Life Extension Magazine®

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The Most Important Blood Tests Available for Assessing Cardiovascular Risk

Standard cholesterol blood testing is often not sufficient to properly diagnose or prevent heart disease. Life Extension®’s Dr. Scott Fogle discusses innovative blood tests designed to provide detailed data to best assess your risk of heart disease.

Scientifically reviewed by Dr. Gary Gonzalez, MD, in August 2023. Written by: Dr. Scott Fogle, ND, Physician.

Scott Fogle, ND
Scott Fogle, ND

LE: Are there better tests for checking cardiovascular risk than just the cholesterol test my doctor does every year?

SF: That is a great question that more people should be asking. Yes, there are several tests that are fantastic for assessing your cardiovascular risk. What is surprising to me is that more doctors aren’t doing them!

While the cholesterol test your doctor does is important, it is just the tip of the iceberg regarding possible important information. That test is ancient technology, and it is like comparing an old rotary landline phone to a new state-of-the-art iPhone. Why keep using only very old technology when we have incredible new technology that provides a wealth of important health information?

For example, the standard cholesterol test that your doctor performs will give you a LDL value, which is important, but what few people realize is that this value is NOT the number of particles of LDL circulating in your blood. It is only the total amount of cholesterol found in the particles. It does NOT tell you if that amount of LDL is being carried by a large number of small LDL particles or carried by a small number of large particles. This difference is important because we now know that a higher amount of smaller particles is much more dangerous than a smaller amount of larger particles. It is important to know your LDL particle count. You want to have a low particle count. If yours is high, it is important to address the issue as soon as possible.

LE: I have heard about small dense LDL versus large buoyant LDL. Is that tied into particle count?

SF: Yes, both are important to know. Small dense LDL cholesterol is problematic because its small size allows it to more easily penetrate the blood vessel wall and start the process of plaque formation. That is not what you want if you hope to maintain good health. New blood testing technology can tell you both your particle count and the size of your LDL. The best result you can get is a low particle count combined with large buoyant LDL. The worst result is a high particle count with small dense LDL, which is a very bad combination.

LE: How can I get my particle size and count tested?

SF: A great test called NMR LipoProfile® provides this information using nuclear magnetic resonance (NMR) spectroscopy to directly measure particle count and size.

There are several key points to pay special attention to on the NMR LipoProfile®. The first is your LDL-P, which is your LDL particle count. Next is your small LDL-P, the number of small LDL particles. If either is high, there is a potential cardiovascular problem. The test also provides HDL-P, the particle count for HDL, which is your good cholesterol so you want that number high. Also, look at LDL size where bigger is better, meaning it correlates with large buoyant LDL, which is the better type of LDL as opposed to the bad, small, dense LDL. Pay attention to the LP-IR Score, which is an insulin resistance marker where the higher your number, the greater probability of insulin resistance: For optimal health you want that number lower. The report also includes a helpful particle concentration and size chart that reveals where lower cardiovascular disease risk is and where higher risk is. This is helpful in assessing the cardiovascular risk of your different numbers. To summarize, you want a low LDL-P, low small LDL-P, and low LP-IR Score combined with a high HDL-P and large LDL size for the lowest cardiovascular risk.

What About the VAP® Test?

The VAP® test was one of my favorite tests and they were in business for 20 years. But while writing this article I was shocked to hear they suddenly closed their doors. They cited “adverse changes in the regulatory environment, increased pressure from commercial insurance payors, and continued compression of profit margins” as the reason on their website. It is always painful for me to hear that regulatory and commercial interests destroyed a company that was advancing preventative medicine through cutting-edge testing. Medicine should be about helping people live longer and healthier, but too often regulatory and commercial interests corrupt that goal. The loss of the VAP® test left a terrible gap. Fortunately we recently negotiated a price decrease in the NMR LipoProfile® test, bringing it down to the same price as the VAP® test and providing much of the same information. There is hope that another company will pick up the VAP® test and we may be able to offer it in the future. However, the information is too important to hold off waiting and now that the NMR LipoProfile® price is the same as the VAP® test was, people should use that test instead. The information it provides for those who may be at cardiovascular risk is just too valuable.

LE: I’m surprised more doctors aren’t using this improved technology. Are there other tests regarding cholesterol that should be considered?

SF: Yes. Particle size and particle count represent huge improvements over your standard lipid panel. But there are more tests that round out your risk profile. These have to do with whether your LDL cholesterol is oxidized or glycated. Both are important because oxidized cholesterol is much more dangerous than non-oxidized cholesterol. A perfect example of oxidation occurs when you partially eat an apple and in 10 to 20 minutes, the core has turned an unpleasant brown color. This effect is due to oxidation from free radicals that are beginning the decaying process. The same thing can happen to your LDL particles. They start to oxidize just like the decaying apple, and that is not good. A key point to understand is that small dense particles are notorious for oxidizing faster. Oxidized LDL particles then penetrate the wall of your artery and start a cascade of inflammatory and reactionary events that lead to immune cells trying, mostly unsuccessfully, to get rid of them. All this inflammation and chaos in the wall of your artery eventually leads to foam cells building, which ultimately leads to the dreaded outcome of plaque buildup. If you can measure oxidized LDL and its related markers of inflammation, you have a better idea of what is really happening in your arteries.

LE: Can you test for oxidized LDL?

SF: Yes, we now have the technology to do this and it is exciting. Only recently were we able to offer not only oxidized LDL testing but also F2-Isoprostanes and MPO (myeloperoxidase). Of the three tests, the oxidized LDL is the most important, but if you can, get all three tests.

MPO is an enzyme released by white blood cells when they attack. It causes death to microbes and amplifies inflammation and immune cell recruitment. This is great if there is a foreign invader, but it is terrible if it’s happening in the arteries in response to oxidized LDL. It amplifies inflammation there and causes problems that increase plaque and often the worse kind of plaque, the soft vulnerable plaque that is prone to rupture. To make matters worse, MPO also oxidizes LDL, making it more plaque-promoting, and even oxidizes HDL (your good cholesterol) rendering it dysfunctional so it can no longer be helpful. These effects result in inflammation linked to plaque buildup inside the artery wall. Thus, MPO is a very interesting cardiovascular marker that is worth checking, especially in those with family history of cardiovascular disease or who make poor lifestyle choices.

F2-Isoprostanes are produced when free radicals react with neighboring molecules in a process called “oxidative stress,” which causes a cascade of damage in the cells, initiating destructive pathways. F2-Isoprostanes may be elevated at the earliest stages of plaque development, and research has shown that people with high levels of F2-Isoprostanes are up to 30 times more likely to develop heart disease. Note, this test is not a blood test. It is a urine test, but it’s a very exciting test that is now finally available.

LE: You mentioned glycated LDL. How does that tie in with oxidized LDL?

SF: Glycation in the body signifies high insulin, high glucose, and dysfunctional glucose transporters. However, it also has a specific effect on LDL. If LDL is glycated, meaning a sugar molecule is inappropriately attached to it, it won’t fit properly into the normal LDL receptor it is supposed to go into. This lack of fit poses a problem because it means that an LDL particle is now going to circulate more. This greater amount of time spent circulating means there is a greater chance for it to become oxidized. The more glycation happening to your LDL, the more problems you have due to increased oxidized LDL levels.

LE: Can you test for glycated LDL?

SF: Currently, there is not a good test that is commercially available. However, we can use the excellent HbA1c test instead. It measures hemoglobin that has a sugar attached to it, which happens more and more as a person’s blood sugar level elevates. Red blood cells carry hemoglobin and they live about three months. Therefore, the HbA1c test is a fantastic way to look at the effects of average blood sugar over a three-month period. As a bonus, not only does it provide important information about sugar metabolism, it also allows us to assume that when it elevates, so does your glycated LDL. Thus, it provides an indirect prediction of glycated LDL levels.

LE: Can you sum up what are the best and worst results a person can have for these important cardiovascular risk markers?

SF: The best results are a low LDL-P, low small LDL-P, high HDL-P, high LDL size, low LP-IR Score, low oxidized LDL, low MPO, low F2-Isoprostanes, and low HbA1c. These are all associated with significantly lower cardiovascular risk.

The worst results are a high LDL-P, high small LDL-P, low HDL-P, low LDL size, high LP-IR Score, high-oxidized LDL, high MPO, high F2-Isoprostanes, and high HbA1c. That combination is a serious scenario that needs to be quickly addressed as a heart attack or stroke could be imminent.

LE: Do most Life Extension® customers have high-oxidized LDL?

SF: We expected that customers who are taking our quality products would have low levels and as it turns out, that’s what we are seeing. This result is exactly what we want for our customers. We want them to have the lowest cardiovascular risk possible. We want them to exercise, make good dietary choices, reduce stress, and have access to premium quality supplements that can help support healthy blood biomarkers.

LE: Are there any new tests Life Extension® has recently added?

SF: Yes, we had numerous requests for MTHFR (methylenetetrahydrofolate reductase) gene testing, which deals with methylation, folate metabolism, and homocysteine levels. Originally, the pricing was just too high, around $300 dollars. We are also excited about COMT (catechol-O-methyltransferase), an innovative blood test that looks at how specific neurotransmitters are metabolized. Together, both tests can easily run around $600, providing you can find a doctor who knows about them and is willing to administer these tests. Recently, we approved a new lab that will do both MTHFR and COMT. This test retails for $198.66. During our annual Blood Test Super Sale, the price for the MTHFR/COMT Genetic Methylation Profile is discounted to just $111.75.

LE: What do these tests tell you?

SF: MTHFR is a gene that produces an enzyme that activates folate (folic acid) and thus helps control homocysteine levels. It also relates to methylation in biochemical pathways. There are two main genetic variants that affect MTHFR levels, which are the C677T and A1298C variants. A person can have one or both variants and the C677T is the more powerful of the two. The more variants a person has, the more trouble he or she will have creating activated folate. As a result, this person will have higher homocysteine levels. These variants can even impact methotrexate medication users.

Also, since folate levels are directly related to memory scores and are even related to depressive symptoms, it is worth knowing your genetic status. The best result is a C/C for C677T and A/A for A1289C. If you are not a C/C and A/A, then you should use more activated folate, like 5-methyltetrahydrofolate acid (5-MTHF), instead of regular folic acid.

The COMT gene codes for an essential COMT enzyme that is involved in the inactivation of specific neurotransmitters such as dopamine and norepinephrine. The various genetic combinations of this gene can provide interesting information about an individual. For example, if you’re a G/G, you exhibit higher enzyme activity that provides greater stress resiliency because you degrade stress neurotransmitters faster than most, but you also have lower dopamine levels. Those with G/G genetic makeup often have greater resistance to pain, yet may have a higher requirement for morphine in pain relief. It can even tell you about hormone metabolism since G/G carriers have a greater capacity to degrade estrogens and as a result have lower estradiol levels. The report is customized for your specific genetic carrier status and it relates to how you respond to things like stress, pain, hormones, emotions, short-term memory, abstract thinking, and behavior inhibition.

LE: Are there any underutilized cardiovascular tests Life Extension® offers that people should be using?

SF: Yes. There is a little known but very powerful test called the OmegaCheck™ that provides a wealth of information about omega-3s and omega-6s in a person’s blood. It also provides very helpful information about total saturated fat levels (cheese, meat, butter), total monounsaturated fat levels (especially olive oil), and total polyunsaturated fat levels (plant and fish oils). This specialized test also measures total omega-6 and omega-3 fatty acids and uses that information to provide the incredibly important omega-6 to omega-3 ratio. A typical omega-6 to omega-3 ratio found in the US is around 8.1 (with some Americans even at a shockingly unhealthy 25 level). A ratio of 4 or less is ideal.

Resolvins are molecules generated from omega-3s and are growing in recognition for their ability to counter inflammation. In order for a person’s body to manufacture these important compounds that stop inflammation, it is critical to have enough of the omega-3 building blocks on board to make them. Even if a person is taking fish oils, checking omega-3 levels and the critical omega-6 to omega-3 ratio can help customize a fish oil dose that is ideal for that person’s unique biochemistry and physiology.

But the valuable information from this test doesn’t stop there. The test also provides four important scores that are based on cardiovascular risk. The first is the whole blood score of long-chain omega-3 fatty acids and a higher score here is associated with a lower risk of sudden cardiac death (a score of 5.5 or greater is best). The second is an omega-3 equivalence score, where a result of greater than 7.2 is associated with a 32% risk reduction in heart disease compared to a score of less than 5. The third is an EPA+DHA equivalence score where a number of 4.6 or greater is associated with a 70% reduced risk of death from fatal ischemic heart disease.

Patient’s Approximate MTHFR Enzyme Activity

The fourth cardiovascular score on the OmegaCheck™ is the very important Omega-3 Red Blood Cell Equivalence Score (Omega-3 Index). Here, red blood cells are measured for omega-3 content and a value of 8% to 11% offers the greatest protection against sudden myocardial infarction. This effect occurs because red blood cell composition reflects long-term intake of EPA and DHA. An important study by W. Harris and colleagues that came out in 2004 stated, “The omega-3 Index was inversely associated with risk for CHD [coronary heart disease] mortality.” Since that time, many more studies using the omega-3 Index have come out. For example, a recent 2014 study concluded “…higher omega-3 Index is associated with increased insulin sensitivity and a more favorable metabolic profile in middle-aged overweight men.” Recently, a 2015 study by K. Langlois and colleagues on Canadian adults found that “omega-3 Index levels among Canadian adults were strongly related to age, race, supplement use, fish consumption, smoking status, and obesity. Fewer than 3% of adults had omega-3 Index levels associated with low risk for coronary heart disease.” This is an alarming result and I suspect it would be even worse in the US.

Omega-3 Whole Blood Test Results

If that weren’t enough, the OmegaCheck™ also provides a key marker of inflammation, which is the arachidonic acid (AA):EPA ratio. When this ratio is higher, there is preferred incorporation of AA into membranes over EPA, leading to a pro-inflammatory environment. While both of these fatty acids are essential to human health, the optimal ratio of AA: EPA is around 1.7. Far too many people have a ratio that is out of balance, mine included. I was surprised when I got my own results back and had to make adjustments to my supplement program.

Thus, the OmegaCheck™ provides valuable and important information about cardiovascular risk including the omega-3 Index, a person’s ability to make resolvins, their saturated fat status, the vital AA:EPA ratio, and the critical omega-6 to omega-3 ratio. For those not taking fish oil, it provides guidance on dietary gaps that need to be corrected. For those taking fish oil, it provides information about needed changes in dose, type, and quality of the fish oil they are taking.

Signs and Symptoms of Sleep Apnea
Signs and Symptoms of Sleep Apnea

Daytime symptoms may include:

  • Morning headache
  • Dry or sore throat upon awakening
  • Hypertension
  • Daytime sleepiness
  • Personality and mood changes (including anxiety and depression)
  • Cognitive deficits
  • Decreased libido and impotence

Nocturnal symptoms may include:

  • Insomnia and restless sleep
  • Snoring (loud and bothersome)
  • Gasping sensation that can wake the person
  • Nighttime urination (nocturia)

LE: Beyond labs, what are the other top-three risks for cardiovascular disease we should look out for?

SF: There are many risk factors I would consider, but if I could only pick three, they would be family history, high blood pressure, and undiagnosed sleep apnea. I learned quickly in private practice to pay attention to family history because history really does repeat itself. For example, if a person has a strong family history of heart attacks or strokes at an early age, I would order all the tests previously mentioned.

Also, high blood pressure cannot be underestimated. The physiological damage that the pressure causes is due to shearing forces of the fluid pressure on the blood vessel walls. And it is worse where the blood vessel twists and turns. Just like flowing water can carve away rock over time, high pressure will cause damage on the arterial wall. It is at the site of this damage where plaque will build up first. Therefore, it is imperative to get high blood pressure under control.

The last of my top three is sleep apnea. Many years ago, I worked as a polysomnographic technician in a hospital sleeping disorder center. That experience was tremendously valuable to me as I quickly learned of the power of sleep and the incredible prevalence of sleep disorders that are robbing people of their lives. Many people are walking around with undiagnosed sleep disorders nowadays. Sleep apnea puts an incredible burden on the body and new studies are connecting it to cardiovascular disease. In fact, a recent 2016 study arrived at this conclusion: “It is important to evaluate sleep quality and sleep disorders, aiming at preventing and reducing unfavorable outcomes of cardiovascular disease, particularly for acute myocardial infarction patients.” It is critically important to talk to your doctor if you have symptoms of sleep apnea or other sleeping disorder.

Dr. Scott Fogle is the Executive Director of Clinical Information and Laboratory Services at Life Extension®, where he oversees scientific and medical information and is in charge of the health advisors’ knowledge and continuing education, as well as Life Extension®’s laboratory division.

If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.