407 ‒ Preventing cardiovascular and Alzheimer’s disease: lowering LDL early, APOE4, and more

Cardiovascular disease prevention requires shifting from reactive treatment to primordial intervention, targeting causal drivers like LDL cholesterol early in life. Current clinical strategies often delay aggressive management until after significant plaque buildup, missing the opportunity to prevent disease progression. CETP inhibitors, such as Obicetrapib, offer a promising path forward by significantly lowering LDL and modulating lipid homeostasis, with emerging evidence suggesting additional benefits for metabolic health and Alzheimer’s disease. Specifically, targeting cholesterol metabolism may mitigate the neurodegenerative risks associated with the APOE4 genotype, which impairs cholesterol efflux in the brain. While statins remain foundational, the future of lipid management lies in potent, well-tolerated combination therapies that address residual risk factors like Lp(a) and small LDL particles, ultimately aiming to reduce the long-term burden of both cardiovascular and neurodegenerative conditions.