ApoB: A Crucial Indicator for Cardiovascular, Mental, and Brain Health

Understanding ApoB and Its Significance

Apolipoprotein B (ApoB) serves as a key structural protein within atherogenic lipoproteins, which include low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), and lipoprotein(a) [Lp(a)]. Unlike traditional measures such as total cholesterol or LDL-C, ApoB provides a direct count of the number of these harmful lipoprotein particles, rendering it a more effective marker for assessing cardiovascular risk (Pokharel et al., 2019). High levels of ApoB are significantly correlated with atherosclerosis and its associated complications, including myocardial infarctions and strokes. If you're going to make one investment in your health this year: Lowering your ApoB will likely yield the greatest return in promoting longevity and quality of life! Here's why.

Apolipoprotein B (ApoB) is a crucial marker for assessing cardiovascular, mental, and brain health, as it directly quantifies harmful lipoprotein particles linked to atherosclerosis and cardiovascular disease. Lowering ApoB levels through lifestyle changes and medications, such as statins and PCSK9 inhibitors, is associated with significant health benefits, including reduced risk of heart attacks and cognitive decline. Additionally, a growing body of research is linking elevated ApoB levels to psychiatric disorders, highlighting its importance in overall health management.

The Cardiovascular Advantages of Reducing ApoB

Reducing ApoB is recognized as a highly effective strategy for lowering the risk of cardiovascular disease (CVD). Dr. Peter Attia, a physician and expert in longevity, emphasizes the importance of lowering ApoB levels to below 60 mg/dL to mitigate the risk of atherosclerotic cardiovascular disease (ASCVD) (Attia, n.d.). His insights on the significance of ApoB are presented in his YouTube video: Peter Attia on the Importance of ApoB. Epidemiological evidence supports this recommendation, indicating that elevated ApoB levels are more predictive of CVD than LDL-C levels alone (Pokharel et al., 2019).

Pharmacological Strategies for ApoB Reduction

Statins (e.g., Rosuvastatin, Atorvastatin, Pravastatin) are medications that inhibit HMG-CoA reductase, leading to a decrease in cholesterol production and lowering both LDL-C and ApoB levels. The retail cost of statins ranges from $20-$500 per month, depending on the particularly statin.

PCSK9 Inhibitors are monoclonal antibodies that enhance the recycling of LDL receptors, which improves LDL clearance and significantly reduces ApoB concentrations (Reyes-Soffer et al., 2017). The following are commonly used PCSK9 inhibitors:

- Alirocumab (Praluent): Priced at approximately $500–$700 per month.

- Evolocumab (Repatha): Costs about $450–$650 per month.

- Inclisiran (Leqvio)**: A newer option requiring only two injections per year, with an estimated cost of $3,250 per dose.

Bempedoic Acid (Nexletol), an ACL inhibitor, reduces LDL-C and ApoB by diminishing hepatic cholesterol production. The average retail price for a 30-day supply of Nexletol is approximately $600.

In summary, while there are several agents that lower ApoB, PCSK9 inhibitors appear to be most effective in significantly reducing ApoB, but their costs can be high. I would suggest that even at retail price, their benefit likely justifies their cost (by the way: I have no financial relationships to disclose). However, many insurance plans cover these treatments for patients at high risk or those diagnosed with familial hypercholesterolemia. Physicians typically consider prescribing these medications when statins alone do not achieve the desired ApoB levels. While cardiovascular health is a worthy target, and avoiding "the big one" should be on everyone's health priority list, there is another reason to lower ApoB that can be a significant quality of life investment, that can pay off in later years.

ApoB and Brain Health: A Growing Link

Emerging research highlights a connection between ApoB levels and cognitive decline, as well as mental health disorders. A study conducted by Pokharel et al. (2019) demonstrated that optimal management of atherogenic lipoproteins during midlife is associated with enhanced cognitive health in later years. Elevated ApoB levels have also been linked to increased amyloid-beta (Aβ) accumulation, which is a characteristic feature of Alzheimer’s disease (Button et al., 2019). Reducing ApoB may:

- Mitigate Aβ-induced vascular inflammation, thereby reducing neurovascular injury (Button et al., 2019).

- Enhance Aβ clearance, which could slow cognitive deterioration (Button et al., 2019).

- Stimulate the production of endothelial nitric oxide, improving cerebral blood flow and offering neuroprotective effects (Button et al., 2019).

Translation?: Reducing ApoB appears to improve the health of your blood vessels, supporting blood supply to the brain, reducing brain aging, and reducing stroke and dementia risk.

ApoB and Mental Health

In addition to its role in neurodegeneration, ApoB levels are associated with psychiatric conditions. Individuals with depression tend to exhibit higher ApoB levels, and increased ApoB correlates with more significant cognitive impairments in areas such as delayed memory and language function (Hui et al., 2017). Thus, managing ApoB may contribute to improved cognitive performance in depressed individuals.

The Significance of Vascular Health

Maintaining vascular health is vital for both cardiac and neurological function. Atherosclerosis not only elevates the risk of heart attacks and strokes but also disrupts cerebral blood flow, contributing to cognitive decline. By lowering ApoB, individuals can enhance their overall vascular health, benefitting both cardiovascular and cognitive functions.

Given its substantial impact on cardiovascular, cognitive, and mental health, the reduction of ApoB is one of the most effective health interventions available. Whether through lifestyle modifications, statin therapy, PCSK9 inhibitors, or novel treatments like pemafibrate, lowering ApoB can result in significant health improvements.

References

Attia, P. (n.d.). Early and aggressive lowering of ApoB. Retrieved from https://peterattiamd.com

Button, E., Gilmour, M., Cheema, H., Martin, E., Agbay, A., Robert, J., & Wellington, C. (2019). Vasoprotective functions of high-density lipoproteins relevant to Alzheimer’s disease are partially conserved in apolipoprotein B-depleted plasma. *International Journal of Molecular Sciences, 20*. https://doi.org/10.3390/ijms20030462

Hui, L., Han, M., Du, X., Zhang, B., He, S., Shao, T., & Yin, G. (2017). Serum ApoB levels in depressive patients: Associated with cognitive deficits. *Scientific Reports, 7*. https://doi.org/10.1038/srep39992

Pokharel, Y., Mouhanna, F., Nambi, V., Virani, S., Hoogeveen, R., Alonso, Á., Heiss, G., Coresh, J., Mosley, T., Gottesman, R., Ballantyne, C., & Power, M. (2019). ApoB, small-dense LDL-C, Lp(a), LpPLA2 activity, and cognitive change. *Neurology, 92*, e2580–e2593. https://doi.org/10.1212/WNL.0000000000007574

Reyes-Soffer, G., Pavlyha, M., Ngai, C., Thomas, T., Holleran, S., Ramakrishnan, R., Karmally, W., Nandakumar, R., Fontanez, N., Obunike, J., Marcovina, S., Lichtenstein, A., Matthan, N., Matta, J., Maroccia, M., Becue, F., Poitiers, F., Swanson, B., Cowan, L., Sasiela, W., Surks, H., & Ginsberg, H. (2017). Effects of PCSK9 inhibition with alirocumab on lipoprotein metabolism in healthy humans. *Circulation, 135*, 352–362. https://doi.org/10.1161/CIRCULATIONAHA.116.025253

Yamashita, S., Arai, H., Yokote, K., Araki, E., Tanigawa, R., Saito, A., Suganami, H., Minamikawa, S., & Ishibashi, S. (2023). Pemafibrate has a novel mechanism of action to lower LDL-C and ApoB in patients with higher LDL-C levels: Insights from a phase 2 exploratory clinical pharmacology crossover study. *European Heart Journal*. https://doi.org/10.1093/eurheartj/ehad655.2807