Heart Disease
Coronary artery disease (CAD)-obstruction or narrowing
of the arteries supplying blood flow to the heart- and its complications
remain the most common cause of disability and death in the United
States and Western Europe. In the US, CAD claims more lives each year
than the next 7 leading causes of death combined. The major
complications of CAD are chest pains (angina pectoris), myocardial
infarction ("heart attacks"), congestive heart failure, and
sudden cardiac death.
Atherosclerosis (hardening of the arteries) very often
affects the coronary arteries that supply nourishing blood flow to the
heart muscle. The word atherosclerosis is derived from the Greek athero
(gruel) and sclerosis (hardening). The lesions or "plaques"
within the artery walls consist of localized deposits of fat compounds
(lipids) surrounded by cells recruited from the blood stream and scar
tissue. Cholesterol is the major lipid found in plaques. Lipids in the
artery wall act as irritants. Some plaques are mechanically unstable,
and like abscesses, may rupture and expose their contents to the
streaming blood. In response to the irritation, white blood cells and
platelets are summoned to the scene. White blood cells produce chemicals
that cause inflammation just as they would if they were battling an
infection. These chemicals promote blood clotting and the formation of
scar tissue. Blood clots therefore tend to form at the site of the
plaque. Because plaque substances are very potent in causing blood to
clot, the ruptured plaques are often covered by clotted blood. As the
blood clot grows, it may critically reduce the diameter of the artery so
that blood flow is decreased or even stopped. Deprival of blood flow to
the cells downstream is known as ischemia (literally "withheld
blood"). When ischemia becomes severe enough, the survival of heart
muscle cells is endangered and myocardial infarction can result. Even if
blood flow is not reduced enough to kill the cells, it may be
insufficient to allow the cells to carry on normal activity.
CAD, even when severe, may produce no or few symptoms.
In many patients, the first symptom of CAD may represent two
catastrophic events - sudden death or a heart attack. In other patients,
reduced blood flow or ischemia may cause episodic chest pressure or
pain, a symptom signaling the presence of CAD.
CAD is a multifactorial disease where genetic and
environmental factors interact in complex ways to cause the disease to
progress. The incidence and mortality of CAD increase with age, but the
development of CAD is not a simply a result of the aging process.
Studies of large populations have identified several characteristics
that are associated with increased probability of developing CAD. These
"risk factors" include elevated blood cholesterol, high blood
pressure, diabetes, obesity, cigarette smoking, and family history of
CAD. The sex difference in the incidence and severity of CAD reflects
the fact that female hormone (estrogen) has protective effects against
CAD and that the male hormone (testosterone) has aggravating effects on
CAD progression. The mortality rate for males is 5 times greater than
that for females at ages 35-44, but after menopause the mortality rate
in females approaches that for age matched males. The risk of cardiac
disease in any individual rises substantially when two or more risk
factors are present.
Cholesterol and triglycerides are transported in the
bloodstream as particles (lipoproteins) in which the lipids are bound
to specific proteins. Cholesterol is an essential component of cell
membranes and it is the precursor of vital steroid hormones such as
cortisone and estrogen. Triglycerides contain fatty acids, a major
source of energy for muscles and other organs. Increased dietary fat
loads and decreased disposal of lipids due to genetic defects or
inactivity can lead to the accumulation of triglyceride- and
cholesterol-rich lipoproteins in blood and artery walls. These
accumulations are responsible for initiating atherosclerosis and CAD.
It has been estimated that severe genetic defects for
handling of lipoproteins occur in at least one out of 500 people in
the US. Genetic defects in the handling of lipoproteins become
particularly serious when "bad genes" are inherited from
both parents. However, many more people in the US are thought to have
less severe but still important inherited abnormalities in the
handling of lipids. Minor genetic abnormalities of lipoprotein
metabolism (dyslipidemia) can be demonstrated in most persons that eat
a typical American diet and exhibit elevated blood lipids. Genetic
abnormalities of lipid metabolism are often linked with genetic
abnormalities producing high blood pressure. As many as 60% of persons
with high blood lipids also suffer from high blood pressure. Insulin
resistance (sometimes significant enough to cause diabetes) has also
been associated with genetic abnormalities of lipid metabolism.
The characterization of abnormal lipid metabolism that
may increase atherosclerosis requires blood testing beyond simple
measurements of cholesterol levels. However, identification of
increased risk can often be made with relatively simple blood testing
for cholesterol and triglycerides. There is general agreement that
both "bad" (LDL) cholesterol and "good" (HDL)
cholesterol should be screened routinely. The extent to which
screening should include detailed characterizations of blood lipids
has been controversial.
Modern lifestyles in industrialized countries have
contributed to increased atherosclerosis. Diets high in fat and low
levels of exercise work together to cause fat deposition in the body.
In many such individuals, exercise and reduction in fat intake may
suffice to reduce blood lipids to acceptable levels. However, for
persons unable to change their lifestyle and for those suffering from
severe genetic defects in lipoprotein metabolism, medications are
necessary to prevent high blood lipids and their consequences.
Hypertension is usually defined as blood pressure
greater than 140/90 mmHg. Hypertension accelerates the development of
CAD and increases the workload of the heart. The presence of
hypertension more than doubles the CAD risk at any given level of
cholesterol. As noted elsewhere, hypertension is often found to
coexist with other CAD risk factors. Effective drugs exist to lower
elevated blood pressure. However, lowering the blood pressure may not
by itself halt the atherosclerotic process since other associated
abnormalities, in particular dyslipidemia, obesity, and diabetes, so
frequently accompany hypertension.
The combination of heightened energy demand and
limited energy supply due to CAD has adverse effects on the heart
muscle and may represent the major mechanism of chronic heart failure.
Beside its effects on the heart, uncontrolled hypertension is also
associated with increased risk of stroke, aortic aneurysm formation,
and kidney failure.
Diabetics have two times the incidence of CAD as
nondiabetics, and CAD is the leading cause of death among adult
diabetics. The metabolic interactions between high blood lipids,
hypertension, and abnormal insulin function (insulin resistance and
hyperinsulinism) are very complex and beyond the scope of this text.
Most diabetics in the US suffer from type II diabetes
mellitus, a disorder in which the body continues to produce insulin
but in amounts insufficient to control the blood sugar. Insulin
resistance-failure of the body to respond normally to insulin-is the
factor most responsible for the development of overt diabetes. In
response to insulin resistance, the body overproduces insulin. Beside
controlling the blood sugar, insulin may act as a growth factor for
cells in the blood vessels, causing them to grow inappropriately. High
blood glucose levels cause glucose to attach to proteins in the blood
(including lipoproteins) in the blood vessels, changing the structure
of the molecules and altering the way they function.
Controlling diabetes is an important part of
controlling the progression of CAD. Mortality from CAD is elevated in
patients with poor diabetes control, and good control of diabetes
appears to decrease the CAD mortality of the diabetic patient back to
the level of nondiabetic patients. Management of diabetes includes
careful attention to diet, regular exercise, and drug therapy. Some
drugs (the sulfonylurea compounds) have been suggested to cause
increases in the risk of myocardial infarction, but why this may occur
is not clear. Control of diabetes also improves the lipid profile of
diabetic patients.
The number of overweight and obese people is rising
worldwide in industrialized countries. Obesity is on the verge of
becoming the leading modifiable risk factor for illness and death in
the US. As noted above, obesity is associated with the development of
hypertension, diabetes, insulin resistance, and hyperlipidemia.
Control of obesity involves decreasing caloric intake
and increasing energy expenditure. Low fat diets alone are seldom
successful in controlling obesity since the patient often increases
caloric intake from lower fat foods to compensate for the hunger
feelings that often persist when fat intake is decreased. Decreasing
caloric intake requires decreasing the intake of all foods. Increasing
energy expenditure is also very important in the management of
obesity. Activities as simple as walking increase caloric expenditure
and build muscle mass, which in turn increase energy expenditure
further. Exercise can also help suppress appetite.
Control of obesity is a lifelong activity for most
people. Eating habits must be watched constantly, and exercise should
be continued. Support of family and friends is very important in
weight control.
The risk of death from CAD is up to 6 times higher in
smokers than in nonsmokers. Smoking acts by adversely altering the
lipid profile and by enhancing the inflammatory response to high blood
lipids, leading to blood clot formation in the arteries. Smoking also
increases levels of stress hormones and increases platelet
adhesiveness. These effects combine to increase markedly the
likelihood of arrhythmias and heart attacks.
The risk of CAD increases with the number of
cigarettes smoked. Filtered cigarettes, which result in delivery of
decreased amounts of tar and nicotine, have not proven to be
beneficial in decreasing the risk of CAD. Stopping smoking decreases
the risk myocardial infarction and of death from CAD up to 50% in the
first few years after smoking cessation. The risk of CAD never
decreases to that of nonsmokers, however.
Many risk factors can be modified by changes in
lifestyle or drug interventions. Correction of risk factors is
important even in the absence of any symptoms. Severe complications of
CAD including sudden cardiac death occur often without any warning
symptoms. Individuals with known risk factors, especially young
persons with a family history of premature heart disease, require
aggressive risk factor management.
Risk factor interventions include altered lifestyle
such a diet (reduced fat and salt) and regular exercise. Drug therapy
is recommended when lifestyle interventions are insufficient or
unsuccessful. Remarkably effective drug regimes have become available
to correct high blood pressure and high cholesterol levels. These
include the so-called "statins" (HMGCoA - reductase
inhibitors) to lower cholesterol and beta blockers and ACE -
inhibitors (angiotensin converting enzyme inhibitors) to lower blood
pressure. Aspirin, a drug that suppresses blood clot formation, has
been shown to reduce the risk of heart attacks and prolong life
expectancy. Estrogen replacement therapy may be effective in reducing
post-menopausal CAD progression. In the future, it is hoped that
specific genetic defects will be cured by gene therapy.
In persons sustaining an acute heart attack, blood
clots that block blood flow can be opened with blood-clot dissolving
drugs (thrombolytic agents or "clot busters") or by
advancing a balloon catheter and dilating the artery at the site of
the blockage. These therapies have markedly reduced deaths from heart
attacks but must be used as soon after the onset of the symptoms as
possible to be very effective. Drug therapy with beta blockers and ACE
inhibitors has also been shown to decrease he damage caused by acute
myocardial infarctions.
In persons suffering from chronic symptoms of limited
blood flow to the heart, such as chest pains on exertion, narrowed
artery segments can often be dilated with balloon catheters. If the
blockages occur in critical locations or in several arteries
simultaneously, surgeons can often place artery grafts that bypass the
aterial narrowing.
In individuals whose first manifestation of CAD is
ventricular arrhythmias, treatment with balloon catheters
(angioplasty) and coronary bypass surgery may not reduce the risk of
sudden arrhythmic death. These patients require specific
anti-arrhythmic treatments.