Potential Benefits of Advanced Cholesterol Testing, Part One

By Paul E. Lemanski, MD, MS, FACP

Editor’s Note: This is the 112th in a series on optimal diet and lifestyle to help prevent and treat disease. Any planned change in diet, exercise or treatment should be discussed with and approved by your personal physician before implementation. The help of a registered dietitian in the implementation of dietary changes is strongly recommended.

Medicines are a mainstay of American life and the healthcare system not only because they are perceived to work by the individuals taking them, but also because their benefit may be shown by the objective assessment of scientific study. Clinical research trials have shown that some of the medicines of Western science may reduce the risk of Type 2 diabetes, heart attacks, strokes, cardiovascular death and even some cancers.

In the first 111 installments of the Non-Medicated Life, a healthy diet and lifestyle has been shown to accomplish naturally for the majority of individuals most of the benefits of medications in the prevention of the chronic medical conditions mentioned above. In order to maximize the benefit of lifestyle changes it is best to first establish a baseline of laboratory tests of so called “surrogate markers” of risk. Markers such as fasting blood sugar, Hgb a1c, total cholesterol, HDL (the good cholesterol) and LDL (the bad cholesterol) and Triglycerides (blood fats) are routinely followed serially to determining increasing or decreasing risk. After a discussion with your primary care physician or cardiologist additional testing may be helpful. “Advanced” cholesterol testing such as High Sensitivity C-Reactive Protein (HS-CRP), Apolipoprotein B (Apo B), Trimethylamine-N Oxide (TMAO), and Nuclear Magnetic Resonance LipoProfile (NMR LipoProfile) may offer additional identification of risk and when measured serially may help direct and refine lifestyle choices. In this two-part article, Part One will address the first two advanced tests, Part Two the remaining advanced tests.

HS-CRP (cardiac CRP) is a marker of inflammation. Atherosclerosis (literally, athero equals artery, sclerosis equals stiffening), the hallmark of arterial disease-and the cause of heart attacks and strokes-occurs as a consequence of inflammation. LDL (the bad) cholesterol normally exists as spherical particles in the blood and, generally, when the concentration is low atherosclerosis risk is low. However, when excess LDL cholesterol is produced, it penetrates the arterial wall, where it forms a structure called a plaque. A decreased consumption of the natural antioxidants in vegetables and fruit results in the LDL in the plaque becoming oxidized (Ox-LDL). Ox-LDL is recognized by the immune system as non-self and is attacked by specialized white blood cells called macrophages. Literally, it is the infiltration of macrophages into the plaque that causes the plaque to become inflamed setting up the conditions for a heart attack or a stroke.

In most non-acutely ill individuals HS-CRP measures the inflammation caused by the process of atherosclerosis. Unfortunately, if someone were to be acutely ill with a cold or flu this could cause the HS-CRP to be elevated as well. It is, therefore, best to measure when you are not acutely ill and if elevated it is best to remeasure a second time, the lowest value generally being the most accurate measure of risk. Individuals with other inflammatory conditions such as rheumatoid arthritis and inflammatory bowel disease may not use the test to indicate cardiac risk. Physicians may use HS-CRP to determine whether medication is needed in individuals at an intermediate level of cardiovascular risk as determined by the American Heart Association and American College of Cardiology risk calculator (tools.acc.org/ldl/ascvd_risk_estimator). Elevated HS-CRP values greater than 3.0mg/dl generally indicate higher risk, 1-3mg/dl moderate risk, and less than 1.0mg/dl lower risk.

How does an individual lower HS-CRP with lifestyle changes? Daily aerobic exercise, increasing the consumption of vegetables and fruit, and the consumption of whole grains as with a Mediterranean diet, increasing consumption of omega-3 and omega-9 oils (olive), and decreasing consumption of omega-6 oils, avoiding an excess of simple sugars, losing weight when overweight, and stopping smoking, all will help lower HS-CRP. The benefit of the test is that it provides you a quantitative measure of the benefit of such lifestyle changes.

Apo B is another advanced marker of cardiovascular risk and in clinical trials proves a better predictor of risk that the more widely used LDL (bad) cholesterol. In part, this is because while a major contributor to risk for most individuals, LDL is only one of several plaque forming particles including more rare species called intermediate density lipoprotein (IDL) and chylomicron remnants (CR). In part, it is because LDL particles come in different sizes that carry different levels of risk.

LDL exists as particles of varied sizes, some particles being smaller, some medium sized, and some larger. The relative number of particles of different sizes approximate a bell curve in normal individuals, with medium size particles at the central portion of the bell curve predominating.  Individuals at higher risk have proportionately more numerous smaller particles and fewer medium size and large particles- at the same total level of LDL. Moreover, the smaller LDL particles are more likely to form a plaque because they more easily penetrate between the cells that line the artery walls to get deeper layers where plaque accumulates. Thus, an LDL equal to 100 mg/dl may be achieved by more numerous smaller particles or fewer larger particles and routine testing does not differentiate between the two.  Because a single apo B molecule is found in each atherogenic particle regardless of size, a measure of apo B gives an accurate measure of all atherogenic particles, including LDL as well as IDL and CR.

Unfortunately, apo B is a significantly more expensive test than LDL, and may not be covered by insurance. However, a close approximation of apo B derived risk may be gleaned from a normal, inexpensive lipid profile by calculating the non-HDL cholesterol. Indeed, the National Cholesterol Education Program (NCEP) guideline recommends using the non-HDL cholesterol as a secondary target of treatment after LDL. In short, the non-HDL cholesterol equals the total cholesterol – the HDL (good) cholesterol. Thus, the total minus the good yields what’s bad and this would include all bad species of particles including LDL, IDL and CR. NCEP recommends a non-HDL cholesterol 30mg/dl higher than LDL target. Thus, for example, if you had a heart attack, the LDL target would be 50-70mg/dl and the non-HDL target would be 80-100mg/dl.

How do you lower apo B or the non-HDL cholesterol using lifestyle? The two most powerful ways would be weight loss, if overweight, and daily aerobic exercise. The benefit of this test is that it provides you a quantitative measure of the benefit of such lifestyle changes.

In summary, in most individualS the standard lipid profile provides important information in calculating an individual’s global cardiovascular risk. More recently, “advanced” cholesterol testing has become available to further refine the calculation of risk. HS-CRP and apo B are two markers of cardiovascular risk that may help in this regard. Beginning with a baseline, serial measures may allow a quantitative measure of the benefit of lifestyle changes, and serve as both useful feedback and an aid in sustaining such changes. Look to Part Two (January 2024) for a discussion of two additional “advanced” tests, TMAO and NMR LipoProfile.

Paul E. Lemanski, MD, MS, FACP (plemanski3@gmail.com) is a board-certified internist practicing internal medicine and lifestyle medicine in Albany. Paul has a master’s degree in human nutrition, he’s an assistant clinical professor of medicine at Albany Medical College, and a fellow of the American College of Physicians.