Taking Control of Your Cholesterol – APOE and Cardiovascular Disease

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At your annual exam two months ago, your cholesterol levels were through the roof. Your doctor was worried that you may be at high risk for a heart attack. You try a low-fat diet and here you are back at the doctors’ office, not feeling much different, but expecting good news nevertheless. The blood tests are back, but the results are not good. Time for more drastic measures and the doctor prescribes Lipitor. The doctor can only hope that this treatment will be effective, but you wish there was a better way to predict which treatment works best for you.

Cardiovascular disease involves the narrowing or the blocking of blood vessels that can lead to heart attack, stroke and chest pain or angina. Heart attacks and strokes account for over one-quarter of deaths each year in North America. There are known disease risk factors, such as high blood pressure, high cholesterol, smoking, poor diet, physical inactivity, excess weight, age and genetics. Treatment options include simple diet changes, increased physical activity, and medications to lower cholesterol levels.

One genetic risk factor, a gene called APOE, can indicate whether or not someone is at increased risk of cardiovascular disease and which treatment option is likely to be the most effective. There are three genetic versions, or ‘alleles’, of APOE, called APOE e2, APOE e3 and APOE e4. We inherit one copy of APOE from each parent, which means that we each have two copies of this gene. People with either two copies of e2 or one copy each of e2 and e3 generally don’t benefit as well from a low-fat diet, but respond well to statins (cholesterol-lowering medication). On the other hand, people with two copies of e4 or one copy each of e3 and e4 may not respond to statins, but instead benefit more from a low-fat diet to lower their cholesterol levels.

The different genetic versions of APOE (e2, e3, e4) influence how we respond to treatment because APOE encodes a protein, apolipoprotein E, that controls the uptake of cholesterol and fats from the bloodstream into the cells. Even small variations in this protein can dramatically affect the level of cholesterol in the blood. Individuals with one or more copies of the e4 allele have an increased risk of coronary heart disease due to elevated LDL-cholesterol levels. The e3 allele is the most common allele and is associated with a normal level of blood cholesterol. The e2 allele results in lower LDL-cholesterol levels, but can be associated with an increased risk of type III hyperlipoproteinaemia, which is another factor that contributes to heart problems.

Thanks to advances in DNA technologies, you can now determine which alleles of APOE you have inherited. If you have high cholesterol, knowing which versions of APOE you have, may help you and your doctor devise a treatment plan that is personalized to your genetics. Even if you don’t have high cholesterol, simply knowing there is an increased risk for cardiovascular disease just might prompt you to make better lifestyle choices to minimize your risk. There are 32.4 million heart attacks and strokes worldwide every year. Knowing your risks may be able to help you take more control of your cholesterol levels and stop you from becoming another statistic.

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