Shining Light on Pulmonary Embolism: The Hidden Role of Vitamin D – A Retrospective Multicenter Nationwide Study

Shining Light on Pulmonary Embolism: The Hidden Role of Vitamin D – A Retrospective Multicenter Nationwide Study | 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 Shining Light on Pulmonary Embolism: The Hidden Role of Vitamin D – A Retrospective Multicenter Nationwide Study Zamir Kemal Erturk, Mustafa Hamidullah Turkkani, Naim Ata, Ahmet Emre Ay, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7779539/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Pulmonary embolism (PE) is a life-threatening condition with significant morbidity and mortality. Recent studies have suggested a potential link between vitamin D deficiency and increased risk of thromboembolic events, including PE. However, large-scale, population-based evidence remains limited. Objective: To investigate the association between vitamin D deficiency and the occurrence of pulmonary embolism using nationwide retrospective data from Turkey. Methods: We conducted a retrospective study including 3,169 adult patients who underwent pulmonary computed tomography (CT) angiography between 2017 and 2019 in Turkey. Patients with available serum vitamin D levels measured within 24 months prior to imaging were included. The cohort was divided into two groups: patients diagnosed with PE and those without PE. Vitamin D levels were compared between the groups, and statistical analyses were performed to assess the association between vitamin D deficiency and PE. Results: The mean serum vitamin D level was significantly lower in the PE group compared to the non-PE group (p < 0.05). Vitamin D deficiency (< 20 ng/mL) was more prevalent among patients with PE. However, the discriminatory power of vitamin D levels for predicting PE was limited, as indicated by receiver operating characteristic (ROC) curve analysis. Multivariate analysis adjusting for potential confounders confirmed that vitamin D deficiency was independently associated with an increased risk of PE. Conclusion: Our nationwide retrospective study demonstrates a significant association between vitamin D deficiency and pulmonary embolism. Although vitamin D levels alone may not serve as a strong predictor for PE, these findings highlight the importance of considering vitamin D status in the risk assessment of thromboembolic diseases. Further prospective studies are warranted to clarify the causal relationship and underlying mechanisms. Vitamin D deficiency Pulmonary embolism Thrombosis Risk assessment Figures Figure 1 Introduction PE is a serious medical condition that occurs when a blood clot blocks one or more arteries in lungs. These blood clots typically travel to the lungs from the legs or other parts of the body, such as the pelvis, arms, or head. These clots can impede the normal blood flow, potentially causing damage to lung tissues and affecting overall respiratory and cardiovascular function. In severe cases, it can be fatal [ 1 ]. Clinical signs and symptoms of PE can vary widely, often making diagnosis difficult. Symptoms may include shortness of breath, chest pain, hemoptysis, palpitations, hypoxemia, and even cardiovascular shock. Diagnosis is made through tests such as clinical history, physical examination findings, and imaging studies (e.g., lung computed tomography, vascular ultrasonography, perfusion-ventilation scintigraphy) [ 2 ]. The exact prevalence of PE is unknown due to absence of surveillance methods.[ 3 ]. As it known that PE is third most common cause of cardiovascular death worldwide after stroke and heart attack[ 4 ]. The known risk factors for developing PE are deep vein thrombosis, surgery, trauma, immobility, cancer, genetic factors, pregnancy, smoking but there is many unkown risk factor for developing PE [ 3 ]. Resent studies shows that vitamin D deficiency may be new risk factor for PE [ 5 ] Vitamin D, often referred to as the "sunshine vitamin," plays a crucial role in human physiology beyond just bone health. Vitamin D is synthesized in the skin under the influence of sunlight, which contains ultraviolet B radiation. For most people, the main source of vitamin D is skin synthesis. Dietary sources are important when exposure to sunlight containing the appropriate wavelength is limited [ 6 ]. Vitamin D acts as a steroid hormone that binds to the Vitamin D receptor (VDR). The VDR is present in various tissues and cells, including immune cells, endothelial cells, and cardiomyocytes [ 7 ]. Vitamin D has a direct effect on the epigenome and the expression of more than 1000 genes in most human tissues and cell types [ 8 ]. Vitamin D has been associated with anti-thrombotic properties through several mechanisms. Vitamin D improves endothelial function, reducing the risk of clot formation. Adequate Vitamin D levels may suppress inflammatory pathways linked to thrombosis. Vitamin D may inhibit platelet aggregation, preventing excessive clotting [ 9 ]. All this aspects suggest that Vitamin D deficiency might play a role in the risk of developing PE [ 5 ]. Unfortunatelly, current research lacks a comprehensive exploration of the link between vitamin D supplementation and the prevention of PE. Understanding how vitamin D levels impact these processes could provide valuable insights into new preventive and treatment strategies for this serious condition. In our study, we assessed the incidence of PE based on the vitamin D levels of patients, aiming to ascertain whether vitamin D deficiency constitutes a risk factor for PE. Material Method Ethics and Authorization Statement This study was conducted with authorization obtained from the Turkish Ministry of Health, and the authors were officially assigned to this study as part of the Ministry’s efforts to develop health policies, in accordance with the official decree. The study was carried out under the scope of the Ministry’s approval and conducted in accordance with the principles of the Declaration of Helsinki. Due to the retrospective nature and the extensive dataset analyzed, the requirement for individual informed consent was waived, and all patient data were anonymized prior to analysis. Study Design: This retrospective study was conducted using data retrieved from the centralized national database managed by the Turkish Ministry of Health. The database includes comprehensive health data repositories spanning the entire country, established in 2014 to employ informatics applications with centrally gathered data. The study aimed to investigate the relationship between serum vitamin D levels and the occurrence of pulmonary embolism (PE) in patients who underwent pulmonary CT angiography between 2017 and 2019. To minimize bias, we confined data extraction to 2017–2019, a period preceding the COVID-19 pandemic, thereby avoiding pandemic-related alterations in healthcare utilization, inflammatory burden, and thrombosis incidence. Study Population: A total of 3,980 patients were initially identified from the database. However, systematic errors in the data submitted by hospitals were noted, leading to the exclusion of erroneous records. After data cleaning, the final analysis was conducted on 3,169 patients. The inclusion and exclusion criteria for the study were as follows: Inclusion Criteria: Adults aged 18 years and older. Patients who underwent CT angiography for pulmonary arteries between 2017 and 2019. Patients with vitamin D levels measured within 24 months prior to the CT angiography evaluation. Exclusion Criteria: Patients diagnosed with the following conditions (according to ICD-10 codes) or treatments were excluded: Atrial fibrillation and flutter (I48) Cardiac implants or complications (T82) Rheumatic valve disease (I05-I09) Non-rheumatic mitral valve disease (I34) Malignant neoplasms (C00-D09, D34, D37-D48) Metastatic neoplasms (D00-D09) Benign neoplasms of blood-forming and lymphoid tissues (D34) In situ neoplasms (D00-D09) Blood diseases (D50-D89) Endocrine, nutritional, and metabolic diseases (E00-E07, E20-E46) Benign neoplasms of the skin (L40) Sepsis (M88-M90) Certain viral diseases (B20, B21, B22, B24) Use of vitamin D medications within 24 months prior to the CT angiography. Use of anticoagulant medications within 24 months prior to the CT angiography. Grouping and Classification: The CT angiography reports were reviewed and categorized into two groups: patients with detected PE and those without. There is no consensus on the optimal levels of 25-hydroxyvitamin D in serum [ 10 ]. Vitamin D levels were classified according to the 2011 Institute of Medicine Guidelines [ 11 ]. Toxic: >50 ng/mL Normal: 20 ≤ x ≤ 50 ng/mL Insufficient: 12 ≤ x < 20 ng/mL Deficient: x < 12 ng/mL For patients with multiple vitamin D measurements, the mean vitamin D levels were calculated and used for classification. Statistical Analysis: Demographic parameters, reasons for hospital admission, and vitamin D levels were evaluated. Statistical comparisons were performed between the PE and non-PE groups using SPSS software version 20.0. Continuous variables were expressed as mean ± standard deviation (SD) or median (range), and categorical variables were presented as frequencies and percentages. Comparisons between groups were conducted using the independent t-test for normally distributed data, the Mann-Whitney U test for non-normally distributed data, and the chi-square test for categorical variables. Multivariate logistic regression analysis was performed to identify independent risk factors for PE, adjusting for potential confounders such as age, sex, and comorbidities. A p-value of < 0.05 was considered statistically significant. Outcomes: The primary outcome of the study was the association between serum vitamin D levels and the presence of PE. Secondary outcomes included the distribution of vitamin D levels across the study population and potential confounding factors affecting this relationship. Results The general characteristics of patients with and without PE were analyzed. A total of 3,169 patients participated in the study, with 356 patients diagnosed with PE and 2,813 without PE. Gender distribution was similar between the two groups; females represented 12% of the PE group and 88% of the non-PE group, while males constituted 11% of the PE group and 89% of the non-PE group. The difference in gender distribution between the groups was not statistically significant (p = 0.194). Additionally, the median age of patients with PE was slightly higher compared to those without PE. Among females, the median age was 65 years (interquartile range: 52–75) in the PE group and 59 years (46–75) in the non-PE group. For males, the median age was 63 years (51–75) in the PE group and 58 years (45–69) in the non-PE group. However, this difference in median age was also not statistically significant (p = 0.382). These findings regarding gender distribution and median age are detailed in Table 1 . Table 1 General Characteristics of Patients with and without Pulmonary Embolism Category Pulmonary Embolism Present Pulmonary Embolism Absent Total p-value Number of Patients 356 2,813 3,169 - Gender 0.194 Female (%) 12% 88% 1,660 Male (%) 11% 89% 1,509 Median Age 0.382 Female 65 (52–75) 59 (46–75) - Male 63 (51–75) 58 (45–69) - The distribution of vitamin D levels among patients with and without PE is summarized in Table 2 . Among patients with PE, 50.6% had deficient vitamin D levels (< 12 ng/mL), whereas 38.7% of patients without PE fell into this category. Insufficient vitamin D levels (12–20 ng/mL) were observed in 23.6% of patients with PE, compared to 31.1% of those without PE. Normal vitamin D levels (20–50 ng/mL) were present in 24.4% of patients with PE and 27.9% of those without PE. Toxic vitamin D levels (> 50 ng/mL) were rare, observed in only 1.4% of patients with PE and 2.3% of patients without PE. Additionally, departmental distribution showed that most patients were admitted to Emergency Medicine (49.8%), followed by Pulmonary Diseases (28.6%), Cardiology (7.2%), Internal Medicine (6.3%), and Surgical Units (8.1%). Table 2 Distribution of Vitamin D Levels and Departments Among Patients with and without Pulmonary Embolism Category Pulmonary Embolism Present (n = 356) Pulmonary Embolism Absent (n = 2,813) Total (n = 3,169) Vitamin D Levels (%) Deficient (< 12 ng/mL) 50.6% (n = 180) 38.7% (n = 1,089) 40% (n = 1,269) Insufficient (12–20 ng/mL) 23.6% (n = 84) 31.1% (n = 875) 30.3% (n = 959) Normal (20–50 ng/mL) 24.4% (n = 87) 27.9% (n = 785) 27.5% (n = 872) Toxic (> 50 ng/mL) 1.4% (n = 5) 2.3% (n = 64) 2.2% (n = 69) Departments (%) Emergency Medicine 52.2% (n = 186) 49.5% (n = 1,392) 49.8% (n = 1,578) Cardiology 4.5% (n = 16) 7.5% (n = 211) 7.2% (n = 227) Pulmonary Diseases 30.9% (n = 110) 28.3% (n = 797) 28.6% (n = 907) Internal Medicine 7% (n = 25) 6.2% (n = 175) 6.3% (n = 200) Surgical Units 5.3% (n = 19) 8.5% (n = 238) 8.1% (n = 257) To further analyze the data, vitamin D levels were categorized into two groups: Insufficient-Deficient (< 20 ng/mL) and Normal-Toxic (≥ 20 ng/mL). Statistical analysis was performed using the Pearson Chi-Square test, as shown in Table 3 . Among patients with PE, 74.2% had insufficient-deficient vitamin D levels, whereas 69.8% of patients without PE fell into this category. Conversely, normal-toxic vitamin D levels were observed in 25.8% of patients with PE and 30.2% of patients without PE. The Pearson Chi-Square test resulted in a p-value of 0.089, indicating no statistically significant association between categorized vitamin D levels and the presence of pulmonary embolism. Table 3 Analysis of Vitamin D Levels Categorized as Insufficient-Deficient and Normal-Toxic in Patients with and without Pulmonary Embolism Vitamin D Levels Pulmonary Embolism Doesn't Exist (n = 2,813) Pulmonary Embolism Exists (n = 356) Total (n = 3,169) Insufficient-Deficient n = 1,963 (69.8%) n = 264 (74.2%) n = 2,227 (70.3%) Normal-Toxic n = 850 (30.2%) n = 92 (25.8%) n = 942 (29.7%) Total n = 2,813 n = 356 n = 3,169 Pearson Chi-Square (p = 0,089) In summary, while patients with PE tended to have a higher proportion of deficient and insufficient vitamin D levels, the statistical analysis did not reveal a significant relationship between vitamin D levels and PE. The study compared vitamin D levels between patients with and without PE, revealing that the average vitamin D level in patients with PE was 15.4 ± 0.6 ng/mL, whereas it was 17.2 ± 0.2 ng/mL in patients without PE, with this difference being statistically significant (p = 0.011). Additionally, among patients diagnosed with PE, 60.1% (214 patients) were found to have thrombus present in both pulmonary arteries. When vitamin D levels were analyzed based on the location of the thrombus, no statistically significant difference was observed between the groups (p = 0.059). The ROC curve analysis demonstrated a limited discriminatory ability of the test, as the curve closely followed the diagonal reference line. The visual assessment suggests that the area under the curve is approximately 0.5, indicating that the test performed no better than random chance in distinguishing between the two conditions (Graph 1). Discussion In this study, we analyzed all pulmonary CT angiography reports conducted in our country between 2017 and 2019 to explore the relationship between vitamin D levels and PE. We limited the analysis to a pre-COVID-19 timeframe to exclude pandemic-related effects on thrombosis and vitamin D levels. Statistical analyses were conducted based on these reports. According to our research, we did not come across a study in the literature that includes such a wide patient population. In our study, we found that vitamin D levels in patients with PE were significantly lower on CT compared to patients without embolism This aligns with previous studies in the literature, which have also reported lower vitamin D levels in individuals with PE [ 5 ]. Vitamin D deficiency is widespread, impacting approximately 30–60% of the global population[ 10 ]. In our study, it was observed that the prevalence of vitamin D deficiency was 40% while insufficiency was 30.3%. Despite Turkey being a country with high exposure to sunlight, the incidence of vitamin D deficiency was found to be higher compared to other populations. This situation may be associated with two different factors. Firstly, due to religious reasons or traditional behaviours especially among the female population, our society tends to dress more conservatively, which may reduce exposure to sunlight. Secondly, in determining the sample group for this study, patients with vitamin D levels were included. Physicians often conduct this test for patients where low vitamin D levels are expected. Therefore, individuals with low vitamin D levels may have been more represented in the sample group. Hemostasis is a dynamic process that ensures a delicate balance between clot formation and mechanisms that prevent excessive clotting [ 11 ]. Numerous studies have demonstrated the anti-thrombotic effects of vitamin D on the coagulation system. These findings suggest that vitamin D possesses anticoagulant properties, which may help mitigate hypercoagulability and reduce thrombotic risk [ 12 ]. For instance, studies on rodents have shown increased platelet aggregation and reduced expression of antithrombin and thrombomodulin genes in animals lacking vitamin D receptors [ 13 ]. Furthermore, Koyama et al. reported a decrease in tissue factor levels, a key regulator of the coagulation cascade, further supporting the role of vitamin D in modulating coagulation [ 14 ]. In critically ill COVID-19 patients, where excessive inflammation and coagulation are major contributors to disease severity and mortality, vitamin D supplementation has been proposed as a potential therapeutic strategy. Its combined anti-inflammatory and anticoagulant effects may offer significant benefits in this context [ 15 ]. The hypothesis suggests that vitamin D supplementation could complement anticoagulant therapy in COVID-19 patients, potentially enabling lower anticoagulant doses and reducing the risk of bleeding complications [ 15 ]. Tanık et al. investigated the prognostic value of vitamin D levels in patients hospitalized with pulmonary embolism (PE). They identified ≤ 6.47 ng/mL as the optimal threshold for predicting in-hospital mortality, with a sensitivity of 71.4% and a specificity of 86.9% [ 16 ]. However, our study found that vitamin D levels had lower sensitivity and specificity for predicting PE, indicating that its prognostic utility may vary depending on the studied population and clinical context. PE is most commonly caused by Deep Vein Thrombosis (DVT) [ 17 ]. There are publications in the literature suggesting a relationship between venous thrombosis and vitamin D. It has been shown that low vitamin D levels are associated with an increased risk of DVT in patients with traumatic brain injury [ 18 ]. In a study conducted by Korkmaz et al. it was observed that the group of patients who had experienced DVT, matched for age and gender, had lower vitamin D levels compared to a healthy normal population [ 19 ]. In a large-scale prospective cohort study conducted by Brøndum-Jacobsen et al [ 20 ]. Serum 25-hydroxyvitamin D levels were analyzed in relation to venous thromboembolism risk across a Danish population of over 18,000 individuals. The study demonstrated that individuals with low vitamin D levels had a 28–37% increased risk of VTE compared to those with sufficient levels, even after adjusting for confounders such as age, sex, and lifestyle factors. These findings provide robust epidemiological evidence for a potential link between vitamin D deficiency and thrombotic events. This large sample-based study supports our conclusion that low vitamin D levels are associated with increased risk of PE, particularly given the nationwide scope and statistical power of both studies. In our study, it was not possible to determine the percentage of PE cases that developed after deep vein thrombosis. This information could not be determined due to the unavailability of the patients' venous system doppler ultrasound reports in our dataset. Therefore, we cannot make any comments regarding the occurrence of PE following deep vein thrombosis. Vitamin D receptors are expressed in the pulmonary arteries and are associated with pulmonary arterial hypertension [ 21 ]. Low vitamin D levels may directly increase thrombosis in the pulmonary arteries through expressed vitamin D receptors, unlike the probability of deep vein thrombosis. However, the data obtained in our study are not suitable for making futher comment to this issue. There were several limitations in our study. Some errors occurred during the transfer of test results and CT findings from hospital automation systems to the Ministry of Health database, leading to the exclusion of those patients from the analysis. Additionally, clinical information regarding the patients and their presenting symptoms could not be retrieved from the database, which limited our ability to conduct a more comprehensive evaluation of the cases. Moreover, detailed follow-up data on the patients' vitamin D levels were not available, hindering the assessment of potential correlations between vitamin D changes over time and the development of PE. These limitations should be considered when interpreting the results of our study. In conclusion, this study is the first to gather and analyze nationwide data, demonstrating that vitamin D levels in cases of PE are lower compared to other populations. Vitamin D supplementation in various populations has been shown to reduce thrombin generation and thrombotic events, further reinforcing its potential protective effect against thrombosis [ 22 ]. Given that vitamin D deficiency is common and easily modifiable, its role as a potential co-factor in thromboembolic risk stratification should not be overlooked. Recent reviews have emphasized the need to integrate vitamin D status into broader cardiovascular risk models [ 22 ]. Further research is needed to determine whether vitamin D supplementation is effective in the treatment of the PE to elucidate the pathophysiology. Conclusion Vitamin D deficiency is significantly associated with pulmonary embolism. This study highlights the importance of considering vitamin D status in thromboembolic risk assessment. Further prospective studies are needed to determine the causal relationship and assess the potential of vitamin D supplementation in reducing PE risk. Declarations Acknowledgements The authors would like to express their gratitude to the Turkish Ministry of Health for providing access to the national health data used in this study and for their support in fostering scientific research and development. Artificial intelligence, as a cornerstone of modern science and a driving force for future innovation, has played a pivotal role in the preparation of this study. We extend our sincere gratitude to artificial intelligence algorithms and the engineers behind them for their invaluable contributions. In this study, artificial intelligence was utilized in various stages such as data analysis and English language translation processes. Its integration has significantly enhanced the efficiency and accuracy of ourwork. Conflict of Interest The authors declare that they have no financial or non-financial conflicts of interest related to this study. Author Contributions Author 1 and Author 2: Conceptualization, study design, data acquisition, statistical analysis, and drafting of the manuscript. Author 3, Author 4, and Author 5: Interpretation of the data and critical revisions to enhance the scientific quality of the manuscript. Author 6: Final review of the manuscript, ensuring its intellectual integrity and approving it for submission. Data Availability Statement The datasets generated and analyzed during the current study can be shared by the authors upon reasonable request and with the approval of the Turkish Ministry of Health. Funding The authors declare that no external funding was received for the conduction of this study. References Rali, P., M. Rali, and M. Sockrider, Pulmonary Embolism Part 1. American journal of respiratory and critical care medicine, 2018. 197 (9): p. P15-P16. Howard, L., Acute pulmonary embolism. Clin Med (Lond), 2019. 19 (3): p. 243-247. Beckman, M.G., et al., Venous Thromboembolism: A Public Health Concern. American Journal of Preventive Medicine, 2010. 38 (4): p. S495-S501. Essien, E.O., P. Rali, and S.C. Mathai, Pulmonary Embolism. Med Clin North Am, 2019. 103 (3): p. 549-564. CoŞGun, Z., et al., Can vitamin D level be a marker for predicting risk in pulmonary thromboembolism? Comparative evaluation with pulmonary embolism severity index and CT angiography obstruction index. Journal of Surgery and Medicine, 2022. 6 (2): p. 106-109. Holick, M.F., J.A. MacLaughlin, and S. Doppelt, Regulation of cutaneous previtamin D3 photosynthesis in man: skin pigment is not an essential regulator. Science, 1981. 211 (4482): p. 590-593. Christakos, S., et al., Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects. Physiol Rev, 2016. 96 (1): p. 365-408. Carlberg, C., Vitamin D: A Micronutrient Regulating Genes. Curr Pharm Des, 2019. 25 (15): p. 1740-1746. Mohammad, S., A. Mishra, and M.Z. Ashraf, Emerging Role of Vitamin D and its Associated Molecules in Pathways Related to Pathogenesis of Thrombosis. Biomolecules, 2019. 9 (11). Holick, M.F., Vitamin D deficiency. N Engl J Med, 2007. 357 (3): p. 266-81. Korzonek-Szlacheta, I., et al., Mean platelet volume is associated with serum 25-hydroxyvitamin D concentrations in patients with stable coronary artery disease. Heart and Vessels, 2018. 33 (11): p. 1275-1281. Dehghani, K., et al., Effect of Vitamin D deficiency in lower extremity and pulmonary venous thromboembolism. Biomedical Research and Therapy, 2019. 6 (4): p. 3107-3112. Aihara, K.-i., et al., Disruption of Nuclear Vitamin D Receptor Gene Causes Enhanced Thrombogenicity in Mice *. Journal of Biological Chemistry, 2004. 279 (34): p. 35798-35802. Koyama, T., et al., Anticoagulant effects of 1alpha,25-dihydroxyvitamin D3 on human myelogenous leukemia cells and monocytes. Blood, 1998. 92 (1): p. 160-7. Blondon, M., et al., Associations of Cholecalciferol Supplementation with Thrombin Generation and Fibrin Clot Structure in Severe Vitamin D Deficiency: A Prospective Cohort Study . 2017, American Society of Hematology Washington, DC. Tanık, V.O., T. Çınar, and B. Şimşek, The prognostic value of vitamin D level for in-hospital mortality in patients with acute pulmonary embolism. Turk Kardiyol Dern Ars, 2020. 48 (1): p. 20-25. Becattini, C., et al., Risk Stratification of Patients With Acute Symptomatic Pulmonary Embolism Based on Presence or Absence of Lower Extremity DVT: Systematic Review and Meta-analysis. Chest, 2016. 149 (1): p. 192-200. Moore, M., et al., Low Vitamin D Level Is Associated with Acute Deep Venous Thrombosis in Patients with Traumatic Brain Injury. Brain Sci, 2021. 11 (7). Korkmaz, U.T.K., et al., Association between vitamin D levels and lower-extremity deep vein thrombosis: a case-control study. Sao Paulo Med J, 2021. 139 (3): p. 279-284. Brøndum-Jacobsen, P., et al., 25-Hydroxyvitamin D concentrations and risk of venous thromboembolism in the general population with 18 791 participants. Journal of Thrombosis and Haemostasis, 2013. 11 (3): p. 423-431. Yu, H., et al., 1,25(OH)(2)D(3) attenuates pulmonary arterial hypertension via microRNA-204 mediated Tgfbr2/Smad signaling. Exp Cell Res, 2018. 362 (2): p. 311-323. Blondon, M., et al., Associations of Cholecalciferol Supplementation with Thrombin Generation and Fibrin Clot Structure in Severe Vitamin D Deficiency: A Prospective Cohort Study. Blood, 2017. 130 (Supplement 1): p. 2374-2374. Tables Table 1: General Characteristics of Patients with and without Pulmonary Embolism Category Pulmonary Embolism Present Pulmonary Embolism Absent Total p-value Number of Patients 356 2,813 3,169 - Gender 0.194 Female (%) 12% 88% 1,660 Male (%) 11% 89% 1,509 Median Age 0.382 Female 65 (52-75) 59 (46-75) - Male 63 (51-75) 58 (45-69) - Table 2 : Distribution of Vitamin D Levels and Departments Among Patients with and without Pulmonary Embolism Category Pulmonary Embolism Present (n = 356) Pulmonary Embolism Absent (n = 2,813) Total (n = 3,169) Vitamin D Levels (%) Deficient (<12 ng/mL) 50.6% (n = 180) 38.7% (n = 1,089) 40% (n = 1,269) Insufficient (12-20 ng/mL) 23.6% (n = 84) 31.1% (n = 875) 30.3% (n = 959) Normal (20-50 ng/mL) 24.4% (n = 87) 27.9% (n = 785) 27.5% (n = 872) Toxic (>50 ng/mL) 1.4% (n = 5) 2.3% (n = 64) 2.2% (n = 69) Departments (%) Emergency Medicine 52.2% (n = 186) 49.5% (n = 1,392) 49.8% (n = 1,578) Cardiology 4.5% (n = 16) 7.5% (n = 211) 7.2% (n = 227) Pulmonary Diseases 30.9% (n = 110) 28.3% (n = 797) 28.6% (n = 907) Internal Medicine 7% (n = 25) 6.2% (n = 175) 6.3% (n = 200) Surgical Units 5.3% (n = 19) 8.5% (n = 238) 8.1% (n = 257) Table 3: Analysis of Vitamin D Levels Categorized as Insufficient-Deficient and Normal-Toxic in Patients with and without Pulmonary Embolism Vitamin D Levels Pulmonary Embolism Doesn't Exist (n = 2,813) Pulmonary Embolism Exists (n = 356) Total (n = 3,169) Insufficient-Deficient n = 1,963 (69.8%) n = 264 (74.2%) n = 2,227 (70.3%) Normal-Toxic n = 850 (30.2%) n = 92 (25.8%) n = 942 (29.7%) Total n = 2,813 n = 356 n = 3,169 Pearson Chi-Square (p=0,089) Additional Declarations No competing interests reported. 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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-7779539","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":540348064,"identity":"29c63237-ab4f-426f-8aa6-a634329041bc","order_by":0,"name":"Zamir Kemal 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09:58:23","extension":"html","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":80810,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7779539/v1/2b5979cabee700edc63a7be2.html"},{"id":95285751,"identity":"70e7847c-8b3d-40ff-bf5c-67c02d4a4429","added_by":"auto","created_at":"2025-11-06 09:58:23","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":39200,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eGraph 1: Prognostic Value of Vitamin D Levels in PE Diagnosis: ROC Analysis\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Graph1.png","url":"https://assets-eu.researchsquare.com/files/rs-7779539/v1/8f10e02259d4122ee1323a49.png"},{"id":95315739,"identity":"8ea0c260-008a-4631-8ade-4b6bda318535","added_by":"auto","created_at":"2025-11-06 15:56:54","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1210138,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7779539/v1/0bb11468-c27c-4607-ad7d-8e443f0a937b.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Shining Light on Pulmonary Embolism: The Hidden Role of Vitamin D – A Retrospective Multicenter Nationwide Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePE is a serious medical condition that occurs when a blood clot blocks one or more arteries in lungs. These blood clots typically travel to the lungs from the legs or other parts of the body, such as the pelvis, arms, or head. These clots can impede the normal blood flow, potentially causing damage to lung tissues and affecting overall respiratory and cardiovascular function. In severe cases, it can be fatal [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eClinical signs and symptoms of PE can vary widely, often making diagnosis difficult. Symptoms may include shortness of breath, chest pain, hemoptysis, palpitations, hypoxemia, and even cardiovascular shock. Diagnosis is made through tests such as clinical history, physical examination findings, and imaging studies (e.g., lung computed tomography, vascular ultrasonography, perfusion-ventilation scintigraphy) [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe exact prevalence of PE is unknown due to absence of surveillance methods.[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. As it known that PE is third most common cause of cardiovascular death worldwide after stroke and heart attack[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe known risk factors for developing PE are deep vein thrombosis, surgery, trauma, immobility, cancer, genetic factors, pregnancy, smoking but there is many unkown risk factor for developing PE [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Resent studies shows that vitamin D deficiency may be new risk factor for PE [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eVitamin D, often referred to as the \"sunshine vitamin,\" plays a crucial role in human physiology beyond just bone health. Vitamin D is synthesized in the skin under the influence of sunlight, which contains ultraviolet B radiation. For most people, the main source of vitamin D is skin synthesis. Dietary sources are important when exposure to sunlight containing the appropriate wavelength is limited [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Vitamin D acts as a steroid hormone that binds to the Vitamin D receptor (VDR). The VDR is present in various tissues and cells, including immune cells, endothelial cells, and cardiomyocytes [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eVitamin D has a direct effect on the epigenome and the expression of more than 1000 genes in most human tissues and cell types [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Vitamin D has been associated with anti-thrombotic properties through several mechanisms. Vitamin D improves endothelial function, reducing the risk of clot formation. Adequate Vitamin D levels may suppress inflammatory pathways linked to thrombosis. Vitamin D may inhibit platelet aggregation, preventing excessive clotting [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAll this aspects suggest that Vitamin D deficiency might play a role in the risk of developing PE [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Unfortunatelly, current research lacks a comprehensive exploration of the link between vitamin D supplementation and the prevention of PE. Understanding how vitamin D levels impact these processes could provide valuable insights into new preventive and treatment strategies for this serious condition.\u003c/p\u003e\u003cp\u003eIn our study, we assessed the incidence of PE based on the vitamin D levels of patients, aiming to ascertain whether vitamin D deficiency constitutes a risk factor for PE.\u003c/p\u003e"},{"header":"Material Method","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eEthics and Authorization Statement\u003c/h2\u003e\u003cp\u003e This study was conducted with authorization obtained from the Turkish Ministry of Health, and the authors were officially assigned to this study as part of the Ministry\u0026rsquo;s efforts to develop health policies, in accordance with the official decree. The study was carried out under the scope of the Ministry\u0026rsquo;s approval and conducted in accordance with the principles of the Declaration of Helsinki. Due to the retrospective nature and the extensive dataset analyzed, the requirement for individual informed consent was waived, and all patient data were anonymized prior to analysis.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eStudy Design:\u003c/h3\u003e\n\u003cp\u003eThis retrospective study was conducted using data retrieved from the centralized national database managed by the Turkish Ministry of Health. The database includes comprehensive health data repositories spanning the entire country, established in 2014 to employ informatics applications with centrally gathered data. The study aimed to investigate the relationship between serum vitamin D levels and the occurrence of pulmonary embolism (PE) in patients who underwent pulmonary CT angiography between 2017 and 2019. To minimize bias, we confined data extraction to 2017\u0026ndash;2019, a period preceding the COVID-19 pandemic, thereby avoiding pandemic-related alterations in healthcare utilization, inflammatory burden, and thrombosis incidence.\u003c/p\u003e\n\u003ch3\u003eStudy Population:\u003c/h3\u003e\n\u003cp\u003eA total of 3,980 patients were initially identified from the database. However, systematic errors in the data submitted by hospitals were noted, leading to the exclusion of erroneous records. After data cleaning, the final analysis was conducted on 3,169 patients. The inclusion and exclusion criteria for the study were as follows:\u003c/p\u003e\n\u003ch3\u003eInclusion Criteria:\u003c/h3\u003e\n\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003eAdults aged 18 years and older.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003ePatients who underwent CT angiography for pulmonary arteries between 2017 and 2019.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003ePatients with vitamin D levels measured within 24 months prior to the CT angiography evaluation.\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\n\u003ch3\u003eExclusion Criteria:\u003c/h3\u003e\n\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003ePatients diagnosed with the following conditions (according to ICD-10 codes) or treatments were excluded:\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003eAtrial fibrillation and flutter (I48)\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eCardiac implants or complications (T82)\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eRheumatic valve disease (I05-I09)\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eNon-rheumatic mitral valve disease (I34)\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eMalignant neoplasms (C00-D09, D34, D37-D48)\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eMetastatic neoplasms (D00-D09)\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eBenign neoplasms of blood-forming and lymphoid tissues (D34)\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eIn situ neoplasms (D00-D09)\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eBlood diseases (D50-D89)\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eEndocrine, nutritional, and metabolic diseases (E00-E07, E20-E46)\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eBenign neoplasms of the skin (L40)\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eSepsis (M88-M90)\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eCertain viral diseases (B20, B21, B22, B24)\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eUse of vitamin D medications within 24 months prior to the CT angiography.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eUse of anticoagulant medications within 24 months prior to the CT angiography.\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eGrouping and Classification:\u003c/h2\u003e\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eThe CT angiography reports were reviewed and categorized into two groups: patients with detected PE and those without. There is no consensus on the optimal levels of 25-hydroxyvitamin D in serum [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Vitamin D levels were classified according to the 2011 Institute of Medicine Guidelines [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eToxic: \u003e50 ng/mL\u003c/h3\u003e\n\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003eNormal: 20\u0026thinsp;\u0026le;\u0026thinsp;x\u0026thinsp;\u0026le;\u0026thinsp;50 ng/mL\u003c/h2\u003e\u003cdiv id=\"Sec11\" class=\"Section3\"\u003e\u003ch2\u003eInsufficient: 12\u0026thinsp;\u0026le;\u0026thinsp;x\u0026thinsp;\u0026lt;\u0026thinsp;20 ng/mL\u003c/h2\u003e\u003cdiv id=\"Sec12\" class=\"Section4\"\u003e\u003ch2\u003eDeficient: x\u0026thinsp;\u0026lt;\u0026thinsp;12 ng/mL\u003c/h2\u003e\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eFor patients with multiple vitamin D measurements, the mean vitamin D levels were calculated and used for classification.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis:\u003c/h2\u003e\u003cp\u003eDemographic parameters, reasons for hospital admission, and vitamin D levels were evaluated. Statistical comparisons were performed between the PE and non-PE groups using SPSS software version 20.0. Continuous variables were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) or median (range), and categorical variables were presented as frequencies and percentages. Comparisons between groups were conducted using the independent t-test for normally distributed data, the Mann-Whitney U test for non-normally distributed data, and the chi-square test for categorical variables. Multivariate logistic regression analysis was performed to identify independent risk factors for PE, adjusting for potential confounders such as age, sex, and comorbidities. A p-value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003eOutcomes:\u003c/h2\u003e\u003cp\u003eThe primary outcome of the study was the association between serum vitamin D levels and the presence of PE. Secondary outcomes included the distribution of vitamin D levels across the study population and potential confounding factors affecting this relationship.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe general characteristics of patients with and without PE were analyzed. A total of 3,169 patients participated in the study, with 356 patients diagnosed with PE and 2,813 without PE. Gender distribution was similar between the two groups; females represented 12% of the PE group and 88% of the non-PE group, while males constituted 11% of the PE group and 89% of the non-PE group. The difference in gender distribution between the groups was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.194). Additionally, the median age of patients with PE was slightly higher compared to those without PE. Among females, the median age was 65 years (interquartile range: 52\u0026ndash;75) in the PE group and 59 years (46\u0026ndash;75) in the non-PE group. For males, the median age was 63 years (51\u0026ndash;75) in the PE group and 58 years (45\u0026ndash;69) in the non-PE group. However, this difference in median age was also not statistically significant (p\u0026thinsp;=\u0026thinsp;0.382). These findings regarding gender distribution and median age are detailed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eGeneral Characteristics of Patients with and without Pulmonary Embolism\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCategory\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePulmonary Embolism Present\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePulmonary Embolism Absent\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNumber of Patients\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e356\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2,813\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3,169\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGender\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.194\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e88%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1,660\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e89%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1,509\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMedian Age\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.382\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e65 (52\u0026ndash;75)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e59 (46\u0026ndash;75)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e63 (51\u0026ndash;75)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e58 (45\u0026ndash;69)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe distribution of vitamin D levels among patients with and without PE is summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Among patients with PE, 50.6% had deficient vitamin D levels (\u0026lt;\u0026thinsp;12 ng/mL), whereas 38.7% of patients without PE fell into this category. Insufficient vitamin D levels (12\u0026ndash;20 ng/mL) were observed in 23.6% of patients with PE, compared to 31.1% of those without PE. Normal vitamin D levels (20\u0026ndash;50 ng/mL) were present in 24.4% of patients with PE and 27.9% of those without PE. Toxic vitamin D levels (\u0026gt;\u0026thinsp;50 ng/mL) were rare, observed in only 1.4% of patients with PE and 2.3% of patients without PE. Additionally, departmental distribution showed that most patients were admitted to Emergency Medicine (49.8%), followed by Pulmonary Diseases (28.6%), Cardiology (7.2%), Internal Medicine (6.3%), and Surgical Units (8.1%).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDistribution of Vitamin D Levels and Departments Among Patients with and without Pulmonary Embolism\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCategory\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePulmonary Embolism Present\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;356)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePulmonary Embolism Absent\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;2,813)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTotal (n\u0026thinsp;=\u0026thinsp;3,169)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVitamin D Levels (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDeficient (\u0026lt;\u0026thinsp;12 ng/mL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e50.6% (n\u0026thinsp;=\u0026thinsp;180)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e38.7% (n\u0026thinsp;=\u0026thinsp;1,089)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e40% (n\u0026thinsp;=\u0026thinsp;1,269)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInsufficient (12\u0026ndash;20 ng/mL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e23.6% (n\u0026thinsp;=\u0026thinsp;84)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e31.1% (n\u0026thinsp;=\u0026thinsp;875)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e30.3% (n\u0026thinsp;=\u0026thinsp;959)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNormal (20\u0026ndash;50 ng/mL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24.4% (n\u0026thinsp;=\u0026thinsp;87)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e27.9% (n\u0026thinsp;=\u0026thinsp;785)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e27.5% (n\u0026thinsp;=\u0026thinsp;872)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eToxic (\u0026gt;\u0026thinsp;50 ng/mL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.4% (n\u0026thinsp;=\u0026thinsp;5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.3% (n\u0026thinsp;=\u0026thinsp;64)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.2% (n\u0026thinsp;=\u0026thinsp;69)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDepartments (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEmergency Medicine\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e52.2% (n\u0026thinsp;=\u0026thinsp;186)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e49.5% (n\u0026thinsp;=\u0026thinsp;1,392)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e49.8% (n\u0026thinsp;=\u0026thinsp;1,578)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCardiology\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.5% (n\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7.5% (n\u0026thinsp;=\u0026thinsp;211)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7.2% (n\u0026thinsp;=\u0026thinsp;227)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePulmonary Diseases\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e30.9% (n\u0026thinsp;=\u0026thinsp;110)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28.3% (n\u0026thinsp;=\u0026thinsp;797)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e28.6% (n\u0026thinsp;=\u0026thinsp;907)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInternal Medicine\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7% (n\u0026thinsp;=\u0026thinsp;25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.2% (n\u0026thinsp;=\u0026thinsp;175)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6.3% (n\u0026thinsp;=\u0026thinsp;200)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSurgical Units\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5.3% (n\u0026thinsp;=\u0026thinsp;19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8.5% (n\u0026thinsp;=\u0026thinsp;238)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8.1% (n\u0026thinsp;=\u0026thinsp;257)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eTo further analyze the data, vitamin D levels were categorized into two groups: Insufficient-Deficient (\u0026lt;\u0026thinsp;20 ng/mL) and Normal-Toxic (\u0026ge;\u0026thinsp;20 ng/mL). Statistical analysis was performed using the Pearson Chi-Square test, as shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Among patients with PE, 74.2% had insufficient-deficient vitamin D levels, whereas 69.8% of patients without PE fell into this category. Conversely, normal-toxic vitamin D levels were observed in 25.8% of patients with PE and 30.2% of patients without PE. The Pearson Chi-Square test resulted in a p-value of 0.089, indicating no statistically significant association between categorized vitamin D levels and the presence of pulmonary embolism.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eAnalysis of Vitamin D Levels Categorized as Insufficient-Deficient and Normal-Toxic in Patients with and without Pulmonary Embolism\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVitamin D Levels\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePulmonary Embolism Doesn't Exist (n\u0026thinsp;=\u0026thinsp;2,813)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePulmonary Embolism Exists (n\u0026thinsp;=\u0026thinsp;356)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTotal (n\u0026thinsp;=\u0026thinsp;3,169)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eInsufficient-Deficient\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;1,963 (69.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;264 (74.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;2,227 (70.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNormal-Toxic\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;850 (30.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;92 (25.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;942 (29.7%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTotal\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;2,813\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;356\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;3,169\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cb\u003ePearson Chi-Square (p\u0026thinsp;=\u0026thinsp;0,089)\u003c/b\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eIn summary, while patients with PE tended to have a higher proportion of deficient and insufficient vitamin D levels, the statistical analysis did not reveal a significant relationship between vitamin D levels and PE.\u003c/p\u003e\u003cp\u003eThe study compared vitamin D levels between patients with and without PE, revealing that the average vitamin D level in patients with PE was 15.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6 ng/mL, whereas it was 17.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2 ng/mL in patients without PE, with this difference being statistically significant (p\u0026thinsp;=\u0026thinsp;0.011). Additionally, among patients diagnosed with PE, 60.1% (214 patients) were found to have thrombus present in both pulmonary arteries. When vitamin D levels were analyzed based on the location of the thrombus, no statistically significant difference was observed between the groups (p\u0026thinsp;=\u0026thinsp;0.059).\u003c/p\u003e\u003cp\u003eThe ROC curve analysis demonstrated a limited discriminatory ability of the test, as the curve closely followed the diagonal reference line. The visual assessment suggests that the area under the curve is approximately 0.5, indicating that the test performed no better than random chance in distinguishing between the two conditions (Graph 1).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we analyzed all pulmonary CT angiography reports conducted in our country between 2017 and 2019 to explore the relationship between vitamin D levels and PE. We limited the analysis to a pre-COVID-19 timeframe to exclude pandemic-related effects on thrombosis and vitamin D levels. Statistical analyses were conducted based on these reports. According to our research, we did not come across a study in the literature that includes such a wide patient population.\u003c/p\u003e\u003cp\u003eIn our study, we found that vitamin D levels in patients with PE were significantly lower on CT compared to patients without embolism This aligns with previous studies in the literature, which have also reported lower vitamin D levels in individuals with PE [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eVitamin D deficiency is widespread, impacting approximately 30\u0026ndash;60% of the global population[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. In our study, it was observed that the prevalence of vitamin D deficiency was 40% while insufficiency was 30.3%. Despite Turkey being a country with high exposure to sunlight, the incidence of vitamin D deficiency was found to be higher compared to other populations. This situation may be associated with two different factors. Firstly, due to religious reasons or traditional behaviours especially among the female population, our society tends to dress more conservatively, which may reduce exposure to sunlight. Secondly, in determining the sample group for this study, patients with vitamin D levels were included. Physicians often conduct this test for patients where low vitamin D levels are expected. Therefore, individuals with low vitamin D levels may have been more represented in the sample group.\u003c/p\u003e\u003cp\u003eHemostasis is a dynamic process that ensures a delicate balance between clot formation and mechanisms that prevent excessive clotting [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Numerous studies have demonstrated the anti-thrombotic effects of vitamin D on the coagulation system. These findings suggest that vitamin D possesses anticoagulant properties, which may help mitigate hypercoagulability and reduce thrombotic risk [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. For instance, studies on rodents have shown increased platelet aggregation and reduced expression of antithrombin and thrombomodulin genes in animals lacking vitamin D receptors [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Furthermore, Koyama et al. reported a decrease in tissue factor levels, a key regulator of the coagulation cascade, further supporting the role of vitamin D in modulating coagulation [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn critically ill COVID-19 patients, where excessive inflammation and coagulation are major contributors to disease severity and mortality, vitamin D supplementation has been proposed as a potential therapeutic strategy. Its combined anti-inflammatory and anticoagulant effects may offer significant benefits in this context [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The hypothesis suggests that vitamin D supplementation could complement anticoagulant therapy in COVID-19 patients, potentially enabling lower anticoagulant doses and reducing the risk of bleeding complications [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eTanık et al. investigated the prognostic value of vitamin D levels in patients hospitalized with pulmonary embolism (PE). They identified\u0026thinsp;\u0026le;\u0026thinsp;6.47 ng/mL as the optimal threshold for predicting in-hospital mortality, with a sensitivity of 71.4% and a specificity of 86.9% [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. However, our study found that vitamin D levels had lower sensitivity and specificity for predicting PE, indicating that its prognostic utility may vary depending on the studied population and clinical context.\u003c/p\u003e\u003cp\u003ePE is most commonly caused by Deep Vein Thrombosis (DVT) [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. There are publications in the literature suggesting a relationship between venous thrombosis and vitamin D. It has been shown that low vitamin D levels are associated with an increased risk of DVT in patients with traumatic brain injury [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. In a study conducted by Korkmaz et al. it was observed that the group of patients who had experienced DVT, matched for age and gender, had lower vitamin D levels compared to a healthy normal population [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. In a large-scale prospective cohort study conducted by Br\u0026oslash;ndum-Jacobsen et al [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Serum 25-hydroxyvitamin D levels were analyzed in relation to venous thromboembolism risk across a Danish population of over 18,000 individuals. The study demonstrated that individuals with low vitamin D levels had a 28\u0026ndash;37% increased risk of VTE compared to those with sufficient levels, even after adjusting for confounders such as age, sex, and lifestyle factors. These findings provide robust epidemiological evidence for a potential link between vitamin D deficiency and thrombotic events. This large sample-based study supports our conclusion that low vitamin D levels are associated with increased risk of PE, particularly given the nationwide scope and statistical power of both studies.\u003c/p\u003e\u003cp\u003eIn our study, it was not possible to determine the percentage of PE cases that developed after deep vein thrombosis. This information could not be determined due to the unavailability of the patients' venous system doppler ultrasound reports in our dataset. Therefore, we cannot make any comments regarding the occurrence of PE following deep vein thrombosis. Vitamin D receptors are expressed in the pulmonary arteries and are associated with pulmonary arterial hypertension [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Low vitamin D levels may directly increase thrombosis in the pulmonary arteries through expressed vitamin D receptors, unlike the probability of deep vein thrombosis. However, the data obtained in our study are not suitable for making futher comment to this issue.\u003c/p\u003e\u003cp\u003eThere were several limitations in our study. Some errors occurred during the transfer of test results and CT findings from hospital automation systems to the Ministry of Health database, leading to the exclusion of those patients from the analysis. Additionally, clinical information regarding the patients and their presenting symptoms could not be retrieved from the database, which limited our ability to conduct a more comprehensive evaluation of the cases. Moreover, detailed follow-up data on the patients' vitamin D levels were not available, hindering the assessment of potential correlations between vitamin D changes over time and the development of PE. These limitations should be considered when interpreting the results of our study.\u003c/p\u003e\u003cp\u003eIn conclusion, this study is the first to gather and analyze nationwide data, demonstrating that vitamin D levels in cases of PE are lower compared to other populations. Vitamin D supplementation in various populations has been shown to reduce thrombin generation and thrombotic events, further reinforcing its potential protective effect against thrombosis [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Given that vitamin D deficiency is common and easily modifiable, its role as a potential co-factor in thromboembolic risk stratification should not be overlooked. Recent reviews have emphasized the need to integrate vitamin D status into broader cardiovascular risk models [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Further research is needed to determine whether vitamin D supplementation is effective in the treatment of the PE to elucidate the pathophysiology.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eVitamin D deficiency is significantly associated with pulmonary embolism. This study highlights the importance of considering vitamin D status in thromboembolic risk assessment. Further prospective studies are needed to determine the causal relationship and assess the potential of vitamin D supplementation in reducing PE risk.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to express their gratitude to the Turkish Ministry of Health for providing access to the national health data used in this study and for their support in fostering scientific research and development.\u003c/p\u003e\n\u003cp\u003eArtificial intelligence, as a cornerstone of modern science and a driving force for future innovation, has played a pivotal role in the preparation of this study. We extend our sincere gratitude to artificial intelligence algorithms and the engineers behind them for their invaluable contributions. In this study, artificial intelligence was utilized in various stages such as data analysis and English language translation processes. Its integration has significantly enhanced the efficiency and accuracy of ourwork.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no financial or non-financial conflicts of interest related to this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAuthor 1 and Author 2: Conceptualization, study design, data acquisition, statistical analysis, and drafting of the manuscript.\u003c/p\u003e\n\u003cp\u003eAuthor 3, Author 4, and Author 5: Interpretation of the data and critical revisions to enhance the scientific quality of the manuscript.\u003c/p\u003e\n\u003cp\u003eAuthor 6: Final review of the manuscript, ensuring its intellectual integrity and approving it for submission.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and analyzed during the current study can be shared by the authors upon reasonable request and with the approval of the Turkish Ministry of Health.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that no external funding was received for the conduction of this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eRali, P., M. Rali, and M. Sockrider, \u003cem\u003ePulmonary Embolism Part 1.\u003c/em\u003e American journal of respiratory and critical care medicine, 2018. \u003cstrong\u003e197\u003c/strong\u003e(9): p. P15-P16.\u003c/li\u003e\n\u003cli\u003eHoward, L., \u003cem\u003eAcute pulmonary embolism.\u003c/em\u003e Clin Med (Lond), 2019. \u003cstrong\u003e19\u003c/strong\u003e(3): p. 243-247.\u003c/li\u003e\n\u003cli\u003eBeckman, M.G., et al., \u003cem\u003eVenous Thromboembolism: A Public Health Concern.\u003c/em\u003e American Journal of Preventive Medicine, 2010. \u003cstrong\u003e38\u003c/strong\u003e(4): p. S495-S501.\u003c/li\u003e\n\u003cli\u003eEssien, E.O., P. Rali, and S.C. Mathai, \u003cem\u003ePulmonary Embolism.\u003c/em\u003e Med Clin North Am, 2019. \u003cstrong\u003e103\u003c/strong\u003e(3): p. 549-564.\u003c/li\u003e\n\u003cli\u003eCoŞGun, Z., et al., \u003cem\u003eCan vitamin D level be a marker for predicting risk in pulmonary thromboembolism? 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Ashraf, \u003cem\u003eEmerging Role of Vitamin D and its Associated Molecules in Pathways Related to Pathogenesis of Thrombosis.\u003c/em\u003e Biomolecules, 2019. \u003cstrong\u003e9\u003c/strong\u003e(11).\u003c/li\u003e\n\u003cli\u003eHolick, M.F., \u003cem\u003eVitamin D deficiency.\u003c/em\u003e N Engl J Med, 2007. \u003cstrong\u003e357\u003c/strong\u003e(3): p. 266-81.\u003c/li\u003e\n\u003cli\u003eKorzonek-Szlacheta, I., et al., \u003cem\u003eMean platelet volume is associated with serum 25-hydroxyvitamin D concentrations in patients with stable coronary artery disease.\u003c/em\u003e Heart and Vessels, 2018. \u003cstrong\u003e33\u003c/strong\u003e(11): p. 1275-1281.\u003c/li\u003e\n\u003cli\u003eDehghani, K., et al., \u003cem\u003eEffect of Vitamin D deficiency in lower extremity and pulmonary venous thromboembolism.\u003c/em\u003e Biomedical Research and Therapy, 2019. \u003cstrong\u003e6\u003c/strong\u003e(4): p. 3107-3112.\u003c/li\u003e\n\u003cli\u003eAihara, K.-i., et al., \u003cem\u003eDisruption of Nuclear Vitamin D Receptor Gene Causes Enhanced Thrombogenicity in Mice *.\u003c/em\u003e Journal of Biological Chemistry, 2004. \u003cstrong\u003e279\u003c/strong\u003e(34): p. 35798-35802.\u003c/li\u003e\n\u003cli\u003eKoyama, T., et al., \u003cem\u003eAnticoagulant effects of 1alpha,25-dihydroxyvitamin D3 on human myelogenous leukemia cells and monocytes.\u003c/em\u003e Blood, 1998. \u003cstrong\u003e92\u003c/strong\u003e(1): p. 160-7.\u003c/li\u003e\n\u003cli\u003eBlondon, M., et al., \u003cem\u003eAssociations of Cholecalciferol Supplementation with Thrombin Generation and Fibrin Clot Structure in Severe Vitamin D Deficiency: A Prospective Cohort Study\u003c/em\u003e. 2017, American Society of Hematology Washington, DC.\u003c/li\u003e\n\u003cli\u003eTanık, V.O., T. \u0026Ccedil;ınar, and B. Şimşek, \u003cem\u003eThe prognostic value of vitamin D level for in-hospital mortality in patients with acute pulmonary embolism.\u003c/em\u003e Turk Kardiyol Dern Ars, 2020. \u003cstrong\u003e48\u003c/strong\u003e(1): p. 20-25.\u003c/li\u003e\n\u003cli\u003eBecattini, C., et al., \u003cem\u003eRisk Stratification of Patients With Acute Symptomatic Pulmonary Embolism Based on Presence or Absence of Lower Extremity DVT: Systematic Review and Meta-analysis.\u003c/em\u003e Chest, 2016. \u003cstrong\u003e149\u003c/strong\u003e(1): p. 192-200.\u003c/li\u003e\n\u003cli\u003eMoore, M., et al., \u003cem\u003eLow Vitamin D Level Is Associated with Acute Deep Venous Thrombosis in Patients with Traumatic Brain Injury.\u003c/em\u003e Brain Sci, 2021. \u003cstrong\u003e11\u003c/strong\u003e(7).\u003c/li\u003e\n\u003cli\u003eKorkmaz, U.T.K., et al., \u003cem\u003eAssociation between vitamin D levels and lower-extremity deep vein thrombosis: a case-control study.\u003c/em\u003e Sao Paulo Med J, 2021. \u003cstrong\u003e139\u003c/strong\u003e(3): p. 279-284.\u003c/li\u003e\n\u003cli\u003eBr\u0026oslash;ndum-Jacobsen, P., et al., \u003cem\u003e25-Hydroxyvitamin D concentrations and risk of venous thromboembolism in the general population with 18 791 participants.\u003c/em\u003e Journal of Thrombosis and Haemostasis, 2013. \u003cstrong\u003e11\u003c/strong\u003e(3): p. 423-431.\u003c/li\u003e\n\u003cli\u003eYu, H., et al., \u003cem\u003e1,25(OH)(2)D(3) attenuates pulmonary arterial hypertension via microRNA-204 mediated Tgfbr2/Smad signaling.\u003c/em\u003e Exp Cell Res, 2018. \u003cstrong\u003e362\u003c/strong\u003e(2): p. 311-323.\u003c/li\u003e\n\u003cli\u003eBlondon, M., et al., \u003cem\u003eAssociations of Cholecalciferol Supplementation with Thrombin Generation and Fibrin Clot Structure in Severe Vitamin D Deficiency: A Prospective Cohort Study.\u003c/em\u003e Blood, 2017. \u003cstrong\u003e130\u003c/strong\u003e(Supplement 1): p. 2374-2374.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1: General Characteristics of Patients with and without Pulmonary Embolism\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 178px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCategory\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePulmonary Embolism Present\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePulmonary Embolism Absent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 178px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber of Patients\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e356\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e2,813\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e3,169\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 178px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.194\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 178px;\"\u003e\n \u003cp\u003eFemale (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e12%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e88%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e1,660\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 178px;\"\u003e\n \u003cp\u003eMale (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e11%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e89%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e1,509\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 178px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian Age\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.382\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 178px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e65 (52-75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e59 (46-75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 178px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e63 (51-75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e58 (45-69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2 : Distribution of Vitamin D Levels and Departments Among Patients with and without Pulmonary Embolism\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"603\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCategory\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePulmonary Embolism Present\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n = 356)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePulmonary Embolism Absent\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n = 2,813)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal (n = 3,169)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVitamin D Levels (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003eDeficient (\u0026lt;12 ng/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e50.6% (n = 180)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e38.7% (n = 1,089)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e40% (n = 1,269)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003eInsufficient (12-20 ng/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e23.6% (n = 84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e31.1% (n = 875)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e30.3% (n = 959)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003eNormal (20-50 ng/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e24.4% (n = 87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e27.9% (n = 785)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e27.5% (n = 872)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003eToxic (\u0026gt;50 ng/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e1.4% (n = 5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e2.3% (n = 64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e2.2% (n = 69)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDepartments (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003eEmergency Medicine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e52.2% (n = 186)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e49.5% (n = 1,392)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e49.8% (n = 1,578)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003eCardiology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e4.5% (n = 16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e7.5% (n = 211)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e7.2% (n = 227)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003ePulmonary Diseases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e30.9% (n = 110)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e28.3% (n = 797)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e28.6% (n = 907)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003eInternal Medicine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e7% (n = 25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e6.2% (n = 175)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e6.3% (n = 200)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003eSurgical Units\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e5.3% (n = 19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e8.5% (n = 238)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e8.1% (n = 257)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3: Analysis of Vitamin D Levels Categorized as Insufficient-Deficient and Normal-Toxic in Patients with and without Pulmonary Embolism\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVitamin D Levels\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 161px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePulmonary Embolism Doesn\u0026apos;t Exist (n = 2,813)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 161px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePulmonary Embolism Exists (n = 356)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal (n = 3,169)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eInsufficient-Deficient\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003en = 1,963 (69.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003en = 264 (74.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003en = 2,227 (70.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNormal-Toxic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003en = 850 (30.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003en = 92 (25.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003en = 942 (29.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003en = 2,813\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003en = 356\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003en = 3,169\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003ePearson Chi-Square (p=0,089)\u003c/strong\u003e\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Vitamin D deficiency, Pulmonary embolism, Thrombosis, Risk assessment","lastPublishedDoi":"10.21203/rs.3.rs-7779539/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7779539/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground:\u003c/h2\u003e\u003cp\u003ePulmonary embolism (PE) is a life-threatening condition with significant morbidity and mortality. Recent studies have suggested a potential link between vitamin D deficiency and increased risk of thromboembolic events, including PE. However, large-scale, population-based evidence remains limited.\u003c/p\u003e\u003ch2\u003eObjective:\u003c/h2\u003e\u003cp\u003eTo investigate the association between vitamin D deficiency and the occurrence of pulmonary embolism using nationwide retrospective data from Turkey.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e\u003cp\u003eWe conducted a retrospective study including 3,169 adult patients who underwent pulmonary computed tomography (CT) angiography between 2017 and 2019 in Turkey. Patients with available serum vitamin D levels measured within 24 months prior to imaging were included. The cohort was divided into two groups: patients diagnosed with PE and those without PE. Vitamin D levels were compared between the groups, and statistical analyses were performed to assess the association between vitamin D deficiency and PE.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e\u003cp\u003eThe mean serum vitamin D level was significantly lower in the PE group compared to the non-PE group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Vitamin D deficiency (\u0026lt;\u0026thinsp;20 ng/mL) was more prevalent among patients with PE. However, the discriminatory power of vitamin D levels for predicting PE was limited, as indicated by receiver operating characteristic (ROC) curve analysis. Multivariate analysis adjusting for potential confounders confirmed that vitamin D deficiency was independently associated with an increased risk of PE.\u003c/p\u003e\u003ch2\u003eConclusion:\u003c/h2\u003e\u003cp\u003eOur nationwide retrospective study demonstrates a significant association between vitamin D deficiency and pulmonary embolism. Although vitamin D levels alone may not serve as a strong predictor for PE, these findings highlight the importance of considering vitamin D status in the risk assessment of thromboembolic diseases. Further prospective studies are warranted to clarify the causal relationship and underlying mechanisms.\u003c/p\u003e","manuscriptTitle":"Shining Light on Pulmonary Embolism: The Hidden Role of Vitamin D – A Retrospective Multicenter Nationwide Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-06 09:58:18","doi":"10.21203/rs.3.rs-7779539/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f3ebc626-347a-45c0-9507-871e4a04ea2b","owner":[],"postedDate":"November 6th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-06T12:08:46+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-06 09:58:18","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7779539","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7779539","identity":"rs-7779539","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}