Idiopathic pulmonary fibrosis is a risk factor for cardiovascular disease: potential role of KL-6 and systemic inflammation

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal disease of the lungs. It is characterized by pulmonary and extrapulmonary comorbidities. So far, little is known as regards the prevalence of cardiovascular comorbidities in IPF patients. This study aims to investigate the prevalence of cardiovascular comorbidities in patients with IPF and correlate it with different radiological and laboratory indices of disease severity. Methods This prospective case–control study was performed on 134 IPF patients above 18 years. Diagnosis of IPF was based on diagnostic radiologic criteria addressed by ATS guidelines. Patients were recruited from the Pulmonology Department, Assiut University Hospitals, from June 2023 to June 2024. Cardiac comorbidities were assessed by ECG and echocardiography. All patients had C-reactive protein (CRP), Krebs von den Lungen-6 (KL-6), and lipid profile including cholesterol level, triglyceride level, HDL-cholesterol level, and LDL-cholesterol level measured. Patients were divided into two groups: IPF patients with cardiovascular comorbidities and IPF patients without cardiovascular comorbidities. Comparison between both groups as regards clinical, radiological, and laboratory criteria was carried out. Results The studied group consists predominantly of females (65%). Sixty out of the 134 documented IPF patients had cardiovascular comorbidities (44.7%), cardiomyopathy (mean ± SD: 43.63 ± 10.56), pulmonary hypertension (mean ± SD: 41.67 ± 15.32), ECG-ischemic changes (40.0%), and atrial fibrillation (13.3%). IPF patients with cardiovascular comorbidities vs. patients without 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, KL-6, cholesterol level, triglyceride level, and LDL-cholesterol level (P value < 0.001). Box plot analysis demonstrated significantly higher KL-6 serum level among IPF patients with cardiovascular comorbidities. Sensitivity 90.0%, specificity 94.6%, and accuracy 92.5% were associated with a cutoff value of KL-6 ≥ 299 for prediction of associated cardiovascular comorbidities among the studied IPF group. Conclusions Dyslipidemia and cardiovascular comorbidities were detected in a large group of IPF patients. These comorbidities were associated with a high HRCT TFS score. High serum levels of CRP and KL-6 were predictors of associated cardiovascular comorbidities in IPF. Trial registration ClinicalTrials.gov. NCT06539962.