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Why Cholesterol May Not Be the Cause of Heart Disease
We have all been led to believe that cholesterol is bad and that lowering it is good. Because of extensive pharmaceutical marketing to both doctors and patients we think that using statin drugs is proven to work to lower the risk of heart attacks and death.
But on what scientific evidence is this based? What does that evidence really show?
Roger Williams once said something that is very applicable to how we commonly view the benefits of statins: "There are liars, damn liars, and statisticians."
We see prominent ads on television and in medical journals -- things like 36 percent reduction in risk of having a heart attack. But we don't look at the fine print. What does that REALLY mean and how does it affect decisions about who should really be using these drugs? Before I explain that, here are some thought provoking findings to ponder.
- If you lower bad cholesterol (LDL) but have a low HDL (good cholesterol), there is no benefit to statins.[i]
- If you lower bad cholesterol (LDL) but don't reduce inflammation (marked by a test called C-reactive protein), there is no benefit to statins.[ii]
- If you are a healthy woman with high cholesterol, there is no proof that taking statins reduces your risk of heart attack or death.[iii]
- If you are a man or a woman over 69 years old with high cholesterol, there is no proof that taking statins reduces your risk of heart attack or death.[iv]
- Aggressive cholesterol treatment with two medications (Zocor and Zetia) lowered cholesterol much more than one drug alone, but led to more plaque build up in the arteries and no fewer heart attacks.[v]
- 75 percent of people who have heart attacks have normal cholesterol
- Older patients with lower cholesterol have higher risk of death than those with higher cholesterol.[vi]
- Countries with higher average cholesterol than Americans, such as the Swiss or Spanish, have less heart disease.
- Recent evidence shows that it is likely statins' ability to lower inflammation is what accounts for the benefits of statins, not their ability to lower cholesterol.
So for whom do the statin drugs work anyway? They work for people who have already had heart attacks to prevent more heart attacks or death. And they work slightly for middle-aged men who have many risk factors for heart disease like high blood pressure, obesity, or diabetes.
So why did the 2004 National Cholesterol Education Program guidelines expand the previous guidelines to recommend that more people take statins (from 13 million to 40 million) and that people who don't have heart disease should take them to prevent heart disease? Could it have been that 8 of the 9 experts on the panel who developed these guidelines had financial ties to the drug industry? Thirty-four other non-industry affiliated experts sent a petition to protest the recommendations to the National Institutes of Health saying the evidence was weak. It was like having a fox guard the chicken coop.
The heart of the matter
It's all in the spin. The spin of the statistics and numbers. And it's easy to get confused. Let me try to clear things up.
When you look under the hood of the research data you find that the touted "36% reduction" means a reduction of the number of people getting heart attacks or death from 3 percent to 2 percent (or about 30-40 percent).
And these data also show that treatment only really works if you have heart disease already. In those who DON'T have documented heart disease, there is no benefit.
In those at high risk for heart disease, about 50 people would need to be treated for 5 years to reduce one cardiovascular event. Just to put that in perspective: If a drug works, it has a very low NTT (number needed to treat). For example, if you have a urine infection and take an antibiotic, you will get nearly a 100 percent benefit. The number needed to treat is "1." So if you have an NTT of 50, like statins do for preventing heart disease in 75 percent of the people who take them, it is basically a crap shoot.
Yet at a cost of over $28 billion a year, 75 percent of all statin prescriptions are for exactly this type of unproven primary prevention. Simply applying the science over 10 years would save over $200 billion. This is just one example of reimbursed but unproven care.We need not only to prevent disease but also prevent the wrong type of care.
If these medications were without side effects, then you may be able to justify the risk -- but they cause muscle damage, sexual dysfunction, liver and nerve damage, and other problems in 10-15 percent of patients who take them. Certainly not a free ride.
So if lowering cholesterol is not the great panacea that we thought, how do we treat heart disease, and how do we get the right kind of cholesterol? High HDL, low LDL and low triglycerides have cholesterol particles that are large, light, and fluffy rather than small, dense, and hard, which is the type that actually causes heart disease and plaque build up.
We know what causes the damaging small cholesterol particles. And it isn't fat in the diet. It is sugar. Sugar in any form or refined carbohydrates (white food) drives the good cholesterol down, causes triglycerides to go up, creates small damaging cholesterol particles, and causes metabolic syndrome or pre-diabetes. That is the true cause of most heart attacks, NOT LDL cholesterol.
One of the reasons we don't hear about this is because there is no good drug to raise HDL. Statin drugs lower LDL -- and billions are spent advertising them, even though they are the wrong treatment.
If you're like most of the patients I see in my practice, you're convinced that cholesterol is the evil that causes heart disease. You may hope that if you monitor your cholesterol levels and avoid the foods that are purported to raise cholesterol, you'll be safe from America's number-one killer.
We are all terrified of cholesterol because for years well-meaning doctors, echoed by the media, have emphasized what they long believed is the intimate link between cholesterol and death by heart disease. If only it were so simple!
The truth is much more complex. Cholesterol is only one factor of many -- and not even the most important -- that contribute to your risk of getting heart disease.
First of all, let's take a look at what cholesterol actually is. It's a fatty substance produced by the liver that is used to help perform thousands of bodily functions. The body uses it to help build your cell membranes, the covering of your nerve sheaths, and much of your brain. It's a key building block for our hormone production, and without it you would not be able to maintain adequate levels of testosterone, estrogen, progesterone and cortisol.
So if you think cholesterol is the enemy, think again. Without cholesterol, you would die.
In fact, people with the lowest cholesterol as they age are at the highest risk of death. Under certain circumstances, higher cholesterol can actually help to increase life span.
To help clear the confusion, I will review many of the cholesterol myths our culture labors under and explain what the real factors are that lead to cardiovascular disease.
One of the biggest cholesterol myths out there has to do with dietary fat. Although most of us have been taught that a high-fat diet causes cholesterol problems, this isn't entirely true. Here's why: The type of fat that you eat is more important than the amount of fat. Trans fats or hydrogenated fats and saturated fats promote abnormal cholesterol, whereas omega-3 fats and monounsaturated fats actually improve the type and quantity of the cholesterol your body produces.
Consumption of high fructose corn syrup, which is present in sodas, many juices, and most processed foods, is the primary nutritional cause of most of the cholesterol issues we doctors see in our patients.
So the real concern isn't the amount of cholesterol you have, but the type of fats and sugar and refined carbohydrates in your diet that lead to abnormal cholesterol production.
Of course, many health-conscious people today know that total cholesterol is not as critical as the following:
Your levels of HDL "good" cholesterol vs. LDL "bad" cholesterol
Your triglyceride levels
Your ratio of triglycerides to HDL
Your ratio of total cholesterol to HDL
Many are also aware that there are different sizes of cholesterol particles. There are small and large particles of LDL, HDL, and triglycerides. The most dangerous are the small, dense particles that act like BB pellets, easily penetrating your arteries. Large, fluffy cholesterol particles are practically harmless--even if your total cholesterol is high. They function like beach balls and bounce off the arteries, causing no harm.
Another concern is whether or not your cholesterol is rancid. If so, the risk of arterial plaque is real.
Rancid or oxidized cholesterol results from oxidative stress and free radicals, which trigger a vicious cycle of inflammation and fat or plaque deposition under the artery walls. That is the real danger: When small dense LDL particles are oxidized they become dangerous and start the build up of plaque or cholesterol deposits in your arteries.
Now that we've explored when and how cholesterol becomes more problematic, let's take a look at other factors that play a more significant role in cardiovascular disease.
Prime contributors to cardiovascular disease
First of all, cardiovascular illness results when key bodily functions go awry, causing inflammation,[vii] imbalances in blood sugar and insulin, and oxidative stress.
To control these key biological functions and keep them in balance, you need to look at your overall health as well as your genetic predispositions, as these underlie the types of diseases you're most likely to develop. It is the interaction of your genes, lifestyle, and environment that ultimately determines your risks -- and the outcome of your life.
This is the science of nutrigenomics, or how food acts as information to stall or totally prevent some predisposed disease risks by turning on the right gene messages with our diet and lifestyle choices. That means some of the factors that unbalance bodily health are under your control, or could be.
These include diet, nutritional status, stress levels, and activity levels. Key tests can reveal problems with a person's blood sugar and insulin, inflammation level, level of folic acid, clotting factors, hormones, and other bodily systems that affect your risk of cardiovascular disease.
Particularly important are the causes of inflammation, which are many, and need to be assessed. Inflammation can arise from poor diet (too much sugar and trans and saturated fats), a sedentary lifestyle, stress, autoimmune disease, food allergies, hidden infections such as gum disease, and even toxins such as mercury. All of these causal factors need to be considered anytime there is inflammation.
Combined together, all of these factors determine your risk of heart disease. And I recommend that people undergo a comprehensive medical evaluation to see what their risk really is.
Zeroing in on key factors for heart disease
There's no doubt about it, inflammation is a key contributor to heart disease. A major study done at Harvard found that people with high levels of a marker called C-reactive protein (CRP) had higher risks of heart disease than people with high cholesterol. Normal cholesterol levels were NOT protective to those with high CRP. The risks were greatest for those with high levels of both CRP and cholesterol.
Another predisposing factor to heart disease is insulin resistance or metabolic syndrome, which leads to an imbalance in the blood sugar and high levels of insulin. This may affect as many as half of Americans over age 65. Many younger people also have this condition, which is sometimes called pre-diabetes.
Although modern medicine sometimes loses sight of the interconnectedness of all our bodily systems, blood sugar imbalances like these impact your cholesterol levels too. If you have any of these conditions, they will cause your good cholesterol to go down, while your triglycerides rise, which further increases inflammation and oxidative stress. All of these fluctuations contribute to blood thickening, clotting, and other malfunctions -- leading to cardiovascular disease.
What's more, elevated levels of a substance called homocysteine (which is related to your body's levels of folic acid and vitamins B6 and B12) appears to correlate to cardiovascular illness. Although this is still somewhat controversial, I often see this inter-relationship in my practice. While genes may play a part, tests done as part of a comprehensive evaluation of cardiac risk can easily ascertain this factor. Where problematic levels occur, they can be easily addressed by adequate folic acid intake, along with vitamins B6 and B12.
Testing for cardiovascular risk factors
Heart disease is not only about cholesterol. It is important to look at many factors that contribute to your overall risk. And it seems that insulin and blood sugar imbalances, and inflammation, are proving to be more of a risk than cholesterol.
If you want to test your overall risk, you can consider asking your doctor to perform the following tests:
Total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides. Your total cholesterol should be under 200. Your triglycerides should be under 100. Your HDL should be over 60. Your LDL should be ideally under 80. Your ratio of total cholesterol to HDL should be less than 3.0. Your ratio of triglycerides to HDL should be no greater than 4, which can indicate insulin resistance if elevated.
NMR Lipid Profile. This looks at your cholesterol under an MRI scan to assess the size of the particles, which can determine your cardiovascular risk. This is a very important test that can further differentiate the risk of your cholesterol and can be an important factor to track as your system improves and your cholesterol transforms from being small, dense, and dangerous to light and fluffy and innocuous. It is done by a company called Liposcience and is also available through LabCorp.
Glucose Insulin Tolerance Test: Measurements of fasting and 1 and 2 hour levels of glucose AND insulin help identify pre-diabetes and excessively high levels of insulin, and even diabetes itself. Most doctors just check blood sugar and NOT insulin, which is the first thing to go up. By the time your blood sugar goes up, the train has left the station.
Hemaglobin A1c: This measures your average blood sugar level over the last 6 weeks. Anything over 5.5 is high.
Cardio C-reactive protein. This is a marker of inflammation in the body that is essential to understand in the context of overall risk. Your C-reactive protein level should be less than 1.
Homocysteine. Your homocysteine measures your folate status and should be between 6 and 8.
Lipid peroxides or TBARS test, which looks at the amount of oxidized or rancid fat. This should be within normal limits of the test and indicates whether or not you have oxidized cholesterol.
Fibrinogen, which is another test looking at clotting in the blood. It should be less than 300.
Lipoprotein (a), which is another factor that can promote the risk of heart disease, often in men. It should be less than 30.
Genes or SNPs may also be useful in terms of assessing your situation. A number of key genes regulate cholesterol and metabolism, including Apo E genes and the cholesterol ester transfer protein gene. The MTHFR gene, which regulates homocysteine, is also important and may be part of an overall workup.
Get a high-speed CT or (EBT) scan of the heart if you are concerned that you have cardiovascular disease. This may be helpful to assess overall plaque burden and calcium score. A score higher than 100 is a concern, and a score higher than 400 indicates severe risk of cardiovascular disease.
Next week I will review how to lower your risk of heart disease and fix your cholesterol. We'll do this not by lowering the LDL, but by getting more light and fluffy LDL particles, which are protective, and more HDL cholesterol, which is THE most important cholesterol.
Now I'd like to hear from you...
Have you been told that you need to lower your cholesterol?
If so, what were you told to do and how does that compare to what you've read here?
Does any of what you've read here come as a surprise?
Please share your thoughts by adding a comment below.
To your good health,
Mark Hyman, M.D.
[i]Barter P, Gotto AM, LaRosa JC, Maroni J, Szarek M, Grundy SM, Kastelein JJ, Bittner V, Fruchart JC; Treating to New Targets Investigators. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med. 2007 Sep 27;357(13):1301-10.
[ii] Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, Nordestgaard BG, Shepherd J, Willerson JT, Glynn RJ; JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008 Nov 20;359(21):2195-207.
[iii]Abramson J, Wright JM. Are lipid-lowering guidelines evidence-based? Lancet. 2007 Jan 20;369(9557):168-9
[v] Brown BG, Taylor AJ Does ENHANCE Diminish Confidence in Lowering LDL or in Ezetimibe? Engl J Med 358:1504, April 3, 2008 Editorial
[vi] Schatz IJ, Masaki K, Yano K, Chen R, Rodriguez BL, Curb JD. Cholesterol and all-cause mortality in elderly people from the Honolulu Heart Program: a cohort study. Lancet. 2001 Aug 4;358(9279):351-5.
[vii] Hansson GK Inflammation, Atherosclerosis, and Coronary Artery Disease N Engl J Med 352:1685, April 21, 2005