The severe effects of CAD occur as a person ages. In general, CAD symptoms are seen in middle and old age.1 Traditionally, CAD has been regarded as a male disease, but it is increasingly obvious that in modern society it affects both genders.¹ The average age for a person having a first heart attack is 64.5 years for men and 70.3 years for women.¹ Starting at age 75 years, the prevalence of cardiovascular disease is higher among women than men.^2,3 CAD rates for postmenopausal women are two to three times higher than those for premenopausal women of the same age.¹ People of color and multiracial populations of both genders have higher CAD mortality rates than do white populations of similar socioeconomic status.¹

A positive family history is one in which a close blood relative has had a myocardial infarction (MI) or stroke before the age of 60. This family history suggests a genetic or lifestyle predisposition to the development of CAD. Individuals with a family history had a 50% greater risk of having an acute MI in the INTERHEART study.4 This was a large, international, standardized case-control study of similar cohorts in 52 countries that was designed to examine the importance of risk factors for CAD on a worldwide basis.⁴

Hyperlipidemia is a leading factor responsible for severe atherosclerosis and the development of CAD. Determining total serum cholesterol and triglyceride levels is a helpful start in the evaluation process.3,5 A lipid panel blood test can measure the following values:

Treatment of hyperlipidemia has advanced beyond the concept of lowering total cholesterol to treatment of specific lipoprotein abnormalities.^3,6–8 The target levels for specific serum lipids are listed in Table 12-1.

A diet rich in saturated fats leads to elevated cholesterol levels in the blood. The first line of treatment to lower elevated serum cholesterol is a low-fat, high-fiber diet and increased physical exercise.7,8 If these measures are not effective, lipid-lowering drugs are indicated.¹ This approach sounds simple, but less than one half of the people who qualify for lipid reduction therapy are taking their medications; only one third of treated patients reach their LDL target; and fewer than 20% of patients with CAD are at their LDL goal.¹ Although lipid-lowering drugs are very helpful for some, they are not a panacea for everyone.

Obesity is a disease of modern times. Global estimates are more than 1 billion overweight adults, and at least 300 million of these people are obese. Obesity is often associated with a sedentary lifestyle. A high risk of coronary heart disease is among the well-established adverse health effects associated with excess weight. Hypertension, hypercholesterolemia, and diabetes are among the clinical conditions that are important mediators of this association.12 In the United States in 2001, 122 million adults were overweight or obese.¹³ In 2006 144 million adults, or 66% of the U.S. adult population, were overweight or obese.¹ Obesity is defined using the body mass index (BMI).

The BMI is calculated as the weight in kilograms divided by the square of the height in meters (kg/m²); it assesses body weight relative to height. BMI is used to evaluate the threat of excess pounds as a risk factor for CAD and permits comparisons of people of different gender, age, height, and body type.¹ BMI is calculated as the weight in kilograms divided by the square of the height in meters (kg/m²). The BMI calculation in metric units is shown in Box 12-2. A normal BMI is between 18.5 and 25 kg/m². A BMI between 25 and 30 kg/m² indicates the person is overweight. A BMI greater than 30 kg/m² is the definition of obesity.¹

The distribution pattern of fat on the body is a CAD risk factor. The more weight carried in the abdominal area, producing a large waist, the greater the risk of CAD. Excess abdominal adiposity (apple body shape) indicates additional fat around the abdominal organs compared with individuals who have a smaller waist and larger hips (pear body shape). A waist size greater than 40 inches in men and 35 inches in women increases their risk for CAD. Physical exercise assists with weight reduction, lowers the risk for CAD, and decreases the risk of developing type 2 diabetes.

Regular vigorous physical activity using large muscle groups promotes physiological adaptation to aerobic exercise that can prevent the development of CAD and reduce symptoms in patients with established cardiovascular disease.14 Exercise also reduces the incidence of many other diseases, including type 2 diabetes, osteoporosis, obesity, depression, and cancers of the colon and breast.¹⁴ Many research trials have demonstrated the positive effects of physical activity on the other major cardiac risk factors.¹⁴ Exercise alters the lipid profile by decreasing LDL cholesterol and triglyceride levels and increasing HDL cholesterol levels.¹⁴ Exercise reduces insulin resistance at the cellular level, lowering the risk for developing type 2 diabetes, especially if combined with a weight-loss program.¹⁴ Epidemiological studies indicate that physical athletics as a young person do not confer protection in later years. A sedentary lifestyle has negative effects, regardless of age, gender, BMI, smoking status, presence or absence of hypertension, or abnormal lipoprotein profile. Lifelong physical activity is necessary to prevent atherosclerotic CAD and stroke.¹⁴ In 2005 the prevalence of adults not engaging in any physical activity during leisure or work time was 10.3% in the United States.¹ In affluent countries, only one third of the population exercises moderately for the recommended 30 minutes, five times per week.

Hypertension is a cardiac risk factor because the high SBP damages the arterial endothelium, leading to vascular inflammation that encourages formation of plaque. Hypertension is a complex, multifactorial disease process. Hypertension is divided into stages for the purposes of treatment, as shown in Table 12-2.

Prehypertension is an SBP of 120 to 139 mm Hg or DBP above 85 mm Hg.^1,13 In the United States, one in five adults is prehypertensive. Hypertension is diagnosed when the blood pressure is above 140/90 mm Hg. Hypertension affects another one in four adults in the United States. After the blood pressure is above 140/80 mm Hg, hypertension is described as stage 1 or stage 2 depending on the severity (see Table 12-2).

Hypertension is often described as the “silent killer,” because 30% of those affected are unaware they have seriously elevated blood pressure.¹ A higher percentage of men than women have hypertension until age 45, but from the ages of 45 to 54 years, the percentage of men and women with hypertension is similar.¹ It is essential that patients understand that sustained elevation of blood pressure leads inexorably toward atherosclerosis, heart failure, kidney failure, stroke, and heart attack.¹³ So widespread is hypertension in industrialized societies that even a normotensive person at age 55 has a 90% lifetime risk of developing hypertension. This implies that even normotensive persons should adopt interventions to maintain a normal blood pressure.¹³ The estimated direct and indirect cost of hypertension in the United States for 2010 is $76.6 billion.¹

According to recent guidelines, the goal of treatment for the hypertensive person without other risk factors is to achieve a blood pressure below 140/80 mm Hg. For the hypertensive person who already has diabetes or kidney disease, the target blood pressure is below 130/80 mm Hg. A normal blood pressure is below 120/80 mm Hg.¹³

Lifestyle interventions that can normalize blood pressure include physical exercise, a low-salt diet, limiting alcohol intake, and achieving normal body weight. Most patients are started on a diuretic, and if this is insufficient, they may be placed on an angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), beta-blocker, or calcium channel blocker. Most patients require at least two medications, each from different drug classifications, to normalize their blood pressure.¹³ Hypertensive emergencies with acute organ damage are discussed in the last section of this chapter.

The greater the number of cigarettes smoked per day, the greater the risk of developing CAD, acute MI, and stroke.14,16 In the United States, the prevalence of smoking has always been lower among women than men.¹ Cigarette smoking unfavorably alters serum lipid levels, decreases the HDL cholesterol level, and increases LDL cholesterol and triglyceride levels. In the United States, smoking remains common, with an overall prevalence of 20.6% of the adult population. Smoking increases the risk of coronary heart disease at all levels.¹ Smokers are two to four times more likely to develop CAD than nonsmokers.¹ Passive, secondhand smoke exposure also increases cardiovascular risk; 34.7% of nonsmoking adults are exposed to environmental tobacco smoke at home or at work.^15–17 Nicotine is addictive, and smoking cessation is difficult. People need tremendous support to be able to “kick the habit.” Chapter 25 provides patient education guidelines on how to stop smoking.

Individuals with diabetes mellitus (types 1 and 2) have a higher incidence of coronary heart disease compared with the general population. Data from the Framingham Heart Study indicates a doubling in the incidence of diabetes over the past 30 years and most dramatically during the 1990s.1 Elevated blood glucose level is a known risk factor for development of vascular inflammation associated with atherosclerosis. The normoglycemia range is 70 to 100 mg/dL. It is recommended that patients in critical care have blood glucose levels maintained close to the normal range¹⁸ while avoiding hypoglycemic episodes.

A fasting blood glucose concentration between 100 and 125 mg/dL represents a prediabetic state and is a risk factor for the development of diabetes and CAD (Table 12-3). A fasting blood glucose above 126 mg/dL is indicative of diabetes. Patients with diabetes have an increased risk of developing CAD and have worse clinical outcomes after acute coronary syndrome events.¹⁹ In a multinational study of patients who were seen at hospitals with symptoms of acute coronary syndrome, almost one in four had a known history of diabetes.²⁰

Chronic kidney disease is considered a risk equivalent for CAD.2,3,21 This means patients with chronic kidney disease have as much risk of experiencing a coronary event as if they already had CAD.^2,3,22 The risk of death for the patient with acute MI rises as the serum creatinine level increases.²² In one study, the in-hospital mortality rates for patients with an acute MI were 2% for patients with normal kidney function, 6% for those with mild kidney failure, 14% for those with moderate kidney failure, 21% for those with severe kidney failure, and 30% for patients with end-stage kidney disease.²² Mortality following cardiac surgery is also higher for individuals with chronic kidney disease.²³

Metabolic syndrome refers to the clustering of risk factors associated with cardiovascular disease and type 2 diabetes.1 The prevalence of metabolic syndrome in 2006 for adults in the United States was 34%.¹ Metabolic syndrome is diagnosed when three or more of the following risk factors are present:^24,25

It is perhaps obvious that individuals with the signs of metabolic syndrome are at increased risk for CAD; even so, it is surprising to what degree this holds true. In the Framingham epidemiological study, presence of the factors associated with metabolic syndrome predicted 25% of all new-onset CAD and almost 50% of new-onset diabetes.²³

Serious CAD symptoms occur approximately 5 years later in women than in men.25 The average age for the first acute MI in men is 65.8 years and in women is 70.4 years.¹ Incidence of CAD is two to three times higher among postmenopausal women than women who are premenopausal.¹ In the past, it seemed logical to prescribe hormone replacement therapy (HRT) to treat the symptoms of menopause. However, well-designed research trials discovered an increase in cardiovascular events in the first year of HRT (estrogen plus progestin), although cardiac events declined after the first year.^25,26 Subsequent studies have confirmed this result.²⁴ In 2004 the estrogen-only HRT trial was stopped by the National Institutes of Health (NIH) because of an increased risk of stroke among the women taking estrogen. For these reasons, HRT is no longer recommended for prevention of atherosclerotic cardiovascular disease.²⁷ Data from the Framingham Heart Study indicate the lifetime risk for cardiovascular disease is more than one in two for women at age 40.¹

Cardiovascular disease kills more than one-half million women annually in the United States. To emphasize the magnitude of the problem, this represents more deaths than the next seven fatal diseases for women combined.²⁸ Mortality rates for women after an acute MI are higher than for men: 38% and 25%, respectively. Risk factors more strongly associated with acute MI in women compared to men include hypertension, diabetes mellitus, alcohol intake, and physical inactivity.²⁶ Many reasons contribute to women having higher mortality from acute MI, including waiting longer to seek medical care, having smaller coronary arteries, being older when symptoms occur, and experiencing very different symptoms from those of men of the same age.²⁹ The 2007 evidence-based guidelines for cardiovascular disease prevention in women recommended a plan for a general approach to the female patient that classifies her as high risk, at risk, or at optimal risk.²⁸ In 2007 50% of women surveyed by the American Heart Association (AHA) recognized that heart disease was the leading cause of death among women.

The link between vascular inflammation and atherosclerotic disease is well established.31 Measurement of this link has been more controversial, however.³⁰ Many researchers think the development of atherosclerotic plaque occurs in response to inflammation. Noxious inflammatory agents circulate in the bloodstream and stimulate chemical mediators that directly modify the arterial wall. The initial inflammatory stimuli include increased blood glucose, elevated blood lipids, nicotine, and hypertension. However, other clinical conditions, such as connective tissue disorders and systemic infection, also produce an inflammatory state, and it is not clear what the impact of inflammation produced by these stimuli is on the vessels.³⁰ Research to identify prognostic inflammatory markers is ongoing.

The inflammatory marker most frequently cited is C-reactive protein (CRP). It is measured as high-sensitivity C-reactive protein (hs-CRP).30 The higher the hs-CRP value, the greater the risk of a coronary event, especially if all other potential causes of systemic inflammation such as infection can be ruled out. If other systemic inflammatory conditions such as bronchitis or a urinary tract infection are present, the hs-CRP test loses all predictive value.³¹ CRP and other inflammatory markers are used to estimate the probability of future acute coronary events.^30,31 During acute coronary syndrome events, there is widespread activation of neutrophils in the cardiac circulation (measured from the coronary sinus), which suggests that inflammation is not limited to one unstable plaque.³² Debate continues about whether CRP is simply a marker of vascular inflammation or also contributes to the proinflammatory state.⁹

Atherosclerosis is a chronic inflammatory disorder that is characterized by an accumulation of macrophages and T lymphocytes in the arterial intimal wall. A high LDL cholesterol concentration is one of the triggers of vascular inflammation. The inflammation injures the wall, allowing the LDL cholesterol to move into the vessel wall below the endothelial surface.9 Blood monocytes adhere to endothelial cells and migrate into the vessel wall. Within the artery wall, some monocytes differentiate into macrophages that unite with and then internalize LDL cholesterol. The foam cells that result are the marker cells of atherosclerosis.⁹

Elevated LDL cholesterol levels promote low-level endothelial inflammation that allows lipoproteins to infiltrate the intimal vessel wall. After it has infiltrated under the endothelium, LDL cholesterol tends to stay within the vessel wall rather than return to the circulation.⁹ This contrasts with the actions of HDL cholesterol, which enters the vessel wall, helps efflux cholesterol from cells, and then returns to the circulation.⁹ The actions of HDL cholesterol may help minimize the number of foam cells in the artery wall.⁹

When a mature atherosclerotic plaque develops, it is not uniform in composition. It has a lipid liquid center filled with procoagulant factors. A connective tissue fibrous cap covers the top of the fluid lipid center.30–32 The abrupt rupture of this cap allows procoagulant lipids to flood into the vessel lumen and rapidly form a coronary thrombosis, as shown in Table 12-4. As the enlarging clot blocks blood flow through the coronary artery, a “heart attack” will occur unless there is adequate collateral circulation from other coronary vessels. Symptoms and suggested cardiac interventions at appropriate stages in development of CAD are listed in Table 12-4.

TABLE 12-4

TIMELINE OF ATHEROGENESIS DEVELOPMENT DEPICTED BY LONGITUDINAL SECTION OF AN ARTERY

ATHEROGENESIS/THROMBOGENESIS	ASSOCIATED SYMPTOMS	CARDIAC INTERVENTION
A. Normal artery, normal vessel wall.	No symptoms	Primary prevention of CAD recommended: consume a low-fat diet, take regular physical exercise, avoid smoking, and achieve normal BMI
B. Lipids in bloodstream.	No symptoms
C. Extracellular lipid accumulates in the intima of the artery (atheroma).	No symptoms
D. Lipid accumulation evolves to become a fatty-fibrous (atherosclerotic) lesion. Some lesions contain a lipid interior covered by a fibrous cap.	Chest pain with exercise that is relieved by rest or NTG (stable angina) or possibly no symptoms until the lesion fills more than 75% of the vessel lumen	PCI if stable angina is present and CAD is diagnosed by cardiac catheterization
E. Rupture of the cap allows lipid in the center to be released into the bloodstream, stimulating clot formation (thrombogenesis).	Chest pain not relieved by rest or NTG (ACS – unstable angina)	Call 911 for immediate transport to a hospital, preferably one with experience treating ACS
F. Fresh clot blocks the vessel; spasm of the artery may occur near the thrombus.	Chest pain unrelieved by rest or NTG – severity, location of angina, and associated symptoms vary greatly among individuals (ACS – acute MI)	Emergency intervention to open the artery: fibrinolytic or catheter-based procedure (PCI)
G. Vessel is open, but the atherosclerotic lesion remains.	No symptoms	Secondary prevention of CAD to prevent repeat MI; beta-blockers to prevent arrhythmias; ACE-1 drugs to prevent ventricular remodeling and heart failure; elective PCI

ACE-1, angiotensin-converting enzyme 1; ACS, acute coronary syndrome; BMI, body mass index; CAD, coronary artery disease; MI, myocardial infarction; NTG, nitroglycerin; PCI, percutaneous coronary intervention.

(Modified from Antman EM, et al: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction – executive summary, Circulation 110(5):588, 2004.)

Plaques that are likely to rupture are saturated with macrophages and other inflammatory cells. These vulnerable plaques are usually not obstructive and are situated at bends or branch points in the arterial tree.³ It is not known what factors cause the fibrous cap to rupture or erode. As deep fissures in the cap expose the procoagulant factors to the blood plasma, an unstoppable cycle is put into motion. When platelets in the bloodstream are exposed to collagen, necrotic debris, von Willebrand factor, and thromboxane, a clot is formed that can occlude the coronary artery. Highly fibrotic plaques do not rupture. The type of atherosclerotic plaque that is prone to rupture has a weak fibrous cap and a large amount of liquid cholesterol within the core (see Table 12-4).³²

A reduction in blood cholesterol decreases atherosclerotic plaque size by decreasing the amount of liquid cholesterol within the plaque core.7 Lowering cholesterol levels does not change the dimensions of the fibrous or calcified portions of the plaque. However, lower cholesterol levels reduce vascular inflammation and make vulnerable plaque less likely to rupture.

If diet is not effective in lowering blood cholesterol, lipid-lowering drugs are prescribed to lower the LDL cholesterol level below 100 mg/dL for patients at risk for CAD and to aim for an LDL level below 70 mg/dL for individuals with the highest-risk profile.⁷ Drugs, diet, and exercise are used to lower the triglyceride levels to less than 150 mg/dL, and to raise HDL cholesterol levels above 40 mg/dL for men and above 50 mg/dL for women (see Table 12-1).^3,7,8,33

Angina pectoris, or chest pain, caused by myocardial ischemia is not a separate disease, but rather a symptom of CAD. It is caused by a blockage or spasm of a coronary artery, leading to diminished myocardial blood supply. The lack of oxygen causes myocardial ischemia, which is felt as chest discomfort, pressure, or pain. Angina may occur anywhere in the chest, neck, arms, or back, but the most commonly described location is pain or pressure behind the sternum. The pain often radiates to the left arm but can also radiate down both arms and to the back, the shoulder, the jaw, or the neck (Figure 12-1). Angina symptoms are not the same for all individuals, many patients may describe pressure or discomfort rather than pain and presenting symptoms can be highly individualized, as described in Box 12-3. Patients and families must be taught that angina does not always present in the dramatic heart attack scenario seen on television and in movies, in which the person clutches the throat or chest and exhibits extreme distress.³

Complaints of chest discomfort (angina) must be evaluated quickly, because angina is an indicator of myocardial ischemia. The patient is asked to rate the intensity of the chest discomfort on a scale of 0 to 10. Pain levels must be assessed with sensitivity to differences in cultural manifestations of pain. The words “chest pain” are not to be used exclusively, because some patients describe their angina as “pressure” or “heaviness.” It is important to document the characteristics of the pain and the patient’s heart rate and rhythm, blood pressure, respirations, temperature, skin color, peripheral pulses, urine output, mentation, and overall tissue perfusion. A 12-lead ECG is used to identify the area of ischemic myocardium. The major concern is that the chest pain may represent preinfarction angina, and early identification is essential so that the patient can be immediately treated. A range of treatments are available that include fibrinolytic infusion immediately, or transfer to the cardiac catheterization laboratory for a coronary arteriogram and opening of a blocked artery. If the hospital does not have a cardiac catheterization laboratory, GP IIb/IIIa receptor blockers may be infused to prevent the evolution of the acute MI before transfer.3,5 Figure 12-2 presents additional information about transfer between hospitals in this circumstance.

In the critical care unit, control of angina is achieved by a combination of supplemental oxygen, nitrates, analgesia, and surveillance of the angina and of the effects of pharmacological therapy.

The outer region of the infarcted myocardial area is the zone of ischemia, as illustrated in Figure 12-3. It is composed of viable cells. Priority interventions are targeted to save this viable muscle. Repolarization in this zone is temporarily impaired but eventually will be restored to normal. Electrical conduction from areas of viable myocardium produces a normal QRS configuration as shown in Figure 12-4, A. Repolarization of ischemic myocardial cells manifests as T-wave inversion (see Figure 12-4, B).

The infarcted zone is surrounded by injured but still potentially viable tissue in an area known as the zone of injury (see Figure 12-3). Cells in this area do not fully repolarize because of the deficient blood supply. This is recorded on the ECG as elevation of the ST segment (see Figure 12-4, C).

The area of dead muscle (necrosis) in the myocardium is known as the zone of infarction (see Figure 12-3). On the ECG, evidence of this zone is seen by new pathological Q waves, which reflect a lack of depolarization from the cardiac surface involved in the MI (see Figure 12-4, D). As healing takes place, the cells in this area are replaced by scar tissue.

MIs are classified according to the location on the myocardial surface and the muscle layers affected. Not all infarctions cause necrosis in all layers, as shown in Figure 12-5. A transmural MI involves all three cardiac layers—the endocardium, the myocardium, and the epicardium. A transmural (full-thickness) MI usually provokes significant ECG changes (see Figure 12-4). This is also described as a Q-wave MI. Not every acute MI produces a recognizable series of Q waves on the 12-lead ECG. Some patients who had a demonstrated Q wave on a 12-lead ECG as a result of an acute MI lose the Q wave months or years later. The reasons for this are unknown, but it may represent the development of collateral circulation.

The location of infarction is determined by correlating the ECG leads with Q waves and the ST-segment T-wave abnormalities (Table 12-5). Infarction most commonly affects the left ventricle and the interventricular septum; however, the right ventricle can be infarcted, and many patients who sustain an inferior MI have some right ventricular damage. The ECG manifestations that are used to diagnose an MI and pinpoint the area of damaged ventricle include inverted T waves, ST-segment elevation, and pathological Q waves in specific lead groupings as described subsequently.