Abstract
BACKGROUND: Cardiovascular (CV) comorbidities can affect drug tolerability and health outcomes in patients with idiopathic pulmonary fibrosis (IPF). This systematic review and meta-analysis aimed to quantify the magnitudes of association between IPF and both overall and specific categories of CV disease. METHODS: The PRISMA guidelines and PICO model were followed. We searched PubMed, Embase, Web of Science, Cochrane Library, and Chinese Biomedical Literature Service System (Sinomed) from inception to April 2025 for studies investigating CV disease in IPF patients. Study quality was assessed using the Newcastle-Ottawa Scale (NOS). Pooled odds ratio (OR) for case-control/cross-sectional datasets and relative risk (RR) for cohort datasets were calculated using Review Manager 5.4. The I (2) test was used to evaluate the heterogeneity and the sources of heterogeneity were explored through sensitivity analyses, meta-regression, and subgroup analyses. The funnel plot and Egger's test were used to evaluate publication bias. RESULTS: A total of 28 studies comprising 29 case-control/cross-sectional datasets and four cohort datasets were included, which indicated a positive association between IPF and CV disease (OR 2.44, 95% CI 1.84-3.24, P < 0.001; RR 1.44, 95% CI 1.07-1.92, P = 0.02). Meta-regression and maximized subgroup analyses confirmed the influence of control characteristics (P < 0.001), data source (P = 0.027), Newcastle-Ottawa Scale (NOS) score (P = 0.022), certainty of CV disease diagnosis (P = 0.027), body mass index (BMI), smoking status, and diabetes prevalence on both heterogeneity and risk estimates in the case-control/cross-sectional datasets. The OR varied across the CV disease category, with 1.14- to 2.51-fold increased risks for ischemic heart disease, thromboembolic disease, pulmonary hypertension, and other forms of heart disease. CONCLUSION: Idiopathic pulmonary fibrosis is significantly associated with CV disease, emphasizing the urgent need for systematic screening and risk reduction strategies in IPF patients. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251013917, identifier CRD420251013917.