Endothelial cell-related genetic variants identify LDL cholesterol-sensitive individuals who derive greater benefit from aggressive lipid lowering.

• Tác giả: Daniel I Chasman, Patrick T Ellinor, Jesse M Engreitz, Robert P Giugliano, Rajat M Gupta, Aaron Hakim, Frederick K Kamanu, Helen Kang, Rosa X Ma, Nicholas A Marston, Giorgio E M Melloni, Paul M Ridker, Christian T Ruff, Marc S Sabatine, Gavin Schnitzler
• Ngôn ngữ: eng
• Thông tin xuất bản: United States : Nature medicine , 2025
• Bộ sưu tập: NCBI
• ID: 722366

Tóm tắt

 The role of endothelial cell (EC) dysfunction in contributing to an individual's susceptibility to coronary atherosclerosis and how low-density lipoprotein cholesterol (LDL-C) concentrations might modify this relationship have not been previously studied. Here, from an examination of genome-wide significant single nucleotide polymorphisms associated with coronary artery disease (CAD), we identified variants with effects on EC function and constructed a 35 single nucleotide polymorphism polygenic risk score comprising these EC-specific variants (EC PRS). The association of the EC PRS with the risk of incident cardiovascular disease was tested in 3 cohorts: a primary prevention population in the UK Biobank (UKBB
  n = 348,967)
  a primary prevention cohort from a trial that tested a statin (JUPITER, n = 8,749)
  and a secondary prevention cohort that tested a PCSK9 inhibitor (FOURIER, n = 14,298). In the UKBB, the EC PRS was independently associated with the risk of incident CAD (adjusted hazard ratio (aHR) per 1 s.d. of 1.24 (95% CI 1.21-1.26), P <
  2 × 10