Speaker A
Cholesterol is a lipid molecule that helps maintain the structure of cell membranes and is a precursor to steroid hormones, bile acids, and vitamin D. Although every day some new cholesterol comes in through the diet, most of the cholesterol we need is obtained through recycling existing cholesterol. Most of that recycling happens in the intestines and is facilitated by bile acids, which help us reabsorb LDL cholesterol and bring it back into the bloodstream. There are two main types of cholesterol: HDL or high-density lipoprotein, which is sometimes called good cholesterol, and LDL or low-density lipoprotein, which is sometimes called bad cholesterol. But good and bad is overly simplistic, and like all things, the subtleties matter. LDL is produced by the liver, and it carries cholesterol out to the rest of the body. If all of the cholesterol from LDL is not completely distributed to the peripheral cells, then HDL brings some of that cholesterol back from the peripheral tissues and sends it to the liver. Now, what makes LDL bad and HDL good is that whenever there's a high blood concentration of LDL, LDL can be ingested by macrophages that sit along vessel walls, forming atherosclerotic plaques. Over decades, large atherosclerotic plaques can lead to myocardial infarctions, strokes, and peripheral vascular disease. That's why we want to keep LDL blood levels under control. On the other hand, HDL can remove cholesterol from cells, and that can help reverse the process of atherosclerosis. A diagnosis of hypercholesterolemia requires measuring total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides. Cholesterol is measured either as mg per deciliter or millimoles per liter of blood, and it's recommended to test cholesterol every 5 years for people age 20 or older. Hypercholesterolemia is defined as having cholesterol levels that predict a higher risk of atherosclerosis and cardiovascular disease. The total blood cholesterol is, get this, the total amount of cholesterol in your blood, and it includes the LDL, HDL, and VLDL, and it should be below 200 mg per deciliter or 5.2 millimoles per liter. The HDL level should be above 60 mg per deciliter or 1.55 millimoles per liter, and the LDL level should be below 100 to 130 mg per deciliter or 3.3 millimoles per liter in most individuals, or below 70 mg per deciliter or 1.8 millimoles per liter in people who have previously had a cardiovascular event. And of the three, total cholesterol, LDL, and HDL, the LDL is the most relevant indicator of risk. Finally, triglycerides are also often measured along with cholesterol because elevated triglycerides can contribute to atherosclerosis, and having elevated triglycerides is specifically termed hypertriglyceridemia rather than hypercholesterolemia. Now, first off, individuals with hypercholesterolemia should make lifestyle modifications such as exercise and weight loss to achieve a healthy BMI between 18.5 and 25, avoid cigarettes and tobacco products, and reduce consumption of saturated fats, so eating fewer animal products like meat and dairy. Usually, individuals with a very elevated LDL or with a combination of moderately elevated LDL and other risk factors for cardiovascular disease are prescribed lipid-lowering medications. Common risk factors for cardiovascular disease include being a man over the age of 45 or a woman over the age of 50 with HDL cholesterol less than 40 mg per deciliter or 1 millimole per liter, having diabetes, hypertension, a family history of coronary artery disease and hypercholesterolemia, and cigarette smoking. To be more specific, individuals with an LDL above 190 mg per deciliter or 4.9 millimoles per liter, or those with an LDL above 160 mg per deciliter or 4.1 millimoles per liter with two or more additional risk factors, are started on medication. Treatment is also started in individuals with an LDL above 130 mg per deciliter or 3.4 millimoles per liter with asymptomatic coronary artery disease, as well as individuals above 70 mg per deciliter or 1.8 millimoles per liter who have previously had a cardiovascular event. There are five main classes of lipid-lowering medications: statins, selective cholesterol absorption inhibitors like ezetimibe, fibrates, bile acid sequestrants, and niacin. The first option are statins, and they're generally the first choice in most situations. They lower LDL and triglycerides and raise the HDL. In patients that have never had a cardiovascular event, a low to moderate dose of a statin is used, like 10 to 20 mg of atorvastatin or 5 to 10 mg of rosuvastatin. LDL is usually measured 6 weeks after starting statin therapy to see if there's a response and then done every 6 to 12 months thereafter. The goal is to get the LDL below 100 mg per deciliter or 2.6 millimoles per liter. If the LDL remains above that level, then one option is to gradually increase the statin dose up to 40 to 80 mg of atorvastatin or 20 to 40 mg of rosuvastatin. On the other hand, for patients with a previous cardiovascular event, lifelong high-dose statin therapy with 40 to 80 milligrams of atorvastatin or 20 to 40 mg of rosuvastatin is used regardless of baseline LDL levels. Now, even at maximum doses of statins, some individuals still can't reach their LDL goal, so that's where it may be helpful to add on another lipid-lowering medication, and the choice is mainly based on the potential side effects of each medication. In addition, statins can cause side effects like muscle pain and myopathy, increased risk of diabetes mellitus, and elevated transaminases like an ALT. So if statin therapy isn't well tolerated, then that's another reason to try a different lipid-lowering medication. Next up, there's selective cholesterol absorption inhibitors like ezetimibe, which lower LDL by preventing cholesterol absorption in the intestine. So their main side effect is diarrhea. Ezetimibe is recommended as second-line therapy for those intolerant of statins or as an add-on therapy to statins for those unable to achieve the LDL goal on statins alone. After statins and ezetimibe, if more add-on therapy is needed or if those two aren't well tolerated, then there are a few other options. One is fibrates. They increase HDL levels and also lower triglycerides. Fibrates also decrease LDL, though generally to a lesser degree than statins, so that's why they're typically used in combination with statins or ezetimibe if they aren't effective at reaching their LDL goal by themselves. However, similar to statins, fibrates also cause myopathy and elevated transaminases, so if those are a concern, then it's better to choose another different lipid-lowering medication. The next option would be bile acid sequestrants like cholestyramine, which lower LDL by preventing cholesterol absorption in the intestine as well, and again, the main side effect is diarrhea. Bile acid sequestrants are sometimes preferred because they don't cause myopathy. Finally, there's niacin, which lowers LDL levels and increases HDL levels and is sometimes used in addition to another lipid-lowering medication as a last resort. However, research hasn't shown that adding niacin further lowers the risk of heart disease, so it may not continue to get recommended for hypercholesterolemia in the coming years. The main side effect of niacin is facial flushing, which can be blocked by taking 300 mg of aspirin half an hour before taking niacin. Some people, including some young individuals, have familial hypercholesterolemia and then develop severe hypercholesterolemia. They're often unable to lower their LDL levels with diet and commonly use lipid-lowering medications, so they sometimes need LDL apheresis, which is where a person's blood is passed through an apparatus that filters out LDL and returns the remainder of the blood to the circulation. The procedure takes 2 to 4 hours and must be repeated regularly every few weeks. Another option for individuals who can't do regular LDL apheresis is liver transplantation. A new liver has the functional hepatic LDL receptors that are often absent in familial hypercholesterolemia. Finally, there are some individuals who can't achieve an LDL below 160 mg per deciliter or 4.10 millimoles per liter even with th
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