Remnant Cholesterol and Risk of Aortic Aneurysm and Dissection: A Prospective Cohort Study from the UK Biobank Study and Mendelian Randomization Analysis

Abstract Aim To investigate the associations between remnant cholesterol (RC) and the risk of aortic aneurysm and dissection (AAD). Methods This prospective cohort study included 368,193 European adults from the UK Biobank (UKB). In addition, the causal relationship between RC and AAD was investigated using Mendelian randomization (MR) analyses. Results The UKB cohort investigation identified 1634 cases of abdominal aortic aneurysm (AAA), 698 cases of thoracic aortic aneurysm (TAA), and 184 cases of aortic dissection (AD) during a median follow-up time of 13.65 years. High RC was shown to be linked to a higher risk of AAA when compared to the reference RC ([most vs least]: adjusted HR = 1.63, 95% CI 1.33–2.00). Nevertheless, a high RC exhibited only a minimal correlation with a risk of TAA and AD. Two-sample MR analyses revealed a significant causal effect of RC on the risk of AAA (odds ratio = 2.42, 95% confidence range = 1.91–3.06). Even after accounting for HDL-C and LDL-C, this relationship was still statistically significant. However, the MR analysis findings indicated that there was no overall causal relationship between RC and either AD or TAA. Conclusions The risk of incident AAA was heightened with elevated RC levels, and MR analysis provided compelling evidence supporting a causal association between RC and increased risk of AAA. These findings suggest that RC could serve as a novel predictor for AAA and may play a crucial role in AAA prevention strategies.