The cardiovascular system comprises the heart, veins, arteries , and capillaries, which carry blood back and forth from the heart to the lungs (pulmonary circulation) and from the heart to the rest of the body (systemic circulation). The heart works on electrical impulses and produces them constantly, unless stress , fear, or danger is involved, in which case the impulses will increase dramatically. The body's largest artery is the aorta and the largest vein is the vena cava. Veins are thinner than arteries, which resemble rubber bands in that they expand more easily (depending on the amount of blood passing through them). Smaller blood vessels, or capillaries, channel oxygen and blood to tissues. The process is a cycle in which the capillaries deliver oxygen-rich blood to the body and pick up oxygen-poor blood, which is then taken into the veins and finally to the heart to be "rejuvenated" or cleansed.
Cardiovascular disease (CVD), and the resulting complications, is the main cause of death for both males and females in the United States and other technologically advanced countries of the world. It usually is in the top five causes of death in lesser-developed countries. Diseases of the cardiovascular system include those that compromise the pumping ability of the heart, cause failure of the valves, or result in narrowing or hardening of the arteries. In addition, toxins and infectious agents may damage the heart and blood vessels. Injury or failure of the cardiovascular system, especially the heart, also will affect the peripheral tissues that depend on the delivery of nutrients and the removal of wastes through the blood vascular system. CVD is a family of diseases that includes hypertension , atherosclerosis , coronary heart disease , and stroke .
Hypertension (High Blood Pressure)
Blood pressure is a measure of the force of blood against the walls of arteries. It is recorded as two numbers: the systolic pressure over the diastolic pressure. Systolic pressure is the pressure as the heart beats, while diastolic pressure measures the pressure when the heart relaxes between beats.
Blood pressure is normally measured at the brachial artery with a sphygmomanometer (pressure cuff) in millimeters of mercury (mm Hg) and given as systolic over diastolic pressure. Normal blood pressure is less than 120 mm Hg systolic and less than 80 mm Hg diastolic—usually expressed as "120 over 80." However, normal for an individual varies with the height, weight, fitness level, age, and health of a person. Blood pressure is normally maintained within narrow limits, but it can drop during sleep or increase during exercise. Hypertension (HTN), or high blood pressure, occurs when the force of blood passing through blood vessels is above normal. The increase in pressure forces the blood to hit the blood vessel walls. HTN is called "the silent killer" because many people do not know they have the condition. Consistently high blood pressure increases the risk for a stroke or a heart attack . It may be caused by poor diet , obesity , smoking, stress , and inactivity. The Dietary Approach to Stop Hypertension (DASH) project recommends a diet that is low in sodium and high in fruits, vegetables, and low-fat dairy products. Other approaches to controlling HTN include weight loss, smoking cessation, increased physical activity, and stress management.
Atherosclerosis, or hardening of the arteries, is the cause of more than half of all mortality in developed countries and the leading cause of death in the United States. When the coronary arteries are involved, it results in coronary artery disease (CAD). The hardening of the arteries is due to the build up of fatty deposits called plaque , and mineral deposits. As a result, the supply of blood to the heart muscle (myocardium) is reduced and can lead to ischema (deficiency of blood) to the heart, causing chest pain or a myocardial infarction (heart attack). The hardening of the arteries causes an increase in resistance to blood flow, and therefore an increase in blood pressure. Any vessel in the body may be affected by atherosclerosis; however, the aorta and the coronary, carotid, and iliac arteries are most frequently affected. The process begins early in life. Therefore, physicians should obtain risk-factor profiles and a family history for children.
Coronary Artery Disease
Coronary artery disease (CAD) refers to any of the conditions that affect the coronary arteries and reduces blood flow and nutrients to the heart. It is the leading cause of death worldwide for both men and women. Atherosclerosis is the primary cause of CAD. Controlled risk factors associated with CAD include hypertension, cigarette smoking, elevated blood lipids (e.g., cholesterol , triglyceride ), a high-fat diet (especially saturated fats and trans-fatty acids ), physical inactivity, obesity, diabetes , and stress. Lifestyle changes can assist in prevention of CAD. Uncontrolled risk factors include a family history of CAD, gender (higher in males), and increasing age.
Stroke, or a cerebrovascular accident (CVA), occurs when the brain does not receive sufficient oxygen-rich blood through blood vessels or when a blood vessel bursts. A stroke may result from blockage of the blood vessels due to a blood clot (ischemic) or from ruptures of the blood vessels (hemorrhagic bursts). Uncontrolled hypertension is a major risk factor for strokes.
The symptoms of CVD develop over many years and often do not manifest themselves until old age. Autopsies of young servicemen indicate significant accumulation of plaque and hardening of the arteries (atherosclerosis). Thus, primary prevention for CVD must begin in early childhood. Preventing premature CVD (before age 60) is crucial. Heart attacks between the ages of forty and sixty are primarily due to lifestyle factors.
Smoking, high blood cholesterol, high blood pressure, and lack of physical activity are the most serious risk factors for CVD and heart attack. Controlling one of these risk factors can help control others. For example, regular exercise can help control cholesterol, blood pressure, weight, and stress levels. Smoking is the most preventable risk factor. Smokers have twice the risk for heart attack that nonsmokers have. Tobacco use alters the blood chemistry and increases blood clotting . Nearly one-fifth of all deaths are due to tobacco use, and a smoker lives an average of seven to eight fewer years than a nonsmoker.
The worldwide increase in obesity and type 2 diabetes (in both children and adults) point to a high-fat, high-calorie diet and a sedentary lifestyle. Poverty increases the risk for poor dietary habits and poor access to healthful foods. Many of the world's urban poor have more access to highly processed foods , convenience foods , and fast foods than to fresh fruits and vegetables. But even in the most wealthy and technologically advanced countries, the affluent are choosing to eat more fast foods and processed foods that are high in fat, cholesterol, and sodium. For optimal health, health professionals recommend:
- Maintaining a healthy weight, with a body mass index (BMI) of 18.5–24.9.
- Limiting dietary fat to 30 percent or less of total calories—10 percent saturated fat , 10 percent polyunsaturated fat, and 10 percent monounsaturated fats. Consumers should be aware that ounce for ounce, all sources of fat have approximately the same amounts of calories.
- Limiting saturated fats to 10 percent of calories. Saturated fats come primarily from animal sources (e.g., high-fat dairy and meats), but also are found in coconut and palm oil.
- Limiting polyunsaturated fats to 10 percent of calories. Polyunsaturated fats come primarily from vegetable oils (e.g., corn oil, safflower oil).
- Limiting monounsaturated fats to 10 percent of calories. Monounsaturated fats may have a protective role in heart disease . Excellent sources of monounsaturated fats include olive oils, nuts, avocado, and canola oil.
- Increasing intake of omega-3 fatty acids . Two to four grams daily of omega-3 fatty acids may lower risk for CVD by reducing blood clotting, making platelets less sticky, and lowering triglycerides. Patients should inform their physician if they are using omega-3 supplements, since they may increase the risk of bleeding. Excellent sources of
- omega-3 include fatty fish (such as salmon and sardines), fish oils, and flax seed.
- Limiting sodium intake to 2,400 milligrams per day.
- Increasing potassium intake to at least 3,500 milligrams per day.
- Eating at least five servings a day of fruits and vegetables.
- Eating a plant-based diet consisting primarily of whole grains, fruits, and vegetables is also recommended.
- Eating at least 25 grams of fiber daily.
- Eating 25 grams of soy protein daily.
In addition to diet modification, research is increasingly focused on the role of physical activity in preventing CVD. People who are not physically active have twice the risk of heart disease as those who are active. More than half of U.S. adults do not achieve recommended levels of physical activity. Studies indicate a correlation between the amount of television viewing, playing videos, and other sedentary activities and increased rates of childhood obesity. In general, the more sedentary the activities, the more high-fat and sugary foods are consumed. At least thirty minutes of moderate physical activity, five times a week, is recommended. Moderate physical activity slows down the narrowing of the blood vessels, due to contraction of the smooth muscles in the vessel walls. It also increases coronary blood flow, strengthens the heart muscles, and reduces stress.
Worldwide, HTN is linked to about 50 percent of CVDs and approximately 75 million "lost healthy life years" each year. Thus, controlling HTN may greatly reduce the risk of disability and death from CVD. Secondary prevention involves treating the signs and symptoms of CVD. These strategies include management of hypertension, cholesterol, and other blood lipids. Dietary and lifestyle modification are tried first. However, medication may also be prescribed, depending on other clinical factors. Compliance with a medication regimen is extremely important, as is the monitoring of blood pressure and blood lipids. Recommended total serum cholesterol should not exceed 200 milligrams per deciliter (mg/dl); low-density lipoproteins (LDLs or "bad cholesterol") should not exceed 100 mg/dl, and high-density lipoproteins (HDLs or "good cholesterol") should not be lower than 40 mg/dl.
Surgical intervention may restore cardiovascular function. Vessels may be opened by angioplasty or repaired by the use of grafts or stents, heart valves can be repaired or replaced with artificial valves, and pacemakers or drugs may aid heart function. A heart transplant may be an individual's last resort. Many large-scale international studies have focused on preventing cardiovascular disease through smoking cessation, healthful eating, physical activity, hypertension and cholesterol control, health education, and media campaigns. These include the Stanford Three City, the Stanford Five City Projects, the Framingham Heart Study, the Bogalusa Heart Study, the Multiple Risk Factor Intervention Trial (MRFIT), Active Australia, the Whickham Study (based on the Framingham model), and the North Karelia Study (Finland). Small, gradual changes in diet and exercise and smoking cessation are the best way to produce long-term effects.
see also Arteriosclerosis; Atherosclerosis; Heart Disease.
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The American Heart Association (AHA) uses the term cardiovascular disease (CVD) to describe various diseases that affect the heart and circulatory system. These diseases include coronary artery (heart) disease, hypertension, congestive heart failure, congenital cardiovascular defects, and cerebrovascular disease. CVD is a chronic disease. These diseases frequently progress as people age. This article limits discussion to the two most common forms of CVD—coronary artery disease and hypertension.
Cardiovascular disease is the leading cause of death in the United States, responsible for one death every 33 seconds or 2,600 deaths per day. In 1998 CVD claimed the lives of 949,619 Americans. The second leading cause of death, cancer, was responsible for 541,532 deaths. It is estimated that approximately 60.8 million individuals in the United States have one or more types of CVD. The most common form of cardiovascular disease is hypertension, which affects approximately 50 million Americans, or one in every four individuals. Hypertension is a significant risk factor for the development of other types of CVD, including congestive heart failure and cerebrovascular accidents.
The second most prevalent form of CVD is coronary heart disease or coronary artery disease, which affects approximately 12.4 million individuals. Coronary heart disease includes both angina pectoris (chest pain) and myocardial infarction (heart attack). In 1998 the American Heart Association estimated that 7.3 million individuals had suffered a heart attack, and 6.4 million had experienced chest pain. The third most prevalent form of CVD is congestive heart failure, which affects 4.7 million Americans. Cerebrovascular accidents are the fourth most prevalent form of CVD, affecting 4.5 million individuals. Congenital cardiovascular defects affect 1 million Americans, comprising the fifth most prevalent form of CVD. In general, approximately one in five Americans will develop some form of cardiovascular disease in their lifetime.
Risk factors for CVD may be divided into three classifications: modifiable, nonmodifiable, and contributing factors.
Modifiable factors. Modifiable risk factors are those that an individual can change, including elevated serum cholesterol levels, a diet high in saturated fats, obesity, physical inactivity, hypertension, nicotine, and alcohol use. A serum cholesterol level greater than 200 mg/dl or a fasting triglyceride level more than 200 mg/dl is associated with an increased incidence of coronary artery disease. Obesity is associated with a higher incidence of mortality from CVD. Physical inactivity increases the risk for developing CVD as much as smoking or consuming a diet high in saturated fats and cholesterol.
The National Heart Lung and Blood Institute defines hypertension as a blood pressure greater than 140/90. Hypertension is a significant risk factor for the development of CVD and stroke. The AHA estimates that one in five deaths from cardiovascular disease are directly linked to cigarette smoking. Individuals who smoke are two to six times more likely to develop coronary artery disease than nonsmokers. However, individuals who quit smoking will reduce their risk to levels equivalent to those of a nonsmoker within three years.
Nonmodifiable factors. Nonmodifiable risk factors are those risk factors that an individual cannot change, such as age, gender, ethnicity, and heredity. The incidence of CVD increases as people age. However, 150,000 individuals die from it before 65 years of age. Males are more likely than females to experience CVD, until the age of 65, when the incidence rate equalizes among genders. Young men aged 35 to 44 years old are more than six times as likely to die from CVD than their same-age female counterparts. However, the death rates equalize after 75 years of age. Furthermore, women may experience different symptoms of CVD than those experienced by men, thus causing women to be underdiagnosed or diagnosed at a more advanced stage of the disease.
Ethnicity also plays a role in the development of CVD. Non-Hispanic black males have a higher age-adjusted prevalence of CVD than Caucasian or Mexican-American males. Black and Mexican-American females have a higher age-adjusted prevalence of CVD than Caucasian females. Overall, middle-aged Caucasian males have the highest incidence of heart attacks.
Heredity may also play a role in the development of CVD. Individuals with a family history of early heart disease are at a greater risk for the development of elevated blood lipid levels, which has been associated with the early development of coronary artery disease. Additionally, most individuals who have experienced either chest pain or a heart attack can identify a close family member (father, mother, brother, or sister) who also had or has CVD. It is expected that the role of genetics and heredity will be more fully understood in the future due to the advances associated with the human genome project.
Contributing factors. Contributing factors are those factors that may increase the risk for developing cardiovascular disease. Diabetes mellitus and a stressful lifestyle are examples of contributing factors. Diabetics are more likely than the general population to experience CVD. Additionally, they experience coronary artery disease at an earlier age than the nondiabetic individual. Two-thirds of individuals with diabetes mellitus die from some form of heart or blood vessel disease.
The role of stress in the development of coronary artery disease is not clearly understood. Historically it was believed that individuals with a type A personality were at a greater risk for the development of CVD. However, the research findings were mixed and did not clearly support this relationship. Stress may also increase the process of atherogenesis (formation of plaque in arteries) due to elevated lipid levels.
Ischemic CVD, such as angina pectoris and myocardial infarction, are usually diagnosed based on patient symptoms, electrocardiogram findings, and cardiac enzyme results. Additionally, coronary angiography may be performed to visualize the coronary arteries and determine the exact location and severity of any obstructions. Coronary artery disease can be treated using medical treatments, surgical treatments, or interventional cardiology. The treatment goal for ischemic CVD is to restore optimal flow of oxygenated blood to the heart.
Medical treatment for the patient with angina includes risk factor modification, consumption of a diet low in saturated fats and cholesterol, and administration of pharmacological agents. Medications commonly used to treat chest pain or heart attacks include drugs that decrease cholesterol levels, alter platelet aggregation, enhance the supply of oxygenated blood to the heart, or decrease the heart's need for oxygenated blood. Additionally, the person experiencing an acute anginal attack or a heart attack may also receive supplemental oxygen. Thrombolytic medications may be used to treat a patient experiencing a attack, as they may dissolve the blood clot, thus restoring blood flow to the heart.
The blood flow to the heart may also be restored surgically though the use of a common procedure known as coronary artery bypass grafting (CABG). This procedure bypasses the obstructed coronary artery or arteries, thus restoring the flow of oxygenated blood to the heart. Women have poorer surgical outcomes after coronary bypass surgery than men. Specifically, women have a higher relative risk of mortality associated with CABG, longer intensive care unit stays, and more postoperative complications than men.
Nonsurgical revascularization techniques, such as percutaneous transluminal angioplasty, transmyocardial laser revascularization, or the placement of stents in the coronary arteries, are techniques to restore the flow of oxygenated blood to the heart. Percutaneous transluminal angioplasty involves the insertion of a balloon-tipped catheter into the coronary artery, and inflating the balloon at the location of the vessel obstruction. The balloon widens the blood vessel, restoring blood flow through the obstructed vessel. A wire mesh stent may be inserted into the coronary artery and placed at the location of the obstruction. The stent provides an artificial opening in the blood vessel, which helps to maintain the flow of oxygenated blood to the heart. Transmyocardial laser revascularization is a procedure that uses a laser to create channels in the heart to allow oxygenated blood to reach the heart, and is generally used when other techniques have failed.
Research into the efficacy of cardiac gene therapy is being studied to determine how to eliminate heart disease by replacing malfunctioning or missing genes with normal or modified genes. Gene therapy may be used to stimulate the growth of new blood vessels, prevent cell death, or enhance functioning of genes.
Hypertension is initially treated by behavioral and lifestyle modifications. If these modifications do not successfully manage the individual's hypertension, pharmacological agents are added. The lifestyle modifications recommended to control hypertension include diet, exercise, and weight reduction for the overweight individual. The recommended dietary modifications include increasing consumption of fruits, vegetables, low-fat dairy products, and other foods that are low in saturated fat, total fat, and cholesterol. Furthermore, the individual with hypertension is advised to decrease intake of foods high in fat, red meats, sweets, and sugared beverages. It is advisable for hypertensive individuals to decrease their intake of sodium to less than 1,500 mg/day. Not adding table salt to foods and avoiding obviously salty foods may accomplish this restriction. Doctors suggest that hypertensive individuals limit their consumption of alcohol to one to two drinks per day, and decrease or stop smoking. Smoking causes hardening of the arteries, which may increase blood pressure.
Various classes of pharmacological agents may be used to treat hypertension. They include drugs that relax the blood vessels, causing vasodilation, thus decreasing blood pressure, such as angiotensin converting enzyme inhibitors, calcium channel blockers, angiotensin antagonists, and vasodilators. Drugs such as alpha- and beta-blockers decrease nerve impulses to blood vessels, and decrease the heart rate, slowing blood flow through the arteries, resulting in a decreased blood pressure. Diuretics may also be used to manage hypertension. They work by flushing excess water and sodium from the body, causing a decrease in blood pressure.
Coronary artery disease and hypertension are both chronic diseases that require lifelong treatment. Frequently, interventional cardiology techniques and surgical procedures produce palliative rather than curative results. For example, percutaneous transluminal angioplasty fails in six months in approximately 30 to 60 percent of the cases, resulting in restenosis of the blood vessel. Additionally, 50 percent of the grafts of patients who have undergone coronary artery bypass surgery reocclude within five years. Once this has occurred, the patient may be required to undergo additional procedures or surgery.
Individuals who have experienced a heart attack are at a significantly greater risk for future cardiovascular morbidity and mortality. The death rates for people after experiencing a heart attack are significantly higher than the general public. Twenty-five percent of males and 38 percent of females will die within one year of experiencing a heart attack. Additionally, morbidity from cardiovascular disease is higher in individuals who have previously experienced a heart attack. Two-thirds of all heart attack patients do not make a full recovery. CVD is progressive: Twenty-two percent of males and 46 percent of females who previously experienced a heart attack are disabled with heart failure within six years.
Hypertension increases the rate of atherosclerosis, resulting in common complications such as hypertensive heart disease, cerebrovascular disease, peripheral vascular disease, nephrosclerosis, and retinal damage. Uncontrolled hypertension is strongly correlated with the development of coronary artery disease, enlargement of the left ventricle, and heart failure. Additionally, hypertension is a major risk factor for the development of stroke and end stage renal disease.
See also: Causes of Death; Nutrition and Exercise
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BRENDA C. MORRIS
CARDIOVASCULAR DISEASE is the name of a group of ailments that affect the heart and blood vessels, including but not limited to hypertension, heart attack, stroke, congenital and rheumatic heart disease, and arrhythmia. The leading cause of death in America in the early twenty-first century, heart disease strikes both men and women across racial and ethnic lines, with people age 35 to 64 years old the most susceptible. Approximately one million Americans die of heart disease annually. For the millions of Americans with some form of heart disease, premature and permanent disability is a constant threat.
The diagnosis and treatment of heart disease developed slowly. In the eighteenth century one of the first steps toward diagnosis was Viennese scientist Leopold Auenbrugger's method of percussion. Striking the patient's chest to listen and feel the reverberation allowed Auenbrugger to estimate the size of the heart and the presence of fluid in the chest. Auenbrugger's method was improved by the invention of the stethoscope by French physician René Laënnec. These methods worked well for diseases that produced physical symptoms but not for ailments with no physical signs. Two other important eighteenth-century physicians were Englishmen William Heberden and John Hunter, who concentrated on the manifestation of the disease instead of the causes. The first to use the term "angina pectoris" in a 1772 lecture, Heberden separated myocardial infarction (heart attack) from other types of chest pain.
In 1902 Willem Einthoven, a Dutch physiologist, published the first electrocardiogram, which he recorded on a string galvanometer he had adapted for this purpose. This device was the forerunner of the electrocardiograph (EKG), a device that reads and records the heart's electrical activity. The EKG built on the work of English physicians James Mackenzie, developer of the polygraph, and Thomas Lewis. In Europe, physicians tended to deemphasize the role of technology in diagnoses but American physician James Herrick saw the potential usefulness of the EKG in diagnosing conditions that could not be detected using the unaided senses. In 1912 Herrick was the first to describe coronary artery disease, or hardening of the arteries, as a form of heart disease.
In the spring of 1929, Werner Forssmann, a German physician, took another important step in cardiac research. Forssmann, fascinated by research conducted by nineteenth-century French doctors, inserted a urethral catheter into a main vein in his arm and guided the catheter into his own heart. Three years later two American doctors, Dickinson Richards, Jr. and André Cournand, moved Forssmann's research forward. Richards and Cournand began with the belief that the heart, lungs, and circulatory system were actually a single system. By 1942 the doctors successfully reached the right ventricle, and two years later they successfully inserted a catheter into a patient's pulmonary artery. Using a catheter, the doctors could measure hemodynamic pressure and oxygen in each side of the heart. Richards and Cournand received federal funds to continue their research.
With advances in technology, methods for treating patients suffering from heart disease increased. By 1938 the American Robert Gross had performed the first heart surgery, and by 1952 another American, F. John Lewis, performed the first open-heart surgery. In 1967 the South African surgeon Christiaan Barnard completed the first whole-heart transplant. One of the most striking medical advances is the artificial heart. The Jarvik-7, developed by the American doctor Robert K. Jarvik, was made to operate like a real heart. Made of aluminum, plastic, and Dacron polyester and needing a power source, the Jarvik-7 is bulky and meant to serve only as a temporary solution for those on a transplant list. Jarvik's heart, first used in the 1980s, was not the first artificial heart. In 1957 the Dutch physician Willem Kolff and his team tested an artificial heart in animals, and by 1969 another team led by Denton Cooley of the Texas Heart Institute kept a human artificial-heart patient alive for more than sixty hours. In 1982 the first Jarvik heart was transferred to Barney Clark by a team led by University of Utah's William DeVries. Clark lived for 112 days after the transplant.
Treatments less drastic than transplant surgery were also developed. For instance, in the late 1960s and early 1970s surgeons rerouted blood flow to the heart with coronary artery bypass surgery. Another less invasive procedure called percutaneous transluminal coronary angioplasty was developed in the late 1970s to open occluded cardiac arteries without opening the chest. Angioplasty uses a small device that is threaded through blood vessels to reach a blockage in the cardiac arteries. For patients suffering from abnormal or slow heart rhythm, doctors use a pacemaker, developed in the 1980s. Pacemakers, using lithium batteries lasting seven to ten years, are inserted in the body with wires attached to the heart. When the heart rhythm becomes dangerous the pacemaker delivers a shock to restore a normal heartbeat. The key to survival for heart attack victims is getting to the hospital quickly. Fortunately public awareness and widespread knowledge about CPR, cardiopulmonary resuscitation, greatly increases victims' chances.
Doctors and researchers have also identified certain risk factors that increase a person's chance of developing heart disease. In 1948 the Framingham Heart Study was initiated to track 5,209 people, examining each person every two years. The study's findings demonstrated that men, older people, and people with a family history of heart disease were more likely to develop heart problems. Further, the study indicated that those who smoke, have a poor diet, and lead sedentary lifestyles, are more likely to develop heart disease. The American Heart Association (AHA) was formed in 1924 to help doctors educate the public about heart disease. After launching a public awareness campaign in 1948, the AHA grew rapidly and remains one of the loudest voices for public health in America.
In industrialized countries cardiovascular disease is the leading cause of death. In the United States in 1998, the death rate from heart disease per 100,000 population was 268.2; such deaths numbered 725,000, comprising 31 percent of all deaths. The great majority of coronary heart disease (CHD) occurs among older individuals. In the United States, in 1998, the proportion of CHD deaths occurring to persons 65 years and older was 84 percent–90 percent among women and 77 percent among men. Table 1 shows the steep increase of CHD death rates by age in the United States. Yet coronary heart disease and other cardiovascular diseases such as stroke and peripheral vascular disease are not diseases of aging. There are many populations of older individuals in which the incidence of heart attacks is very low.
Atherosclerosis is the basic pathology that causes heart attacks. The atherosclerotic disease begins early in life and progresses over time. This evolving atherosclerotic disease represents the "silent" or incubation period to the clinical disease, heart attack. The onset of the heart attack can occur rapidly and in about 20 percent of the cases is associated with sudden death. The amount of specific saturated fatty acids, cholesterol, and polyunsaturated fatty acids in the diet, as well as specific genetic susceptibility factors, determine the blood levels of lowdensity lipoprotein (LDL) cholesterol and the number of LDL particles in the blood that together predict, to a considerable degree, the extent of atherosclerosis.
Consequences of Urbanization and Industrialization
With urbanization and industrialization, and with increasing longevity, populations usually experience a transition from a high prevalence of infectious diseases
and nutritional deficiencies to higher caloric intake; decreased physical activity, especially related to work; and higher intakes of both saturated fat and cholesterol in the diet. The rise in the incidence of coronary heart attacks in such populations may not occur until many years after the changes in diet and lifestyle and the rise in LDL cholesterol. The evidence of a rising epidemic of CHD will most likely first be noted among young and middle-aged individuals, signaled by a rise in the LDL cholesterol level. Unfortunately, by the time this occurs, there is extensive atherosclerosis in the population and a likelihood of subsequent higher rates of heart attack.
In developing countries, the rising incidence of CHD initially affects the better educated. There is a major increase in the use of health resources for treating cardiovascular disease in these populations, with a potential drain on resources and technology in other areas of the health system.
These same populations also typically experience an increase in caloric intake and a decrease in work-related energy expenditure. There is an increase in high-fat, calorically dense foods, often resulting in obesity, as well as an increase in processed foods whose salt (sodium chloride) content is undesirably high. These factors lead to elevated blood pressure and hypertension. This pattern is now occurring in Africa, especially in west Africa, as well as in populations of African origin in Caribbean countries.
Obesity, Diabetes, and Other Risk Factors
In many industrialized countries such as the United States, Britain, and Canada, there has been a substantial increase in obesity and diabetes. The risk of diabetes is associated with weight gain and obesity, as well as with specific genetic conditions, i.e., host susceptibility. Populations of southeastern Asian origin, including American Indians and aboriginal populations in Canada, have especially high rates of diabetes–along with the complications of diabetes. The latter include CHD and small-vessel complications of diabetes such as blindness, neurological changes, and kidney failure, and such complications can necessitate amputations. The substantial increases in body weight are due to both an increase in the total caloric intake and a decrease in work-related physical activity without a sufficient compensating increase in leisure-time physical activity.
There are other important lifestyle factors that increase the risk of heart attack among individuals with severe underlying atherosclerosis. These factors act by causing a thrombus or clot in a blood vessel or by changing the characteristics of the atherosclerotic disease.
The increase in cigarette smoking in many countries, in addition to causing major epidemics of smoking-related cancers, leads to increased risk of CHD in populations where dietary changes have increased the prevalence of atherosclerotic disease. Interestingly, in populations where diet has not changed and LDL cholesterol levels have not risen, a high prevalence of cigarette smoking is not associated with a substantial increase of CHD, although it does increase the risk of cancer. This pattern has been found in China and Japan. Unfortunately, in many developing-country populations, the increasing prevalence of cigarette smoking parallels the rise in LDL cholesterol and obesity, creating the potential for severe epidemics of CHD. At the same time, the decline in CHD mortality in many industrialized countries since the 1970s was partly attributable to decreases in cigarette smoking and blood LDL cholesterol levels, along with improved treatment of hypertension.
In all industrialized societies, the number and percent of the population over the age of 65 is increasing. In these older populations, treatment of cardiovascular disease is the leading determinant of health-care costs.
In summary, the extent of cardiovascular disease in a population can be gauged very easily by measurement of a few risk factors, mainly the levels of LDL cholesterol, blood pressure, obesity, cigarette smoking, extent of diabetes, and the age distribution of the population. Cardiovascular diseases are preventable. In the prevention effort the focus, however, needs to be on the prevention of the evolving silent disease, atherosclerosis. Treatment of individuals who have developed clinical CHD and stroke requires a huge commitment of technical and medical resources.
Yusuf, Salim, Srinath Reddy, Stephanie Ounpuu, and Sonia Anand. 2001. "Global Burden of Cardiovascular Diseases. Part I: General Considerations, the Epidemiologic Transition, Risk Factors, and Impact of Urbanization." Circulation 104: 2,746–2,753.
——. 2001. "Global Burden of Cardiovascular Diseases. Part II: Variations in Cardiovascular Disease by Specific Ethnic Groups and Geographic Regions and Prevention Strategies." Circulation 104: 2,855–2,864.
Lewis H. Kuller
Cardiovascular disease is a set of diseases affecting the heart and blood vessels. As with most chronic diseases whose incidence increases with age, it involves both inherited and environmental contributors and is therefore classified as a complex genetic disease. Most researchers believe that all major risk factors for cardiovascular disease have been identified. It is estimated that cigarette smoking, hypertension , abnormal serum cholesterol (low-density lipoprotein cholesterol or high-density lipoprotein cholesterol), obesity, lack of physical exercise, and diabetes account for 50 percent of the variability of risk in high-risk populations. The remaining risk is likely composed of a large number of yet-to-be identified minor risk factors or genetic influences that account for the development of disease in most individuals. Investigators who have attempted to estimate the overall contribution of genetics to the development of cardiovascular disease have proposed numbers ranging from 20 to 60 percent, based upon the analysis of large epidemiologic studies.
Finding Genes for Cardiovascular Disease
Genetics studies of cardiovascular disease involve searches for genes in two general classes: causative genes and disease-susceptibility (or disease-modifying) genes. These are sought through gene-linkage analysis or candidate-gene studies, respectively. Identifying causative genes for this disease is likely several years away at best. Before that time, however, a new understanding will have been reached regarding the relationship between inherited risks and outcomes in cardiovascular disease. With the development of new technology, we also have the promise of a detailed catalogue of disease-modifying genes that may open the door to therapeutic advances.
Gene-linkage analyses involve the study of families that express the cardiovascular trait of interest. In such studies, it is important also to establish the relative risk. Relative risk is defined as the probability of developing a condition (such as cardiovascular disease) if a risk factor (such as a gene) is present, divided by the probability of developing the condition if the risk factor is absent. A relative risk greater than 4.0 (that is, a four-fold greater risk due to presence of a gene or genes) will be associated with a reasonable likelihood of success in finding associated genes, given a study of 200 sibling pairs demonstrating the condition.
One of the best-studied types of cardiovascular disease is early-onset (or premature) coronary artery disease, which has a particularly strong genetic or inherited component. The coronary arteries are those around the heart that supply it with blood. Early-onset is defined as disease presentation (as reversible heart pain, heart attack, or cardiovascular surgery) before the age of 50. Approximately 8 to 10 percent of the U.S. population with cardiovascular disease presents before age 50, according to most surveys. Based upon a number of relatively small epidemiologic studies and several genetics studies in twins, a conservative estimate of the relative risk ratio contributed by genetics to the development of early-onset cardiovascular disease is between 4.0 and 8.0. Despite the fact that it has an inherited component, the actual genes responsible for familial predisposition to early-onset coronary artery disease have been incompletely investigated and remain obscure.
While population-level relative risk for developing cardiovascular disease can be known with a great deal of accuracy, therefore, this knowledge cannot be used to counsel or direct therapy for an individual in any given family. In fact, it has become clear to most practicing cardiologists that even when we know which cardiovascular risk factors are present, we have a very limited ability to predict the development of disease in most individuals.
The ongoing studies of the genetics of cardiovascular disease consist of two general types: those that accumulate individual cases with the goal of performing association candidate-gene studies, and those that collect data from families (sibling pairs or extended families) with the idea of performing gene-linkage studies. Candidate-gene studies examine variations in genes that code for proteins that are likely to be involved in a disease or its prevention, such as genes controlling cholesterol metabolism or blood pressure. Linkage studies look for chromosome regions that are co-inherited with risk for disease, and then look carefully at the region to determine what genes are present.
Patients for both types of studies may be located in similar ways. Disease registry databases contain information on patients with particular conditions, which may have been collected by hospitals, charitable organizations, or research organizations. Clinical trials databases are generated during the testing of a new drug or other treatment. Population-based longitudinal studies collect data on a large number of randomly selected people (not just those with disease) and follow them over many years, to determine what factors lead to development of disease. Each study has its own contribution to make, and only through the combined efforts of multiple studies and approaches will we discover and understand the genetic contributions to the development of cardiovascular disease.
Goals of Genetic Studies
Many of the promises of genetics investigations have probably been grossly overstated. The immediate potential of the ongoing and planned investigations into the genetics of cardiovascular disease is more promising for gene-directed therapy (the use of genetic information to guide the judicious use of medical interventions) than for somatic gene therapy (the use of a gene or gene product which, when introduced into a human organ, changes the function of the organ).
The realistic promises of current genetics studies include the elucidation of disease mechanisms; the identification of new targets for the development of therapeutic pharmacologic agents; and the use of genetic markers to identify individuals for whom a particular agent is either effective or unusually hazardous. This approach, called pharmacogenomics, improves the safety and efficacy of treatments, and enhances the ability to preferentially select subjects for clinical trials based upon genetic predispostion and for gene-directed therapy. In the latter case, for example, a genetic contributor to the development of early-onset cardiovascular disease might be used as an additional risk factor whose identification could focus the allocation of preventive resources, whether educational, behavioral, or pharmacologic, to populations at particularly high risk for the disease.
see also Complex Traits; Gene and Environment; Pharmacogenetics and Pharmacogenomics; Public Health, Genetic Techniques in; Statistics.
Lander, E. S., and N. J. Schork. "Genetic Dissection of Complex Traits." Science 265 (1994): 2035-2048.