Heart Disease Part 3: Comprehensive Risk Assessment

In the previous articles, I’ve discussed some of the more direct causes of heart disease, but what about risk factors and testing? Current lab testing revolves around cholesterol. But, did you know that LDL cholesterol levels are elevated in only 25% of those with heart disease? In other words, 75% percent of those with heart disease have optimal cholesterol levels! You may not be too surprised by this if you’ve read my last two articles on this topic – especially since I mentioned that cholesterol doesn’t really cause heart disease. As I pointed out, the LDL particle number is a much better marker for heart disease risk than LDL cholesterol numbers and I’ll talk about one way to test for this in just a minute. In this article, I’ll go through a number of additional tests that can provide a more comprehensive assessment of risk for heart disease.


Adiponectin is a hormone produced by fat cells which I’ve discussed in more detail here and here. Adequate levels of adiponectin can actually help prevent the oxidation of LDL, while also increasing the production of nitric oxide thereby helping to prevent endothelial dysfunction. Low levels are associated with an increased risk for metabolic syndrome, diabetes and heart disease. Go here to learn more about how to increase adiponectin through diet.

Apoproteins (apoA and apoB)

In the first article of this series, I discussed cholesterol. If you recall, I mentioned that the vehicles that carry cholesterol, such as LDL particles, contain proteins. Different proteins are associated with different particles. ApoB-100 is commonly found on LDL, while apoA-1 is found on HDL particles. If you recall, I also discussed how the LDL particle number is actually more relevant than the LDL cholesterol concentration in assessing risk for heart disease. There are multiple tests to measure LDL particle number and one such way is by measuring the level of these apoproteins in the blood. An elevated ApoB level is going to correlate with an elevated LDL particle number and an increased risk for heart disease.

C-Reactive Protein

C-reactive protein (CRP) is one of several markers of inflammation. It is a protein that is produced by the liver as part of the immune response. CRP can be elevated for a number of reasons including many acute and chronic illnesses. High sensitivity CRP (hs-CRP) is a test that is used to assess the risk for heart disease. While the exact role of CRP in the formation of arterial plaques is not well understood, many studies have shown an association of elevated CRP with heart disease.


Fibrinogen is a clotting factor that binds platelets to each other leading to the formation of a blood clot. Elevated levels of fibrinogen can increase the viscosity of the blood, cause injury to endothelial cells while promoting plaque formation and blood clots. Fibrinogen can be elevated from tobacco use, contraceptives, obesity, stress and aging.


Homocysteine is a by-product of the metabolism of the amino acid methionine. When homocysteine is elevated it can cause damage to blood vessels and promote plaque formation in arteries. Elevation may be caused by a deficiency of folate, B6 or B12 or high psychological stress in some individuals. There is some discussion over whether homocysteine actually causes damage to blood vessels or is simply elevated because of damage to blood vessels. Do you remember the LOX-1 receptor (lectin-like oxidized LDL receptor-1) from the previous article? This is one of the receptors involved in endothelial dysfunction and plaque formation. This receptor is also found on macrophages and plays a role in foam cell formation (discussed in the first article). Research has shown that individuals with elevated homocysteine have more LOX-1 receptors on their macrophages. This effect of homocysteine may in part explain how it promotes vascular inflammation and the formation of plaques. A recent meta-analysis has also suggested that treating elevated homocysteine is beneficial to individuals with coronary artery disease.

Lipoprotein (a)

Another protein that can be found on LDL particles is called apolipoprotein (a) or lipoprotein (a). Research has found that elevated Lp(a) is a significant risk factor for heart disease and is often genetically determined. Lipoprotein (a) may convey this increased risk by slowing the breakdown of clots, contributing to the formation of plaques and promoting the formation of foam cells. Although levels of Lp(a) may be genetically determined, it can be treated with certain nutritional supplements.

Lipoprotein Associated Phospholipase A2

This one is a mouthful. Let’s call it Lp-PLA2. Lp-PLA2 is an enzyme found circulating in the blood attached to LDL particles. This enzyme breaks down oxidized LDL particles and can promote inflammation in the blood vessels when levels are elevated. The test for Lp-PLA2 is called PLAC.

Oxidized LDL

Some labs are beginning to offer a test to measure the levels of oxidized LDL particles in the blood. There is obvious benefit in this since oxidative stress leading to oxidized LDL particles is one of the primary causes of endothelial dysfunction and heart disease.

Particle Size

Just when you were starting to sort out this lipoprotein thing, it gets more complicated. The various particle types (LDL, HDL, etc) can actually come in different sizes. For example, LDL particles can be small and dense or they can be large. It is thought that the small, dense particles are more likely to cause problems as they would more easily pass between the endothelial cells of arteries leading to plaque formation. Measuring the particle size can therefore give a better indication of the risk for heart disease.

Red Cell Distribution Width

RDW or red cell distribution width is found on the very common CBC (complete blood count) panel. RDW tells us variability in size of red blood cells. A high RDW indicates more variation in size, while a lower RDW indicates more uniformity in red blood cell size. RDW is typically used to help diagnose and distinguish various anemias and other diseases. Research is finding, however, that RDW may also be useful in assessing risk for heart disease – especially in assessing prognosis in those already diagnosed with heart disease. A higher RDW is associated with a worse prognosis for those with heart disease.

Vitamin D

Research continues to elucidate the many benefits that vitamin D has to offer. Many observational studies have noted a correlation between low vitamin D status and heart disease. This observation may be due to the fact that low vitamin D can lead to increased parathyroid hormone which in turn can lead to metabolic disturbances and an increased risk for heart disease. While the mechanisms as to how vitamin D deficiency could increase the risk for heart disease may not be clear, given the many benefits of vitamin D and the low cost for supplementation, treating low levels of vitamin D seems worthwhile.

Many of the tests listed above can be found in what’s known as a vertical auto profile (VAP) cholesterol panel. This is a more comprehensive cholesterol panel that is available through most labs. It generally includes a breakdown of LDL and HDL types/sizes, including IDL (intermediate density lipoprotein), as well as apoB, apoA and lipoprotein (a). The remaining tests are also commonly available with the exception of adiponectin and oxidized LDL which are not as commonly available, but are gradually becoming so.

There are a number of natural and pharmaceutical treatments that can be used to treat the above risk factors if they are abnormal. But, for most of these, the best and most proven way is through a healthy diet and physical activity. A balanced diet high in fruits and vegetables combined with physical activity and stress management can address nearly all of the above factors and significantly lower your risk for heart disease or help reverse the progression of established heart disease. In my final article, I’ll address some of the dietary factors that may be involved in heart disease and some of the ongoing controversies.

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