The Role of Apo-E in Cardiovascular Disease

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Apo-E gets a lot of attention for what it's doing in the brain. But I think people are less clear on the relationship of apo-E in the heart. Apo-E4 might have been wonderful in during the ice age, but now it's bad because it's associated with higher LDL. Will you be measuring desmosteral and lactose-to-roll in any of these trials or in all of them? Yes. No, we in the Alzheimer trial,. Which is prevail is the one where you're going to know.

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John Kastelein is a renowned expert in lipoprotein metabolism and atherosclerotic cardiovascular disease (ASCVD) research. In this discussion, John delves deep into familial hypercholesterolemia (FH), a genetic disorder characterized by high levels of LDL cholesterol in the blood that increases the risk of developing heart disease. He covers its definition, genetic underpinnings, and clinical identification. He then explores the therapeutic options available for the prevention and treatment of cardiovascular disease, including the captivating history of CETP inhibitors. He explains the past shortcomings of previous CETP inhibitors before underscoring the compelling potential of the latest iterations, not only for cardiovascular disease but also for conditions like Alzheimer's disease and type 2 diabetes. Moreover, he unveils the intricate role of APOE, shedding light on why the APOE4 isoform codes for a protein that significantly increases the risk of Alzheimer's disease and cardiovascular disease. Concluding the discussion, John shares a profound sense of optimism, envisioning the possibility of targeted therapeutic interventions for high-risk patients in the near future.

We discuss:

Familial hypercholesterolemia (FH): a genetic condition [4:30];
Differentiating between phenotype and genotype when it comes to FH [9:45];
The pathophysiology related to mutations of FH [15:30];
Clinical presentations, physical manifestations, and diagnosis of FH [22:00];
Why a small fraction of people with FH do not develop premature ASCVD [34:15];
Treatment and prevention for those with FH [39:45];
Addressing the assertion by some that elevated LDL is not casual in cardiovascular disease [52:45];
The history of CETP inhibitors, and the role of the CETP protein [55:45];
The thrifty gene hypothesis and why genes underlying FH may have been preserved [1:09:00];
The compelling potential of the latest CETP inhibitor (obicetrapib) [1:13:00];
Promising results from phase 3 trials exploring obicetrapib [1:27:45];
Why the APOE4 allele increases the risk of Alzheimer’s disease, and the connection to blood lipids [1:41:30];
The role of APOE in cardiovascular disease [1:51:45];
Takeaways and looking ahead [1:57:00]; and
More.