本期播客探讨了脂蛋白(a) [Lp(a)] 与动脉粥样硬化性心血管疾病 (ASCVD) 风险之间的关系。研究科学家Benoît Arsenault解释了Lp(a)的生物学特性，其遗传方式，以及测量Lp(a)水平的重要性。讨论涵盖了Lp(a)与心血管疾病风险的关联，基因组研究的发现，以及临床检测方法。此外，节目还探讨了降低Lp(a)水平的潜在治疗方法，包括烟酸、他汀类药物和PCSK9抑制剂，以及有前景的反义寡核苷酸疗法。此次讨论旨在提高对Lp(a)在心血管健康中的重要性的认识。

🧬 Lp(a)是心血管疾病风险的重要遗传因素。Benoît Arsenault解释了Lp(a)的生物学特性，它与ASCVD风险密切相关。

🔬 基因研究揭示了Lp(a)的作用。全基因组关联研究 (GWAS) 提供了关于Lp(a)的遗传基础的深入见解，有助于理解其在疾病风险中的作用。

🩺 临床检测对于评估Lp(a)水平至关重要。讨论了测量Lp(a)的临床测试，强调了定期检测对于风险评估的重要性。

💊 探讨了降低Lp(a)水平的治疗方法。节目讨论了包括烟酸、他汀类药物和PCSK9抑制剂在内的现有治疗方法，以及有前景的反义寡核苷酸疗法。

❤️‍🩹 强调了提高对Lp(a)重要性的认识。节目强调了在医生和患者中提高对Lp(a)重要性的认识，以改善心血管疾病的风险管理。

View the Show Notes Page for This Episode

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Benoît Arsenault is a research scientist focused on understanding how lifestyle and genetic factors contribute to cardiovascular disease risk. In this episode, the discussion casts a spotlight on Lp(a)—the single most important genetically-inherited trait when it comes to atherosclerotic cardiovascular disease (ASCVD) risk. Benoît explains the biology of Lp(a), how it’s inherited, the importance of measuring Lp(a) levels, and the diseases most associated with high Lp(a). He dives into data on the possible treatments for lowering Lp(a) such niacin, statins, and PCSK9 inhibitors, as well as the most exciting new potential therapeutic—antisense oligonucleotides.

We discuss:

• How Benoît came to study Lp(a)—a new marker for cardiovascular risk [3:15];
• The relationship between Lp(a) and CVD risk [6:45];
• What genome-wide association studies (GWAS) revealed about Lp(a) [16:00];
• Clinical tests to measure Lp(a) [22:00];
• The biology of Lp(a) [25:45];
• How statins lower LDL-cholesterol and why this doesn't work for an Lp(a) [29:15];
• The structure of LDL-p and Lp(a) and what makes Lp(a) more atherogenic than an equivalent LDL particle [34:00];
• The role of Lp(a) in aortic valve disease [42:45];
• How greater numbers of Lp(a) particles are associated with increased risk of disease [48:00];
• The genetics and inheritance of Lp(a) and how and when to measure Lp(a) levels [52:00];
• Niacin and other proposed therapies to lower Lp(a), apoB, and CVD risk [1:00:45];
• Why awareness of Lp(a) among physicians remains low despite the importance of managing risk factors for ASCVD [1:14:00];
• The variability of disease in patients with high Lp(a) [1:19:00];
• Diseases most associated with high Lp(a) [1:26:30];
• The biology of PCSK9 protein, familial hypercholesterolemia, and the case for inhibiting PCSK9 [1:35:00];
• The variability in PCSK9 inhibitors’ ability to lower Lp(a) and why we need more research on individuals with high levels of Lp(a) [1:50:30];
• Peter’s approach to managing patients with high Lp(a), and Benoît’s personal approach to managing his risk [1:54:45];
• Antisense oligonucleotides—a potential new therapeutic for Lp(a) [1:57:15]; and
• More.

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