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

90 snips

May 22, 2023

John Kastelein, a distinguished expert in lipoprotein metabolism and cardiovascular disease, discusses familial hypercholesterolemia (FH) and its genetic underpinnings. He explores innovative therapeutic options that could transform heart disease prevention, detailing the history and future of CETP inhibitors. Kastelein also delves into the APOE gene's significant role in both Alzheimer's and cardiovascular health. His insights emphasize the potential for targeted interventions, sparking optimism for high-risk patients in the near future.

Ask episode

AI Snips

Chapters

Transcript

Episode notes

INSIGHT

Familial Hypercholesterolemia Overview

Familial hypercholesterolemia (FH) is a common genetic disorder causing high LDL cholesterol.
This elevates heart disease risk, often manifesting in teenage years with tendon and eye deposits.

INSIGHT

FH Diagnosis and Genetics

Over 3,500 FH mutations exist, making genetic testing complex.
Diagnosing FH in children, where secondary causes are rare, boasts a 95% mutation detection rate.

ANECDOTE

Diagnosing FH by Sight

Physical signs of FH, like tendon xanthomas, can appear in various locations due to frequent movement.
John Kastelein diagnosed FH in a flight attendant by noticing an arcus cornealis in her eyes.

Get the Snipd Podcast app to discover more snips from this episode

Get the app

View the Show Notes Page for This Episode

Become a Member to Receive Exclusive Content

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.

Connect With Peter on Twitter, Instagram, Facebook and YouTube