08/03/2024
Patient education: High cholesterol and lipids (Beyond the Basics)
INTRODUCTION
A high cholesterol level (also called "hypercholesterolemia") can significantly increase your risk of developing chest pain, heart attack, and stroke. Fortunately, a number of effective treatment options are available.
While total cholesterol has been a primary focus in the past, current guidelines focus on low-density lipoprotein (LDL) cholesterol. Higher levels of LDL cholesterol are associated with greater risk of heart attack, stroke, need for stenting or coronary bypass surgery, and death. Studies over the past 50 years have shown that lowering LDL cholesterol leads to lower rates of these cardiac events. A second type of cholesterol, triglycerides, also has been associated with increased risk. Conversely, high-density lipoprotein (HDL) cholesterol is associated with lower risk, although studies have suggested that changing HDL is not a way to change risk.
Cholesterol levels (notably LDL cholesterol and triglycerides) can almost always be lowered with a combination of weight loss (achieved with diet and exercise), and medications. As your level decreases, so does your risk of developing cardiovascular disease (CVD), including disease of the blood vessels supplying the heart (coronary artery disease), brain (cerebrovascular disease), and limbs (peripheral vascular disease). This results in a decrease in your risk of having a heart attack or stroke. Even if you already have established CVD, it's not too late to lower your risk.
A full explanation of what cholesterol is, how it affects your health, and when a level should be measured is available separately (see "Patient education: High cholesterol and lipids (Beyond the Basics)"). This topic will discuss when treatment is recommended, the available treatment options, and the risks, benefits, and effectiveness of each approach.
TYPES OF LIPIDS
The term "lipids" includes cholesterol and triglycerides, although there are other types of lipids, too. Standard lipid blood tests include a measurement of total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, and triglycerides.
Total cholesterol — A high total cholesterol level can increase your risk of cardiovascular disease. However, decisions about when to treat high cholesterol are usually based upon the level of LDL or HDL cholesterol rather than the level of total cholesterol (see 'LDL cholesterol' below and 'HDL cholesterol' below). In general:
●A total cholesterol level of less than 200 mg/dL (5.17 mmol/L) is normal.
●A total cholesterol level of 200 to 239 mg/dL (5.17 to 6.18 mmol/L) is borderline high.
●A total cholesterol level of 240 mg/dL (6.21 mmol/L) or greater is high.
The total cholesterol level can be measured any time of day. It is not necessary to fast (ie, avoid eating) before testing.
LDL cholesterol — This is sometimes called "bad" cholesterol, as high LDL levels raise your risk of cardiovascular disease. Some health care providers make decisions about how to treat hyperlipidemia based on the LDL cholesterol level. Your goal LDL cholesterol depends on your overall risk for a cardiovascular event (heart attack or stroke). Several factors affect your personal risk, including whether you have a history of cardiovascular disease and your risk of developing cardiovascular disease in the future (based on your age, s*x, and other major risk factors) (see 'Calculating your risk of cardiovascular disease' above). People at higher risk are often given a lower LDL cholesterol goal.
If your health care provider plans to measure your LDL cholesterol level, he or she may ask you to fast (avoid eating) for nine hours or longer in order to obtain an accurate result. A fasting test is more important if you have elevated triglycerides (>200 mg/dL) (see 'Triglycerides' below) or when your health care provider plans to measure your fasting blood sugar (glucose). However, in many cases, your LDL cholesterol can be measured even after you have eaten recently.
HDL cholesterol — Not all cholesterol is bad. High levels of HDL ("good") cholesterol is often an indicator of a lower risk of cardiovascular disease. A level of 60 mg/dL (1.55 mmol/L) or higher is excellent, while levels of HDL cholesterol less than 40 mg/dL (1.03 mmol/L) are considered lower than desirable. There is no treatment that lowers your risk for a cardiovascular event by raising HDL cholesterol.
As with total cholesterol, the HDL cholesterol can be measured with a blood test at any time, regardless of whether you have been fasting.
Non-HDL cholesterol — "Non-HDL" cholesterol includes LDL cholesterol as well as other types of plaque-forming lipids that do not fall into these categories. Non-HDL cholesterol accounts for the cholesterol carried by very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), and lipoprotein (a). It can be calculated by subtracting HDL cholesterol from total cholesterol. Since total cholesterol and HDL cholesterol can be measured accurately without fasting, so can non-HDL cholesterol. Non-HDL cholesterol is generally considered a better predictor of cardiovascular risk than LDL cholesterol.
An appropriate non-HDL cholesterol goal can be calculated by adding 30 mg/dL (0.78 mmol/L) to your LDL cholesterol goal. As discussed, the LDL cholesterol goal depends on a number of factors. (See 'LDL cholesterol' above.)
Triglycerides — High triglyceride levels are also associated with an increased risk of cardiovascular disease. Triglyceride levels are divided as follows:
●Normal – Less than 150 mg/dL (1.7 mmol/L)
●Mildly increased – 150 to 499 mg/dL (1.7 to 5.6 mmol/L)
●Moderately increased – 500 to 886 mg/dL (5.6 to 10.0 mmol/L)
●Very high – Greater than 886 mg/dL (10.0 mmol/L)
Triglycerides should be measured after fasting for at least nine hours. Some people with increased triglyceride levels may need treatment with medication.
WHEN SHOULD I START LIPID SCREENING?
Many expert groups have guidelines for lipid screening, which typically involves a "lipid profile" that includes blood tests to measure cholesterol and triglyceride levels. The guidelines differ in their recommendations about when to start screening, how frequently you should be screened, and when to stop.
Your health care provider can talk with you about your situation and whether and when you should be screened. An initial screening profile is often measured by the pediatrician during childhood, and should be measured again at age 18 years. Below are some commonly used guidelines.
For men:
●Regular lipid screening should start at age 35 years if there are no other risk factors for cardiovascular disease. (See 'Other risk factors for cardiovascular disease' above.)
●Screening should start at age 25 to 30 years if there are other risk factors, such as obesity, diabetes, high blood pressure, smoking, or family history of cardiovascular disease at a young age.
For women:
●Regular lipid screening should start at age 45 years if there are no other risk factors for cardiovascular disease. (See 'Other risk factors for cardiovascular disease' above.)
●Screening should start at age 30 to 35 years if there are other risk factors, such as obesity, diabetes, high blood pressure, smoking, or family history of cardiovascular disease at a young age.
The optimal time interval between screenings is uncertain. A reasonable approach is to repeat the lipid profile every five years for people who are unlikely to be candidates for treatment based on past results, and more frequently (eg, every three years) for people who are near or above the threshold for treatment.
There is no specific recommendation to stop screening at a particular age. However, once a person has had a lipid profile with normal results, it is probably of less value to continue screening beyond the age of 65, as lipid levels are less likely to increase after this point.
HIGH CHOLESTEROL TREATMENT
You can help lower your lipid levels with lifestyle changes, medications, or a combination of both. In certain cases, a health care provider will recommend a trial of lifestyle changes before recommending a medication. The best approach for you will depend on your individual situation, including your lipid levels, health conditions, risk factors, medications, and lifestyle.
Lifestyle changes — If you have high low-density lipoprotein (LDL) cholesterol, you should try to make some changes in your day-to-day habits, including reducing the amount of total and saturated fat in your diet, losing weight (if you are overweight or obese), getting regular aerobic exercise, and eating plenty of fruits and vegetables (see "Patient education: Exercise (Beyond the Basics)" and "Patient education: Diet and health (Beyond the Basics)"). A plant-based diet is an effective strategy to lowering LDL cholesterol.
The benefits of these lifestyle changes usually become evident within 6 to 12 months. However, the success of lipid lowering with lifestyle modification varies widely, and health care providers sometimes recommend beginning medication sooner.
Medications — There are many medications available to help lower elevated levels of LDL cholesterol. Each category of medication varies in how it works, how effective it is, and how much it costs. Your health care provider will recommend a medication or combination of medications based on your blood lipid levels and other individual factors.
Statins — Statins are one of the best-studied classes of medications and the most commonly used drugs for lowering LDL cholesterol. They are the most effective drugs for prevention of coronary heart disease, heart attack, stroke, and death. Available statins include atorvastatin (former brand name: Lipitor), rosuvastatin (former brand name: Crestor), and several other similar medications (table 1). Statins decrease the body's production of cholesterol and increase removal of cholesterol by the liver, so they reduce LDL cholesterol levels by as much as 25 to 55 percent. In addition, they can lower triglycerides. Statins may also reduce inflammation and may prevent heart attacks and strokes through this mechanism.
While most people tolerate statins well, there are some potential side effects, mainly muscle pain, aches, or weakness. Use of statins may also increase the risk of developing diabetes, although the risk is seen mostly in those with prediabetes, and the benefit in reduction on heart attack and stroke is about four times that of the risk of developing diabetes. Changing statins and using low doses often can avoid these issues, but if not, non-statin medications can be used to lower LDL cholesterol.
It is important to closely follow the dosing instructions for when to take statins; some are more effective when taken before bedtime while others should be taken with a meal. In addition, some foods, such as grapefruit or grapefruit juice, can increase the risk of side effects of statins. Most manufacturers recommend that people who take lovastatin, simvastatin, or atorvastatin consume no more than one-half of a grapefruit or 8 ounces of grapefruit juice per day.
Ezetimibe — Ezetimibe (brand name: Zetia) blocks the body's ability to actively transport cholesterol from food as well as cholesterol that the body produces internally. It lowers LDL cholesterol levels by 20 to 25 percent and has relatively few side effects. It is usually prescribed in combination with a statin but is also used alone in patients who cannot tolerate a statin. When used in combination with a statin after an acute coronary syndrome (eg, heart attack), ezetimibe provides a small additional reduction in the risk of having another cardiovascular event.
PCSK9 inhibitors — PCSK9 monoclonal antibody inhibitors are another class of drugs that lower LDL cholesterol levels (sample brand names: Praluent, Repatha) (table 1); they are given by injection under the skin every two to four weeks. They reduce cardiovascular events (such as heart attack or stroke) and potentially death. Aside from mild skin reactions at the site of injection, they have few side effects. Inclisiran (brand name Leqvio) is a PCSK9 inhibitor that is given by injection once, 90 days later, and then every six months. However, they are expensive and their use is limited to patients treated with maximal tolerated statins who have persistent elevations of LDL cholesterol.
Bile acid sequestrants — The bile acid sequestrants include colesevelam (brand name: Welchol), colestipol (brand name: Colestid), and cholestyramine (sample brand names: Prevalite, Questran) (table 1). These medications bind to bile acids in the intestine, reducing the amount of cholesterol the body absorbs from foods. They are used only occasionally. They lower LDL cholesterol only modestly (10 to 15 percent).
Side effects can be bothersome and may include nausea, bloating, cramping, and liver damage. Taking psyllium (a fiber supplement, such as Metamucil) can sometimes reduce the dose required and the side effects.
Bile acid sequestrants can interact with some medications, including as digoxin (brand name: Lanoxin) and warfarin (brand name: Jantoven), and with the absorption of fat-soluble vitamins (including vitamins A, D, K, and E). Taking these medications at different times of day can solve these problems in some cases.
Bempedoic acid — Bempedoic acid (brand name: Nexletol) is the newest lipid-lowering agent, and it is approved for lowering LDL cholesterol. It works by inhibiting cholesterol synthesis at a step before the HMG-CoA reductase or the enzyme inhibited by statin therapy. Bempedoic acid alone or in combination with a statin or ezetimibe (brand name: Nexlizet) lowers LDL cholesterol as well as other atherogenic proteins. Bempedoic acid can reduce the risk of cardiovascular events (such as heart attacks). Side effects include an increase in the incidence of gout, gallstones, kidney damage, and small increases in liver enzymes. Early studies reported Achilles tendon rupture as a rare side effect; however, this effect was not seen in a recent large trial.
Omega-3 — Oily fish, such as mackerel, herring, bluefish, sardines, salmon, and anchovies, contain two important fatty acids called docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Eating a diet that includes one to two servings of oily fish per week can lower triglyceride levels and reduce the risk of death from coronary heart disease.
Fish oil supplements, supplements with low-dose mixed fish oils (usually approximately 1 gram per day of combined DHA and EPA), had been thought to provide cardiac benefit, but large trials have found no significant benefit. As such, they are no longer recommended.
A specific high-dose preparation (4 grams per day of icosapent ethyl or 1800 mg per day of highly purified EPA) has been found to reduce the risk of heart attack, stroke, need for stent of bypass surgery, and cardiac death when used with a statin in people who have mild hypertriglyceridemia (149 to 500 mg/dL) and either established CVD or diabetes plus other cardiovascular risk factors.
A second study of a high-dose agent that had both EPA and DHA failed to provide benefit, suggesting that the EPA only preparation at the 4 g dose is important. However, the trials found that omega-3 fatty acid medications increase the risk of atrial fibrillation. Therefore, a discussion with your cardiologist on the net benefit or harm from taking fish oil supplements including icosapent ethyl is needed before starting this treatment.
Nicotinic acid (niacin) — Nicotinic acid is a vitamin that is available in immediate-release, sustained-release, and extended-release formulations (table 1). Nicotinic acid is rarely used for a high cholesterol. In most situations, ezetimibe or a PCSK9 inhibitor is tried before nicotinic acid. Historically, this agent used to be used to raise HDL cholesterol levels, but that is no longer recommended. It is sometimes used for patients with high lipoprotein(a) levels and LDL cholesterol that is refractory to more effective and better-tolerated medications (statins, ezetimibe and PCSK9 inhibitors).
Nicotinic acid is associated with many side effects, including flushing (when the face or body turns red and becomes warm), itching, nausea, numbness and tingling, and worsening of gout. This medication can also cause liver damage; people who use it require regular blood tests to monitor their liver function.
Due to these risks, the FDA no longer recommends its use with statins or cautious use.
Nutritional supplements
Red yeast rice — Red yeast rice is a fermented rice product that can lower serum cholesterol. Red yeast rice contains naturally occurring substances called monacolins that act to reduce cholesterol by a mechanism similar to that of statins. Although red yeast rice is effective for lowering total and LDL cholesterol, there is not evidence that it decreases rates of cardiovascular events or that it is safe to take long-term. Moreover, red yeast rice supplements are not standardized in the United States. Different commercial preparations vary widely in the amount of the active ingredient, and some commercial preparations have been shown to contain potentially toxic substances or lovastatin, a statin medication.
Soy protein — Soy protein contains isoflavones, which mimic the action of estrogen. A diet high in soy protein can slightly lower levels of total cholesterol, LDL cholesterol, and triglycerides and raise levels of high-density lipoprotein (HDL) cholesterol. However, normal protein should not be replaced with soy protein or isoflavone supplements in an effort to lower cholesterol levels.
Soy foods and food products (eg, tofu, soy butter, edamame, some soy burgers) are likely to have beneficial effects on lipids and cardiovascular health because they are low in saturated fats and high in unsaturated fats.
Garlic — Garlic has not been proven to be effective in lowering cholesterol.
Plant stanols and sterols — Plant stanols and sterols may act by blocking the absorption of cholesterol in the intestine. They are naturally found in some fruits, vegetables, vegetable oils, nuts, seeds, and legumes. They are also available in commercially prepared products such as margarine (Promise Active and Benecol), orange juice (Minute Maid Premium Heart Wise), and rice milk (Rice Dream Heart Wise) as well as dietary supplements (Benecol SoftGels and Cholest-Off).
Despite lowering cholesterol levels, there are no studies demonstrating a reduced risk of coronary heart disease in people who consume supplemental plant stanols and sterols. These products need to be studied more before they can be recommended.
Information about how to decide on treatment for hyperlipidemia, and the available treatment options, is available separately.
