How to lower your apoB

Summary

This script discusses advancements in managing apolipoprotein B (apoB) levels, a key risk factor for atherosclerotic cardiovascular disease (ASCVD). The speaker emphasizes the shift from high-dose statins to a variety of pharmacological and nutritional tools, including PCSK9 inhibitors and dietary adjustments. They also highlight the importance of individualized treatment, the potential of new drugs in the pipeline, and the considerations for long-term statin use, balancing efficacy with potential side effects.

Takeaways

• 😲 Today's medical tools for managing apolipoprotein B (apoB) are far more advanced than 20 years ago, offering alternatives to high doses of statins.
• 🏃 Exercise does not significantly impact apoB levels or lipoprotein risk factors, but it can affect cardiovascular health in other ways.
• 💊 Pharmacological interventions are the most potent method for lowering apoB levels, with nutrition being a less potent but still significant approach.
• 🍚 Reducing carbohydrates can lower triglycerides and, consequently, apoB burden, as fewer triglycerides need to be transported with cholesterol.
• 🥩 Cutting saturated fat intake can reduce cholesterol synthesis and upregulate LDL receptors, leading to a decrease in LDL and apoB levels.
• 🥗 A low-carb, low-saturated-fat diet could theoretically lower apoB to levels that might make atherosclerotic cardiovascular disease (ASCVD) less of a concern.
• 💡 Individual dietary choices and sustainability are important, with the speaker noting their own apoB levels and how they manage them without extreme restrictions.
• 🎯 The speaker's target apoB level is 30 to 40 milligrams per deciliter, which requires pharmacological intervention due to their genetic predisposition to ASCVD.
• 🤒 Concerns about high doses of statins include potential side effects such as muscle aches, liver function test elevations, and insulin resistance.
• 💊 The speaker takes a combination of three drugs, including a PCSK9 inhibitor and a combo drug containing bempedoic acid and aetam, to manage their apoB levels.
• 💰 The cost of PCSK9 inhibitors has decreased over time, and the availability of alternative drugs, such as a once-every-six-months injection, may further reduce costs.
• 🔬 A drug in development targets the synthesis of APO(a), potentially offering a new treatment for high Lp(a) levels, which are associated with an increased risk of cardiovascular events.

Q & A

What has changed in the medical field regarding the treatment of high apob levels over the past 20 years?

Over the past 20 years, there has been a significant advancement in the tools available for treating high apob levels. Previously, the only option was high doses of statins, but now there are various other pharmacological options available.

What is the impact of exercise on managing lipoprotein risk factors?

Exercise has no meaningful impact on managing lipoprotein risk factors directly through lipoproteins. Its benefits are seen in other ways, but for managing lipoprotein risk, pharmacology and nutrition are more effective.

How does reducing carbohydrates affect apob levels?

Reducing carbohydrates can lower triglycerides, which in turn can lower the apob burden because fewer triglycerides need to be trafficked with cholesterol.

What is the effect of cutting saturated fat on cholesterol synthesis and LDL levels?

Cutting saturated fat reduces cholesterol synthesis and can also upregulate LDL receptors, leading to more LDL being pulled out of circulation, which can lower apob levels.

What are the two main dietary approaches to lowering apob levels as mentioned in the script?

The two main dietary approaches to lowering apob levels are reducing carbohydrates to lower triglycerides and cutting saturated fat to reduce cholesterol synthesis and upregulate LDL receptors.

What is the speaker's target apob level and why?

The speaker's target apob level is 30 to 40 milligrams per deciliter. This target is set because the speaker has a genetic predisposition to ASCVD and wants to minimize the risk factor.

What pharmacological treatments does the speaker take to manage their apob levels?

The speaker takes a PCSK9 inhibitor called Batha, a combo drug called NEXletapide which contains bempedoic acid and ezetimibe, and possibly a statin, although they prefer to avoid high doses.

How does bempedoic acid work differently from statins in cholesterol synthesis inhibition?

Bempedoic acid is a prodrug that is only active in the liver, where it inhibits cholesterol synthesis. Unlike statins, which inhibit cholesterol synthesis throughout the body, bempedoic acid is more selective and less potent.

What are the common side effects of statins mentioned in the script?

The common side effects of statins mentioned are muscle aches, elevations of transaminases (liver function tests), and insulin resistance.

What is the speaker's view on the future availability and cost of PCSK9 inhibitors?

The speaker believes that the availability and cost of PCSK9 inhibitors will improve due to the introduction of a new drug with a different mechanism that can be administered less frequently and as more drugs become available, there will be continued price pressure.

What is the drug being developed to target high LP(a) levels and how does it work?

The drug being developed for high LP(a) levels is an antisense oligonucleotide that disrupts the process of DNA making RNA to make APO(a), thereby interrupting the synthesis of the protein that turns an LDL into an LP(a).

What is the current status of the drug for high LP(a) levels and what is being tested in phase three trials?

The drug for high LP(a) levels has shown promising results in phase two trials with no side effects and complete obliteration of LP(a). The ongoing phase three trials are testing whether eliminating LP(a) via this mechanism reduces clinical events and major adverse cardiac events.