This study seeks to delve deeper into these issues; we utilize a series of weak IV and pleiotropy robust Mendelian randomization (MR) methods and causal mediation analysis by MR approach to explore the causal mechanisms (causal relationship and biological mechanisms) of DPP4 and various CVDs, including HF, atrial fibrillation (AF), myocardial infarction (MI), and stroke within a European population. This evidence concerns the gene DPP4 and stroke disorder.