High lipoprotein(a): Actionable strategies for risk assessment and mitigation

High lipoprotein(a): Actionable strategies for risk assessment and mitigation

17 March 2024 | Gissette Reyes-Soffer, Calvin Yeang, Erin D Michos, Wess Boatwright, Christie M Ballantyne
High levels of lipoprotein(a) (Lp(a)) are a significant risk factor for atherosclerotic cardiovascular disease (ASCVD). Despite being the most prevalent inherited dyslipidemia and the strongest genetic ASCVD risk factor, Lp(a) remains underappreciated in clinical practice. This review highlights the importance of measuring Lp(a) levels and provides actionable guidance for mitigating CVD risk in individuals with high Lp(a). Key points include: 1. **Epidemiology and Prevalence**: Lp(a) is highly prevalent, affecting approximately one in five individuals worldwide. It varies significantly by race, with higher levels in Black individuals compared to other racial groups. 2. **Genetics and Clinical Implications**: The expression of Lp(a) is highly regulated by the *LPA* gene, which codes for apolipoprotein(a) (apo(a)). Variants in the *LPA* gene significantly influence Lp(a) levels, and understanding these genetic associations is crucial for personalized medicine. 3. **Clinical Presentations**: High Lp(a) is strongly associated with CAD, ischemic stroke, peripheral artery disease (PAD), and calcific aortic valve stenosis (CAVS). It also shows a strong association with heart failure (HF) and atrial fibrillation (AF). 4. **Mechanisms of Action**: Lp(a) contributes to atherogenesis, inflammation, and thrombosis/coagulation. Its pro-atherogenic, pro-inflammatory, and pro-thrombotic properties are key factors in its role in cardiovascular disease. 5. **Importance of Lp(a) Screening**: Multiple clinical guidelines recommend universal Lp(a) screening to improve CVD risk assessment. Lp(a) testing can help identify individuals at higher risk and guide more intensive risk factor management. 6. **Management Strategies**: For individuals with high Lp(a), risk calculators, imaging modalities, and lifestyle modifications are recommended. Pharmacological therapies, such as statins and anti-PCSK9 mAbs, can also be used to intensify risk factor management. Lipoprotein apheresis is currently the only FDA-approved therapeutic option for high Lp(a). 7. **Challenges and Future Directions**: Despite the growing evidence of Lp(a)'s role in cardiovascular disease, there are gaps in implementation and targeted therapeutic options. Ongoing research and clinical trials are needed to further understand and address the risks associated with high Lp(a). This review emphasizes the importance of early and routine Lp(a) screening to enhance CVD risk assessment and management, particularly in high-risk populations.High levels of lipoprotein(a) (Lp(a)) are a significant risk factor for atherosclerotic cardiovascular disease (ASCVD). Despite being the most prevalent inherited dyslipidemia and the strongest genetic ASCVD risk factor, Lp(a) remains underappreciated in clinical practice. This review highlights the importance of measuring Lp(a) levels and provides actionable guidance for mitigating CVD risk in individuals with high Lp(a). Key points include: 1. **Epidemiology and Prevalence**: Lp(a) is highly prevalent, affecting approximately one in five individuals worldwide. It varies significantly by race, with higher levels in Black individuals compared to other racial groups. 2. **Genetics and Clinical Implications**: The expression of Lp(a) is highly regulated by the *LPA* gene, which codes for apolipoprotein(a) (apo(a)). Variants in the *LPA* gene significantly influence Lp(a) levels, and understanding these genetic associations is crucial for personalized medicine. 3. **Clinical Presentations**: High Lp(a) is strongly associated with CAD, ischemic stroke, peripheral artery disease (PAD), and calcific aortic valve stenosis (CAVS). It also shows a strong association with heart failure (HF) and atrial fibrillation (AF). 4. **Mechanisms of Action**: Lp(a) contributes to atherogenesis, inflammation, and thrombosis/coagulation. Its pro-atherogenic, pro-inflammatory, and pro-thrombotic properties are key factors in its role in cardiovascular disease. 5. **Importance of Lp(a) Screening**: Multiple clinical guidelines recommend universal Lp(a) screening to improve CVD risk assessment. Lp(a) testing can help identify individuals at higher risk and guide more intensive risk factor management. 6. **Management Strategies**: For individuals with high Lp(a), risk calculators, imaging modalities, and lifestyle modifications are recommended. Pharmacological therapies, such as statins and anti-PCSK9 mAbs, can also be used to intensify risk factor management. Lipoprotein apheresis is currently the only FDA-approved therapeutic option for high Lp(a). 7. **Challenges and Future Directions**: Despite the growing evidence of Lp(a)'s role in cardiovascular disease, there are gaps in implementation and targeted therapeutic options. Ongoing research and clinical trials are needed to further understand and address the risks associated with high Lp(a). This review emphasizes the importance of early and routine Lp(a) screening to enhance CVD risk assessment and management, particularly in high-risk populations.
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