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Cholesterol and Cardiovascular Disease, CVD:

The Whole Picture?

By Radhia Gleis, C.C.N. MEd.














In 1989, my mother died, suddenly, of a massive heart attack.  A year and a half later, my father, after suffering and recovering from 2 strokes, died of congestive heart failure.  Besides my brother, I am the only living member on both sides of the family that has not died of a heart related disease.  There is no doubt that both my brother and I have a high genetic risk of cardiovascular disease (CVD).  So, it is of great interest to me that I keep abreast of the latest prevention methods available. 


Most people go to their doctor and have their cholesterol checked, and are told that if it is in normal range and they exercise, eat a low fat diet and not smoke they are safe.  But is that enough?  Research has found that there are other factors that lead to CVD beside elevated cholesterol or triglycerides. This idea has been gaining popularity since researchers have long known that at least “50% of the people who suffer a heart attack had normal total cholesterol levels” (1).


Many studies have found that in fact low cholesterol is in certain respects worse than high cholesterol; for instance, in 19 large studies of more than 68,000 deaths, it showed that low cholesterol predicted an increased risk of dying from gastrointestinal and respiratory diseases (2).  


Consider the finding of Dr. Harlan Krumholz of the Department of Cardiovascular Medicine at Yale University, who reported in 1994 that old people with low cholesterol died twice as often from a heart attack as did old people with high cholesterol (3).


Let’s take a closer look at cholesterol. You have heard of “good” cholesterol and “bad” cholesterol; well, there really is no such thing as “good” or “bad”, all cholesterol both LDLs and HDLs have very important functions; from making every new cell in your body to making hormones. The outer membrane of every cell is called a phospholipid, the “lipid” is cholesterol. The “sterol” in cholesterol is the building material for your steroid hormones, such as estrogen, testosterone, etc. and glucocordicosteroid hormones that enable the body to cope with stressors by increasing concentrations of glucose, fatty acids and amino acids, in the blood and by raising blood pressure. All of these functions are vital to life and rely on LDLs. HDLs, which have been considered “good” cholesterol, are “good” because they carry LDLs back to the liver to be recycled.


So when you go to your doctor and get a cholesterol test and your LDLs are high, is this a problem or is this the body’s response to other factors? A mentor, who taught me advanced blood analysis, once said, “The body doesn’t make mistakes”.  In this case, the body doesn’t just make excess cholesterol for no reason. When the body is out of balance our complex, physiological system is programmed to do what ever it can to respond to the body’s needs. When the emergency phone is ringing off the hook, instead of just cutting the cord, like suppressing the symptoms with cholesterol lowering drugs, answer the phone. In other words, I believe we should try and find the underlining cause of the elevated cholesterol and help the body re-balance itself.


With all that being said, there can be a problem with LDLs but just knowing your LDL count is not the whole picture. There is a difference in the size of LDLs and in this case -- size matters. LDL patterns A and B refer to the size of LDL cholesterol particles in the blood. Persons with LDL cholesterol pattern A have large, buoyant LDL cholesterol particles that bounce along through the arteries with no obstruction. Small LDL cholesterol particles in the blood however, can get snagged on tiny lesions on the lining of the blood vessels and clog the artery which may pose a greater risk for developing atherosclerosis and heart attacks. We can test for these cholesterol particle size variations, also known as, “fractionated LDLs”.  A special blood test called polyacrylamide gradient gel electrophoresis can measure particle size and determine whether a person has blood cholesterol LDL pattern A or LDL pattern B. A more common name for this test is a “NMR Lipo Profile”.


Though many physicians both in private practice and some at academic medical centers have had their doubts about the importance of cholesterol, testing is a widely accepted part of the routine physical examination of all adults.  The American public has been educated to know their cholesterol scores and think that by just knowing the score they can protect themselves from heart disease. Factors such as the fractionated LDLs mentioned above are rarely checked but other important factors are very often overlooked in blood work as well, such as: Apo A-1 /Apo B, CRP (C-reactive protein), fibrinogen, and homocysteine levels. Research is now showing evidence that these may have an equal to or greater role in determining an individuals risk for CVD.  


Lipoprotein (a) (Lp(a)) is an LDL cholesterol particle that is attached to a special protein called apo(a). In large part, a person's level of Lp(a) in the blood is genetically inherited. Lipoprotein A or LP(a), is a lipoprotein that resembles low-density lipoprotein (LDL) cholesterol but has a sticky, Velcro nature, causing it to easily tie up in blood vessels which gives it a more atherogenic characteristic.  Atherogenic means the formation of a fatty thickening of the walls of our arteries, as found in atherosclorisis, or hardening of the arteries. Approximately 20 percent of the population has elevated levels of lipoprotein A which is believed to be the threshold to increase the risk of CVD twofold. The risk is even more significant if the Lp(a) cholesterol elevation is accompanied by high LDL/HDL ratios (4).

Findings from Oxford University found that cardiac patients with high levels lipoprotein-a in their blood are 70 percent more likely to have a heart attack than those with lower concentrations (5).


Estrogen has been shown to lower Lp(a) cholesterol levels by approximately 20% in women with elevated Lp(a) cholesterol. Therefore, women who are in post-menopause have a greater risk for CVD than younger women. Estrogen can also increase HDL cholesterol levels when given to postmenopausal women (6). Additionally, nicotinic acid (Niacin or Niaspan) in high doses has been found to be effective in lowering Lp(a) cholesterol levels by approximately 30%.

Research studies from The American Heart Association National Center, showed that Apolipoprotein “B”,  (apo B), a protein associated with LDLs, appears to be a reliable predictor of increased risk of Ischemic Heart Disease, which is damage to the heart muscle caused by artery blockages.  Some studies suggest that apo B may be even a more accurate forecaster of increased risk from atherosclerosis, than LDL itself (7).


The "A" apolipoproteins (Apo A) form is the major proteins found in high density lipoproteins, ((HDL) the “good” cholesterol). Many studies using different approaches have suggested that elevated HDL levels may reduce the risk of coronary artery disease, (CAD) whereas; reduced levels are associated with increased risk for coronary artery disease. Deficient levels of Apo A-1 have been reported to be one of the most reliable predictors of CAD. In fact, the studies show that men with the highest levels of apo B and the lowest levels of apo A-1 were nearly four times as likely to have a fatal heart attack than those with opposite values (8). The blood test “Apolipoproteins Assessment” can be done to check your status.


Another very important marker for CVD is C-reactive Protein. A revolutionary eight year-long study of 27,939 women, was specifically designed to address how C reactive Protein (CRP) measurement might help better identify those at high risk for heart disease.  Researchers at the Brigham and Women’s Hospital (BWH) have shown that this simple and inexpensive blood test for CRP, a substance produced in the liver when arteries become inflamed, is a more powerful predictor of a person's risk of suffering a heart attack or stroke than screening based on LDL cholesterol (9).

Paul Ridker, MD, Director of the Center for Cardiovascular Disease Prevention at the BWH and lead author of the study, estimates that approximately 25 percent of the United States population has elevated CRP levels, but normal to low levels of cholesterol.  This means that millions of Americans may be unaware that they are at increased risk for future heart problems, even if they are routinely screened for elevated cholesterol (10).


The CRP test is a general test to check for inflammation in the body. It is not a specific test. That means, it can reveal that you have inflammation somewhere in your body, but it cannot pinpoint the exact location. A more sensitive CRP test, called a high-sensitivity C-reactive protein (hs-CRP) assay, is available to determine a person's risk for heart disease. Many consider a high CRP level to be a risk factor for heart disease. However, it is not known whether CRP is merely a sign of cardiovascular disease or if it actually plays a role in causing heart problems (11,12).


Another test that can be easily performed is your fibrinogen level.  In order for blood to clot, fibrinogen is converted to fibrin by the action of an enzyme called thrombin. Fibrin molecules clump together to form long filaments which trap blood cells to form a solid clot. 


Fibrinogen rises sharply during tissue inflammation or injury. When this occurs, high fibrinogen levels may be a predictor for an increased risk of heart or circulatory disease.  Other conditions in which fibrinogen is elevated are cancers of the stomach, breast, or kidney, and inflammatory disorders like rheumatoid arthritis (13). 


 Several years ago I had a Cardiovascular Risk Assessment test to check all of these factors, although my Cholesterol and triglycerides were normal my fibrinogen was quite out of range.  My father had two strokes, five of my uncles died of stroke and my mother had a blood clot in her leg when she was my age.  I took a simple, specific enzyme supplement for this and in two months my fibrinogen was normal…needless to say, the test is worth it.


Another important CVD marker often overlooked is Homocysteine. Homocysteine ("ho-mo-sist-een") is an amino acid (a building block of protein) that is produced in the human body. The hypothesis is that homocysteine can have a toxic effect on the cells that make up the innermost layer of blood vessels. Homocysteine may irritate blood vessels, leading to blockages in the arteries (14).


High homocysteine levels in the blood can also cause cholesterol to change to something called oxidized low-density lipoprotein, LDL, which is more damaging to the arteries. In addition, high homocysteine levels can make blood clot more easily than it should, increasing the risk of blood vessel blockages. A blockage might cause you to have a stroke or a problem with blood flow. Up to 20% of people with heart disease have high homocysteine levels (15). Studies are not yet clear whether high homocysteine levels are the cause of CVD or just a marker. Further studies are needed to clarify the role of homocysteine in atherosclerosis and thrombosis. But enough studies indicate that elevated homocysteine can increase your risk for:


  • Coronary artery disease (atherosclerosis)

  • Heart attack

  • Stroke

  • Peripheral arterial disease

  • Venous thrombosis

  • Deep vein thrombosis

  • Pulmonary embolism

  • Dementia

  • Having a child with a neural tube defect (ie, spina bifida)



The good news is that elevated homocysteine levels can be lowered. We know that folic acid, vitamin B6, and vitamin B12 are all involved in breaking down homocysteine in the blood. Therefore, increasing your intake of folic acid and B vitamins may lower your homocysteine level.


Several conditions may increase your blood homocysteine level such as an inadequate dietary folic acid intake, (green leafy vegetables), smoking, drugs (i.e. methotrexate, synthetic hormones like Birth Control Pills, antiepileptics), renal failure and an inherited gene polymorphism of methylene-tetra-hydro-folate-reductase (MTHFR). This polymorphorphism or gene defect decreases your ability to metabolize folic acid (16,17,18).


I noticed that in both my brother’s blood work and my blood work we always seem to have an elevated MCV, MCH, MCHC; which is a clear indication of B12/Folic acid deficiency. Several years ago I did a genomic profile and sure enough my test indicated a polymorphism in my MTHFR.


A standard CBC will tell you what your MCV, MCH, MCHC are, which is a start but it is clearly not the whole picture. In that CBC you may also check your RDW.  My mentor used to call the RDWs a poor-man’s homocysteine test because if your RDWs are elevated it’s a good chance that your homocysteine will be too…not an absolute but a pointer. If you have any familial history of CVD it is very important to have your homocysteine tested. If you’ve had an elevated homocysteine level in the past, you may want to check your blood for that polymorphorphism or gene defect that decreases your ability to metabolize folic acid. The test is called MTHFR, DNA Analysis that checks for two mutations: C677T/A1298C. These mutations and their associated risks are inherited, so if you test positive, then testing of at-risk family members should be considered.


Once an elevated homocysteine level has been found and folic acid and/or vitamin B6 and B12 therapy is initiated, it is worth while to recheck a level about two months later to make sure that it has normalized. If it has not normalized, the dose of folic acid or vitamin B6 and B12 can be increased. It is reasonable to then recheck levels another two months later. You may need to use the 5MTHF, (5-Methyltetrahydrofolate) supplement which is the predominant metabolic form of folic acid; in other words a pre-metabolized folate.


There are other causes for CVD such as viral infections, e.g. herpes simplex, Hepititis C or cytomeglia virus, or bacterial infections such as endocarditis, and H Pylori. A standard CBC will indicate if there is an infection and you can ask your doctor to run further tests to determine which kind it is. You can also run immune assays and genomic profiles but I suggest you start with the basics and take prudent precautions. The best way to protect yourself from CVD is to find out what your status is. All of these tests are included in the Boston Heart test. In most cases the treatment is a matter of diet/nutritional support, and lifestyle changes.  If you want to learn more about the Cardiovascular Risk Assessment or how to prevent or lower your risk factors for CVD.  



(1). Paul Ridker, a cardiologist at Harvard-affiliated Brigham and Women’s Hospital in Boston. Gregg C. Fonarow, M.D., professor, cardiovascular medicine and science, University of California, Los Angeles; Manesh Patel, M.D., assistant professor, medicine, Duke University, Chapel Hill, N.C.; Jan. 12, 2009, American Heart Journal

(2). Jacobs D and others. Report of the conference on low blood cholesterol: Mortality associations; reviewed by Professor David R. Jacobs and his co-workers from the Division of Epidemiology at the University of Minnesota,  Circulation 86, 1046–1060, 1992.

(3). Krumholz HM and others. Lack of association between cholesterol and coronary heart disease mortality and morbidity and all-cause mortality in persons older than 70 years; Journal of the American Medical Association 272, 1335-1340, 1990.

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