Understanding Cholesterol and Lipoproteins

 Cholesterol is probably the most controversial topic I get into with my patients. This is because many of them have heard that cholesterol drugs (statins) cause cancer, damage the liver, deplete CoQ10, or don’t work, or are a waste of money. For arterial plaque to occur there needs to be disruption of the endothelial layer (inner blood vessel wall). Then LDL particles find their way through the inner arterial wall and activate the immune system causing inflammation. The immune system ingests these particles and then the cells die. As this continues, a core of lipid develops and it can eventually rupture causing heart attack. (Refer to Figure 1 below, labelled:  Atherosclerosis timeline)

Understanding LDL

Low-density lipoprotein (LDL) is the “bad” cholesterol that most of us have heard about. While elevated LDL is a risk factor for heart attack, LDL alone is not a good predictor of an individual’s risk. Because of this problem, more-sensitive cholesterol tests have been developed which look at cholesterol particle size, number, and density. Although cholesterol abnormalities contribute to atherosclerosis there is more to the story. For example, LDL particle number is the
more important risk indicator.

An issue that feeds the cholesterol controversy is the fact that LDL levels in populations both with and without CAD (Coronary Artery Disease) significantly overlap. In the Framingham Heart Study, for instance, 80 percent of heart attack patients had cholesterol levels similar to those who did not experience a heart attack; and 50 percent of the heart attack victims had normal cholesterol (Castelli, 1996) . This is why you hear people talking about a cholesterol myth or saying things like cholesterol does not cause heart attacks. Elevated LDL remains a well-established independent risk factor for CAD despite what you may have heard. It is important to remember that there are many causes of arterial disease. Cholesterol is just a mediator; a driver of the process.

Key points and action steps regarding LDL cholesterol:
If your LDL is elevated you should work to get it down through diet and lifestyle first. Aerobic exercise, reducing dietary saturated fats and increasing fiber along with fruit and vegetables and whole grains can help lower cholesterol. If there is a personal or family history of CAD you’re going to get the most protection by keeping your LDL down to about 70. Simply lowering cholesterol may not be enough in a high risk patient. If you already have CAD, you want to manage your lipids aggressively/eat a whole foods based Mediterranean style diet with no processed foods and less than 2000 mg of sodium per day.

Understanding Lipoproteins

Lipoproteins are a better measure of risk, and lipoprotein testing represents a new era in preventive cardiology. Just measuring LDL and treating it (while still somewhat effective) may not be enough for ultimate heart attack prevention, because it does not reflect lipoprotein size, density, or particle number.

LDL and HDL are just not enough when it comes to evaluating your risk of a heart attack. This is particularly true if the small, dense LDL particle number is elevated. From here on I will refer to LDL particle number as LDL-P. Most of the cholesterol in your blood is not just freely floating around. Rather, it is in the form of a little ball called a lipoprotein. Apolipoproteins are the protein component of the lipoprotein. They play an important role in what cholesterol does in your body. The apolipoprotein tells the cholesterol particle what to do and where to go, as well as determines if it’s going to be a good guy or a bad guy.

At any level of LDL cholesterol, if you have smaller LDL particles, you will have more of them. This can be seen below,  in Figure 2 (Lipoprotein Subclasses), where the scale holds 130 mg/dL of cholesterol on both sides, but the patient on the right is at higher risk because there are more particles and they are smaller. (Refer to Figure 3 below: Particle Size and Number). Why are small particles bad? Think of the net that divides a tennis court. The net represents the first layer in your artery wall. Large particles are like tennis balls that cannot pass through the net; small particles are like golf balls that can pass right through. Small particles get into the artery wall and accelerate plaque progression. The more lipoprotein particles a person has, the higher the risk for plaque buildup regardless of how much cholesterol those particles carry! This is why LDL alone is not a good way to measure risk. (Graphic below: Normal Apo B)

ApoLipoprotein-B
ApoLipoprotein-B (or ApoB) is just another way of LDL measuring particle number. Some people can have high particle numbers even if LDL cholesterol is normal so measuring ApoB is useful. Recent studies indicate that it is the best way to assess LDL particle number and that it is a much better risk marker than LDL cholesterol. ApoB testing also less expensive than other ways of measuring particle number. When the LDL goal is less than 70 mg/dL, the equivalent for
ApoB is under 60 mg/dL (Mudd, et al., 2007) .

Key points and action steps regarding cholesterol:
Particle number and particle size contribute to the confusion about the role of cholesterol and heart attacks in atherosclerosis. Lipoprotein analysis is most beneficial for people with normal or moderately elevated LDL (100 to 140 mg/dL). Addressing cholesterol size and particle number is an important tool for reversing atherosclerosis. Insurance often covers lipoprotein testing. At the bare minimum ask your doctor for an ApoB test on your next blood draw. An unfavorable lipoprotein profile may explain why you continue to build plaque year after year despite excellent traditional lipid numbers. If your triglycerides are over 150 this will interfere with accurate LDL and HDL readings. You’d better get to work!

Understanding HDL
High density lipoprotein (HDL) is the “good” cholesterol. It’s considered good because it facilitates reverse cholesterol transport (RCT). Low HDL cholesterol is an important risk factor for CAD. HDL helps remove cholesterol from arteries in the early stages of disease and from established atherosclerotic plaque. This is why having low HDL is a risk factor and also why raising HDL to as high a level as possible helps reverse plaque! Data shows that raising HDL gets similar or even better results than lowering LDL. The prevalence of CAD increases by 25 to 30 percent for every 10 mg/dL decrease in HDL (below 45 mg/dL) (Castelli, et al., 1986) . Statistics show that people with HDL of less than 45 mg/dL have two to seven times more occurrence of CAD compared to people with HDL greater than or equal to 65 mg/dL (Castelli, et al., 1986) . The risk of cardiovascular events increases markedly with decreasing HDL concentration at every level of LDL concentration. (Kannel, 1987) . This means that even in people whose LDL is less than 100 mg/dL, the risk of developing atherosclerosis increases as HDL declines (Kannel, 1987) . People with LDL below 70 mg/dL but whose HDL is in the highest 25 percentile have a reduced risk of major cardiovascular events compared with people in the lowest 25 percentile. HDL promotes arterial repair and prevents and corrects endothelial dysfunction (Norata & Catapano, 2005) . HDL has been shown to help arteries relax and to inhibit white blood cells from entering plaques (Norata & Catapano, 2005; Shah, Kaul, Nilsson, & Cercek, 2001) . HDL’s antioxidant properties inhibit the oxidation of LDL. Oxidized cholesterol is associated with increased damage to the endothelium and continues to be investigated as a risk factors in CAD (Libby, 2002; Norata & Catapano, 2005) . Raising your HDL to above 60 mg/dL may also reduce factors that increase the risk of forming a blood clot and help the body break down blood clots (Griffin, Kojima, Banka, Curtiss, & Fernandez, 1999) .

As a rule of thumb I tell people 60/60/60. This is easy to remember and means that your LDL should be 60, your HDL should be at least 60 and your triglycerides should be around 60. Regular aerobic exercise (such as walking, jogging, or bike riding that raises your heart rate for 20 to 30 minutes at a time) is an effective way to increase HDL levels. In the May 28 issue of the Archives of Internal Medicine (Kodama, et al., 2007) , investigators reported that the duration exercise, rather than the intensity, is the more important factor in raising HDL cholesterol. In individuals who exercised for at least 20 minutes, each additional 10-minute increase in exercise duration increased HDL levels by an additional 1.4 mg/dL (Kodama, et al., 2007) .

Key points and action steps regarding raising HDL:
Aerobic exercise—longer is better (20 minutes minimum, 5-6 days a week). I ask my patients to get low to moderate intensity aerobic exercise for 1 hour 5 days/week Losing fat, especially around the abdomen. Niacin supplementation (with medical supervision) Pantethine 900 mg. Goal HDL level is at least 60 mg/dL. Insulin resistance: If you have it, treat aggressively. HDL is vasoprotective and prevents the oxidation of LDL. The prevalence of CAD increases by 25% to 30% for every 10-mg/dL decrease in HDL (below 45 mg/dL). As HDL-C declines, the risk of developing atherosclerosis continuously increases.