#255 ‒ Latest therapeutics in CVD, APOE’s role in Alzheimer’s disease and CVD, familial hypercholesterolemia, and more | John Kastelein, M.D., Ph.D. | The Peter Attia Drive

Intro

In this episode of “The Peter Attia Drive” podcast, Peter Attia interviews John Kastelein, M.D., Ph.D., about the latest therapeutics in cardiovascular disease (CVD), the role of APOE in Alzheimer’s disease and CVD, familial hypercholesterolemia (FH), and more. Dr. Kastelein shares insights into the diagnosis, treatment, and genetic causes of FH, as well as the potential game-changing impact of CTEP inhibitors in CVD, Alzheimer’s disease, and type 2 diabetes. The conversation also delves into the significance of the ApoE protein and its isoforms in the risk of Alzheimer’s disease and CVD.

Main Takeaways

Familial Hypercholesterolemia (FH)

• Familial hypercholesterolemia is the second most common form of hereditary heart disease after elevated Lp(a).
• FH is a genetic condition that starts early in life and becomes symptomatic in teenage years, leading to severe heart conditions.
• FH is defined by elevated LDL cholesterol without any other abnormality and a family history of premature coronary disease.
• Diagnosis of FH is more accurate in children, with 95% of cases having a mutation found through sequencing.
• Treatment for FH at a young age is necessary to prevent premature risk of heart disease.

CTEP Inhibitors and Potential Game Changer

• The most recent version of CTEP inhibitors may be a potential game changer for CVD, Alzheimer’s disease, and type 2 diabetes.
• CTEP inhibitors lower CTP activity, which is associated with the worst progression of coronary disease.
• CTEP inhibitors have the potential to improve lipoprotein metabolism and protect against heart disease, Alzheimer’s disease, and renal disease.

Role of ApoE in Alzheimer’s Disease and CVD

• The ApoE protein, coded by the ApoE gene, plays a significant role in the risk of Alzheimer’s disease and CVD.
• The ApoE4 isoform produces a much greater increase in the risk of Alzheimer’s disease and CVD than the ApoE3 isoform.
• Some individuals with FH may be immune to the elevated LDL cholesterol, with about 5% showing no disease symptoms at all.
• Women with FH and high HDL cholesterol may have a more efficient reverse cholesterol transport system, which could be protective against heart disease.

Therapeutic Molecules and Future Outlook

• There is optimism that within the next five years, therapeutic molecules can be used for high-risk patients such as those with APOE4.
• Early prevention and intervention with LDL-lowering medication can add 15-20 years to a patient’s life.
• PCSK9 inhibitors have been established as safe and effective in treating FH and other forms of hypercholesterolemia.

Summary

Familial Hypercholesterolemia (FH)

Familial hypercholesterolemia (FH) is a genetic condition characterized by elevated LDL cholesterol levels without any other abnormality and a family history of premature coronary disease. It is the second most common form of hereditary heart disease after elevated Lp(a). FH starts early in life and becomes symptomatic in teenage years, leading to severe heart conditions. Diagnosis of FH is more accurate in children, with 95% of cases having a mutation found through sequencing. Treatment for FH at a young age is necessary to prevent premature risk of heart disease.

CTEP Inhibitors and Potential Game Changer

The most recent version of CTEP inhibitors shows promise as a potential game changer in the treatment of cardiovascular disease (CVD), Alzheimer’s disease, and type 2 diabetes. CTEP inhibitors lower CTP activity, which is associated with the worst progression of coronary disease. By improving lipoprotein metabolism, CTEP inhibitors have the potential to protect against heart disease, Alzheimer’s disease, and renal disease.

Role of ApoE in Alzheimer’s Disease and CVD

The ApoE protein, coded by the ApoE gene, plays a significant role in the risk of Alzheimer’s disease and cardiovascular disease (CVD). The ApoE4 isoform produces a much greater increase in the risk of Alzheimer’s disease and CVD than the ApoE3 isoform. Some individuals with FH may be immune to the elevated LDL cholesterol, with about 5% showing no disease symptoms at all. Additionally, women with FH and high HDL cholesterol may have a more efficient reverse cholesterol transport system, which could be protective against heart disease.

Therapeutic Molecules and Future Outlook

There is optimism that within the next five years, therapeutic molecules can be used for high-risk patients such as those with APOE4. Early prevention and intervention with LDL-lowering medication, such as PCSK9 inhibitors, can add 15-20 years to a patient’s life. PCSK9 inhibitors have been established as safe and effective in treating FH and other forms of hypercholesterolemia.

Conclusion

This episode of “The Peter Attia Drive” podcast provides valuable insights into the diagnosis, treatment, and genetic causes of familial hypercholesterolemia (FH). It also explores the potential game-changing impact of CTEP inhibitors in cardiovascular disease (CVD), Alzheimer’s disease, and type 2 diabetes. The discussion on the role of the ApoE protein in Alzheimer’s disease and CVD sheds light on the importance of early prevention and intervention. Overall, this episode offers a comprehensive understanding of these complex topics and highlights the potential for future therapeutic advancements.