PaCO\u003csub\u003e2\u003c/sub\u003e, partial pressure of arterial carbon dioxide; sST2, soluble suppression of tumorigenicity 2; BNP/NT-proBNP, B-type natriuretic peptide/N-terminal pro-B-type natriuretic peptide; cTnI, cardiac troponin I; DVT, deep vein thrombosis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssociation between serum complement C3 and central PE.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe first evaluated the association between serum complement C3 levels and the presence of central PE in the overall study population of acute PE patients (\u003cstrong\u003eTable 2\u003c/strong\u003e). In the fully adjusted logistic regression model (Model IV), each unit increase in serum complement C3 was associated with significantly higher odds of central PE (OR = 7.83, 95% CI: 3.02\u0026ndash;20.30, \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001). Similarly, when complement C3 was analyzed as a categorical variable by quartiles, participants in the highest quartile (Q4) had over fourfold increased odds of central PE compared to those in the lowest quartile (Q1) (Model IV: OR = 4.21, 95% CI: 2.05\u0026ndash;8.66, \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001). A significant positive trend was observed across increasing quartiles in all models (\u003cem\u003eP\u003c/em\u003e for trend \u0026lt; 0.001). In the unadjusted model (Model I), complement C3 as a continuous variable was also strongly associated with central PE (OR = 6.12, 95% CI: 2.80\u0026ndash;13.39, \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001), and this association remained consistent across progressively adjusted models. RCS analysis, after full adjustment for covariates, revealed a significant overall association between serum complement C3 levels and central PE (\u003cem\u003eP\u003c/em\u003e for overall \u0026lt; 0.001), with limited evidence of nonlinearity (\u003cem\u003eP\u003c/em\u003e for nonlinearity = 0.076), supporting a generally monotonic positive relationship (\u003cstrong\u003eFig. 2\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003eTable 2. Multivariable logistic regression models examining the association between serum complement C3 levels and the presence of central PE in acute PE patients.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eModel I\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eModel II\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eModel III\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eModel IV\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eOR\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(95%CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eOR\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(95%CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eOR\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(95%CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eOR\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(95%CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ecomplementC3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e6.12 (2.8~13.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7.14 (3.15~16.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e8.51 (3.46~20.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7.83 (3.02~20.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ecomplementC3 quantile\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eQ1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.00 (Reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.00 (Reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.00 (Reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.00 (Reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eQ2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.71 (0.98~2.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.058\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.79 (1.02~3.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.042\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.57 (0.87~2.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.134\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.47 (0.81~2.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.208\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eQ3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.26 (1.28~4.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.43 (1.36~4.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.40\u003c/p\u003e\n \u003cp\u003e(1.29~4.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.21 (1.17~4.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.015\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eQ4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.64 (1.99~6.66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4.05 (2.15~7.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4.43 (2.25~8.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4.21 (2.05~8.66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e for trend\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eModel I: unadjusted.\u003c/p\u003e\n\u003cp\u003eModel II: adjusted for age and gender.\u003c/p\u003e\n\u003cp\u003eModel III: adjusted for model II covariates + heart rate, systolic pressure, hypertension, diabetes mellitus, chronic pulmonary disease, chronic heart failure, atrial fibrillation, history of VTE, smoking history, alcohol consumption history.\u003c/p\u003e\n\u003cp\u003eModel IV: adjusted for model III covariates + serum creatinine, hs-CRP, DVT.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSubgroup Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo comprehensively evaluate the robustness of the association between serum complement C3 levels and the presence of central PE, multi-subgroup analyses with interaction tests were conducted, adjusted for Model IV covariates and visually summarized in the corresponding forest plot (\u003cstrong\u003eFig. 3\u003c/strong\u003e). In the diabetic subgroup, this correlation did not reach statistical significance as the 95%CI crossed 1, which might be attributed to the small sample size. Subgroup analysis indicated that the relationship between serum complement C3 and central PE remained consistent across patient subgroups stratified according to gender, age, hypertension, and diabetes. (\u003cem\u003eP\u003c/em\u003e values for interaction\u0026gt;0.05).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eROC analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eROC curve analysis was performed to evaluate the diagnostic performance of serum complement C3 for identifying central PE. The area under the ROC curve (ACU) was 0.641(95% CI: 0.585 \u0026ndash; 0.698), indicating a moderate discriminatory ability of serum complement C3 for central PE. The optimal cut-off value was 1.305 g/L, corresponding to a sensitivity of 0.704 and a specificity of 0.521(\u003cstrong\u003eFig. 4\u003c/strong\u003e).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eTo the best of our knowledge, this is the first cross-sectional study to investigate the association between serum complement C3 levels and the presence of central PE in Chinese patients with acute PE. We found that elevated serum complement C3 levels were statistically significantly associated with an increased likelihood of central PE, irrespective of whether C3 was analyzed as a continuous or categorical variable. The statistically significant association remained after adjusting for potential confounders. Consistently, subgroup analyses further confirmed the robustness of this association across clinical subpopulations. The non-linear relationship between serum complement C3 levels and the presence of central PE was not statistically significant in RCS analysis. ROC analysis demonstrated a moderate discriminatory ability of serum complement C3 for central PE. This finding extends the understanding of complement’s role from other thrombotic and vascular disorders, such as intrahepatic thrombophlebitis[23] and preeclampsia[24-26], to a specific high-risk phenotype of acute PE.\u003c/p\u003e\n\u003cp\u003eIn recent years, the interplay between thrombosis and the innate immune system, particularly the complement system—termed “thromboinflammation”—has emerged as a major focus of research in cardiovascular disease[7, 8]. Complement C3, acting as the convergence point for all activation pathways (classical, lectin, and alternative), plays a pivotal role in both inflammation and thrombosis through its activation fragments[9, 10]. Upon activation, C3 cleavage releases potent fragments like the anaphylatoxin C3a, which, via its receptor (C3aR), drives a pro-inflammatory cascade involving immune cell recruitment, vascular dysfunction, and thrombosis[13, 14]. For example, in a Klebsiella pneumoniae liver abscess model, C3 deposited on neutrophil extracellular traps was found to mediate localized endothelial damage and thrombophlebitis[23]. Venous air embolism in a porcine model was found to induce selective activation of complement C3, thereby eliciting a robust thromboinflammatory response[27]. Moreover, genetic deletion of complement C3 attenuated the development of RVD and fibrosis in a murine model of right heart failure[28]. Collectively, these findings may indicate that the complement C3–thromboinflammation axis mediates the association between serum C3 levels and acute PE pathogenesis.\u003c/p\u003e\n\u003cp\u003eClinical studies found that elevated baseline serum complement C3 levels were associated with an increased risk of adverse clinical outcomes at 3 months after ischemic stroke and each standard deviation increment in log‑transformed complement C3 was associated with a 13% higher risk of the primary outcome (95% CI: 2%–25%)[18, 19]. A large-scale population-based cohort study showed that higher baseline levels of complement C3 in individuals without VTE were significantly associated with an increased risk of developing VTE, including DVT and PE. Furthermore, the multivariable-adjusted hazard ratio for VTE per 1 g/L increase in complement C3 was 2.43 (95% CI = 1.74–3.40)[16]. Another clinical study involving 109 normotensive, non-cancer white adults with acute PE reported an increase in the proportion of central PE across rising tertiles of complement C3 levels, although this trend did not reach statistical significance. However, this study found that C3a levels were independently associated with the RVD and each tertile increase in C3a was associated with an approximately 1.9-fold higher risk of RVD. Furthermore, C3a levels were positively correlated with clot lysis time, indicating formation of denser and poorly lysable clots in subjects with elevated C3a[17]. Our study revealed that serum complement C3 levels were positively correlated with the presence of central PE and the difference was statistically significant. This discrepancy with our findings may be explained by the fact that the aforementioned study excluded high-risk PE patients and was conducted exclusively in a White adult population. Therefore, integrating evidence from previous research and the current study, the collective findings demonstrate that elevated serum C3 levels are associated with an increased propensity for intravascular thrombogenesis. This pro-thrombotic state may provide a plausible biological link to the more extensive and proximally located thrombus burden characteristic of acute PE.\u003c/p\u003e\n\u003cp\u003eThis study has several limitations. First, this is a cross-sectional study with a small sample size, so the causal relationship between serum complement C3 levels and the presence of central PE cannot be deduced. Second, the single-center, retrospective design might introduce selection bias, though we employed consecutive enrollment to minimize this potential. Third, although measuring activation fragments such as C3a may directly reflect complement activity, such assays are not routinely accessible in our clinical practice. Therefore, we cannot verify the relationship between complement C3a and central PE. Future research should address these limitations by employing multicenter, prospective study designs to enhance external validity and by including more ethnically diverse populations. And future research should conduct mechanistic studies to elucidate the specific role of complement C3 in the initiation, localization, and progression of acute PE, and explore the therapeutic potential of targeting the complement pathway as a novel strategy for acute PE.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study identified a statistically significant association between serum complement C3 levels and the presence of central PE in Chinese patients with acute PE. Future research should validate these findings through well-designed longitudinal and multiethnic cohort studies to strengthen the robustness and generalizability of the conclusions.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003ePE: Pulmonary embolism\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOR: Odds ratio\u003c/p\u003e\n\u003cp\u003eCI: Confidence interval.\u003c/p\u003e\n\u003cp\u003eRCS: Restricted cubic spline\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eROC: Receiver operating characteristic\u003c/p\u003e\n\u003cp\u003eCTPA: Computed tomographic pulmonary angiography\u003c/p\u003e\n\u003cp\u003eCTEPH: Chronic thromboembolic pulmonary hypertension\u003c/p\u003e\n\u003cp\u003eSLE: Systemic lupus erythematosus\u003c/p\u003e\n\u003cp\u003eVTE: Venous thromboembolism\u003c/p\u003e\n\u003cp\u003ehs-CRP: high-sensitive C-reactive protein\u003c/p\u003e\n\u003cp\u003eAPTT: Activated partial thromboplastin time\u003c/p\u003e\n\u003cp\u003eLDL-C: Low-density lipoprotein cholesterol\u003c/p\u003e\n\u003cp\u003eHDL-C: High-density lipoprotein cholesterol\u003c/p\u003e\n\u003cp\u003ePaO2: Partial pressure of arterial oxygen\u003c/p\u003e\n\u003cp\u003ePaCO2: Partial pressure of arterial carbon dioxide\u003c/p\u003e\n\u003cp\u003esST2: soluble suppression of tumorigenicity 2\u003c/p\u003e\n\u003cp\u003eBNP/NT-proBNP: B-type natriuretic peptide/N-terminal pro-B-type natriuretic peptide\u003c/p\u003e\n\u003cp\u003ecTnI: cardiac troponin I\u003c/p\u003e\n\u003cp\u003eDVT: deep vein thrombosis\u003c/p\u003e\n\u003cp\u003eQ1: The first quartile\u003c/p\u003e\n\u003cp\u003eQ2: The second quartile\u003c/p\u003e\n\u003cp\u003eQ3: The third quartile\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eQ4: The fourth quartile\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors’ contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBW: Writing – original draft. JZ: Writing – review \u0026amp; editing. LZ: Writing – review \u0026amp; editing, Data curation. BL: Formal analysis,Writing – review \u0026amp; editing. ML: Formal analysis, Writing – review \u0026amp; editing. HZ: Visualization, Writing – review \u0026amp; editing. XY: Visualization, Writing – review \u0026amp; editing. WZ: Project administration, Writing – review \u0026amp; editing. QT: Project administration, Writing – review \u0026amp; editing, Funding acquisition.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData supporting the findings of this study are available from the corresponding author upon request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe studies involving humans were approved by Ethics Committee of First Hospital of Jilin University (Approval No. 2026-117). The studies were conducted in accordance with the local legislation and institutional requirements. Given that the research was retrospective and based solely on the analysis of anonymized data, the committee granted an exemption from obtaining informed consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the Medical and Health Talents Special Program of Jilin Province (JLSRCZX2025-002).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKeller K, Hobohm L, Ebner M, Kresoja KP, M\u0026uuml;nzel T, Konstantinides SV, et al. 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Stroke. 2021;52(3):868\u0026ndash;77.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAl-Dorzi HM, Almutawa FM, AlRuhaymi BA, Alhusaini AO, Alnamlah AM, Shaman AMB, et al. Characteristics, management and outcomes of central versus peripheral pulmonary embolism: a retrospective cohort study. Thromb J. 2025;23(1):22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKonstantinides SV, Meyer G, Becattini C, Bueno H, Geersing GJ, Harjola VP, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020;41(4):543\u0026ndash;603.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, B\u0026ouml;hm M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. 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Hypertension. 2012;60(3):712\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStorm BS, Ludviksen JK, Christiansen D, Fure H, Pettersen K, Landsem A, et al. Venous Air Embolism Activates Complement C3 Without Corresponding C5 Activation and Trigger Thromboinflammation in Pigs. Front Immunol. 2022;13:839632.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIto S, Hashimoto H, Yamakawa H, Kusumoto D, Akiba Y, Nakamura T, et al. The complement C3-complement factor D-C3a receptor signalling axis regulates cardiac remodelling in right ventricular failure. Nat Commun. 2022;13(1):5409.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pulmonary-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pulm","sideBox":"Learn more about [BMC Pulmonary Medicine](http://bmcpulmmed.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/pulm/default.aspx","title":"BMC Pulmonary Medicine","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"serum complement C3, central pulmonary embolism, cross-sectional study, thromboinflammation","lastPublishedDoi":"10.21203/rs.3.rs-9369379/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9369379/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eAcute pulmonary embolism (PE) is a major cause of cardiovascular mortality. The complement system is implicated in inflammatory and thrombotic processes. This study aimed to explore the association between serum complement C3 levels and the presence of central PE in patients with acute PE.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis cross-sectional study enrolled 416 acute PE patients from the First Hospital of Jilin University. Acute PE was diagnosed based on computed tomographic pulmonary angiography. Logistic regression models and subgroup analyses were used to evaluate the association between serum complement C3 and central PE. Restricted cubic spline (RCS) analysis was conducted to investigate potential non-linear relationships. The discriminatory ability of serum complement C3 for central PE was assessed using receiver operating characteristic (ROC) curve analysis.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong the 416 patients, 270 (64.9%) were diagnosed with central PE. In fully adjusted models, higher serum complement C3 was significantly associated with a higher likelihood of central PE (highest vs. lowest quartile: OR\u0026thinsp;=\u0026thinsp;4.21, 95% CI: 2.05\u0026ndash;8.66, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Subgroup analyses according to gender, age, hypertension, and diabetes status showed consistent trends without significant interaction. RCS analysis indicated a linear dose-response relationship. ROC curve analysis demonstrated that serum complement C3 had moderate discriminative ability for central PE, with an area under the curve (AUC) of 0.641.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThis study demonstrated a significant association between serum complement C3 levels and central PE in Chinese patients with acute PE. Specifically, higher serum complement C3 levels were associated with a higher prevalence of central PE. Further prospective longitudinal studies are needed to validate these findings.\u003c/p\u003e","manuscriptTitle":"Association of serum complement C3 with central pulmonary embolism in patients with acute pulmonary embolism: a cross-sectional study in Jilin Province, China","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-18 08:18:22","doi":"10.21203/rs.3.rs-9369379/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"233585308131701231196554711137110525019","date":"2026-05-14T13:37:23+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-08T10:35:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"259731102254443918444488338025568505099","date":"2026-05-07T22:41:06+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-05-07T18:30:23+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-04-14T11:40:49+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-14T04:05:42+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-14T04:05:11+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pulmonary Medicine","date":"2026-04-09T13:34:39+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pulmonary-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pulm","sideBox":"Learn more about [BMC Pulmonary Medicine](http://bmcpulmmed.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/pulm/default.aspx","title":"BMC Pulmonary Medicine","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"06226642-9efa-4cea-8db0-912b66d0f11b","owner":[],"postedDate":"May 18th, 2026","published":true,"recentEditorialEvents":[{"type":"reviewerAgreed","content":"233585308131701231196554711137110525019","date":"2026-05-14T13:37:23+00:00","index":54,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-08T10:35:55+00:00","index":35,"fulltext":""},{"type":"reviewerAgreed","content":"259731102254443918444488338025568505099","date":"2026-05-07T22:41:06+00:00","index":34,"fulltext":""},{"type":"reviewersInvited","content":"30","date":"2026-05-07T18:30:23+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-18T08:18:23+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-18 08:18:22","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9369379","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9369379","identity":"rs-9369379","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}