Title: Idiopathic pulmonary fibrosis is a risk factor for cardiovascular disease; Potential role for systemic inflammation

Abstract Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, parenchymal disease, now considered as fatal disease of the lungs, characterized by pulmonary and extrapulmonary comorbidities. So far, little is known regarding the cardiovascular comorbidities in patients with idiopathic pulmonary fibrosis. This study aims to: investigate the prevalence and impact of cardiovascular comorbidities in patients with IPF and its correlation with different radiological and laboratory indices of disease severity. Methods: This prospective case-control study was performed on 134 idiopathic pulmonary fibrosis patients in the age group of 18 to 70 years. Diagnosis of idiopathic pulmonary fibrosis was done based on diagnostic radiologic criteria addressed by ATS clinical practice guidelines. Patients were recruited from pulmonology department, Assiut university hospitals from October 2023 to October 2024. Cardiac comorbidities were assessed by ECG and echocardiography. All patients had CRP, KL6, total lipid profile including cholesterol level, Triglyceride level, HDL-cholesterol level, LDL-cholesterol level measured. Patients were divided into two groups: IPF patients with cardiovascular comorbidities, and IPF patients without cardiovascular comorbidities. Correlations were done between IPF patient’s criteria and presence of cardiovascular comorbidities. Results: Female represented the majority of the studied group 65%. 60 out of 134 documented IPF patients had cardiovascular comorbidities. Patients with CVD comorbidities vs IPF patients without CVD comorbidities had higher radiological HRCT Total fibrosis score TFS. P value <0.001. As regards laboratory serum biomarkers, the group with comorbidities showed significantly higher CRP, KL6, cholesterol level, triglyceride level, HDL cholesterol level, LDL cholesterol level. P value <0.001. A cutoff value KL6 of ≥299; the areas under the ROC curves were 89.7% (95%CI: 0.832 – 0.963, P<0.001) with a sensitivity of 90.0%, a specificity of 94.6%, and accuracy of 92.5% were associated with the presence of cardiac comorbidities. Conclusions: Dyslipidemia and cardiac comorbidities were detected in a large group of patients with IPF. These findings were associated with increased severity of the disease. High serum levels of CRP and KL6 was a significant finding in this group of patients.