HEART DISEASE

Cardiovascular disease is the leading cause of mortality worldwide. As cigarette smoking continues to be a status symbol in developing countries, this ranking is expected to continue well into twenty-first century. Heart disease rates increase with age, and older adults have worse outcomes and face special problems, including unusual disease presentation, increasing complications, and particular effects on daily activities and quality of life.

The heart is a muscle in the center of the chest. It is approximately the size of a fist and pumps blood throughout the body, working continuously and requiring a large blood supply. The heart can function through a large range of demands, from sleep to vigorous activity.

Ischemic heart disease

With increasing age, narrowings may develop in the coronary arteries that lead to the heart. This reduced blood supply causes ischemia (insufficient blood supply for the heart's work) and may produce chest pain or angina. Sudden blockages will result in a heart attack, also known as myocardial infarction (MI).

The incidence of heart disease begins to increase in men after the age of forty-five and in women after the age of fifty-five, but the rate for women tends to equal that of men after the age of seventy. It was once believed that hormone replacement therapy would protect women from heart disease, but more recent studies suggest this is not true. The Heart and Estrogen/Progestin Replacement Study (HERS) showed no benefit, as well as an increased risk of blood clots in the leg (deep vein thrombosis) and of gallbladder disease. Along with age, male gender, family history, and ethnicity are nonmodifiable risk factors for heart disease.

The most modifiable risk factor for heart disease is smoking, which leads to increased obstruction of the coronary arteries. Each cigarette also causes spasms in these arteries. Smokers have twice the risk of heart attacks as nonsmokers, and death rates for heavy smokers are two to three times that of nonsmokers. Quitting smoking at any age likely confers benefit. This implies that it reduces disease progression and reduces the risk of MI and stroke; it also leads to a 25 to 50 percent reduction in mortality and recurrent heart attacks (MI).

There are many aids available to help quit smoking. These include nicotine gum (although people with dentures find the gum difficult to use). A nicotine patch is also available. Success rates for quitting using nicotine replacement are 18 to 25 percent, compared to 5 to 10 percent without nicotine replacement. Patients with heart disease may be concerned that nicotine replacement is not safe (potential dangers are dream abnormalities, insomnia, and application site reaction, also known as patch-rash), but if the options are replacement therapy or continued smoking, replacement therapy is probably safer.

Other aids in quitting smoking include medication (e.g., Bupropion, cloridine, mortiptyline) that can help relieve the agitation associated with quitting. Success rates are in the range of 30 percent. Other aids include hypnosis, acupuncture, laser therapy, and relaxation therapy. It is not important which method is chosen; what is important is the need to stop smoking.

The next major modifiable risk factor is diabetes. Diabetes, like heart disease, also increases with age, and prevalence approaches 10 to 20 percent in people over the age of sixty-five. People with diabetes have a two- to four-fold increased risk of coronary artery disease. While good control of diabetes probably reduces risk for heart disease, it seems that control of blood pressure is even more important for diabetics in reducing the risk of developing heart disease.

High blood pressure has also been strongly associated with heart disease, and it also increases with aging. Treating hypertension with low-dose thiazide diuretics and long-acting dihydropyridine calcium channel blockers has been shown to reduce heart attack, stroke, and death for people over the age of sixty.

Cholesterol has also been shown to be a significant risk factor for increasing coronary artery disease (CAD). The HMG-CoA reductase inhibitors (statins) have consistently shown a 20 to 30 percent reduction in heart attacks and death. The cholesterol-lowering trials of statins excluded elderly patients over the age of seventy-five, but the medications are still considered safe. This is because there is wide experience with statins outside the elderly community, randomized trials have proven safe, and side effects have very rarely been reported. In addition, older patients have the greatest risk and suffer the greatest burden from heart attacks and strokes and therefore have the most to gain from the use of these drugs.

Obesity and physical inactivity are also associated with heart disease. Regular physical activity five to seven times per week for twenty to thirty minutes a day can reduce the risk of heart disease by 20 percent. This may pose problems for some older adults, as there is an increase in arthritis in the older population, which can limit their physical ability. The use of a stationary bicycle allows people to sit while exercising and takes the weight off the lower joints, as does swimming and water exercise.

The use of antioxidants such as vitamin E and beta carotene have proven to be of no benefit in reducing heart disease. Fish oil supplements, which contain polyunsaturated fatty acids, have been shown to have a small but significant benefit in those with established heart disease. A Mediterranean-style diet has also been shown to be protective for heart disease. Such a diet includes "more bread, more root vegetables and green vegetables, more fish, less meat (beef, lamb, and pork to be replaced with poultry), no day without fruit, and butter and cream to be replaced with. . . a rapeseed (canola) oil-based margarine" (de Lorgeril, 1994).

Angina is classified into four stages. Functional class I indicates symptoms only with vigorous exertion. Class II indicates symptoms with moderate exertion; such as climbing a flight of stairs, or walking more than two blocks. Functional class III occurs with less activity, and functional class IV occurs at rest or with very low levels of activity such as walking around the room. The classic symptoms of angina are central pressure or chest pain, although the full range of symptoms felt may also include burning; a feeling of heaviness, squeezing, tightness, or fullness; an ache or sharp pain; or even no chest symptoms at all. The chest pain often radiates up into the shoulder and neck and down the arm (the left more so than right). It may also present in the upper abdomen, back, and ears or jaw as well. Other typical features include shortness of breath, a cold sweat (diaphoresis), weakness, nausea and vomiting, or even a loss of consciousness. Typically, these symptoms occur with exertion and are resolved with rest. If there is a change in symptoms with less activity or if they are more severe or prolonged, then the condition is considered unstable angina. Worsening of symptoms is related to an increase in the amount of obstruction of the coronary arteries. At the extreme of this spectrum of acute ischemic syndromes or unstable angina is a myocardial infarction, or heart attack. This occurs when the circulation is insufficient to keep the heart muscle alive. Typically, it is associated with a blood clot forming on a partial obstruction in the coronary arteries.

Unfortunately, as people get older they are less likely to present with typical symptoms. They may not have pain or discomfort; problems with nausea, diaphoresis, and weakness may not be attributed to a heart problem; and, frequently, people do not seek attention. Also, diabetics and women are more prone not to have typical symptoms, resulting in misdiagnosis and undertreatment.

More alarmingly, the rates of death from heart attack increase sharply with increasing age. Mortality under the age of sixty-five is probably in the range of 4 percent. Mortality over the age of seventy-five climbs to 20 percent. Complications after an infarct are also increased in the elderly.

When presenting with a heart attack, patients are treated initially with aspirin. Provided there has been no recent surgery or problems with bleeding, they may also be treated with medication to dissolve the clot causing the heart attack. Best results occur if treated within an hour after the onset of symptoms, but benefits are still seen even six to twelve hours after the onset of pain. These thrombolytic medications (e.g., streptokinase, tissue plasminogen activator, reteplase, tenecteplase) have been shown to significantly reduce death, but they are also associated with an increased risk of bleeding. This can be controlled, however, unless there is bleeding in the head, which is almost always fatal. The benefits of the medication outweigh the risks, and, given that older patients have a much greater risk of dying, they also enjoy a much greater absolute benefit from this therapy. For two to three days following an infarct, patients are treated with intravenous medication or an injection of heparin, which keeps the blood thin.

Another possible treatment at the time of a myocardial infarction is angioplasty. Angioplasty has the greatest success for treating MIs, but requires rapid availability and experienced physicians.

Other medications given to patients to reduce mortality after a heart attack are beta blockers and ACE inhibitors. Calcium channel blockers and nitroglycerin under the tongue, in a pill or patch form, or even intravenously, help control pain with acute ischemic syndromes.

With an uncomplicated heart attack, people can expect to be in the hospital five to seven days. After one to two days of rest, patients start to mobilize. This is done while being monitored. Medications are adjusted as tolerated, and patients generally have an assessment of their heart function by an echocardiogram (ultrasound of the heart) or a wall motion study (a nuclear X-ray). Prior to going home, most patients have an exercise stress test in which they walk on a treadmill while heart rate, blood pressure, and any changes in the electrocardiogram, as well as any recurrence of symptoms, are monitored. If these occur at low levels of activity, there is increased risk and more aggressive investigations or treatment are warranted. If not, the patient is considered low risk and should be safe for discharge.

Following discharge, patients can gradually increase their physical activity, watching for any recurrence of symptoms. Walking for five to ten minutes twice a day, and gradually increasing this up to thirty minutes twice a day, and then to forty to sixty minutes of walking or exercise once a day is recommended.

Congestive heart failure

Congestive heart failure (CHF), or cardiomyopathy, occurs when the pumping action of the heart has been weakened, causing shortness of breath, fatigue, and swelling, particularly in the legs and feet. There is decreased circulation to the major organs, and the kidneys retain more fluid to compensate. There are also neurohormonal factors that tend to stimulate or overdrive the heart. This ultimately can lead to further damage and deterioration of the heart function. Patients with functional class III to IV heart failure, where they are short of breath with low levels of activity or at rest, have a three- to four-year mortality rate of 35 to 45 percent. Mortality may be higher in older patients.

The most common cause of congestive heart failure is ischemic heart disease or prior myocardial infarctions. Older patients with congestive heart failure and coronary artery disease may benefit from revascularization, and they are at higher risk for silent ischemia or missed infarcts. While this accounts for 70 percent of the patients with congestive heart failure, there are numerous other causes, including hypertension, valvular heart disease, viral infection, and arrhythmias. Another age-related problem is chemotherapy (e.g., adriamycin, anthracycline, herceptin, taxanes, and others) for cancer.

With acute congestive heart failure, patients become suddenly short of breath, cannot lie flat, and develop edema. Patients in an emergency room will be treated with oxygen therapy as well as intravenous diuretics and nitroglycerin to help remove the fluid.

CHF can also be more insidious, with a gradual or progressive course of increasing shortness of breath over hours and days. This may be related to a change in fluid or salt intake. CHF patients require polypharmacy (the use of multiple medications, as heart patients often take anywhere from four to twelve drugs a day) to control their symptoms and improve survival. Angiotensin-converting enzyme (ACE) inhibitors have been shown to significantly reduce symptoms, hospitalizations, and mortality. For patients who are intolerant of ACE inhibitors, a reasonable next choice would probably be angiotensin receptor blockers (ARBs).

Beta blockers lower blood pressure, slow the heart rate, and decrease the heart's workload. Previously felt to worsen CHF, studies have shown that beta blockers actually improve survival, reduce symptoms, and improve heart function. Side effects may include fatigue or depression, and it is important that such side effects not be simply blamed on "old age."

Patients with severe heart failure (functional class III to IV) and an ejection fraction less than 30 percent should be treated with spironolactone. This medication is a diuretic with unique neurohormonal-blocking properties that have been shown to significantly reduce mortality. Other diuretics are also useful to help control symptoms of fluid retention.

Digoxin also reduces symptoms and decreases hospitalizations in heart failure. There are other inotropic medications available that make the heart stronger and can temporarily improve symptoms. Unfortunately, these medications decrease survival. Some patients with very severe CHF, however, may feel the benefit of fewer symptoms is worth the risk of not living as long as they would otherwise.

Certain medications are generally contraindicated in heart failure. Most calcium channel blockers worsen heart failure, though amilodipine and felodipine have been shown to be safe. Nonsteroidal anti-inflammatory drugs (NSAIDS) used to treat arthritis may also aggravate heart failure, as can alcohol, which should generally be avoided. Exercise is useful but must be individualized to a patient's physical state. Most lifestyle modifications are probably best coordinated through a heart function clinic run by nurse specialists.

Heart transplantation is an option only if patients have failed all other medical treatments and still have severe heart failure. It is also restricted to patients under sixty-five, as older patients do not do as well with the burden of aggressive immunosuppressive therapy.

Valvular heart disease

The heart consists of four chambers. The two upper chambers, or atria, pump blood into the lower chambers, or ventricles. The right ventricle pumps blood through the lungs, and the blood then returns with oxygen to the left ventricle. The left ventricle pumps blood to the rest of the body and the veins return blood to the right atria. The valves between the atria and ventricle are the tricuspid valve (right) and the mitral valve (left). The valves out of the heart are the pulmonary valve (right) and the aortic valve (left). These prevent blood from going backwards, optimizing pumping efficiency. There are two possible malfunctions with any valve. The valves can become stenotic, or tight, and cause a flow obstruction, or the valves can become loose or floppy and allow backward flow, or insufficiency. Most valve disease in adults involves the mitral valve or the aortic valve. Rheumatic fever is probably the most common cause of valvular heart disease worldwide. Caused by untreated streptococcal infections, rheumatic fever can cause either stenosis or insufficiency. This is much less common where antibiotics are widely available. The aortic and the mitral valve are also prone to calcification, or thickening, and stenosis with aging.

Mild-to-moderate mitral insufficiency does not require any surgical intervention, but if the insufficiency becomes severe, or if there are signs of worsening heart failure, then repair or replacement of the mitral valve may be necessary. If the mitral valve is too tight, it can cause CHF. This is diagnosed by an echocardiogram. Mitral stenosis can be repaired either by surgery or with a balloon (valvuloplasty). The balloon prevents the need for invasive surgery but may result in some mitral insufficiency. If a patient is not a good candidate for open heart surgery, a valvuloplasty is an attractive option.

Artificial valves are either tissue or metal. Tissue valves are frequently used on older patients because they do not require anticoagulation and cause less risk of stroke, but they tend to wear out within ten to fifteen years. Metal or mechanical valves require special blood thinners (e.g., warfarin) to prevent the valve from clotting up and blocking, and to prevent strokes. These blood thinners do increase the risk of bleeding and require regular monitoring.

The aortic valve occasionally shows significant leaking. If this is mild or moderate, it can be treated with medication. Nifedipine has been shown to reduce the progression and the need for surgery. If regurgitation is severe, valve replacement may be necessary. Aortic stenosis causes an increased strain on the pumping action of the heart. This can lead to angina, CHF, or loss of consciousness (syncope). Surgery is the only definitive treatment with severe aortic stenosis.

The risks of valvular surgery is increased in elderly patients, including an increased rate of perioperative mortality, increased postoperative infection, stroke and renal failure, prolonged hospital stay, and postoperative disability. Operative risks also depend on other comorbidities. Surgical consideration must be individualized for each patient and a balanced discussion of all reasonable risks and benefits is necessary for making the right decision.

Patients with valvular heart disease or artificial heart valves are at increased risk for developing endocarditis—an infection on the heart valve. Antibiotics are needed to prevent such infections when undergoing surgery and dental work.

Arrhythmias

The sinus node is the pacemaker of the heart. It sits high in the atria and sends out a regular signal for the heart to beat. This signal is controlled by neurological and hormonal triggers that make the heart speed up and slow down as needed. There is a delay switch between the atria and ventricle that is called the AV node. Arrhythmias occur when the heart is either beating too fast (tachycardia) or too slow (bradycardia). The most common arrhythmias consist of isolated and premature atrial contractions (PACs), and extra beats, called premature ventricular contractions (PVCs). These are normal. Some people are quite sensitive and can feel the heart skip or flip in their chest, followed by a brief pause before the heart returns to its normal rhythm. Most people notice this when sitting quietly or lying in bed. Triggers include smoking, alcohol, coffee, tea, chocolate, or other stimulants. These are not life threatening and do not require treatment.

PVCs are also associated with CHF. While frequent PVCs may be a sign of increased risk in patients with ischemic heart disease and congestive heart failure, treating these with antiarrhythmic medication has been proven to increase mortality. Treatment is therefore reserved only for symptomatic and sustained ventricular tachycardia (VT), which causes symptoms of weakness, lightheadedness, or syncope. Sustained VT can cause sudden death and requires defibrillation with electrical paddles. This is commonly depicted in television and movies, with survival rates on television of approximately 75 percent. In reality, survival rates are generally less than 20 percent.

Unfortunately, medications that have been used to treat ventricular tachycardia have had modest success at best. Newer automatic implantable cardiac defibrillators (AICD) are special pacemakers, and they can be programmed to give a shock to restore normal rhythm when VT is detected. These devices are very expensive, but very effective.

Other common arrhythmias in the upper chamber of the heart include supraventricular (SVT) or atrial tachycardias. If prolonged, these can cause palpitations, shortness of breath, fatigue, weak spells, and even syncope.

Atrial fibrillation is an irregular SVT that can occur intermittently or continuously. Increasing age is a major risk factor for atrial fibrillation, which occurs in 5 percent of people over sixty-five and as many as 10 percent of people over the age of eighty. Patients who have infrequent atrial fibrillation lasting only a few minutes may not require any antiarrhythmic medication. If atrial fibrillation causes weakness, shortness of breath, angina, or heart failure, treatment with medication is warranted.

If patients do not convert (from abnormal to normal rhythm) with medication or are unstable, they may require electrical cardioversion, in which patients are sedated ,or asleep, and then shocked with external paddles to restore normal rhythm.

Frequently, patients are not symptomatic with atrial fibrillation, and it may be picked up incidentally. This can happen when a patient undergoes an electrocardiogram (ECG) as part of a routine or presurgical check-up and atrial fibrillation is discovered as a result. In this situation, there is no clear benefit to trying to restore sinus rhythm, as many antiarrhythmic medications carry significant side effects. Beta blockers or calcium channel blockers may be used to control heart rates with atrial fibrillation. The other important risk is stroke. Patients who have atrial fibrillation and no valvular disease, as well as no other risk factors, have a risk of stroke of 1 percent per year. Risk factors include age greater than seventy-five, prior stroke or transient ischemic attack (TIA), diabetes, and hypertension. These risks increase the annual stroke rate to 4 to 5 percent per year. Anticoagulation using warfarin reduces the risk of stroke by 70 to 80 percent. The major risk associated with using this medication is an increased risk of bleeding. If warfarin is deemed unsafe, aspirin reduces the risk by 35 percent.

Bradycardia, or slow heart rate, is caused by sinus node disease, AV node disease, or heart block (which means the electrical impulse fails to reach the ventricle; heart block is caused by AV node disease). It also increases in frequency with increasing age. Symptoms include weakness or lightheadedness, fatigue, shortness of breath, or syncope. Bradyarrhythmias can be diagnosed by an ECG at the time of symptoms. Additionally, a holter monitor (a small device worn for twenty-four to forty-eight hours to record all heart beats) can detect and record arrhythmias.

Several cardiac medications, such as beta blockers, calcium channel blockers, and digoxin, can cause bradyarrhythmias and may need to be stopped. A pacemaker is used to treat bradycardia, and is generally inserted in the operating room or in a cardiac care unit. Pacemakers have a single wire in the ventricle and sometimes a second one in the atria. Modern pacemakers are no longer affected by interference caused by micro-waves, metal detectors, or store security systems, though there has been some interactions noted with cellular phones. As the world becomes more electronically busy, the potential for interference with pacemakers changes, and pacemaker manufacturers must continue to strive to keep ahead of new potential hazards.

Driving and heart disease

Regulations regarding driving and heart disease vary in different locations. Patients who are functional class IV should not drive, while those who are functional class III or better may drive, provided their doctor agrees. Following unstable angina or a heart attack, patients should be stabilized one month before driving. Patients should also wait one month after bypass surgery or insertion of a pacemaker before driving. Patients with AICD and documented episodes of VT should probably not drive if spells or shocks are frequent.

Sex and heart disease

Sexual activity is an important part of people's lives, including both older adults and patients with heart disease. Many of the problems that give rise to heart disease, such as diabetes, hypertension, and various medications, can also give rise to sexual dysfunction. More commonly, patients and their partners may be afraid to engage in sexual intercourse for fear it may trigger a heart attack, though the risk of precipitating a heart attack or heart disease during intercourse is quite low.

The first question to be asked is whether the heart can cope with the physical exertion involved. A middle-aged person uses approximately four to five METS (metabolic equivalent units) during intercourse. This is the equivalent of a brisk walk or of climbing two to three flights of stairs. An exercise stress test is measured in METS, and this is an easy way to determine if the work of intercourse will bring on angina. In general, it is safe to resume sexual activity two to three weeks after a heart attack. While elderly patients likely exert less energy than younger individuals during sexual intercourse, if symptoms such as angina or excessive shortness of breath develop, then the activity should be stopped and, if necessary, nitroglycerin may be used to relieve angina.

The question of patients with heart disease using Viagra raises some serious concerns. While Viagra is a highly effective and popular medication to treat erectile dysfunction, it is contraindicated in patients who are using nitroglycerin. This includes patients who are using nitroglycerin pills or patches, or people who need to use nitroglycerin by spray or pills under the tongue to relieve angina. Viagra and nitroglycerin taken together may cause significant and severe drops in blood pressure. This effect may occur up to twenty-four hours after using Viagra, and the potential exists for these effects occurring even later in elderly patients.

Glossary of cardiac medication

Angiotensin-converting enzyme (ACE) inhibitors improve survival with congestive heart failure and ischemic heart disease, reduce complications and incidence of diabetes, and lower blood pressure. They may decrease kidney function, increase potassium levels, and cause a dry cough. Also present the rare risk of angioedema. Angiotensin receptor blockers are useful to lower blood pressure and for congestive heart failure with no cough. However, they may cause renal failure or elevated potassium levels.

Aspirin is a blood thinner that reduces death from heart attacks and angina and reduces the chance of strokes. It does present a very small increased risk of bleeding and ulcer irritation may occur.

Beta blockers improve survival following heart attacks with congestive heart failure and with hypertension, lower blood pressure, have antiarrhythmic benefits, and also improve heart function. Side effects include possible fatigue, depression, erectile dysfunction, and bradycardia. Beta blockers are contraindicated in asthmatics. Calcium channel blockers are used to reduce blood pressure and help with angina. May be associated with constipation or reflux. Constipation may be a bigger problem with older patients, especially if immobility is present. Edema is another possible problem associated with these drugs.

Clopedigrol is a blood thinner used to reduce heart attack or stroke and may be used with or instead of aspirin.

Digoxin is used in the treatment of heart failure and reduces symptoms and hospitalizations. Adverse effects include nausea, GI upset, and bradycardia.

Diuretics are useful for lowering blood pressure and treating symptoms of congestive heart failure. May be associated with postural hypotension. Also can cause electrolyte abnormalities, including low potassium. May increase uric acid and precipitate gouty attacks.

Nitroglycerin is used to treat symptoms of angina. It may cause headaches, but tolerance develops.

Spironolactone is used to treat severe congestive heart failure, but may increase potassium and decrease renal function. It also may cause gynecomastia and increased hair growth.

Statins (HMG-CoA reductase inhibitors) are useful in reducing cholesterol and decreasing the risk of heart attacks and strokes. Very rare problems with liver abnormalities or muscle pain sometimes occur.

Warfarin is used to prevent strokes with valvular heart disease and with atrial fibrillation. Negative effects include the increased risk of bleeding.

Paul MacDonald

See also Aging; Cholesterol; Dementia; Dementia with Lewy Bodies; Diabetes Mellitus; Disease Presentation; Exercise; Fainting; High Blood Pressure; Revascularization: Bypass Surgery and Angioplasty; Stroke; Vascular Dementia; Vascular Disease; Vitamins.

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SOLVD Investigators. "Effect of Enalapril on Survival in Patients with Reduced Left Ventricular Ejection Fractions and Congestive Heart Failure." New England Journal of Medicine 325 (1991): 293–302.

SPAF III Writing Committee for the Stroke Prevention in Atrial Fibrillation Investigators. "Patients with Nonvalvular Atrial Fibrillation at Low Risk of Stroke During Treatment with Aspirin." Journal of the American Medical Association 279 (1998): 1273–1277.

Staessen, J. A.; Fagard, R.; Thijs, L.; et al. "Randomised Double-Blind Comparison of Placebo and Active Treatment for Older Patients with Isolated Systolic Hypertension." Lancet 350 (1997): 757–764.

Tobacco Use and Dependence Clinical Practice Guideline Panel, Staff, and Consortium Representatives. "A Clinical Practice Guideline for Treating Tobacco Use and Dependence." Journal of the American Medical Association 283 (2000): 3244–3254.

U.K. Prospective Diabetes Study Group. "Tight Blood Pressure Control and Risk of Macrovascular and Microvascular Complications in Type 2 Diabetes: UKPDS 38." British Medical Journal 317 (1998): 703–713.

Yusus, S. Evidence Based Cardiology, 1st ed. London: British Medical Journal Publications, 1998.

Zijlstra, F.; Hoorntje, J. C. A.; De Boer, M.; et al. "Long-Term Benefit of Primary Angioplasty as Compared with Thrombolytic Therapy for Acute Myocardial Infarction." New England Journal of Medicine 341 (1999): 1413–1419.

Cholesterol, high

Definition

High cholesterol (hypercholesterolemia or hyperlipidemia) refers to the presence of higher than normal amounts of total cholesterol circulating in the bloodstream. Cholesterol is a fatty substance (lipid) that is essential to the body as protection for the walls of the vasculature (veins and arteries) and linings of body organs, a component in the manufacture of hormones, and a factor in the digestion of consumed fats in foods. It is manufactured in the liver and carried throughout the body in the bloodstream. Cholesterol is also a component of animal tissue and can be consumed in products such as meat, eggs, fish, milk, and milk products such as butter and cheese. Elevated cholesterol levels can result in the accumulation of fatty deposits on blood vessel walls, narrowing veins and arteries and impeding blood flow to the heart, brain, and other organs.

Description

Cholesterol has both a good form and a bad form that add up to total cholesterol when measured together. The body needs cholesterol to produce bile acids that help digest fats ingested in food, make hormones, protect cell walls, and participate in other processes that help maintain health. Ironically, cholesterol can also be a problem, if too much is manufactured by the liver or consumed through the diet and not metabolized or used. The utilization of fat in the body, or fat metabolism, is a complex process, complicated even more by abnormally high levels of cholesterol found circulating in the blood. Although high cholesterol is not often found in young children, it may begin to develop in adolescents or young adults either as an inherited condition or through unhealthy eating habits and can continue into adulthood, creating potentially serious health problems. High cholesterol levels and fatty deposits in veins and arteries (atherosclerosis) have been found during autopsies of children who have died of accidents and other causes.

The liver metabolizes cholesterol, including the cholesterol obtained from foods in the diet. The components of cholesterol are then carried into the bloodstream bound to the surface of certain lipoproteins. Low-density lipoproteins or LDLs carry about 75 percent of the cholesterol into the blood and high-density lipoproteins carry the other 25 percent. LDL is the lipoprotein known as bad cholesterol because it consists primarily of cholesterol and is most associated with the development of vascular disease. Cholesterol is not the major part of HDL, the so-called good cholesterol, and the presence of higher amounts of HDL in the blood actually helps reduce the more harmful LDL levels. Another lipoprotein, very low-density lipoprotein (VLDL), carries harmful fats known as triglycerides but does not carry a significant amount of cholesterol. Triglycerides are also measured as part of a lipid profile and high levels are associated with vascular disease and heart disease. Cholesterol levels in blood serum vary considerably from day to day and even from one time of a day to another related to the consumption of fats in the diet.

High LDL (low-density lipoprotein) is a major precursor of vascular disease and heart disease. This form of cholesterol combines with triglycerides, cellular waste, calcium, and scar tissue to form a waxy deposit (plaque) on the inner walls of large and medium-sized arteries, causing a condition called hardening of the arteries (atherosclerosis or arteriosclerosis). Plaque typically builds up as people get older, more in some people than others depending on lifestyle (diet, exercise , alcohol consumption, and smoking ) and heredity. The result may be a narrowing (stenosis) or blockage of blood vessels, interrupting the essential flow of blood and oxygen to the heart, brain, abdominal organs, and peripheral circulation to the arms and legs. Eventually this can lead to heart attack or stroke , permanent damage to the heart or brain, and life-threatening complications.

The population as a whole is at some risk of developing high LDL cholesterol. Specific risk factors include a family history of high cholesterol, obesity , coronary artery disease (atherosclerosis), stroke, alcoholism , diabetes, high blood pressure, and lack of regular exercise. The chances of developing high cholesterol increase after the age of 45. One of the primary causes of high LDL cholesterol is a combination of too much fat and sugar in the diet, especially through the consumption of fast foods and refined or packaged foods, a problem that has been especially true in the United States since the advent of manufactured foods. A renewed interest in whole foods may help to alter the prevalence of high cholesterol and vascular disease.

An increased serum cholesterol may be found in familial hyperlipidemia or hypercholesterolemia, underactive thyroid (hypothyroidism ), untreated diabetes, a high-fat diet, pregnancy, heart attack, stress, and certain liver conditions (cirrhosis). A decreased level may be found in liver dysfunction, overactive thyroid (hyperthyroidism ), malabsorption, malnutrition , or advanced cancer , among other conditions.

Although high cholesterol has been shown to be a risk factor for developing atherosclerosis in adults, with associated increased morbidity and mortality, studies have not indicated that high cholesterol in children and adolescents is related to the development of specific illness or increasing mortality in adulthood. There is strong evidence in numerous research studies, however, that a family history of high cholesterol, atherosclerosis, heart attack, or stroke increases the risk of a child developing high cholesterol levels.

High cholesterol is often diagnosed and treated by general practitioners or family practice physicians. In some cases, the condition is treated by an endocrinologist or cardiologist. Pediatricians will generally refer affected children to the appropriate specialist.

Demographics

The U.S. Food and Drug Administration (FDA) estimates that 90 million American adults, roughly half the adult population, have elevated cholesterol levels. This estimate does not indicate that as many children are candidates for high cholesterol levels; however, about 2 percent of the U.S. population has a family history of hypercholesterolemia in parents or grandparents, and this history is the most common predictor of high cholesterol levels in children and adolescents. Before puberty , average total and LDL cholesterol levels are higher in girls than in boys. Both LDL and HDL levels are higher in non-Hispanic black children than in non-Hispanic whites and Mexican-American children.

Causes and symptoms

The causes of high cholesterol may be genetic or hereditary factors in the manufacture of cholesterol by the liver or in fat metabolism, a diet high in saturated fats and trans-fatty acids, obesity, alcoholism, smoking, and lack of exercise.

There are no readily apparent symptoms that indicate high cholesterol, high LDL, high triglycerides, or low HDL. Obesity is a general indication of possible high cholesterol levels. Labored breathing or general feelings of sluggishness and lack of energy may warrant examination by a physician and testing of cholesterol. Families or individuals who regularly consume a high-fat diet consisting of animal products, fast foods, and refined foods may also benefit from being tested for abnormal cholesterol levels.

When to call the doctor

Excess weight may be the only sign of possible high cholesterol in children. It is wise for parents to consult a physician if a child is consistently overweight and diet or exercise does not seem to make a significant difference. Sluggishness may also be noted if a child's veins and arteries are consistently filled with higher than normal amounts of fatty substances that are not being metabolized by the body.

Diagnosis

Total serum cholesterol is the cholesterol most often measured and reported in medical office tests, home tests, and blood cholesterol screening clinics; people who quote their cholesterol level as high may be talking about a total cholesterol of over 200mg/dL. A definitive diagnosis of high cholesterol, however, ideally includes measuring LDL, HDL, total cholesterol, and triglyceride levels, as well as the cholesterol to HDL ratio. This combination of tests performed in the clinical laboratory is called a lipid panel or lipid profile. Most physicians want to know the results of a lipid panel before diagnosing high cholesterol and recommending treatment. Screening for lipid levels in all children is not usually recommended. It is recommended that children whose parents have a total cholesterol level over 200mg/dL or whose family history includes heart disease or stroke in either parents or grandparents have a cholesterol screening performed. If the fasting blood level of cholesterol is 170 to 199 mg/dL, total cholesterol should be repeated and the two tests averaged. A final result of 200 mg/dL or over indicates that the entire lipid panel should be done to determine if hyperlipidemia is present.

In most adults the recommended levels for cholesterol and triglycerides, measured as milligrams per deciliter (mg/dL) of blood, are: total cholesterol, less than 200; LDL, less than 130; HDL, more than 35; triglycerides, 30–200; and cholesterol to HDL ratio, four to one. However, the recommended cholesterol levels may vary from person to person, depending on other risk factors such as a family history of heart disease or stroke or the presence of hypertension , diabetes, advanced age, alcoholism, or smoking.

The physician may recommend nuclear magnetic resonance (NMR) lipoprofile testing for individuals whose lipid measurements, history, and risk factors are not diagnostic, that is they are not revealing why an individual has coronary artery disease. Doctors have always been puzzled by why some people develop heart disease while others with identical HDL and LDL levels do not. Research studies in the early 2000s indicate that it may be due to the size of the cholesterol particles in the bloodstream. Nuclear magnetic resonance (NMR) lipoprofile exposes a blood sample to a magnetic field to determine the size of the cholesterol particles. Particle size also can be determined by a centrifugation test, in which blood samples are spun very quickly to allow particles to separate and move at different distances. The smaller the particles, the greater the chance of developing heart disease. It allows physicians to treat patients who have normal or close to normal results from a lipid panel but abnormal particle size.

Treatment

The primary goal of cholesterol treatment is to lower LDL to under 160 mg/dL in people without heart disease and who are at lower risk of developing it. The goal in people with higher risk factors for heart disease is less than 130 mg/dL. In patients who already have heart disease, the goal is under 100 mg/dL, according to FDA guidelines. Also, since low HDL levels increase the risk of developing heart disease, the goal for all individuals is to maintain an HDL of more than 35 mg/dL. These values apply to children and adolescents as well as adults.

First-line treatment of high cholesterol for all ages includes diet, exercise, and weight loss. The National Cholesterol Education Program recommends that children over age two eat a variety of foods for healthy development and ideal weight, consuming no more than 30 percent total fat in the diet and no more than 10 percent saturated fat as in animal foods. The American Heart Association Step 2 diet has been tested as a dietalone treatment and in conjunction with drug therapy for children with high cholesterol, with good results. Regular exercise through aerobic activity is recommended.

In addition to diet and exercise, a variety of prescription medicines are available to help reduce cholesterol levels in the blood; these medications may not always be recommended for children, except for those whose parents or grandparents have high cholesterol and coronary artery disease. A class of drugs called statins is known to help lower LDL in combination with dietary changes and exercise, and studies have shown that they have no adverse effects in children. A class of drugs called fibric acid derivatives is sometimes recommended to lower triglycerides and raise HDL. Doctors decide which drug is most effective for an individual based on the cause and the severity of the cholesterol problem and other health conditions that may be present, as well as possible side effects of the drug. Diet and exercise remain important factors in reducing elevated cholesterol levels, even if drug therapy is prescribed.

Alternative treatment

Alternative treatment of high cholesterol may include high doses of garlic, niacin, soy protein, algae, or other fatty acids, and the Chinese medicine supplement Cholestin (a red yeast fermented with rice).

GARLIC A number of clinical studies have indicated that garlic can offer modest reductions in cholesterol. A 1997 study by nutrition researchers at Pennsylvania State University found that men who took garlic capsules for five months reduced their total cholesterol by 7 percent and LDL by 12 percent. Another study showed that seven cloves of fresh garlic a day significantly reduced LDL, as did a daily dose of four garlic extract pills.

CHOLESTIN Cholestin has been available since 1997 as a cholesterol-lowering dietary supplement. It is a processed form of red yeast fermented with rice, a traditional herbal remedy used for centuries in China. Two studies released in 1998 showed Cholestin lowered LDL cholesterol by 20 to 30 percent. It also appeared to raise HDL and lower triglyceride levels. Although the supplement contains hundreds of compounds, the major active LDL-lowering ingredient is lovastatin, a chemical also found in the prescription drug Mevacor. The product is available as a dietary supplement, not a drug; its actual mechanism is not known. No serious side effects have been reported, but minor side effects, including bloating and heartburn, have been noted.

OTHER TREATMENT A study released in 1999 indicated that blue-green algae contains polyunsaturated fatty acids that lower cholesterol. The algae, known as Aphanizomenon flos-aquae (AFA) is available as an over-the-counter dietary supplement. Flax seed oil is another source of fatty acids known to reduce cholesterol levels. Niacin, also known as nicotinic acid or vitamin B3, has been shown to reduce LDL levels by 10 to 20 percent and raise HDL levels by 15 to 35 percent. It also reduces triglycerides. Because an extremely high dose of niacin is needed to treat cholesterol problems, it should only be taken under a doctor's supervision to monitor possible toxic side effects. Niacin can also cause flushing when taken in high doses. Soy protein with high levels of isoflavones also has been shown to reduce LDL levels by up to 10 percent. In 2003, a Cuban research study revealed that policosanol, a substance made from sugar cane wax or beeswax, lowered LDL cholesterol nearly 27 percent in study subjects.

Nutritional concerns

Several specific diet options have been shown to be beneficial for reducing cholesterol. A vegetarian diet provides up to 100 percent more fiber and up to 50 percent less cholesterol from food than a meat-based diet. A balanced vegetarian diet consists of at least six servings of whole grain foods, three or more servings of green leafy vegetables, two to four servings of fruit, two to four servings of legumes (protein source), and one or two servings of non-fat dairy products daily. The macrobiotic diet is similar, with brown rice being a staple, but with the addition of other protein sources such as fish and fowl, tofu, and other soy products (miso, tempeh). The low glycemic or diabetic diet is known to raise the HDL (good cholesterol) level by as much as 20 percent in three weeks. Low glycemic foods promote a slow but steady rise in blood glucose levels following a meal, which increases the level of HDL. They also lower total cholesterol and triglycerides. Low glycemic foods include certain fruits, vegetables, beans, and whole grains. Processed (packaged foods) and refined foods (white flour products, white rice) and refined sugars (white sugar, brown sugar, molasses, and products made with them) should be avoided in all diets. Soy protein can be added to the daily diet to help replace animal sources of protein and reduce cholesterol; a diet containing 62 mg of isoflavones in soy protein is recommended and can be incorporated into other diet regimens, including vegetarian, macrobiotic, and low glycemic.

Prognosis

High cholesterol is one of the key risk factors for heart disease and has been shown to be treatable. Left untreated, high levels of LDL and total cholesterol can lead to the formation of plaque, the narrowing of blood vessels, vascular disease, and subsequent heart attacks and stroke.

Prevention

Since a large number of people with high cholesterol are overweight, a healthy diet and regular exercise are probably the most beneficial ways to control cholesterol levels. Exercise is an extremely important part of burning calories obtained by eating fats and helps maintain lower bad cholesterol and higher levels of good cholesterol. Exercise should consist of 20 to 30 minutes of vigorous aerobic exercise at least three times a week. Exercises that cause the heart to beat faster include fast walking, bicycling, jogging, roller skating, swimming, and walking up stairs.

Nutritional concerns

In general, the nutritional goals for preventing high levels of cholesterol are to substantially reduce or eliminate foods high in animal fat, including meat, shellfish, eggs, and dairy products. The use of polyunsaturated fats in cooking is also recommended, including cold pressed oils such as olive oil, canola oil, and sesame oil. Many vegetable oils are hydrogenated or extracted at high temperatures and are best avoided. Trans-fatty acids found in solid shortenings, most margarines, and hydrogenated oils or products containing them should also be avoided because they are known to increase levels of LDL.

Parental concerns

Parents need not be concerned about high cholesterol levels in their children unless the child is obese or there is a family history of high cholesterol, heart attack, or stroke. Parents who have cholesterol levels over 200 mg/dL themselves may want to have their children's cholesterol levels tested. Much information is available from public health sources and family physicians about diet and exercise recommendations to help people of all ages reduce the risk of vascular disease and related illnesses, such as heart disease and stroke.

KEY TERMS

Atherosclerosis —A disease process whereby plaques of fatty substances are deposited inside arteries, reducing the inside diameter of the vessels and eventually causing damage to the tissues located beyond the site of the blockage.

Fatty acid —The primary component of lipids (fats) in the body. The body requires some, called essential fatty acids, to form membranes and synthesize important compounds.

Glycemic —The presence of glucose in the blood.

Hypertension —Abnormally high arterial blood pressure, which if left untreated can lead to heart disease and stroke.

Legumes —A family of plants, including beans, peas, and lentils, that bear edible seeds in pods. These seeds are high in protein, fiber, and other nutrients.

Lipids —Organic compounds not soluble in water, but soluble in fat solvents such as alcohol. Lipids are stored in the body as energy reserves and are also important components of cell membranes. Commonly known as fats.

Polyunsaturated fat —A non-animal oil or fatty acid rich in unsaturated chemical bonds. This type of fat is not associated with the formation of cholesterol in the blood.

Trans-fatty acid —A type of fat created by hydrogenating polyunsaturated oils. This changes the double bond on the carbon atom from a cis configuration to a trans configuration, making the fatty acid saturated, and a greater health concern. For example, stick margarines are known to contain more trans-fatty acids than liquid oils.

Resources

BOOKS

Bratman, Steven, and David Kroll. Natural Pharmacist: Natural Treatments for High Cholesterol. Roseville, CA: Prima Publishing, 2000.

PERIODICALS

"Eating a Vegetarian Diet that Includes Cholesterol-lowering Foods May Lower Lipid Levels as Much as Some Medications." Environmental Nutrition (March 2003): 8.

Sage, Katie. "Cut Cholesterol with Policosanol: This Supplement Worked Better than a Low-fat Diet in One Study." Natural Health (March 2003): 32.

ORGANIZATIONS

National Cholesterol Education Program. NHLBI Information Center, PO Box 30105, Bethesda, MD 20824–0105. Web site: <www.nhlbi.nih.gov>.

WEB SITES

"Cholesterol." MedlinePlus. Available online at <www.nlm.nih.gov/medlineplus/cholesterol.html> (accessed December 8, 2004).

L. Lee Culvert Ken R. Wells Teresa G. Odle

Cholesterol, High

Definition

Cholesterol is a fatty substance found in animal tissue and is an important component to the human body. It is manufactured in the liver and carried throughout the body in the bloodstream. Problems can occur when too much cholesterol forms an accumulation of plaque on blood vessel walls, which impedes blood flow to the heart and other organs. The highest cholesterol content is found in meat, poultry, shellfish, and dairy products.

Description

Cholesterol is the Dr. Jekyll and Mr. Hyde of medicine, since it has both a good side and bad side. It is necessary to digest fats from food, make hormones, build cell walls, and participate in other processes for maintaining a healthy body. When people talk about cholesterol as a medical problem, they usually are referring to high cholesterol. This can be somewhat misleading, since there are four components to cholesterol. These are:

• LDL, the so-called bad cholesterol
• HDL, the so-called good cholesterol
• triglycerides, a blood fat lipid that increases the risk for heart disease
• total cholesterol

High LDL (low-density lipoprotein) is a major contributing factor of heart disease. The cholesterol forms plaque in the heart's blood vessels, which restricts or blocks the supply of blood to the heart, and causes a condition called atherosclerosis. This can lead to a "heart attack," resulting in damage to the heart and possibly death. The U.S. Food and Drug Administration (FDA) estimates that 90 million American adults, roughly half the adult population, have elevated cholesterol levels.

The population as a whole is at some risk of developing high LDL cholesterol in their lifetimes. Specific risk factors include a family history of high cholesterol, obesity, heart attack or stroke, alcoholism, and lack of regular exercise. The chances of developing high cholesterol increase after the age of 45. One of the primary causes of high LDL cholesterol is too much fat or sugar in the diet, a problem especially true in the United States. Cholesterol also is produced naturally in the liver and overproduction may occur even in people who limit their intake of high cholesterol food. Low HDL and high triglyceride levels are also risk factors for atherosclerosis.

Causes and symptoms

There are no readily apparent symptoms that indicate high LDL or triglycerides, or low HDL. The only way to diagnose the problems is through a simple blood test. However, one general indication of high cholesterol is obesity. Another is a high-fat diet.

Diagnosis

High cholesterol often is diagnosed and treated by general practitioners or family practice physicians. In some cases, the condition is treated by an endocrinologist or cardiologist. Total cholesterol, LDL, HDL, and triglyceride levels as well as the cholesterol to HDL ratio are measured by a blood test called a lipid panel. The cost of a lipid panel is generally $40-100 and is covered by most health insurance and HMO plans, including Medicare, providing there is an appropriate reason for the test. Home cholesterol testing kits are available over the counter but test only for total cholesterol. The results should only be used as a guide and if the total cholesterol level is high or low, a lipid panel should be performed by a physician. In most adults the recommended levels, measured by milligrams per deciliter (mg/dL) of blood, are: total cholesterol, less than 200; LDL, less than 130; HDL, more than 35; triglycerides, 30-200; and cholesterol to HDL ratio, four to one. However, the recommended cholesterol levels may vary, depending on other risk factors such as hypertension, a family history of heart disease, diabetes, age, alcoholism, and smoking.

Doctors have always been puzzled by why some people develop heart disease while others with identical HDL and LDL levels do not. New studies indicate it may be due to the size of the cholesterol particles in the bloodstream. A test called a nuclear magnetic resonance (NMR) LipoProfile exposes a blood sample to a magnetic field to determine the size of the cholesterol particles. Particle size also can be determined by a centrifugation test, where blood samples are spun very quickly to allow particles to separate and move at different distances. The smaller the particles, the greater the chance of developing heart disease. It allows physicians to treat patients who have normal or close to normal results from a lipid panel but abnormal particle size.

Treatment

A wide variety of prescription medicines are available to treat cholesterol problems. These include statins such as Mevacor (lovastatin), Lescol (fluvastatin), Pravachol (pravastatin), Zocor (simvastatin), Baycol (cervastatin), and Lipitor (atorvastatin) to lower LDL. A group of drugs called fibric acid derivatives are used to lower triglycerides and raise HDL. These include Lopid (gemfibrozil), Atromid-S (clofibrate), and Tricor (fenofibrate). Doctors decide which drug to use based on the severity of the cholesterol problem, side effects, and cost.

Alternative treatment

The primary goal of cholesterol treatment is to lower LDL to under 160 mg/dL in people without heart disease and who are at lower risk of developing it. The goal in people with higher risk factors for heart disease is less than 130 mg/dL. In patients who already have heart disease, the goal is under 100 mg/dL, according to FDA guidelines. Also, since low HDL levels increase the risks of heart disease, the goal of all patients is more than 35 mg/dL.

In both alternative and conventional treatment of high cholesterol, the first-line treatment options are exercise, diet, weight loss, and stopping smoking. Other alternative treatments include high doses of niacin, soy protein, garlic, algae, and the Chinese medicine supplement Cholestin (a red yeast fermented with rice).

Diet and exercise

Since a large number of people with high cholesterol are overweight, a healthy diet and regular exercise are probably the most beneficial natural ways to control cholesterol levels. In general, the goal is to substantially reduce or eliminate foods high in animal fat. These include meat, shellfish, eggs, and dairy products. Several specific diet options are beneficial. One is the vegetarian diet. Vegetarians typically get up to 100% more fiber and up to 50% less cholesterol from food than non-vegetarians. The vegetarian low-cholesterol diet consists of at least six servings of whole grain foods, three or more servings of green leafy vegetables, two to four servings of fruit, two to four servings of legumes, and one or two servings of non-fat dairy products daily.

A second diet is the Asian diet, with brown rice being the staple. Other allowable foods include fish, vegetables such as bok choy, bean sprouts, and black beans. It allows for one weekly serving of meat and very few dairy products. The food is flavored with traditional Asian spices and condiments, such as ginger, chilies, turmeric, and soy sauce.

Another regimen is the low glycemic or diabetic diet, which can raise the HDL (good cholesterol) level by as much as 20% in three weeks. Low glycemic foods promote a slow but steady rise in blood sugar levels following a meal, which increases the level of HDL. They also lower total cholesterol and triglycerides. Low glycemic foods include certain fruits, vegetables, beans, and whole grains. Processed and refined foods and sugars should be avoided.

Exercise is an extremely important part of lowering bad cholesterol and raising good cholesterol. It should consist of 20-30 minutes of vigorous aerobic exercise at least three times a week. Exercises that cause the heart to beat faster include fast walking, bicycling, jogging, roller skating, swimming, and walking up stairs. There are also a wide selection of aerobic programs available at gyms or on videocassette.

Garlic

A number of clinical studies have indicated that garlic can offer modest reductions in cholesterol. A 1997 study by nutrition researchers at Pennsylvania State University found men who took garlic capsules for five months reduced their total cholesterol by 7% and LDL by 12%. Another study showed that seven cloves of fresh garlic a day significantly reduced LDL, as did a daily dose of four garlic extract pills. Other studies in 1997 and 1998 back up these results. However, two more recent studies have questioned the effectiveness of garlic in lowering "bad cholesterol."

Cholestin

Cholestin hit the over-the-counter market in 1997 as a cholesterol-lowering dietary supplement. It is a processed form of red yeast fermented with rice, a traditional herbal remedy used for centuries by the Chinese. Two studies released in 1998 showed Cholestin lowered LDL cholesterol by 20-30%. It also appeared to raise HDL and lower triglyceride levels. Although the supplement contains hundreds of compounds, the major active LDL-lowering ingredient is lovastatin, a chemical also found in the prescription drug Mevacor. The FDA banned Cholestin in early 1998 but a federal district court judge lifted the ban a year later, ruling the product was a dietary supplement, not a drug. It is not fully understood how the substance works and patients may want to consult with their physician before taking Cholestin. No serious side effects have been reported, but minor side effects, including bloating and heartburn, have been reported.

Other treatments

One study indicated that blue-green algae contains polyunsaturated fatty acids that lower cholesterol. The algae, known as alga Aphanizomenon flos-aquae (AFA) is available as an over-the-counter dietary supplement. Niacin, also known as nicotinic acid or vitamin B₃, has been shown to reduce LDL levels by 10-20%, and raise HDL levels by 15-35%. It also can reduce triglycerides. But because an extremely high dose of niacin (2-3) is needed to treat cholesterol problems, it should only be taken under a doctor's supervision to monitor possible toxic side effects. Niacin also can cause flushing when taken in high doses. Soy protein with high levels of isoflavones also have been shown to reduce bad cholesterol by up to 10%. A daily diet that contains 62 mg of isoflavones in soy protein is recommended, and can be incorporated into other diet regimens, including vegetarian, Asian, and low glycemic. In 2003, research revealed that policosanol, a substance made from sugar cane wax or beeswax, lowered LDL cholesterol nearly 27% in study subjects in a Cuban study.

Prognosis

High cholesterol is one of the key risk factors for heart disease. Left untreated, too much bad cholesterol can clog the blood vessels, leading to chest pain (angina), blood clots, and heart attacks. Heart disease is the number one killer of men and women in the United States. By reducing LDL, people with heart disease may prevent further heart attacks and strokes, prolong and improve the quality of their lives, and slow or reverse cholesterol build up in the arteries. In people without heart disease, lowering LDL can decrease the risk of a first heart attack or stroke.

Prevention

The best way to prevent cholesterol problems is through a combination of healthy lifestyle activities, a primarily low-fat and high-fiber diet, regular aerobic exercise, not smoking, and maintaining an optimal weight. In a small 2003 Canadian study, people who ate a low-fat vegetarian diet consisting of foods that are found to help lower cholesterol dropped their levels of LDL cholesterol as much as results from some statin drugs. But for people with high risk factors for heart disease, such as a family history of heart disease, diabetes, and being over the age of 45, these measures may not be enough to prevent the onset of high cholesterol. There are studies being done on the effectiveness of some existing anti-cholesterol drugs for controlling cholesterol levels in patients who do not meet the criteria for high cholesterol but no definitive results are available.

Resources

BOOKS

Bratman, Steven, and David Kroll. Natural Pharmacist: Natural Treatments for High Cholesterol. Roseville, CA: Prima Publishing, 2000.

Ingels, Darin. The Natural Pharmacist: Your Complete Guide to Garlic and Cholesterol. Roseville, CA: Prima Publishing, 1999.

Murray, Michael T. Natural Alternatives to Over-the-Counter and Prescription Drugs. New York: William Morrow & Co., 1999.

PERIODICALS

Carter, Ann. "Cholesterol in Your Diet." Clinical Reference Systems July 1, 1999: 282.

"Eating a Vegetarian Diet that Includes Cholesterol-lowering Foods may Lower Lipid Levels as Much as Some Medications." Environmental Nutrition March 2003:8.

Marandino, Cristin. "The Case for Cholesterol." Vegetarian Times August 1999: 10.

Sage, Katie. "Cut Cholesterol with Policosanol: This Supplement Worked Better than a Low-fat Diet in One Study." Natural Health March 2003: 32.

Schmitt, B.D. "Treating High Cholesterol Levels." Clinical Reference Systems July 1, 1999: 1551.

VanTyne, Julia, and Lori Davis. "Drop Your Cholesterol 25 to 100 Points." Prevention November 1999: 110.

ORGANIZATIONS

National Cholesterol Education Program. NHLBI Information Center, P.O. Box 30105, Bethesda, MD 20824-0105. 〈http://www.nhlbi.nih.gov〉.

KEY TERMS

Atherosclerosis— A buildup of fatty substances in the inner layers of the arteries.

Estrogen— A hormone that stimulates development of female secondary sex characteristics.

Glycemic— The presence of glucose in the blood.

Hypertension— Abnormally high blood pressure in the arteries.

Legumes— A family of plants that bear edible seeds in pods, including beans and peas.

Lipid— Any of a variety of substances that, along with proteins and carbohydrates, make up the main structural components of living cells.

Polyunsaturated fats— A non-animal oil or fatty acid rich in unsaturated chemical bonds not associated with the formation of cholesterol in the blood.

CHOLESTEROL

Cholesterol, cholesterol esters, and triglycerides are fats, or lipids. On their own these would not be soluble enough to circulate, so to circulate in blood, these lipids are combined with phospholipids and protein in particles called lipoproteins. Generally, only three lipoproteins—very low density lipoproteins (VLDL), low density lipoproteins (LDL), and high density lipoproteins (HDL)—are found in the serum of fasting persons.

Cholesterol is absorbed from the intestine and transported to the liver where it is taken up by the LDL receptors. Cholesterol from the liver enters the circulation as VLDL and is metabolized to remnant lipoproteins after an enzyme (lipoprotein lipase) removes triglycerides. The remnant lipoproteins are removed by LDL receptors or further metabolized to LDL and then removed by LDL receptors. Cholesterol also is transported from peripheral cells to the liver by HDL. Cholesterol is recycled to LDL and VLDL or is taken up in the liver by an enzyme known as hepatic lipase. Cholesterol is excreted in bile.

LDL is the major cholesterol-containing lipoprotein, the major lipoprotein implicated in the development of atherosclerosis, and the primary target of therapeutic interventions. LDL cholesterol may be increased because of increased dietary saturated fat and cholesterol, obesity, or genetic disorders, or because of other secondary causes such as hypothyroidism, a kidney disorder known as nephrotic syndrome, biliary cirrhosis, and renal failure.

HDL is synthesized in both the liver and intestine and exerts a protective effect on the development of atherosclerotic vascular disease, a condition also sometimes referred to as "hardening of the arteries." HDL reverses cholesterol transport and removes cholesterol from cells to be delivered directly to the liver or indirectly via transfer of other lipoproteins for catabolism (breakdown into simpler substances with the release of energy). HDL also prevents oxidation and aggregation of LDL in the arterial wall. Low HDL cholesterol may be genetically determined or associated with nutritional habits, cigarette smoking, and lack of exercise.

VLDL is a triglyceride-rich lipoprotein synthesized and secreted by the liver. Hypertriglyceridemia is associated with genetic disorders, obesity, heavy alcohol intake, diabetes mellitus, renal failure, and drugs such as estrogens.

The measurement of levels of LDL cholesterol, HDL cholesterol, and triglycerides in the serum is used to assess risk for atherosclerotic vascular disease. Serum total cholesterol = LDL cholesterol + HDL cholesterol + 1/5 triglycerides. Hypercholesterolemia is a serum total cholesterol of 200 mg/dL or higher. An elevated serum LDL cholesterol is 130 mg/dL or higher. An abnormally low serum HDL cholesterol is 35 mg/dL or lower. Hypertriglyceridemia is serum triglycerides of 190 mg/dL or higher.

An elevated serum total cholesterol, an elevated serum LDL cholesterol, and a low serum HDL cholesterol are risk factors for coronary artery disease, stroke, and peripheral arterial disease in older and younger men and women. The higher the serum total cholesterol, the higher the serum LDL cholesterol, and the lower the serum HDL cholesterol, the greater the incidence of atherosclerotic vascular disease in older and younger men and women.

Elevated serum triglycerides is associated with an increased risk of atherosclerotic vascular disease. However, except for being a weak independent risk factor for new coronary events in elderly women, hypertriglyceridemia is not an independent risk factor for atherosclerotic vascular disease in older or younger men and women.

Because the incidence of atherosclerotic vascular disease is much higher in older men and women than in younger men and women, hypercholesterolemia, an elevated serum LDL cholesterol, and a low serum HDL cholesterol contribute more to the absolute incidence of atherosclerotic vascular disease in older than in younger men and women.

In addition to dyslipidemia, cigarette smoking, hypertension, and diabetes mellitus are major risk factors for atherosclerotic vascular disease. The greater the number and severity of major risk factors, the higher the incidence of atherosclerotic vascular disease.

Persons with dyslipidemia should have secondary causes of dyslipidemia treated, lose weight if obese, and begin dietary treatment. A Step II American Heart Association diet should be used if drug therapy is being considered. The Step II diet contains no more than 30 percent of calories from fat, less than 7 percent of calories from saturated fatty acids, and less than 200 mg of cholesterol daily. Other major risk factors for atherosclerotic vascular disease must be treated.

Increased plasma homocysteine is also an independent risk factor for atherosclerotic vascular disease in older and younger men and women. The presence of both increased plasma homocysteine and dyslipidemia increases independently the incidence of atherosclerotic vascular disease.

Statins are drugs that reduce the synthesis of cholesterol and the secretion of VLDL and increase the activity of LDL receptors. Bile acid– binding resins increase the secretion of bile acids. Nicotinic acid reduces the secretion of VLDL and the formation of LDL and increases the formation of HDL. Fibrates reduce the secretion of VLDL and increase the activity of lipoprotein lipase, thereby increasing the removal of triglycerides.

Older and younger men and women with atherosclerotic vascular disease and a serum LDL cholesterol greater than 125 mg/dL despite dietary treatment should be treated with statin drugs to lower the serum LDL cholesterol to below 100 mg/dL. Statins will decrease serum total and LDL cholesterol and triglycerides, increase serum HDL cholesterol, and reduce in these patients all-cause mortality, cardiovascular mortality, major coronary events, stroke, heart failure, angina pectoris, and peripheral arterial disease. Because mortality rates and cardiovascular events increase with age, statins will reduce all-cause mortality, cardiovascular mortality, and cardiovascular events approximately twice as much in men and women sixty-five years of age and older than in men and women younger than sixty-five years.

Older and younger men and women with atherosclerotic vascular disease and a normal serum LDL cholesterol but a low serum HDL cholesterol should be treated with nicotinic acid or gemfibrozil to reduce cardiovascular events.

Older and younger persons without atherosclerotic vascular disease with a serum LDL cholesterol of 160 mg/dL or higher and two other coronary risk factors (including older age, male gender, smoking, hypertension, diabetes mellitus, low serum HDL cholesterol, and family history), or with a serum LDL cholesterol of 130 mg/dL or higher and a low serum HDL cholesterol, or with a serum LDL cholesterol of 190 mg/dL or higher and no other coronary risk factors should be treated with statins to reduce cardiovascular events.

Wilbert S. Aronow

See also Heart Disease; High Blood Pressure; Stroke.

BIBLIOGRAPHY

Aronow, W. S. "Treatment of Hypercholesterolemia in Older Persons with Coronary Artery Disease." Clinical Geriatrics 7 (1999): 93–100.

Aronow, W. S. "Risk Factors for Coronary Artery Disease, Peripheral Arterial Disease, and Atherothrombotic Brain Infarction in Elderly Persons." In Vascular Disease in the Elderly. Edited by W. S. Aronow, E. A. Stemmer, and S. E. Wilson. Armonk, N.Y.: Futura Publishing Co., 1997. Pages 81–103.

Downs, J. R.; Clearfield, M.; Weis, S.; Whitney, E.; Shapiro, D. R.; Beere, P. A.; Langendorfer, A.; Stein, E. A.; Kruyer, W.; and Gotto, A. M., Jr. "Primary Prevention of Acute Coronary Events with Lovastatin in Men and Women with Average Cholesterol Levels. Results of AFCAPS/TexCAPS." Journal of the American Medical Association 279 (1998): 1615–1622.

Larosa, J. C. "Hyperlipidemia in the Elderly." In Cardiovascular Disease in the Elderly Patient, 2d ed. Edited by D. D. Tresch and W. S. Aronow. New York: Marcel Dekker, Inc., 1999. Pages 129–137.

Miettinen, T. A.; Pyorala, K.; Olsson, A. G.; Musliner, T. A.; Cook, T. J.; Faergeman, O.; Berg, K.; Pedersen, T.; and Kjekshus, J. "Cholesterol-Lowering Therapy in Women and Elderly Patients with Myocardial Infarction or Angina Pectoris. Findings from the Scandinavian Simvastatin Survival Study (4S)." Circulation 96 (1997): 4211–4218.