Lipids & Lipidology

I recently sat down with Dr. Thomas Dayspring, a pioneer in the field of lipids, to explore the evolving field of lipidology and its critical role in cardiovascular health.

As a clinician, I found this conversation enlightening, as it not only provided a historical perspective on the development of lipid therapies but also offered actionable insights into current best practices for managing cardiovascular risk.

The Evolution of Lipidology

Dr. Dayspring began by recounting his journey from internal medicine to becoming a world-renowned lipidologist. During his early career, the concept of lipidology was virtually nonexistent, with medical training at the time offering little understanding of lipids beyond basic cholesterol measurements. However, driven by the rampant cardiovascular crises he encountered, Dr. Dayspring immersed himself in self-study, eventually leading to his deep expertise in lipid management.

The TLDR on Lipids

Our conversation then shifted to developments in the field. In short, what do we need to know about lipids in 2024?

Risk Markers vs. Risk Factors in Atherosclerosis

One of the most crucial aspects of our discussion was the distinction between risk markers and risk factors in atherosclerosis. Dr. Dayspring clarified:

• Risk Markers: Traditional markers like HDL cholesterol have been commonly monitored but may not be as causally related to cardiovascular disease as previously believed.
• Risk Factors: ApoB is a more reliable predictor of atherosclerotic risk, making its measurement more critical than other markers.

The Misunderstood Role of HDL Cholesterol

We also delved into the misunderstood role of HDL cholesterol. While it has long been considered protective, recent research suggests that the functionality of HDL particles, rather than their sheer quantity, is what truly matters in preventing cardiovascular disease.

Key Insight: This challenges conventional wisdom and underscores the importance of looking beyond standard lipid profiles.

Lp(a) and Its Impact on Cardiovascular Risk

Additionally, Dr. Dayspring introduced the concept of Lp(a), a lipoprotein variant that presents an additional risk for atherosclerosis due to its pro-inflammatory properties. He explained:

• Lp(a) mimics certain clotting factors and exacerbates inflammation in the arterial wall, especially when carrying oxidized phospholipids.
• This insight emphasizes the need for clinicians to assess Lp(a) levels in patients at risk of cardiovascular disease.

Pharmaceutical Strategies for Managing Lipids

In the second half of my conversation with Dr. Dayspring, we explored pharmaceutical strategies for managing lipids—particularly focusing on lowering ApoB levels to reduce cardiovascular risk.

Dr. Dayspring shared the early challenges of lipid management, where therapies like Cholestyramine and Niacin had:

• Limited effectiveness
• Notable side effects

He highlighted Welchol as a more effective bile acid sequestrant that also improves insulin sensitivity, making it a valuable option, especially for pregnant women.

Mechanisms to Lower ApoB

A key takeaway was the importance of increasing LDL receptors on the liver to clear ApoB particles from the bloodstream. Dr. Dayspring explained that depleting the liver’s cholesterol pool is essential to stimulate the production of more LDL receptors, which is crucial for:

• Lowering ApoB levels
• Managing cardiovascular risk

Statins: The Cornerstone Therapy

Statins are the cornerstone of ApoB reduction therapy. Here’s why:

• Inhibit cholesterol synthesis in the liver
• Increase LDL receptor expression
• Lower LDL cholesterol and ApoB levels

Note: While higher doses offer minimal additional benefit, the most significant impact occurs at the lowest doses, reducing the risk of side effects.

Alternative Therapies: Ezetimibe and Bempedoic Acid

Dr. Dayspring discussed the benefits of these alternatives:

• Ezetimibe (Zetia): Reduces cholesterol absorption in the gut.
• Bempedoic Acid (Nexletol): Inhibits cholesterol synthesis through a different pathway.

Combination Therapy: Both drugs are particularly effective when combined with statins, offering a robust approach to lipid management.

The Role of Intestinal Absorption

We explored the role of the intestine in cholesterol absorption:

• Ezetimibe can significantly reduce cholesterol levels in the liver, leading to lower ApoB levels.
• This reinforces the importance of considering cholesterol absorption as a factor in overall lipid management.

Combining Therapies for Optimal Results

Combining different therapies, such as statins with Ezetimibe or Bempedoic Acid, can achieve more effective ApoB reduction. This approach is particularly useful for:

• Patients with high cardiovascular risk
• Offering a tailored approach to lipid management

Personalized Treatment for Hyperabsorbers: For those who absorb cholesterol excessively, individualized strategies may include adjusting nutritional plans or considering alternative medications like PCSK9 inhibitors.

PCSK9 Inhibitors: Advanced Therapy

When more aggressive treatment is necessary, PCSK9 inhibitors offer a powerful option. These inhibitors:

• Prevent degradation of LDL receptors
• Enhance clearance of ApoB particles

Dr. Dayspring highlighted the use of both monoclonal antibodies and small interfering RNA (siRNA) drugs as effective PCSK9 inhibitors that can be used with other therapies for maximum benefit.

Side Effects and Clinical Considerations

Dr. Dayspring provided guidance on managing the side effects of lipid-lowering therapies:

• Ezetimibe: Minimal side effects.
• Bempedoic Acid: Potential to increase uric acid levels, which could trigger gout.
• Statins: Monitoring is crucial, especially for their impact on insulin resistance and diabetes risk.

Important Consideration: Despite these concerns, statins significantly reduce major adverse cardiovascular events (MACE), underscoring their importance in lipid management.

The Broader Implications of Lipid Management

Our conversation also touched on the intersection of lipid management and cognitive health. Dr. Dayspring mentioned:

• Statins’ Potential Impact: Most are neutral on cognition, but careful monitoring is advisable, especially for patients at risk for cognitive decline.
• ApoE4 Gene: Associated with increased cardiovascular and neurological risks, requiring early and aggressive management of ApoB levels.

Conclusion: A Call to Action

It was a rich (and admittedly complex) conversation. Dr. Dayspring reinforced the critical role that pharmacological interventions play in managing cardiovascular risk, particularly through ApoB reduction. At RIFM, we emphasize the incredible impact that lifestyle medicine can make on all aspects of your health—including your heart. But we also believe in good science, and welcome the place of good pharmacology. Dr. Dayspring’s insights have deepened my understanding of how to apply these therapies effectively in my practice. I encourage my colleagues to stay informed about these developments and consider these strategies in their approach to patient care.

Final Thought: The interconnectedness of lipid management with cognitive health and the nuances of treating conditions like hyperabsorption highlight the importance of personalized care. As we continue to evolve in our approach, the goal remains the same: to improve patient outcomes through informed, thoughtful, and comprehensive management of cardiovascular risk.