Advanced Cholesterol Testing 101: What Is It and Why Would I Need It?

Reviewed by Dr. Jonathan Bonnet, MD, MPH


Many healthy young adults don’t consider cholesterol or heart health to be a top preventive health priority, even though heart disease is the number one leading cause of death but still largely preventable. Chances are—if you’re worried about your cholesterol levels at a younger age, it’s probably because you know you have a family history of high cholesterol, heart disease, or both.


Standard cholesterol testing plays an important role in cardiovascular disease prevention, risk assessment, and management. But for some people, residual risk may be left unaddressed even after starting therapies or incorporating lifestyle changes to lower cholesterol levels.


That’s when advanced cholesterol testing (also called advanced lipid testing) can help.


Advanced lipid testing (ALT) can help many individuals gain a deeper understanding of their overall risk for cardiovascular and metabolic disease. Read on to learn more about ALT works and whether it can help you.


What is cholesterol?


Cholesterol is an organic molecule found throughout our body—we eat, make, store, and excrete cholesterol. In fact, most of the cholesterol in our body is made by our body (and 25% of your body’s cholesterol is in your brain). It’s essential for living.


Within the context of heart health, we’re exclusively talking about blood cholesterol.


If someone has high levels of cholesterol in their blood, they can develop fatty deposits in blood vessels, which can eventually make it harder for sufficient blood to flow through the arteries. In serious cases, these deposits can break to form a clot that causes a heart attack or stroke.


More specifically, development of atherosclerosis (hardening of the arteries) requires three things:



  1. Lipoproteins (cholesterol containing transporters)

  2. Inflammation

  3. Endothelial dysfunction (damage to the blood vessel walls).


What is standard cholesterol testing?


A traditional lipid panel usually measures the following:



  • Total cholesterol

  • High-density lipoprotein cholesterol (HDL-C)

  • Low-density lipoprotein cholesterol (LDL-C)

  • Triglycerides


These separate out the different components by centrifuging your blood in a test tube. The concentration of each of the different subclasses gets measured and subsequently reported out on the lab results sheet. These measures represent a well-established platform for cardiovascular disease (CVD) risk prediction and management. But in some cases, going beyond standard lipid panels can help provide deeper insights to your health and individual risk for disease.


What is advanced lipid testing?


It’s true that getting lab tests done is crucial to understanding your health markers. But the right type of test for your needs and circumstances can make all the difference.


Advanced lipid testing (ALT) goes beyond a traditional lipid panel by looking at the number and size of the particles contained within a traditional lipid panel concentration, as well as measuring other molecules that impact disease risk. ALT measurements may include:



  • Lipoprotein(a) (Lp[a]): These genetically determined levels that aren’t easily altered by changes in lifestyles or medication therapies. For that reason, your provider may recommend an advanced lipid testing panel including Lp(a) if you have a family history of premature cardiovascular disease. Elevated levels can indicate an increased risk of CVD and cerebrovascular disease.

  • Apolipoprotein A1 (ApoA1): The primary protein component of high-density lipoprotein (HDL). Decreased levels are associated with an increased risk of CVD.

  • Apolipoprotein B (ApoB): This protein is present on all atherogenic lipoproteins, including low-density lipoprotein (LDL), intermediate-density lipoprotein (IDL), very low-density lipoprotein (VLDL) remnants, and Lp(a). Elevated levels are associated with an increased risk of CVD.

  • LDL-P: Measurement of low-density lipoprotein particle counts and sizes. Even with normal levels of LDL, smaller and more numerous particles can put you at a higher risk of CVD.

  • HDL-P: Measurement of high-density lipoprotein particle counts and sizes. Smaller HDL particle sizes are associated with an increased risk of cardiovascular disease (CVD).

  • Lipoprotein Insulin Resistance score (LPIR): A weighted combination of six lipoprotein subclass measures that has been found to be the primary biochemical marker for predicting heart disease in women. LPIR also predicts type 2 diabetes.


An important concept to understand in comparing a traditional lipid panel to ALT is the idea of concordance and discordance. When the concentration of a substance is measured, it does not necessarily tell you how many particles there are, or how big they might be. For example, a high LDL-C could contain lots of small LDL particles, or fewer large ones. This matters, because someone with a lot of small LDL particles is at much higher risk than someone with fewer larger ones. If someone has a high LDL-C and a lot of small LDL particles, this is described as concordant (since the high LDL-C matches the high number of particles). In this case, LDL-C serves as a reasonable predictor of risk.


Conversely, someone could have a high LDL-C with fewer larger particles. In this case, there is discordance between the high LDL-C and the number and size of the particles. In this case, the LDL-C is not a good predictor of risk and the particle counts are much better. Studies have shown that this discordance can be clinically meaningful and predictive of coronary heart disease. For this reason, advanced lipoprotein testing offers an opportunity to improve risk prediction and offer more targeted and effective forms of therapy.


In other words, one of the biggest advantages of ALT is understanding what the particle counts are (as opposed to standard concentration levels found in a traditional lipid panel) that can help your provider to offer individualized health, diet, and therapy recommendations to help lower your risk of disease.


Is advanced lipid testing for everyone?


Not everyone will benefit from ALT. The best way to determine whether ALT is right for you is to work with a provider who understands your unique risks (or lack thereof) of heart disease.


Though these recommendations are best made on a case-by-case basis, here are some of the generalized groups that may benefit from ALT:



  • People with established cardiovascular disease

  • People with diabetes

  • People with hypertension

  • People with diagnosed metabolic syndrome

  • People with elevated LDL levels (above or equal to 190mg/dL)

  • People with low HDL count levels

  • Men aged 45 years and older

  • Post-menopausal women

  • Those with a family history of premature onset of cardiovascular disease (CVD)

  • People with certain lifestyle risk factors, including:

    • Unhealthy diet

    • Excessive alcohol intake

    • Smoking

    • Chronic stress




Where can I get advanced lipid testing done?


ALT can be done with a simple blood test. However, there are some limitations when it comes to ALT. Because most insurances do not cover the lab testing, fewer clinics perform the services and providers do not always have the familiarity or expertise to interpret the results.


Another issue is that there is not a standardized way that labs measure particle sizes. Getting tests done at the same lab does not generally cause an issue, though having them performed at different labs may preclude making a valid comparison of the results. However, some of the ALT metrics, such as ApoB and Lp(a) are fairly standardized. These can be done and repeated at different labs with generally comparable results. For this reason, some labs and/or clinics may be unable to provide ALT.


Why don’t more physicians do advanced lipid testing?


Unfortunately, there is still very little focus of ALT in medical school curricula or residency training for physicians.


In general, there is typically a 5-10 year delay from bench to bedside in medicine. What that means is that even when new scientific discoveries are reported in literature, it can still take up to ten years until they actually become clinical practice. Though these changes do take place, it can take years (or decades) in some cases.


This delay occurs because it takes time to educate and teach providers the rationale and value of ordering new tests. Most primary care physicians are unaware of what ALT is or how to use it appropriately. At best, these physicians will refer someone to cardiology if a patient asks about this testing, but are unlikely to order the test themselves.


Another reason why many physicians don’t order ALT is because insurance rarely covers the cost, even though they can often be done for less than $100. As a result, there’s little incentive for clinics or patients to advocate for this kind of testing (unless they are highly motivated, educated, and have the resources).


The bottom line


Heart disease accounts for roughly 1 in 4 deaths in the United States each year. Data also shows that nearly half of all Ameircans adults have at least one of the key risk factors for heart disease—and over half of cardiovascular events in men and just under one-third of cardiovascular events in women take place in people 64 and younger. But how many Americans know their risk level?


Working with your provider to get the right lab tests done can help to identify your personal risk of heart disease, diabetes, stroke, peripheral artery disease, and more.


If you know you have a personal or family history of heart disease, ask your provider about whether advanced lipid testing is right for you. With Forfend, we can help you get the right labs and tests done to understand your individual health risks and create a customized care plan for you.


Sources


About Heart Disease. (2021).


Advanced Lipoprotein Testing: Strengths and Limitations. (2014).


Association of Lipid, Inflammatory, and Metabolic Biomarkers with Age at Onset for Incident Coronary Heart Disease. (2021).


Risk of Premature Cardiovascular Disease vs the Number of Premature Cardiovascular Events. (2016).


Test ID: ADMA. (n.d.).


Test ID: APOAB. (n.d.).


The Role of Advanced Lipid Testing in the Prediction of Cardiovascular Disease.


The straight dope on cholesterol - Part I. (2012).

Close up profile view of a woman outside meditating with eyes closed

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