Cardiology

Hyperlipidemia refers to increased levels of lipids (fats) in the blood, including cholesterol and triglycerides. Although hyperlipidemia does not cause symptoms, it can significantly increase your risk of developing cardiovascular disease, including disease of blood vessels supplying the heart (coronary artery disease), brain (cerebrovascular disease), and limbs (peripheral vascular disease). These conditions can in turn lead to chest pain, heart attacks, strokes, and other problems. Because of these risks, treatment is often recommended for people with hyperlipidemia.

Lipid levels can almost always be lowered with combination of diet, weight loss, exerciese, and medications. As lipid levels fall, so does the risk of developing cardiovascular disease (CVD), including disease of blood vessels supplying the heart (coronary artery disease), brain (cerebrovascular disease), and limbs (peripheral vascular disease). This results in a lower risk of suffering a heart attack or stroke. It is not too late if CVD is already present; Lipid-lowering treatment can be lifesaving.

LIPID TYPES

The term lipids includes cholesterol and triglycerides. There are many different types of lipid (also called lipoproteins). Blood tests can measure the level of your lipoproteins. The standard lipid blood tests include a measurement of total cholesterol, LDL (low density lipoproteins) and HDL (high density lipoproteins), 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.

  • 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 greater than or equal to 240 mg/dl (6.21 mmol/L is high.

 The total cholesterol level can be measured any time of day. it is not necessary to fast (avoid eating for 12 hours) before testing.

LDL Choloesterol --- Some health care providers make decisions about how to treat lipids based on the low density lipoprotein (LDL)  cholesterol (sometimes called "bad cholesterol"). High LDL cholesterol levels increase your risk of cardiovascular disease. If your health care provider uses this strategy, your goal LDL cholesterol will depend on several factors, inclulding any history of cardiovascular disease and your risk of developing cardiovascular disease in the future. (See 'Calculating risk' below.) People at higher risk are often assigned a lower LDL cholesterol goal.

In many cases, your LDL-cholesterol can be measured even after you have eaten recently.

10-year risk of developing coronary artery disease

The 10-year risk score is based on information from the Framingham Heart Study, a large study that has followed participants, as well as their children and grandchildren, for greater than 50 years. The 10-year risk can be calculated for women (calculator 1)  and for men.

Triglycerides --- High triglyceride levels are also associated with an increased risk of cardiovascular diseases, although this assocications is not typically important once other risk factors are taken into account. Triglyceride levels are divided as follows:

  • Normal - less than 150 mg/dL (1.69 mmol/L)
  • Borderline high - 150 to 199 mg/dL (1.69 to 2.25 mmol/L)
  • High - 200 to 499 mg/dL (2.25 to 5.63 mmol/L)
  • Very high - greater than 500 mg/dL (5.65 mmol/L)

Trigylcerides should be measured after fasting for 12 or 14 hours.

HDL cholesterol --- Not all cholesterol is bad. Elevated levels of HDL cholesterol actually lower the risk of cardiovascular disease. A level greater than or equal to 60 mg/dL or 1.55 mmol/L is excellent, while levels of HDL cholesterol less than 40 mg/dL or 1.03 mmol/L are lower than desired. There are not treatments for raising HDL cholesterol that has been proven to reduce the risk of heart attacks and strokes.

Similar to total cholesterol, the HDL-cholesterol can be measured on any blood specimen. It is not necessary to be fasting.

Non-HDL cholesterol --- Non-HDL cholesterol is calculated by subtracting HDL cholesterol from total cholesterol. Since total cholesterol and HDL cholesterol and HDL cholesterol can be measured without fasting, so can non-HDL cholesterol. Non-HDL cholesterol is a good predictor of cardiovascular risk and is a better predictor of risk than LDL cholesterol in people with type 2 diabetes and in women.

An appropriate non-HDL cholesterol goal can be calculated by adding 30mg/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.)

CALCULATING RISK

Risk calculators are typically based on large studies of populations that are followed to see who develops cardiovascular disease. One such study, the Framingham Heart Study, has followed participants, as well as their children and grandchildren, for more than 50 years. Data from the Framingham Heart Study are used in the following calculators of 10-year risk for cardiovascular disease for women (calculator 2) and for men (calculator 3), and data from a broader population were used (calculator 1) [1].

WHEN SHOULD I HAVE MY CHOLESTEROL LEVEL TESTED?

Many expert groups have guidelines for cholesterol screening. The guidelines differ in their recommendations about when to start screening, how frequently you should be screened, and when to stop.

One expert group, the United States Preventive Services Task Force recommends the following:

  • Lipid screening should start at age 35 in men without other risk factors for coronary artery disease and at age 20 to 35 in men with risk factors. These include men with:
  • Diabetes
  • A family history of heart disease in a close male relative younger than age 50 or a close female relative younger than age 60
  • A family history of high cholesterol
  • A personal history of multiple coronary disease risk factors (eg, smoking, high blood pressure).
  • Lipid screening should definitely start at age 45 and perhaps at age 20 in women with risk factors for coronary disease. No recommendation for or against screening was made for women without risk factors for coronary disease. Up To Date authors believe that even low risk women should be screened starting at age 45.
  • Those at risk for coronary disease should be treated based upon the results of their screening test.
  • Screening should include total cholesterol and HDL-cholesterol levels and can be measured anytime (with or without fasting).
  • The optimal time interval between screenings is uncertain; reasonable options include every five years, with a shorter interval for those with high-normal lipid levels and longer intervals for low-risk individuals with low or normal levels.
  • There is no recommendation to stop screening at a particular age.
  • Screening may be appropriate in older people who have never been screened, although screening a second or third time is less important in older people because lipid levels are less likely to increase after age 65.

WHO NEEDS TREATMENT FOR HIGH CHOLESTEROL?

The decision to start lipid-lowering treatment is made on a case-by-case basis. Healthcare providers consider current lipid levels, the presence or absence of cardiovascular disease (CVD), and other risk factors for CVD.

People with CVD — Several large trials have demonstrated that aggressive lipid lowering is beneficial in people with coronary heart disease. Many healthcare providers recommend treating all patients with CVD with high-dose statin therapy. People who have a heart attack (myocardial infarction or MI) are started on cholesterol-lowering medication while in the hospital and are advised to make lifestyle changes, regardless of their low-density lipoprotein (LDL) cholesterol level (see "Patient education: Heart attack recovery (Beyond the Basics)"). In addition to simply placing a patient on statin therapy, some healthcare providers recommend that lipid lowering treatment achieve specific goals in patients with known CVD:

  • A target LDL cholesterol level below 70 to 80mg/dL(1.81 to 2.07 mmol/L) is recommended for people who have CVD and have multiple major risk factors (eg, people with diabetes or who smoke).
  • A target LDL cholesterol level less than 100mg/dL(2.59 mmol/L) is recommended for people who have CVD but do not have many additional risk factors. Lifestyle changes as well as non statin medications may be recommended when LDL cholesterol levels are higher than 100 mg/dL (2.59 mmol/L).

These general guidelines may be modified by other individual factors.

People without CVD — People without a history of CVD also appear to benefit from lipid lowering therapy, although the treatments are not as aggressive as in patients with CVD. Many experts make recommendations, based on the global risk of developing CVD as predicted by as risk calculator (see "Patient education: High cholesterol and lipids (hyperlipidemia) (Beyond the Basics)," section on 'Calculating risk'). Some clinicians recommend treatment at a particular level of risk (such as a 7.5 percent or 10 percent risk of developing CVD over 10 years), while others may focus more on your individual preferences for taking medications to reduce risk. In either case, as with patients with CVD, when a medication is prescribed the initial choice is almost always a statin.

Other special groups

Hypertriglyceridemia — High triglycerides have not generally been thought to pose the same risk of CHD as LDL cholesterol. However, healthcare providers often recommend treatment for people with elevated triglyceride levels if they:

  • Have very high levels (>500 to 1000mg/dLor 5.65 to 11.3 mmol/L)
  • Also have high LDL cholesterol or low HDL cholesterol levels
  • Have a strong family history of CHD
  • Have other risk factors for CHD

Diabetes mellitus — People with diabetes (type 1 or 2) are at high risk of heart disease. Thus, an LDL level below 100 mg/dL (2.59 mmol/L) is recommended in many people with diabetes. (See "Patient education: Diabetes mellitus type 2: Overview (Beyond the Basics)".)

Elderly — The decision to treat high cholesterol levels in an elderly person depends upon the individual's chronologic age (age in years) and physiologic age (health, fitness). A person with a limited life span and underlying illness is probably not a good candidate for drug therapy. On the other hand, an otherwise healthy elderly person should not be denied drug therapy simply on the basis of age alone. In general, the treatment goals discussed above are followed for elderly people.

HIGH CHOLESTEROL TREATMENT OPTIONS

Lipid levels can be lowered with lifestyle changes, medications, or a combination of these approaches. In certain cases, a healthcare 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 — All patients with high low-density lipoprotein (LDL) cholesterol should try to make some changes in their day-to-day habits, by reducing total and saturated fat in the diet, losing weight (if overweight or obese), performing aerobic exercise, and eating a diet rich in fruits and vegetables.

The benefits of such lifestyle modifications usually become evident within 6 to 12 months. However, the success of lipid lowering with lifestyle modification varies widely, and healthcare providers sometimes elect to begin drug therapy before this time period is over.

Medications — There are many medications available to help lower elevated levels of LDL cholesterol and triglycerides, but only a few for increasing HDL cholesterol. Each category of medication targets a specific lipid and varies in how it works, how effective it is, and how much it costs. Your healthcare provider will recommend a medication or combination of medications based on blood lipid levels and other individual factors.

Statins — Statins are among the most powerful drugs for lowering LDL cholesterol and are the most effective drugs for prevention of coronary heart disease, heart attack, stroke, and death. Statins include lovastatin, pravastatin, simvastatin, fluvastatin, atorvastatin, and rosuvastatin. These medications decrease the body's production of cholesterol and can reduce LDL levels by as much as 20 to 60 percent. In addition, statins can lower triglycerides and slightly raise HDL cholesterol levels. Statins may prevent heart attacks and strokes in more ways than just lowering cholesterol levels. For instance, statins seem to help keep buildups in blood vessels (known as plaques) from rupturing. Plaque rupture is an important event that can lead to a heart attack.

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.

PCSK9 inhibitors — PCSK9 inhibitors are a newer class of drug that can also lower LDL cholesterol levels. Drugs in this class can also lower levels of other lipoproteins, such as lipoprotein(a), that can cause buildup of blood vessel plaques. The PCSK9 inhibitors include alirocumab and evolocumab, which are given by injection every two to four weeks. They have been shown to reduce LDL cholesterol by as much as 70 percent, and by as much as 60 percent in patients who are also on statin therapy. Experience with these drugs is limited and more study is needed to understand the longer-term effects; however, it appears that they can substantially reduce cardiovascular events (such as heart attack or stroke) and mortality.

Ezetimibe — Ezetimibe (brand name: Zetia) impairs the body's ability to absorb cholesterol from food as well as cholesterol that the body produces internally. It lowers LDL cholesterol levels and has relatively few side effects. When used in combination with a statin in treatment after an acute coronary syndrome (eg, heart attack), ezetimibe provides a small additional reduction in cardiovascular events.

Bile acid sequestrants — The bile acid sequestrants include cholestyramine, colestipol, and colesevelam. These medications bind to bile acids in the intestine, reducing the amount of cholesterol absorbed from foods.

Bile acid sequestrants may be recommended to treat mild to moderately elevated LDL cholesterol levels. However, side effects can be bothersome, and may include nausea, bloating, cramping, and liver injury. 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: Coumadin), 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.

Nicotinic acid (Niacin) — Nicotinic acid is a vitamin that is available in immediate-release, sustained-release, and extended-release formulations. Nicotinic acid may be recommended for people with elevated cholesterol levels that do not respond adequately despite maximum tolerated dosages of statins and for people with some types of familial hyperlipidemia, particularly those with high lipoprotein(a) levels. However, most patients taking statins should not take nicotinic acid.

  • Side effects — Nicotinic acid has several possible side effects, including flushing (when the face or body turns red and becomes warm), itching, nausea, and numbness and tingling. This medication can also injure the liver; patients who use it require regular monitoring of liver function.

Taking nicotinic acid with food and taking aspirin (325 to 650 mg) 30 minutes before can decrease the side effects. Side effects often improve after 7 to 10 days. The immediate-release formulation is more likely to produce side effects, but is also more effective at lowering cholesterol levels and less likely to injure the liver than certain sustained-release formulations. The sustained-release and extended-release formulations have fewer side effects. Nicotinic acid should be taken with food or shortly after ingesting the largest meal of the day.

Nicotinic acid can produce other side effects in some people. For example, it can blunt the body's reaction to insulin, which can increase blood sugar levels in diabetics. It can increase uric acid levels in people with gout and is not recommended for this group. Nicotinic acid can also produce low blood pressure in people taking vasodilator medications such as nitroglycerin, and it can sometimes worsen angina pectoris (chest pain). Nicotinic acid can also increase the risk of developing infections and bleeding.

Fibrates — Fibrate medications (gemfibrozil, fenofibrate and fenofibric acid) can lower triglyceride levels and raise HDL cholesterol levels.

Fibrates may be recommended for people with elevated triglyceride and cholesterol levels. Fibrates have been associated with muscle toxicity (causing muscle pain or weakness), especially when used by people with kidney insufficiency or when used in combination with a statin medication. Fenofibrate/fenofibric acid (brand names: Tricor, Triglide, Trilipex) are less likely to interact with statins than gemfibrozil, and are safer in people who must use both medications.

Nutritional supplements

Fish oil — Oily fish, such as mackerel, herring, bluefish, sardines, salmon, and anchovies, contain two important fatty acids, called DHA and EPA. Eating a diet that includes one to two servings of oily fish per week can reduce triglyceride levels and reduce the risk of death from coronary heart disease. Fish oil supplements are believed to have the same benefit. A daily 1 gram fish oil supplement may be recommended if you do not eat enough fish.

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 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, etc.) are likely to have beneficial effects on lipids and cardiovascular health because they are low in saturated fats and high in unsaturated fats.

Garlic — A large trial showed that garlic is not effective in lowering cholesterol [1]. In this study, participants with an elevated LDL took one of several types of garlic extract (raw, powdered, aged) or a placebo (inactive pill) six days per week for six months. At the end of the study, the LDL levels were not improved in the garlic group compared to the group that took the placebo. We do not recommend garlic to lower 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), rice milk (Rice Dream Heart Wise), as well as dietary supplements (Benecol SoftGels and Cholest-Off). The margarines cost about five times what ordinary margarines cost.

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. There is some evidence that these supplements might actually increase risk.

STICKING WITH TREATMENT

The treatment of high cholesterol and/or triglycerides is a lifelong process. Although medications can rapidly lower your levels, it often takes 6 to 12 months before the effects of lifestyle modifications are noticeable. Once you have an effective treatment plan and you begin to see results, it is important to stick with the plan. Stopping treatment usually allows lipid levels to rise again.

Most people who stop treatment do so because of side effects. However, there are a wide variety of medications available today, which should make it possible for most people to find an option that works for them. Talk with a healthcare provider if a specific medication is not working; he or she can recommend alternatives that are compatible with your lifestyle and beliefs.

Links

http://www.uptodate.com/contents/high-cholesterol-and-lipids-hyperlipidemia-beyond-the-basics