A blood test is used to measure cholesterol levels. A person's total cholesterol level includes measurements of LDL (bad cholesterol), HDL (good cholesterol), and triglycerides.
Over the past 2 to 3 years, a different approach to treating abnormal cholesterol levels has been developed. Previous guidelines recommended that doctors use specific target goals for LDL depending on patient risk factors. The newer guidelines take a different approach:
Guidelines recommend drug therapy based on a person's risk for heart disease, stroke, and other problems caused by hardening of the arteries:
The key lifestyle changes to improve unhealthy cholesterol levels are:
Lipids are the building blocks of the fats and fatty substances found in animals and plants. They are microscopic layered spheres of oil, which, in animals, are composed mainly of cholesterol, triglycerides, proteins (called lipoproteins), and phospholipids (molecules made up of phosphoric acid, fatty acids, and nitrogen). Lipids do not dissolve in water and are stored in the body to serve as sources of energy.
Cholesterol is present in all animal cells and in animal-based foods (not in plants). In spite of its bad press, cholesterol is an essential nutrient necessary for many functions, including:
Regardless of these benefits, when cholesterol levels rise in the blood, they can have dangerous consequences, depending on the type of cholesterol. Although the body acquires some cholesterol through diet, about two-thirds is manufactured in the liver, its production stimulated by saturated fat. Saturated fats are found in animal products (meat, egg yolks, and high-fat dairy products) and tropical plant oils (palm, coconut).
Saturated fats are found predominantly in animal products, such as meat and dairy products, and are strongly associated with higher cholesterol levels. Tropical oils -- such as palm, palm kernel, coconut, and cocoa butter -- are also high in saturated fats.
Triglycerides are composed of fatty acid molecules. They are the basic chemicals contained in fats in both animals and plants. High levels of triglycerides, especially in combination with low levels of HDL, are associated with increased risk for heart disease, stroke, diabetes, and fatty liver disease.
Lipoproteins are protein spheres that transport cholesterol, triglyceride, or other lipid molecules through the bloodstream. Most of the vascular effects of cholesterol and triglyceride actually depend on lipoproteins.
Lipoproteins are categorized into five types according to size and density. They can be further defined by whether they carry cholesterol or triglycerides.
These are the lipoproteins commonly referred to as cholesterol.
Low Density Lipoproteins (LDL), the "Bad" Cholesterol
The main villain in the cholesterol story is low-density lipoprotein (LDL). Heart disease is least likely to occur among people with the lowest LDL levels. Lowering LDL is the primary goal of cholesterol drug and lifestyle therapy.
Low-density lipoprotein (LDL) transports about 75% of the blood's cholesterol to the body's cells. It is normally harmless. However, if it is exposed to a process called oxidation, LDL can penetrate and interact dangerously with the walls of the artery, producing a harmful inflammatory response. Oxidation is a natural process in the body that occurs from chemical combinations with unstable molecules. These molecules are known as oxygen-free radicals or oxidants.
In response to oxidized LDL, the body releases various immune factors aimed at protecting the damaged arterial walls. Unfortunately, in excessive quantities they cause inflammation and promote further injury to the areas they target.
High Density Lipoproteins (HDL), the "Good" Cholesterol
High density lipoprotein (HDL) appears to benefit the body in several ways:
HDL helps keep arteries open and reduces the risk for heart attack. High levels of HDL (above 60 mg/dL) may be nearly as protective for the heart as low levels of LDL. HDL levels below 40 mg/dL are associated with an increased risk of heart disease.
Triglycerides interact with HDL cholesterol in such a way that HDL levels fall as triglyceride levels rise. High triglycerides may pose other dangers, regardless of cholesterol levels. For example, they may be associated with blood clots that form and block the arteries. High triglyceride levels are also associated with the inflammatory response -- the harmful effect of an overactive immune system that can cause considerable damage to cells and tissues, including the arteries. Very high triglycerides can also cause pancreatitis a potentially life-threatening condition.
Unhealthy cholesterol levels (low HDL, high LDL, and high triglycerides) increase the risk for heart disease and heart attack. Some risk factors for cholesterol can be controlled (such as diet, exercise, and weight) while others cannot (such as age, gender, and family history).
From puberty on, men tend to have lower HDL (good cholesterol) levels than women. One reason is that the female sex hormone estrogen is associated with higher HDL levels. Because of this, premenopausal women generally have lower rates of heart disease than men.
After menopause, as estrogen levels decline, women catch up in their rates of heart disease. Throughout the post-menopausal years, HDL levels decrease and LDL (bad cholesterol) and triglyceride levels increase. For men, LDL and triglyceride levels also rise as they age and the risks for heart disease increase as well. (There is some evidence that high triglyceride levels carry more risks for women than men.) Heart disease is the main cause of death for both men and women.
Children and Adolescents
Children who have abnormal cholesterol levels are at increased risk of developing heart disease later in life. However, it is difficult to distinguish "normal" cholesterol levels in children. Cholesterol levels which are normally very low at birth tend to naturally rise sharply until puberty, decrease sharply, and then rise again later in life.
Genetics can play a major role in determining a person's blood cholesterol levels. (Children from families with a history of premature heart disease should be tested for cholesterol levels after they are 2 years old.) Genes may influence whether a person has low HDL levels, high LDL levels, high triglycerides, or high levels of other lipoproteins, such as lipoprotein(a). There are several types of inherited cholesterol disorders.
Familial hypercholesterolemia (FH)
FH is a genetic disorder that causes high cholesterol levels, particularly LDL, and premature heart disease. There are two forms of FH:
Familial lipoprotein lipase deficiency is group of rare genetic disorders that causes depletion of the enzyme lipoprotein lipase. This enzyme helps in the removal of lipoproteins that are rich in triglycerides. People who are deficient in lipoprotein lipase have high levels of cholesterol and fat in their blood.
The primary dietary elements that lead to unhealthy blood cholesterol include saturated fats (found mainly in red meat and high-fat dairy products) and trans fatty acids (found in fried foods and some commercial baked food products). Shellfish and egg yolks are also high in dietary cholesterol. Large amounts of added sugars raise triglyceride levels.
Being overweight or obese increases the risks for unhealthy cholesterol levels.
Lack of exercise can contribute to weight gain, decreases in HDL levels, and increases in LDL, triglycerides, and total cholesterol levels.
Smoking reduces HDL cholesterol and promotes build-up of fatty deposits in the coronary arteries.
Heavy consumption of alcohol can increase triglyceride levels.
In the U.S., obesity is at epidemic levels in all age groups. The effect of obesity on cholesterol levels is complex. Overweight individuals tend to have high triglyceride and LDL levels and low HDL levels. This combination is a risk factor for heart disease. Obesity also causes other effects such as high blood pressure and an increase in inflammation that pose major risks to the heart.
Obesity is particularly dangerous when it is one of the components of the metabolic syndrome. Metabolic syndrome consists of:
Metabolic syndrome is a pre-diabetic condition that is significantly associated with heart disease and higher mortality rates from all causes. Obesity is also strongly associated with type 2 diabetes, which itself poses a significant risk for high cholesterol levels and heart disease.
Children who are overweight are at higher risk for high triglycerides and low HDL, which may be directly related to later unhealthy cholesterol levels. Childhood LDL levels and body mass index (BMI) are strongly associated with cardiovascular risk during adulthood. Overweight and obese children who have high cholesterol should also get tested for high blood pressure, diabetes, and other conditions associated with metabolic syndrome.
High Blood Pressure
High blood pressure (hypertension) does not affect your cholesterol level, does contribute to the thickening of the heart's blood vessel walls, which can worsen atherosclerosis (accumulated deposits of cholesterol in the blood vessels). High blood pressure, high cholesterol, and diabetes all act together to increase the risk for developing heart disease.
Low thyroid levels (hypothyroidism) are associated with elevated total and LDL cholesterol and triglyceride levels. Treating the thyroid condition can significantly reduce cholesterol levels. Research is mixed on whether mild hypothyroidism (subclinical hypothyroidism) is associated with unhealthy cholesterol levels.
Hypothyroidism is a decreased activity of the thyroid gland which may affect all body functions. In this condition, the rate of metabolism slows, causing mental and physical sluggishness. The most severe form of hypothyroidism is myxedema, which is a medical emergency.
Polycystic Ovarian Syndrome
Women with this endocrine disorder may have increased risks for high triglyceride and low HDL levels. This risk may be due to the higher levels of the male hormone testosterone associated with this disease.
Certain medications such as specific antiseizure drugs, corticosteroids, and isotretinoin (Accutane) may increase lipid levels.
Atherosclerosis is a common disorder of the arteries. Fat, cholesterol, and other substances collect in the walls of arteries. Larger accumulations are called atheromas or plaque and can damage artery walls and block blood flow. Severely restricted blood flow in the heart muscle leads to symptoms such as chest pain.
Unhealthy cholesterol, particularly low-density lipoprotein (LDL) cholesterol, forms a fatty substance called plaque, which builds up on the arterial walls of the heart. Smaller plaques remain soft, but older, larger plaques tend to develop fibrous caps with calcium deposits.
The long-term result is atherosclerosis, commonly called hardening of the arteries. The heart is endangered in two ways by this process:
This process is accelerated by other risk factors including high blood pressure, smoking, obesity, diabetes, and a sedentary lifestyle. When more than one of these risk factors is present, the risk is compounded.
Coronary Artery Disease
The end result of atherosclerosis is coronary artery disease. Coronary artery disease, sometimes referred to simply as "heart disease" or ischemic heart disease, is the leading cause of death in the U.S.
Studies consistently report a higher risk for death from heart disease with high total cholesterol levels (190 mg/dL and higher). The higher the cholesterol, the greater the risk.
Peripheral artery disease (PAD) is caused by the buildup of plaque in the feet, legs, hands, and arms. It most often occurs in the legs. PAD is associated with atherosclerosis. The risk for PAD increases by 5% to 10% with every 10 mg/dL increase in total cholesterol levels. Lower levels of HDL and high triglyceride levels also increase the risk for PAD.
Having adequate levels of HDL may be the most important lipid-related factor for preventing ischemic stroke, a type of stroke caused by blockage of the arteries that carry blood to the brain. HDL may even reduce the risk for hemorrhagic stroke, a much less common type of stroke caused by bleeding in the brain that is associated with low overall cholesterol levels.
The build-up of plaque in the internal carotid artery may lead to narrowing and irregularity of the artery's channel, preventing proper blood flow to the brain. More commonly, as the narrowing worsens, clots form on the plaque and can break free, travel to the brain, and block blood vessels that supply blood to the brain. This leads to stroke, with possible paralysis, speech impairment, or other deficits.
The effects of high total cholesterol and LDL levels on ischemic stroke are less clear. Some research suggests that the risk for ischemic stroke increases when total cholesterol is high. Other studies suggest that high cholesterol poses a risk for stroke only when specific proteins associated with inflammation are present.
There are no warning signs for high LDL and other unhealthy cholesterol levels. When symptoms finally occur, they usually take the form of angina (chest pain) or heart attack in response to the buildup of atherosclerotic plaque in the heart arteries. When buildups occur in leg arteries, patients may have discomfort with walking (called "claudication").
Atherosclerosis is a disease of the arteries in which fatty material is deposited in the vessel wall, resulting in narrowing and eventual impairment of blood flow. Severely restricted blood flow in the arteries to the heart muscle leads to symptoms such as chest pain. Atherosclerosis shows no symptoms until a complication occurs.
Blood tests can easily measure cholesterol levels. A blood test for cholesterol should include the entire lipoprotein profile: LDL, total cholesterol, HDL, and triglycerides. It is also possible to measure LDL levels by themselves, but LDL levels can be reliably calculated using the other values, unless the triglycerides are very high.
To obtain an accurate cholesterol reading, doctors advise:
Periodic cholesterol testing is recommended in all adults, but the major national guidelines differ on the age to start testing.
Screening with a fasting lipid profile is recommended for children who:
Patients already being treated for high cholesterol may have tests periodically to ensure treatment is working and is being tolerated (especially by the liver). However the new guidelines de-emphasize repeat testing.
If the risk-based calculation for statin therapy is uncertain, the doctor may order three additional tests recommended by the ACC/AHA guidelines:
Other possible tests your doctor may order include:
Lifestyle changes (such as diet, weight control, exercise, and smoking cessation) are the first line of defense for treating unhealthy cholesterol levels. If levels and other risk factors still remain high, drug treatment is an effective next step.
Statins are the first-line drugs for lowering high LDL levels, and reducing the risk for heart disease and stroke. A statin drug is used along with healthy lifestyle habits, not in place of them.
In the past, the choices regarding when and how aggressively to treat hyperlipidemia was driven largely by your LDL and HDL cholesterol level. Doctors advised most adults to target a total cholesterol level of less than 200 mg/dL and an LDL of less than 100 mg/dL. In some people at very high risk, the targeted level was even lower.
However, experts on cholesterol realized there was no solid scientific evidence to support the target number treatment approach. As a result, newer guidelines take what is called a risk-based approach when treating the patient, rather than just treating the lab result. Along with the cholesterol level, other factors which may increase a patient's risk for heart disease are considered. All of this information is then used to decide the following:
The benefit of treating unhealthy cholesterol levels is highest for those who already have symptoms or a history of cardiovascular disease.
Primary prevention refers to treatment of people who have no known cardiovascular disease but are thought to be at increased risk.
For older adults, other factors must be considered. Adults over 75 years who are otherwise healthy may be a candidate for drug therapy for elevated cholesterol levels. However, careful consideration should take place for older adults who appear to have a limited life span due to other illnesses that are present.
Two risk calculators are available and can be used to help your health care provider and you decide.
Your discussion with your doctor should begin with an understanding of your risk profile. You should know your 10-year risk percentage for heart disease and stroke. This percentage number is more important than your cholesterol numbers.
The ACC/AHA recommends that doctors enter the following factors into a "risk calculator" to determine a patient's overall risk for cardiovascular disease:
If the formula indicates a 7.5% or higher risk for having a heart attack or stroke within the next 10 years, then the doctor may recommend treatment with a cholesterol-lowering statin drug. (This risk calculator is designed for people age 40 to 79 years old who do not have existing or prior heart disease.)
If the risk calculation seems uncertain, a doctor may consider additional factors. They include high LDL levels (greater than 160 mg/dL), family history of premature heart disease, increased lifetime heart disease risk, and sometimes the results of other diagnostic tests such as C-reactive protein level, ankle-brachial index, and coronary artery calcification score.
The new cholesterol treatment guidelines are controversial in the medical community. Doctors have debated the accuracy of the risk calculator, and the ACC/AHA's abandoning its former treat-to-target goal guidelines. Some doctors feel that the calculator overestimates risk, and makes more healthy patients eligible for unnecessary statin drug treatment.
The ACC/AHA's position is that individual patient preferences are an important part of the new guidelines. All treatment options should begin with a conversation between the doctor and patient, including discussing how patients feel about the risks and benefits of drug therapy. In addition, lifestyle modification is the most important component for heart disease risk reduction. As with other guidelines, recommendations are likely to change in the future when more information is available from large research studies.
The most important first step for improving cholesterol levels and reducing the risk for heart disease and stroke is to make heart-healthy lifestyle changes. Even when drug therapy is used, lifestyle measures are critical companions.
The main lifestyle principles to reduce unhealthy cholesterol levels include:
The American College of Cardiology (ACC) and American Heart Association (AHA) joint dietary guidelines for reducing unhealthy cholesterol levels recommend:
There are many dietary approaches for protecting heart health, such as the Mediterranean Diet, which emphasizes fruits, vegetables, and healthy types of fats. The DASH diet is very effective for patients with high blood pressure and others who need to restrict sodium (salt) intake. Other heart-healthy diet plans include the American Heart Association diet and the USDA Food Pattern.
Doctors generally agree on the following recommendations for heart protection:
After starting a heart healthy diet, it generally takes an average of 3 to 6 months before any noticeable reduction in cholesterol occurs. However, some people see improved levels in as few as 4 weeks.
A healthy weight is very important for healthy cholesterol levels. For people who are overweight or obese, losing even a modest amount of weight has significant health benefits -- even if an ideal weight is not achieved. There is a direct relationship between the amount of weight lost and an improvement in cholesterol.
In particular, triglyceride is closely linked to weight: a sustained 3% to 5% weight loss can significantly reduce unhealthy triglyceride levels. Even greater amounts of weight loss can help improve LDL and HDL levels. Weight loss also helps reduce the need for blood pressure medication, improve blood glucose (sugar) levels, and lower the risk for developing type 2 diabetes.
Obesity is now considered and treated as a disease, not a lifestyle issue. Doctors' understanding of weight issues has evolved. Scientific evidence has shown that weight gain is a complex process, and weight loss involves more than simple will power. What is clear is that excess weight contributes to many health problems, including increased risks for cardiovascular disease conditions.
Your doctor should check your body mass index (BMI) at least once a year. The BMI estimates how much you should weigh based on your height:
Guidelines recommend your doctor create an individualized weight loss plan for you if you are overweight or obese. The plan should include three components:
A weight loss of 5% to 10% within the first 6 months of starting these changes can help improve cholesterol levels and other health indicators. If you have risk factors for heart disease or diabetes and do not achieve weight loss from diet and lifestyle changes alone, your doctor may recommend adding a prescription medication to your weight loss plan. For patients who have a very high BMI and several cardiovascular risk factors (such as diabetes and high blood pressure), bariatric surgery may be considered.
Inactivity is a major risk factor for coronary artery disease, on par with smoking, unhealthy cholesterol, and high blood pressure. In fact, studies suggest that people who change their diet in order to control cholesterol only achieve a lower risk for heart disease when they also follow a regular aerobic exercise program. Resistance (weight) training offers a complementary benefit to aerobics.
Even moderate exercise reduces the risk of heart attack and stroke. Current guidelines recommend at least 40 minutes of moderate-intensity physical activity on three or more days per week for a total of 200 to 300 minutes per week.
Cigarette smoking lowers HDL and is directly responsible for many deaths from heart disease. The importance of breaking this habit cannot be emphasized enough. Once a person quits smoking, HDL cholesterol levels rise within weeks or months to levels that are equal to their nonsmoking peers. Passive smoking also reduces HDL levels and increases the risk of heart disease in people exposed to second-hand smoke. Cigarette smoking is also associated with high blood pressure.
A number of studies have found heart protection from moderate intake of alcohol (one or two glasses a day). Moderate amounts of alcohol may help raise HDL levels. Although red wine is most often cited for healthful properties, any type of alcoholic beverage appears to have similar benefit. People with high triglyceride levels should drink sparingly, or not at all, because even small amounts of alcohol can significantly increase blood triglycerides. Pregnant women, anyone who cannot drink moderately, and people with liver disease should not drink at all. Because alcohol can be toxic to the heart muscle, some patients with heart disease, specifically heart failure, may be counseled to avoid alcohol.
Manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.
The following natural remedies are of interest for cholesterol control:
Statins are the most effective drugs for lowering LDL (bad cholesterol) levels and reducing the risk for heart disease and stroke. Statins inhibit the liver enzyme HMG-CoA reductase, which the body uses to manufacture cholesterol.
Current guidelines from the American College of Cardiology and American Heart Association recommend a statin drug as the first-line drug treatment for patients at risk for cardiovascular disease. Other cholesterol-lowering medications are not as effective as statins and are not recommended, except in rare cases.
Depending on your LDL cholesterol level, presence of atherosclerotic heart disease, 10-year risk for heart disease, and whether or not you have diabetes, your doctor will recommend either a moderate-intensity or high-intensity statin therapy dosage plan. The exact dosage will depend on the statin drug the doctor prescribes for you.
Once you have been started on a statin the recommended dosage is maintained. For the most part, there is no need to monitor LDL levels for response.
If a particular statin drug does not work for you, or if you experience significant side effects, your doctor may switch you to a different statin drug. In general, if multiple statins are not tolerated, other statin lowering medicines are generally not recommended.
Statins approved in the U.S. include:
Some statins come as fixed-dose combination drugs, which combine two drugs in one pill. Examples include sitagliptin/simvastatin (Juvisync), amlodipine/atorvastatin (Caduet), and ezetimibe/simvastatin (Vytorin).
Statin side effects may include diarrhea, constipation, upset stomach, muscle and joint pain, tendon problems, headache, fatigue, and forgetfulness or memory loss. More serious side effects include liver and muscle damage. Patients should immediately tell their doctor about any unusual muscle discomfort or weakness, fever, nausea or vomiting, or darkening of urine color.
Statins can affect the results of liver tests. Liver enzyme tests should be performed before starting statin therapy. Liver damage is a rare but can occur, particularly at higher doses. Tell your doctor if you have symptoms that indicate liver problems such as unusual fatigue, loss of appetite, upper belly pain, dark-colored urine or yellowing of the skin or whites of the eyes.
A specific safety concern with statins is an uncommon muscle disease called myopathy, in which a patient may experience muscle pains and certain lab tests may be elevated. Severe myopathy called rhabdomyolysis can lead to kidney failure, but fortunately its occurrence is very rare. The risk for myopathy/rhabdomyolysis is highest at higher doses and in older people (over 65 years), those with hyperthyroidism, and those with renal insufficiency (kidney disease).
Rosuvastatin (Crestor) may in particular increase the risk for myopathy, especially when given at the highest dose level (40 mg). The FDA advises that patients should not start therapy at a high dose. In addition, people of Asian heritage appear to metabolize the drug differently and should start treatment at the lowest rosuvastatin dose (5 mg) and 20mg is generally considered the maximum dose for these patients. Maximal doses of simvastatin and lovastatin also appear to increase the risk of myopathy.
Other Safety Concerns
Statins are recommended as the best drugs for improving cholesterol and lipid levels in people with type 1 or type 2 diabetes. However, they may increase blood glucose levels in some patients, especially when taken in high doses. They may also increase the risk for developing type 2 diabetes in patients with risk factors.
There is evidence that statins may increase the risk for developing cataracts.
Interactions with Drugs and Food
Statins may have some adverse interactions with other drugs. Patients should tell their doctors about any other medications they are taking. Medications that should not be taken along with statins include protease inhibitors, telaprevir, cyclosporine, macrolide antibiotics, and certain antifungals. Grapefruit juice and Seville oranges can increase the blood levels of certain statins.
Statins are the primary drugs for treating cholesterol and reducing cardiovascular disease risk. They have replaced the other drugs that were used for lowering cholesterol. These other drugs are still available but the value of their use when statins have not been tolerated or successful enough remains unclear.
Fibrates, also called fenofibrates, are generally reserved for patients with extremely high triglyceride levels or patients with high cholesterol who cannot tolerate a statin drug.
Gemfibrozil (Lopid, generic) is the most commonly prescribed fibrate. Other fibrates include fenofibrate (TriCor, Lofibra) and fenofibric acid (Trilipix). These drugs have many side effects. They can cause gallstones, abnormal heart rhythms, and muscle problems (myopathy), which may lead to kidney damage. A fibrate should only be carefully used in combination with a statin because of increased risk for myopathy.
For many years, high doses of niacin (nicotinic acid or vitamin B3) were considered a treatment option for low HDL cholesterol and high LDL cholesterol and triglyceride levels. Research now suggests that niacin does not add to the benefit of a statin alone for reducing the risk of cardiovascular events, including heart attacks and stroke. In addition, niacin can cause unpleasant and potentially dangerous side effects. Therefore, its use has been declining.
Bile-Acid Binding Drugs
Bile-acid binding drugs are also known as bile acid resins or bile acid sequestrants. They reduce LDL levels. Brands include cholestyramine (generic), colesevelam (Welchol), and colestipol (Colestid, generic).
Bile acid resins commonly cause constipation, heartburn, gas, and other gastrointestinal problems, side effects that many people cannot tolerate. These drugs may increase the risk for osteoporosis, elevate triglyceride levels, and interfere with the absorption of other medications.
Ezetimibe (Zetia) blocks absorption of cholesterol that comes from food. It helps reduce LDL cholesterol, but not as well as statin drugs. One trial showed a benefit to patients of Ezetimibe added to statin therapy following an acute coronary syndrome. Vytorin is a combination of ezetimibe and the statin simvastatin in a single pill. Liptruzet combines ezetimibe and the statin atorvastatin in a single pill.
Prescription Fish Oil Supplements
Lovaza and Vascepa are prescription forms of omega-3 fish oil, which may be prescribed to help lower triglyceride in people who have very high levels. Recent research has questioned the benefits of fish oil supplements for preventing heart attack and stroke.
Mipomersen (Kynamro) and lomitapide (Juxtapid) are approved specifically for treatment of homozygous familial hypercholesterolemia, a very rare genetic condition that can cause heart attack and stroke before the age of 30.
Proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors
A new group of drugs that inhibit a certain enzyme have been released. These drugs not only are able to reduce LDL cholesterol by 60% to 70%, but also appear to reduce the rate of heart attack, death from heart disease, and mortality in all causes.
Two drugs have been approved -- evolocumab and alirocumab. They are a type of drug called monoclonal antibodies. These drugs are quite expensive. Their exact role in the treatment of elevated LDL cholesterol levels remains to be fully determined. Currently they are more likely to be used for patients with inherited cholesterol disorders and those who are unable to take statin drugs.
AIM-HIGH Investigators, Boden WE, Probstfield JL, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365(24):2255-2267. PMID: 22085343 www.ncbi.nlm.nih.gov/pubmed/22085343.
Berglund L, Brunzell JD, Goldberg AC, et al. Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012;97(9):2969-2989 PMID: 22962670 www.ncbi.nlm.nih.gov/pubmed/22962670.
Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe added to statin therapy after acute coronary syndromes. New Engl J Med. 2015;372:2387-2397. PMID: 26039521 www.ncbi.nlm.nih.gov/pubmed/26039521.
Chamberlain JJ, Rhinehart AS, Shaefer CF Jr, Neuman A. Diagnosis and Management of Diabetes: Synopsis of the 2016 American Diabetes Association Standards of Medical Care in Diabetes. Ann Intern Med. 2016;164(8):542-552. PMID: 26928912 www.ncbi.nlm.nih.gov/pubmed/26928912.
Draft Recommendation Statement Statin Use for the Primary Prevention of Cardiovascular Disease in Adults: Preventive Medication. U.S. Preventive Services Task Force. www.uspreventiveservicestaskforce.org/Page/Document/draft-recommendation-statement175/statin-use-in-adults-preventive-medication1.
Eckel RH, Jakicic JM, Ard JD, et al. 2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63(25 Pt B):2960-2984. PMID: 24239922 www.ncbi.nlm.nih.gov/pubmed/24239922.
Fox CS, Golden SH, Anderson C, et al. Update on Prevention of Cardiovascular Disease in Adults With Type 2 Diabetes Mellitus in Light of Recent Evidence: A Scientific Statement From the American Heart Association and the American Diabetes Association. Circulation. 2015;132(8):691-718. PMID: 26246173 www.ncbi.nlm.nih.gov/pubmed/26246173.
Gaziano JM, Ridker PM, Libby P. Primary and secondary prevention of coronary heart disease. In: Bonow RO, Mann DL, Zipes DP, Libby P, Braunwald E, eds. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine. 9th ed. Philadelphia, PA: Elsevier Saunders; 2012:chap 49.
Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63(25 Pt B):2935-2959.
Hartley L, May MD, Loveman E, Colquitt JL, Rees K. Dietary fibre for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2016;1:CD011472. PMID: 26758499 www.ncbi.nlm.nih.gov/pubmed/26758499.
Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. J Am Coll Cardiol. 2014;63(25 Pt B):2985-3023. PMID: 24239920 www.ncbi.nlm.nih.gov/pubmed/24239920.
Leuschen J, Mortensen EM, Frei CR, et al. Association of statin use with cataracts: a propensity score-matched analysis. JAMA Ophthalmol. 2013;131(11):1427-1434. PMID: 24052188 www.ncbi.nlm.nih.gov/pubmed/24052188.
Lee JW, Morris JK, Wald NJ. Grapefruit Juice and Statins. Am J Med. 2016; 129(1):26-29. PMID: 26299317 www.ncbi.nlm.nih.gov/pubmed/26299317.
Lloyd-Jones DM, Hong Y, Labarthe D, et al. Defining and setting national goals for cardiovascular health promotion and disease reduction: The American Heart Association's strategic impact goal through 2020 and beyond. Circulation. 2010; 121:586-613. PMID: 20089546 www.ncbi.nlm.nih.gov/pubmed/20089546.
McGuinness B, Craig D, Bullock R, Passmore P. Statins for the prevention of dementia. Cochrane Database Syst Rev. 2016;1:CD003160. PMID: 26727124 www.ncbi.nlm.nih.gov/pubmed/26727124.
Miller M, Stone NJ, Ballantyne C, et al. Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2011;123(20):2292-2333. PMID: 21502576 www.ncbi.nlm.nih.gov/pubmed/21502576.
Naci H, Brugts J, Ades T. Comparative tolerability and harms of individual statins: a study-level network meta-analysis of 246 955 participants from 135 randomized, controlled trials. Circ Cardiovasc Qual Outcomes. 2013;6(4):390-399. PMID: 23838105 www.ncbi.nlm.nih.gov/pubmed/23838105.
Navarese EP, Kolodziejczak M, Schulze V, et al. Effects of Proprotein Convertase Subtilisin/Kexin Type 9 Antibodies in Adults With Hypercholesterolemia: A Systematic Review and Meta-analysis. Ann Intern Med. 2015; 163(1):40-51. PMID: 25915661 www.ncbi.nlm.nih.gov/pubmed/25915661.
Nordestgaard BG, Varbo A. Triglycerides and cardiovascular disease. Lancet. 2014;384(9943):626-635. PMID: 25131982 www.ncbi.nlm.nih.gov/pubmed/25131982.
Pencina MJ, Navar-Boggan AM, D'Agostino Sr RB, et al. Application of new cholesterol guidelines to a population-based sample. N Engl J Med. 2014;370(15):1422-1431. PMID: 24645848 www.ncbi.nlm.nih.gov/pubmed/24645848.
Robinson JG, Farnier M, Krempf M, et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372(16):1489-1499.PMID: 25773378 www.ncbi.nlm.nih.gov/pubmed/25773378.
Strandberg TE, Kolehmainen L, Vuorio A. Evaluation and treatment of older patients with hypercholesterolemia: a clinical review. JAMA. 2014; 312(11):1136-1144. PMID: 25226479 www.ncbi.nlm.nih.gov/pubmed/25226479.
Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63(25 Pt B):2889-2934. PMID: 24239923 www.ncbi.nlm.nih.gov/pubmed/24239923.
Stone NJ, Robinson JG, Lichtenstein AH, et al. Treatment of blood cholesterol to reduce atherosclerotic cardiovascular disease risk in adults: synopsis of the 2013 American College of Cardiology/American Heart Association cholesterol guideline. Ann Intern Med. 2014;160(5):339-343. PMID: 24474185 www.ncbi.nlm.nih.gov/pubmed/24474185.
Reviewed By: Michael A. Chen, MD, PhD, Associate Professor of Medicine, Division of Cardiology, Harborview Medical Center, University of Washington Medical School, Seattle, WA. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the A.D.A.M. Editorial team.