Understanding atherosclerosis is crucial for early intervention and improved cardiovascular health.
APOB is a valuable metric for identifying individuals at risk of atherosclerosis beyond traditional lipid measurements.
Cholesterol's role in cardiovascular disease is complex, and it is important to consider factors like APOB for a comprehensive view of risk.
Deep dives
The Ubiquity and Impact of Atherosclerosis
Atherosclerosis, the deposition of cholesterol in the artery wall, is a ubiquitous disease that affects virtually everyone as they age. While not everyone dies from atherosclerosis, it is present in individuals who have lived long enough. Understanding and addressing atherosclerosis is crucial because it is the most common chronic disease and a major contributor to adverse cardiac events. By focusing on this disease, we have the opportunity to delay the onset of chronic conditions and improve overall health span and lifespan.
The Importance of APOB as a Metric
APOB is an essential metric to track when examining lipid profiles. It identifies the presence of atherogenic particles that contribute to atherosclerosis. While other risk factors such as smoking and hypertension are recognized, APOB provides valuable information beyond traditional lipid measurements like LDL cholesterol. APOB concentration and particle quality play significant roles in atherogenesis, and understanding these factors helps in identifying individuals who may benefit from specific treatment strategies for preventing cardiovascular events.
Cholesterol: A Vital Molecule and Misconceptions of 'Good' and 'Bad'
Cholesterol is an organic molecule essential for life. It forms the cell membrane structure and serves as a precursor for crucial hormones and bile acids. However, cholesterol's role in the body is complex and often misunderstood. Referring to cholesterol as 'good' or 'bad' oversimplifies its function. Every cell in our body makes cholesterol, and it is transported within lipoproteins. Total cholesterol level or LDL cholesterol alone does not fully capture cholesterol's relationship to cardiovascular disease. Understanding cholesterol's role, in tandem with other metrics like APOB, provides a more comprehensive view of lipoprotein metabolism and atherosclerosis risk.
Understanding the Misconception of Good and Bad Cholesterol
The distinction between good (HDL) and bad (LDL) cholesterol is often misunderstood. The functionality of HDL cholesterol is what matters, not just the quantity. Efforts to raise HDL cholesterol pharmaceutically have mostly failed to improve outcomes. On the other hand, LDL cholesterol is considered bad because it goes into artery walls, gets oxidized, and contributes to atherosclerosis.
The Importance of ApoB as a Superior Metric
ApoB is a more accurate indicator of risk than LDL cholesterol or non-HDL cholesterol. It captures the total concentration of atherogenic lipoproteins, including LDLs, VLDLs, and LPa. Lowering ApoB levels, preferably below 50 milligrams per deciliter, is associated with significant risk reduction. Pharmacologically lowering ApoB with drugs like PCSK9 inhibitors can achieve low ApoB levels without causing harm.
In this special episode of The Drive, we have pulled together a variety of clips from previous podcasts about cardiovascular disease to help listeners understand this topic more deeply, as well as to identify previous episodes which may be of interest. In this episode, Peter highlights the importance of understanding cardiovascular disease and why early intervention is critical. He also provides a primer on lipoproteins and explains the fallacy of the terms “good cholesterol” and “bad cholesterol.” Allan Sniderman discusses the metrics measured in routine blood work – along with the limitations of those standard panels – before explaining why apoB is a superior metric for determining risk. Additionally, Tom Dayspring explains the causal role of apoB in atherosclerotic cardiovascular disease (ASCVD) and the therapeutic goals for apoB concentration, and Peter explains how early and aggressive lowering of apoB could change the landscape of cardiovascular disease prevention.
We discuss:
The importance of understanding atherosclerosis early in life [2:25]
Defining ASCVD, its causes, and the role of cholesterol [8:00];
Why early prevention of atherosclerosis is critical [13:45];
Preventing atherosclerosis—two fatal flaws with the “10-Year Risk” approach [16:00];
Intro to lipids and lipoproteins: why there is no “bad” or “good” cholesterol [23:00];
Limitations of standard blood panels [35:45];
How Mendelian randomization is bolstering the case for apoB as the superior metric for risk prediction [39:30];
Therapeutic goals for apoB concentration [58:15];
How early and aggressive lowering of apoB could change the course of ASCVD [1:10:45]; and