Bidirectional Mendelian Randomization Study: Unraveling the Link Between Idiopathic Pulmonary Fibrosis and Cardiovascular Disease.

Background: Idiopathic pulmonary fibrosis (IPF), the predominant idiopathic interstitial pneumonia, is marked by progressive, irreversible lung damage with a 3-year median survival rate in the elderly. Cardiovascular disease (CVD) is the most common disease in the elderly population and its incidence is increasing all the time, especially in the Asia-Pacific region, coinciding with the rise in global mortality. Despite clinical indications of a link between IPF and CVD, the mechanisms are not well understood. This study applies a bidirectional two-sample Mendelian randomization (MR) approach to explore potential causalities between IPF and CVD.

Methods: Summary data from public genome-wide association study (GWAS) databases for IPF (27,449 participants) and CVD were utilized. Single nucleotide polymorphisms (SNPs) served as instrumental variables in MR analysis, employing inverse variance-weighted (IVW), weighted median (WM), and MR-Egger methods. Heterogeneity was assessed with Cochran's Q test, and sensitivity analyses were conducted using MR-PRESSO.

Results: The IVW analysis revealed no significant associations between genetically predicted IPF and CVD, except for a significant negative association with large artery atherosclerosis stroke and IPF. The WM method supported this inverse relationship. MR-Egger intercept indicated pleiotropy in the link between IPF and heart failure, with no outliers detected by MR-PRESSO. Cochran's Q test showed no significant heterogeneity for the relationships.

Conclusion: The bidirectional MR study suggests a potential negative influence of large artery atherosclerosis stroke on IPF, hinting at a protective role of IPF in stroke incidence. The absence of significant associations with other CVDs and IPF implies a more complex relationship than previously considered. Further research is needed to clarify the intricate connections between IPF and CVD.