ASCVD Risk & Lipid Update: PREVENT, ApoB, Lp(a), and New Therapies with Dr. Laurence Sperling

Understanding ASCVD Risk Assessment

• 🎯 Cardiovascular disease prevention is foundational, starting with risk assessment. The CPR framework (Calculate, Personalize, Reclassify) is key.
• 🧮 Calculate risk using tools like the PREVENT score, Pool Cohort Equation, MESA, or Reynolds score. Remember, risk assessment is the beginning, not the end, of decision-making.
• 🧑‍⚕️ Personalize risk by incorporating cardiovascular risk-enhancing factors such as family history, metabolic syndrome, and other patient-specific details.
• 🔬 Reclassify risk using tools like a cardiac CT calcium score, which is valuable for detecting calcified plaque and can help derisk or increase concern for an individual.

Interpreting Lipid Markers and New Tools

• 📊 Non-HDL cholesterol is a valuable, cost-free measure encompassing all atherogenic particles, calculated as total cholesterol minus HDL.
• 🧬 Apolipoprotein B (ApoB) is a direct measure of atherogenic particle number, but current guidelines do not universally target it. It may be considered in cases of discordance between LDL and ApoB or with severe hypertriglyceridemia.
• ⚠️ Lipoprotein(a) (Lp(a)) is a significant, genetically determined risk factor, present in about 1 in 5 people. It exerts pro-atherogenic, inflammatory, and thrombotic effects and is associated with aortic stenosis progression.
• 🇨🇦🇪🇺🇨🇳 Universal Lp(a) screening is recommended in Canada, Europe, and China, with potential updates expected in US guidelines.

The PREVENT Risk Score and Beyond

• 🚀 The PREVENT risk score offers a step up in risk assessment, providing 10- and 30-year risk estimates for ages 30-79. It incorporates BMI, diabetes status, eGFR, and uses zip code as a surrogate for social deprivation, moving away from race/ethnicity.
• 🏥 PREVENT can also calculate total cardiovascular disease risk and heart failure risk, broadening the conversation beyond just ASCVD.
• 📈 Future guidelines may lower statin initiation thresholds, potentially around 3% 10-year risk, reflecting improved risk discrimination.

Statin Therapy and Lifestyle Interventions

• 🤝 Patient-partnered care is crucial, involving shared decision-making about initiating therapies like statins.
• 💊 Statins are effective and generally well-tolerated, with benefits extending beyond cholesterol lowering to include anti-inflammatory and endothelial function improvements.
• 🥗 Healthy dietary patterns, such as Mediterranean or flexitarian approaches, and regular physical activity are key. The portfolio diet (oats, walnuts, almonds, flaxseed, dark chocolate) can also lower cholesterol.
• 🧬 Familial hypercholesterolemia (FH) requires early intervention, even with lower LDL levels if genetic predisposition is present. Cascade screening of families is essential.

Advanced Therapies and Future Directions

• 💡 PCSK9 inhibitors are powerful tools for lowering LDL cholesterol in high-risk patients, especially those with FH or statin intolerance.
• 🩸 Lipoprotein apheresis is an option for severe hypercholesterolemia, significantly reducing LDL and Lp(a) levels.
• 🔬 Emerging Lp(a)-lowering therapies (e.g., pelacarsen, lepodiscerin, omapacirin) show promise in clinical trials, with potential to significantly reduce Lp(a) levels and impact cardiovascular events.
• 🩺 Cardiovascular disease prevention is achievable through diligent risk assessment, effective therapies, and a commitment to partnered care.