Remnant cholesterol and aortic aneurysm risk: insights from Mendelian randomization and the global burden of disease 2021 study

Aortic aneurysm (AA) is a life-threatening condition with growing global health implications. This study assessed the global burden and temporal trends of AA and explored the causal effect of remnant cholesterol (RC) on aortic diseases using Mendelian randomization (MR). Data from the Global Burden of Diseases (GBD) 2021 were used to estimate age-standardized death rate (ASDR), age-standardized DALY rate (ASDALYR), and their annual percentage changes (EAPC). Analyses were stratified by sex, age, region, country, and Socio-demographic Index (SDI). Two-sample MR was performed using genome-wide association study (GWAS) data to evaluate the causal role of RC in AA, abdominal AA (AAA), thoracic AA (TAA), and aortic dissection (AD). In 2021, AA caused 153,927 deaths worldwide, a 74.3% increase from 1990. However, ASDR declined from 2.54 to 1.86 per 100,000 (EAPC = −1.28%, 95% CI: −1.38 to −1.18), and ASDALYR from 48.79 to 36.54 (EAPC = −1.23%, 95% CI: −1.33 to −1.13). Highest burdens were in Eastern Europe, Central Asia, and parts of Africa and Latin America. Moderate positive correlations were observed between SDI and ASDR at regional (R = 0.466) and national (R = 0.339) levels. MR analyses showed a causal effect of RC on AA (OR = 1.410) and AAA (OR = 2.161), but not on TAA or AD. Despite decreasing global ASDR, regional disparities remain. Moreover, the identified causal role of RC in AA and AAA highlights the potential of RC as a modifiable risk factor in future prevention strategies.