Abstract
Background
Primary hypertension is a major risk factor for various cardiovascular diseases. Although low-density lipoprotein and high-density lipoprotein are known to influence cardiovascular diseases, the role of intermediate-density lipoprotein remains unclear.
Objective
This study investigated the mediating role of intermediate-density lipoprotein particle concentration in primary hypertension in four major cardiovascular diseases (coronary heart disease, peripheral atherosclerosis, stroke, and deep vein thrombosis) using multiomics data and Mendelian randomization methods.
Methods
This study was conducted in three phases: confirming the relationship between hypertension and cardiovascular outcomes via two-step Mendelian randomization, identifying common risk genes through colocalization analysis, and analyzing key genes in lipid metabolism pathways via differential expression and GSEA, with further validation via PheWas analysis.
Results
Primary hypertension significantly increased the risk of four cardiovascular diseases. Intermediate-density lipoprotein particle concentration mediates the risk of hypertension on coronary heart disease and peripheral atherosclerosis, reducing the risk by 22% and 13%, respectively. Colocalization analysis identified 119 common risk genes, with CYP21A2 and HSD17B8 involved in lipid metabolism pathways. GSEA highlighted the importance of the glycerophospholipid metabolism pathway.
Conclusion
This study revealed the mediating role of intermediate-density lipoprotein particle concentration in hypertension and cardiovascular diseases, emphasizing the critical role of lipid metabolism pathways. These findings offer new perspectives and potential therapeutic targets for hypertension-related cardiovascular diseases.