*** This article should be consumed for informational purposes only and does not constitute medical advice. Readers should consult a board certified physician before starting or making changes to their treatment regimen. ***

Introduction

Often when pundits talk about the unprecedented rise in heart disease in the past century they are primarily referring to the rise in a condition known as atherosclerosis. The National Institutes of Health defines atherosclerosis as “a common condition that develops when a sticky substance called plaque builds up inside your arteries.” For decades, LDL cholesterol and Apolipoprotein B (ApoB) have been cast as the boogeymen in the development of atherosclerosis and, subsequently, heart disease. However, a growing body of scientific literature suggests that these are likely not the primary causal factors. 

Interestingly, many patients diagnosed with atherosclerosis do not exhibit high LDL/ApoB levels. This disparity urges us to explore other potential culprits, such as metabolic syndrome, obesity, inflammation, hypertension, and insulin resistance.

Revisiting the Conventional Wisdom: Beyond LDL Cholesterol and ApoB

A 2009 study reveals a startling fact – 75% of heart attack patients do not even display elevated LDL/ApoB levels (1). This contradiction mandates a comprehensive exploration of alternative contributors, potentially having a greater role in atherosclerosis.

An essential area of consideration is metabolic syndrome, a cluster of conditions comprising obesity, insulin resistance, hypertension, and dyslipidemia. Metabolic syndrome doesn’t just up the risk for heart disease; it’s a perfect storm for systemic inflammation (2). This chronic low-grade inflammation poses a substantial threat, as it’s been implicated in the onset and progression of atherosclerosis.

Pivoting our focus onto obesity, we discover it has a distinct relationship with atherosclerosis. Specifically, visceral adiposity, the harmful fat stored around abdominal organs, proves to be a strong independent risk factor for atherosclerosis (3). This association is likely due to the inflammation and hormonal changes sparked by excessive visceral fat, both exacerbating atherosclerosis progression.

Hypertension, or high blood pressure, often runs quietly in the background of our health. Yet, it’s far from benign. The continuous pressure exerted on arterial walls can inflict damage over time, leaving them susceptible to the atherosclerotic process. It promotes the infiltration of cholesterol and other substances into the arterial wall, effectively setting the stage for plaque buildup (4).

In parallel, insulin resistance, a core component of metabolic syndrome, wields influence over the development of atherosclerosis. Insulin resistance is when cells become less responsive to insulin, leading to an excess of glucose and insulin in the bloodstream. This state can encourage inflammation, skew lipid metabolism, and even stimulate vascular cells to proliferate – all factors that can foster atherosclerosis (5).

Arterial Calcium Buildup Versus Cholesterol/ApoB

With the focus by mainstream physicians on LDL/ApoB cholesterol, the importance of calcium has been all but forgotten. The factors discussed above such as hypertension, insulin resistance, inflammation, and metabolic syndrome are all contributors to the build up of calcium in arteries. The mechanisms behind this buildup are complex and multifactorial, often tied to the body’s response to endothelial damage.

The introduction of calcium into arteries starts with initial damage to the arterial wall caused by various types of metabolic dysfunction cited above (ex. Obesity, hypertension, etc…) which allows LDL cholesterol to penetrate the inner lining of the artery. This infiltration triggers an immune response, with white blood cells rushing to the site to “clean up” the LDL cholesterol. Over time, these cells can become engorged with cholesterol, transforming into what we know as foam cells.

These foam cells, alongside other substances, form a fatty streak in the arterial wall, marking the beginning of atherosclerosis. With progression, a fibrous cap forms over the fatty streak, creating an atherosclerotic plaque. Calcium comes into play in later stages, as dying cells within the plaque release calcium, which accumulates and hardens over time. The good news is this calcium can be fairly easily measured using Coronary Artery Calcium (CAC) scoring to reveal risk for atherosclerotic disease.

Coronary Artery Calcium (CAC) scoring is emerging as a useful tool in the early detection of atherosclerosis. By quantifying the amount of calcium in coronary arteries, CAC scoring helps identify the presence of coronary artery disease even before symptoms develop (6). It provides actionable information, allowing for preemptive measures against atherosclerosis.

Other Advanced Diagnostic Tools

Other advanced diagnostic tools offer a deeper, more accurate view of atherosclerosis risk in comparison to measuring LDL/ApoB levels including:

1. Vascular Ultrasound: Offers another non-invasive approach to assess vascular health. It visualizes the blood flow within arteries and identifies areas of plaque buildup, providing insights into the extent and severity of atherosclerosis.
2. Carotid Intima-Media Thickness (CIMT) Testing: CIMT measures the thickness of the two inner layers of the carotid artery. This metric is significant because an increased CIMT is associated with atherosclerosis and future cardiovascular events.
3. Coronary CT Angiography (CCTA) and Stress Testing: CCTA provides high-resolution images of the coronary arteries, enabling the detection of both calcified and non-calcified plaques. Stress testing evaluates how well the heart handles stress and can unmask underlying heart conditions.

Conclusion

The narrative surrounding LDL cholesterol, ApoB, and atherosclerosis is due for revision. The scientific literature makes it clear that these traditional markers are not significant in the development of atherosclerosis. Instead, it appears that LDL/ApoB are part of the process of the development of heart disease but not the causal factors and certainly not worthy of being the main focus of medicine in fighting heart disease. 

Alternatively, we should focus our attention on the diagnosis and treatment of metabolic syndrome and its components, along with the chronic inflammation they generate, for a more holistic view of atherosclerosis risk. Doctors should consider leveraging the advanced diagnostic tools at their disposal to reveal a more comprehensive picture of cardiovascular health. Since metabolic syndrome is primarily caused by lifestyle factors such as poor diet, poor sleep and poor stress management, treatments should involve changes to each. 

By going beyond the status quo and the prevailing narrative surrounding heart disease, we can gain a nuanced understanding of atherosclerosis, enabling better prevention and intervention strategies beyond over simplistic and widespread prescriptions of statin medications to reduce cholesterol and ApoB levels.

References

Beyond LDL Cholesterol and ApoB References

1. Most heart attack patients’ cholesterol levels did not indicate cardiac risk, Science Daily, 2019.
2. Metabolic Syndrome: The Danger Signal in Atherosclerosis, 2006.
3. Visceral adiposity and atherosclerosis, Arteriosclerosis, Thrombosis, and Vascular Biology, 2020.
4. Hypertension as a risk factor for atherosclerosis: Cardiovascular risk assessment, 2022. 
5. Insulin resistance and atherosclerosis, Endocrine Reviews, 2007.

Arterial Calcium Buildup

6. Coronary Artery Calcium Score – A Reliable Indicator of Coronary Artery Disease? 2021.