Lowering Cholesterol Levels
A better approach to testing and treatment
At your annual wellness check it is common for your doctor to run a standard lipid panel. This panel tests total cholesterol, LDL-C, HDL-C, triglycerides and provides a Cholesterol/HDL ratio. If total cholesterol exceeds the upper end of the range provided by the testing lab, your doctor may recommend starting a statin medication. The reasoning behind the medication is that it will lower cholesterol and therefore reduce the risk of an adverse cardiovascular event. This is standard medical testing and treatment of elevated cholesterol, but is it the whole story?
What is cholesterol?
Cholesterol is a waxy fat. Roughly 25% of cholesterol comes from the food we eat, the remaining 75% is made in the liver. Cholesterol plays an incredibly important role in the body. 20% of our body's cholesterol resides in the brain, it is a building block of our cell membranes, it is the precursor to Vitamin D, it makes all our sex hormones (estrogen, testosterone, progesterone, cortisol) and it can be converted to bile salts to help us digest fats.
The good and the bad
Cholesterol is a fat, so it can only be carried in the blood stream by a protein, and these proteins are called apoproteins. When the cholesterol fat binds with the apoprotein transport carrier, it becomes a lipoprotein.
HDL, which stands for high density lipoprotein, is transported via the ApoA-I lipoprotein which carriers cholesterol to adrenals and gonads to make sex hormones, to fat cells for storage, and then back to the liver or digestive tract. When the lipid panel is interpreted, HDL is called the "good" cholesterol. It received this positive name because it was originally thought to be the main player in the Reverse Cholesterol Transport bringing cholesterol from the periphery back to the liver, but we now know that isn't true. LDL plays a role in returning cholesterol to the liver as well. HDL is "good" because it has less triglycerides, which is an ester of three fatty acids and a glycerol, and more proteins than LDL giving it a higher density.
LDL, which stands for low density lipoprotein, is carried on the ApoB lipoprotein, and ApoB also carries vLDL (very low density lipoprotein) and IDL (intermediate-density lipoprotein). LDL is the "bad" cholesterol because only the ApoB lipoprotein can penetrate the endothelium (or cell wall) of the artery where it is used like a spackle to heal inflammation which leads to atherosclerosis, or hardening of the arteries.
Only the ApoB lipoprotein, which carries cholesterol esters for LDL, vLDL and IDL can penetrate the arterial wall and cause atherosclerosis.
Advanced lipid panel testing
For any patient who has elevated total cholesterol (> 200 mg/dl) and elevated LDL-C ( > 100 mg/dl), I will order additional blood work to look at additional markers that provide more insight into the level of risk of developing and presence of existing atherosclerosis. These markers include:
LDL-P: Above we discussed LDL-C, or LDL-cholesterol, which measures the amount of cholesterol carried by low-density lipoprotein. LDL-C tells us how much cholesterol is contained within LDL, but the lipoprotein carries more than cholesterol. LDL-P stands for LDL particle number and measures the number of LDL particles. The particles contain the cholesterol (and the cholesterol content of each particle can be different) and triglycerides. Therefore, the total number of LDL-particles is a more accurate measurement of potential for atherosclerosis.
It is also useful to compare LDL-C with LDL-P. Since particles carry cholesterol and triglycerides, if a person's triglyceride count is high, they will have more particles in the bloodstream to carry cholesterol and triglycerides. So if LDL-C is high, but LDL-P is within range, there is less risk of atherosclerosis. Similarly, if LDL-C is within range, LDL-P can still be high. This discordance is sometimes seen in patients with metabolic syndrome due to higher triglycerides and lower HDL. If only LDL-C is tested, the risk of cardiovascular disease for these patients may be overlooked.
Within LDL-P you can also measure particle size (large, medium or small). Generally speaking, large LDL particles are more protective and small LDL particles have a greater risk of cardiovascular disease. But the total LDL-P is more predictive of atherosclerotic risk than particle size.
ApoB and LDL-P are better predictors of cardiovascular disease risk than LDL-C.
Apolipoprotein-B: ApoB is the principle lipoprotein of LDL, vLDL and IDL cholesterol. As mentioned above, it is the lipoproteins - not cholesterol - that penetrates the arterial wall and contributes to atherosclerosis. Approximately 85% of ApoB is found in LDL particles, so measuring ApoB and LDL-P offers a similar look at the quantity of atherogenic lipoproteins in the blood.
Apolipoprotein-A1 is the lipoprotein of HDL. It is not atherogenic and may be protective. Therefore, a look at the ApoB/ApoA1 ratio can provide useful information about the balance between harmful and protective lipoproteins.
Lipoprotein(a): Called lipoprotein little a, the amount of this lipoprotein in the blood is completely determined by genetics. Lp(a) is a LDL particle with an added apolipoprotein(a) attached to the apoplipoprotein(b) part of the LDL particle. Lp(a) is considered the most inflammatory lipoprotein and is a predictive measure of coronary artery disease, stroke and aortic valve stenosis. Lp(a) also confers protection through reduced bleeding and wound healing.
oxLDL: This metric measures oxidized LDL, or how much LDL has been damaged by free radicals. When the free radicals combine with the LDL, it starts the inflammation cascade. This attracts white blood cells called macrophages to the LDL. When the macrophages engulf the LDL, it creates a foam cell. These foam cells are the soft start to atherosclerotic plaque in the arterial wall. I measure oxLDL to check oxidative stress and cross-check potential for inflammatory deposits in the arterial wall.
LP-PLA2: Lipoprotein-associated phospholipase A2, also known as platelet-activating factor acetylhydrolase (PAF-AH), is a measure of soft plaque in the artery. LP-PLA2 is an inflammatory enzyme that circulates bound mainly to LDL. It is produced by inflammatory cells and hydrolyzes oxidized LDL. This marker points to how much plaque is present in the artery wall.
Each of these labs provide a deeper understanding of the risk and presence of cardiovascular disease. They also allow me as the physician to offer a treatment plan tailored to the individual, instead of offering the same approach to everyone.
In conclusion, cholesterol's role in heart disease is determined by the lipoproteins that carry it in the bloodstream. Therefore, measurements of cholesterol alone does not provide enough information about the true risk for a cardiovascular event. Measuring proteins provides much more significant information about the risk of atherosclerosis. And then once the risk is determined, running additional markers to better understand the presence of disease is important for setting an effective treatment plan.
If your doctor is not running more advanced lipid panels and you are concerned about your cardiovascular health, I recommend you ask for one.
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