Chronic stable angina overview

# Overview
Angina pectoris, commonly known as angina,  is chest pain due to ischemia (a lack of blood and subsequent lack of oxygen supply) of the heart muscle. It is most often due to obstruction or spasm of the coronary arteries (the heart's blood vessels). Coronary artery disease, also referred to as atherosclerosis of the coronary arteries, is the most common cause of angina. The term derives from the Greek ankhon ("strangling") and the Latin pectus ("chest") meaning "a strangling feeling in the chest". In angina pectoris, symptomatic onset may include chest discomfort indicated by a feeling of tightness, heaviness, or pain in the chest cavity.

# Historical Perspective
Chronic stable angina is a form of chest pain characterized by an insufficient blood flow to the myocardium of the heart to match myocardial energy demands (ischemia). The term angina was originally derived from the Greek word ankhon and the Latin word pectus, which when combined, loosely translates as "a strangling feeling in the chest". Attempts to classify this disease state began as early as the 4th century B.C., when Lucius Annaeus Seneca first described the symptoms he was experiencing as "to have any other malady is to be sick; to have this is to be dying".  Throughout history many renowned researchers and health care professionals have contributed to the understanding, definition, and recognition of angina.

# Classification

### Chronic Stable Angina
Angina pectoris is a sensation of chest discomfort that is often described as: a feeling of tightness, heaviness, or pain.  Angina pectoris is a characteristic of coronary heart disease. When it occurs chronically, this is referred to as stable angina.

### Walk Through Angina
Walk through angina is the appearance of anginal chest discomfort early in the course of exertion which subsequently subsides despite continued exertion.

### Mixed Angina
Mixed or variable threshold angina pectoris is a syndrome in which there is substantial variation in the magnitude of physical activity that induces anginal chest pain.

### Nocturnal Angina
Nocturnal angina is the occurrence of anginal discomfort either during the first hours of sleep or during the early morning hours. It is speculated that discomfort caused during the first hours of sleep is due to increased venous return, whereas the discomfort caused during the early morning hours is due to increased vascular tone.

### Postprandial Angina
Postprandial angina pectoris is anginal chest discomfort that occurs following meals. It is thought to be due to an increase in vascular tone or a reduction in coronary blood flow.

### Cardiac Syndrome X
Cardiac syndrome X is angina associated with objective evidence of myocardial ischemia in the absence of epicardial  coronary artery disease.  Syndrome X has been hypothesized to be a disorder of the coronary microvasculature rather than the large caliber epicardial coronary arteries.

### Vasospastic Angina
Coronary vasospasm is a multi-factorial, transient, and abrupt reduction of luminal diameter of an epicardial coronary artery due to inappropriate constriction of coronary smooth muscle that can generate distal ischemia.  This may occur spontaneously or in the context of angioplasty, particularly if denudation of the endothelium or dissection occurs.  In addition, the vasospasm can either be focal or multifocal (which compromises more than one vessel).

# Differentiating Chronic Stable Angina from Urgent Conditions
Stable angina must be differentiated from unstable angina and acute coronary syndromes.  If the pattern of angina is stable, this is termed chronic stable angina. If the magnitude, threshold or frequency of chest pain accelerates, this is termed an acute coronary syndrome.

# Pathophysiology
The primary causes of myocardial ischemia in chronic stable angina are: fixed epicardial stenosis, spasm of the epicardial artery and/or microvascualar disease. The causation of angina is not mutually exclusive. Two or more causes may coexist in the same patient.

# Epidemiology and Demographics
Coronary artery disease (CAD) remains the single leading cause of death in the United States. Stable angina is the initial manifestation of ischemic heart disease in approximately 50% of these patients.

# Risk Stratification
The average mortality in patients with stable angina ranges from 1-3%. However, the prognosis varies widely depending on various factors such as: the duration and severity of symptoms, resting ECG abnormalities, abnormal left ventricular function and associated comorbidities.

# Pretest Probability
Pretest probability is defined as the probability of the target disorder before the result of a diagnostic test is known.  A number of studies have emphasized the importance of pretest probability of coronary artery disease (CAD). Once a thorough patient history and physical examination is complete, it is important to assess the probability of underlying CAD, as this helps both the physician and the patient to determine the next step in the diagnosis and treatment. In patients with chronic stable angina, the strongest predictors contributing to underlying significant CAD include: the age, gender and type of pain (typical, atypical) experienced.

# Prognosis
Ischemic heart disease remains as the number one cause of mortality in developed countries. The prognosis of stable angina varies widely depending on severity of symptoms, extent of atherosclerosis and presence of other risk factors and co-morbidities.  The presence of impaired left ventricular function is associated with a poor prognosis. Reduced LV function, number and location of stenoses, workload in METs calculated using Duke score are the strongest predictors of survival in patients with chronic stable angina.

# Diagnosis

## History and Symptoms
The name 'angina pain' can be thought of as a misnomer as patients often describe the sensation as discomfort rather than physical pain. The best method to characterize this discomfort/pain is through the 'PQRST system'.

## Physical Examination
Among patients with chronic stable angina, the physical examination may be asymptomatic or characteristically normal. Patients that present with left ventricular dysfunction are associated with a poorer prognosis than patients who do not present with dysfunction. All patients should be examined carefully for the presence of rales and other signs of heart failure. The majority of patients present with history of either, chest pain or discomfort categorized as: typical or atypical. Typical presentation would include pain or discomfort in the front or anterior precordium. Atypical presentation can be more convoluted in presentation and involve a wide range of symptoms. For example, an atypical patient may present with dyspnea instead of chest pain and this is termed an angina equivalent. In addition to the historical presentation of chest pain or discomfort, the patient history should be extensively evaluated to include an assessment of cardiovascular risk factors. Physical examination may be normal or asymptomatic. In some cases, a physical examination may reveal heart failure. Additional findings can be important in understanding the onset of the condition. For instance, the presence of peripheral vascular disease may be associated with an increased risk of  coronary artery disease (CAD).

## Test Selection Guideline for the Individual Basis
Criteria for test selection hinges largely on the current disease state of the individual patient and subsequent level of fitness for testing. Potential diagnostic testing modalities include: exercise ECG, ECG at rest, exercise echocardiography, echocardiography at rest, and stress scintigraphy.

## Laboratory Findings
In patients with chronic stable angina, initial laboratory investigations are used to: identify potential causes of ischemia, establish risk factors, and determine the overall prognosis for the patient. An initial laboratory test can provide a wide variety of clinical information. For instance, low hemoglobin levels can cause ischemia. Therefore, assessing hemoglobin as a part of complete blood count provides prognostic information. Biomarkers, such as troponin and CK-MB, are used to exclude myocardial injury. In assessment for risk factor stratification, all patients with ischemic heart disease are recommended to have a a standard round of blood work conducted including fasting plasma glucose levels and a complete lipid profile. Serum creatinine is used to assess renal dysfunction due to associated hypertension or diabetes and remains a negative prognostic factor. In patients with chronic stable angina, an elevation in fasting glucose independently predicts the adverse outcome. Recent research on NT-pro-BNP has demonstrated the ability to predict long-term mortality in patients with chronic stable angina independent of age, ventricular ejection fraction and other risk factors.

## Electrocardiography
A resting 12-lead ECG is performed and recorded in all patients with suspected angina pectoris. However, a normal resting ECG does not exclude the diagnosis of ischemia. Abnormalites commonly observed on resting ECG include: ST-segment changes, left ventricular hypertrophy (LVH), left branch bundle blockage (LBBB), signs of coronary artery disease (CAD) such as previous myocardial infarction (MI) or abnormal repolarization patterns. An ECG recorded during pain helps to identify an underlying vasospasm.

## Exercise EKG
In patients with chronic stable angina, exercise ECG is more sensitive and specific to identify inducible ischemia and to diagnose coronary artery disease. ECG abnormalities associated with MI include: down sloping of ST-segment depression or elevation, accompanying angina that occurs at a low workload during early stages of exercise and persistent for more than 3-minutes after exercise. The reliability of diagnosis is shown to improve with the evaluation of ST changes in relation to heart rate. Bruce protocol or treadmill (expressed in terms of METs) or bicycle ergometer (expressed in terms of watts) are used to detect MI. Exercise ECG test must be terminated on the achievement of maximal predicted heart rate and/or if the patient becomes symptomatic or develops pain with significant ST-segment changes. Exercise ECG test also provides prognostic stratification to evaluate the response to medical therapy or revascularization.

## Chest X-Ray
Routine chest x-ray examination is important in the evaluation of patients with signs or symptoms of congestive heart failure, valvular heart disease, pericardial disease, or aortic dissection/aneurysm. The presentation of cardiomegaly, characterized by  pulmonary congestion on a chest x-ray, is indicative of a poor prognosis for the patient.

## Myocardial Perfusion Scintigraphy with Pharmacologic Stress
Pharmacologic stress testing using myocardial perfusion scintigraphy or echocardiography can be employed in patients with known or suspected angina pectoris who are unable to perform adequate exercise tests. These patients often owe their ineligibility status to associated conditions such as: peripheral vascular disease, musculoskeletal disorders, diseases of the lower extremities, severe obesity, or deconditioning. Pharmacologic stress testing is achieved with the infusion of either dobutamine in incremental dose, which acts by increasing myocardial oxygen consumption and thereby mimic effect of exercise, or with the use of coronary vasodilators such as adenosine or dipyridamole, which acts by differentiating regions based on perfusion. Stress imaging is of great value in the evaluation of patients with low pretest probability of CAD. However, in patients with LBBB, perfusion scintigraphy is shown to have poor diagnostic accuracy.

## Myocardial Perfusion Scintigraphy with Thallium
In patients with baseline ECG abnormalities,a myocardial perfusion test can be used to localize the region of ischemia. Thallium-201 and technetium-99m are the two radio-labeled agents that are frequently used for the assessment of  myocardial perfusion. Myocardial uptake of thallium-201 chloride is directly proportional to the regional myocardial blood flow and is dependent on the presence of viable myocardium. In patients with known CAD, a normal thallium stress test without a perfusion defect is indicative of a benign process and associated with excellent prognosis. Patients with a normal thallium scan are at low risk for CAD and subsequent coronary angiography is indicated only if the patient has a high probabilty Duke treadmill score. Contraindications for thallium stress test include the presence of arrhythmia, acute myocarditis, severe aortic stenosis and acute MI within the past 2 days.

## Echocardiography
Echocardiography is useful to evaluate ventricular function and detect ischemia induced regional wall motion abnormality that occurs at rest, during exercise or with pharmacologic stress test. As a testing modality, two-dimensional echocardiography is often coupled with other testing modalities to detect regional wall motion abnormalities that most frequently occur during induced myocardial ischemia associated with coronary artery disease (CAD). Potential paired testing modalities include: upright treadmill exercise, supine bicycle ergometry, pacing, and pharmacologic stress, particularly with dobutamine. Patients with CAD may respond more adversely to testing modalities than their counterparts. Often, an adverse outcome such as the inability to perform a bicycle ergometry test or exercise treadmill protocol can be characterized as a poor prognostic factor.

## Exercise Echocardiography
Stress echocardiography is echocardiography that is paired with different forms of stressors, such as exercise or pharmacological. Exercise stress echocardiography is the preferred stress echocardiography modality. However, it is not suitable for all patients and may not be feasible in populations that do not meet a minimum level of fitness. In patients who are ineligible for exercise stress echocardiography, pharmacological stress echocardiography can be a useful alternative. Common pharmacological stressors include: adenosine, dipyridamole, and dobutamine. As a testing modality, exercise echocardiography is noted as more sensitive, more specific and has a higher predictive value than exercise ECG. Exercise echocardiography can be helpful in the evaluation of regional wall motion response, location and extent of ischemia  during stress in patients with MI. During exercise, the normal myocardium is hyperdynamic while in patients with MI, the ischemic myocardium is either akinetic or hypokinetic.

## Positron Emission Tomography
Positron emission tomography is of particular value in the assessment of regional coronary blood flow reserve, myocardial perfusion, and the presence and extent of hibernating myocardium.

## Ambulatory ST Segment Monitoring
Ambulatory ECG monitoring (Holter monitor) is used to detect major arrhythmias and myocardial ischemia occurring during normal activities. Ambulatory ECG monitoring adds very little prognostic value in patients with chronic stable angina, however, does play a role in the detection of major arrhythmias in patients with chronic stable angina  and  suspected vasospastic angina.

## Electron Beam Tomography
The extent of coronary artery calcification directly correlates to the area of atheromatous plaque. Hence in patients with chest pain, coronary artery calcium (CAC) scoring is one of the factor to be considered in the risk assessment for coronary artery disease. The methods used for detection and quantification of CAC include electron beam computed tomography (EBCT) and multi-detector computed tomography (MDCT). Agatston score is a computed software that is commonly used to measure CAC based on the density and area of calcified plaques.

## Cardiac Magnetic Resonance Imaging
Cardiac magnetic resonance imaging (CMRI) is a non-invasive test that is useful in the evaluation of overall coronary anatomy and function. CMRI also helps in the identification of inflammation, neovascularization and fibrous cap. It, therefore, holds the potential for plaque characterization.

## Coronary Angiography
Coronary angiography is a gold standard test in the evaluation of severity of coronary artery disease and the possibility for revascularization. Coronary angiography is indicated in patients with a high pretest probability of CAD and in symptomatic patients with inconclusive initial noninvasive tests. Provocative testing with ergonovine during angiography may be useful in patients with vasospastic angina. Major complications such as death, MI and stroke associated with routine angiography is as low as 0.1% - 0.2%.

# Treatment
Treatment of chronic stable angina aims at minimizing symptoms, reducing recurrent ischemia, improving the quality of life and improving prognosis by preventing MI and death. Treatment options include lifestyle modification, pharmacotherapy and revascularization that help in slowing the disease progression, preserving the endothelial function and preventing thrombosis.
Patients with single-vessel CAD may be started on initial pharmacologic therapy and if non-responsive or symptomatic despite on therapy, PCI may be a preferred alternative.
Patients with double-vessel CAD and with normal LV function may be started on initial medical management and in non-responders, PCI may be considered. However, the decision of PCI versus CABG depends on the coronary anatomy, LV function and the need for complete revascularization.
Patients with triple-vessel CAD or left main disease or reduced left ventricular function, CABG is the mainstay of management. However, in cases of mild symptoms or preserved LVEF in patients with triple-vessel disease, initial pharmacologic therapy or PCI may be tried.

## Pharmacotherapy
The goal of the management of chronic stable angina is to improve the quality of life by decreasing the severity and frequency of symptoms and to decrease premature cardiovascular death caused by myocardial infarction or development of heart failure. The mainstays of the treatment of chronic stable angina are patient education, lifestyle changes and medical therapy. In patients with chronic stable angina, immediate symptomatic relief is achieved with short-acting sublingual nitrates and long term symptom relief is achieved with beta blockers as first line therapy, or calcium channel blockers and long-acting nitrates when beta blockers are contraindicated. Drugs that improve the quality of life and are associated with a better prognosis include: low dose aspirin, beta-blockers and ACEIs.

### Anti-platelet Agents
In patients with ischemic heart disease, prophylactic low dose aspirin prevents arterial thrombosis by irreversible inactivation of platelet aggregation.
Dipyridamole is a pyrimidopyrimidine derivative with  poor anti-thrombotic efficacy and therefore not recommended for anti-platelet therapy in patients with chronic stable angina. Dipyridamole may also exacerbate anginal symptoms due to coronary steal phenomenon.
Thienopyridines, such as clopidogrel and ticlopidine, selectively inhibit ADP-induced platelet aggregation and are used as an alternative to aspirin in patients with significant risk of arterial thrombosis.

### Anti-anginal Agents
In patients with chronic stable angina, nitrates remain the mainstay of therapy. Organic nitrates are therapeutic precursors of endothelium-derived relaxing factor that produce their beneficial effects both, by decreasing myocardial oxygen requirements and by improving myocardial perfusion. The most commonly used nitrates are nitroglycerin, isosorbide dinitrate and isosorbide mononitrate. Short acting nitrates, such as sublingual nitroglycerin, are best suited to treat acute episodes of angina and are effective when used for situational prophylaxis. Long-acting nitrates help to reduce the frequency and severity of angina and may increase exercise tolerance in patients with stable angina. Nitrates at therapeutic doses do not affect coronary vascular resistance, thereby reducing the risk of myocardial ischemia due to coronary steal phenomena that is consistent with the use of dipyridamole and other short acting dihydropyridines.
In patients with stable angina, beta blockers are used as a first line of therapy for both, symptomatic relief and the prevention of ischemic events. The physiologic mechanism of benefit of this therapy is a marked reduction in myocardial oxygen consumption by reducing the heart rate and myocardial contractility. Selective beta-1 blockers are preferred to non-selective beta-blockers due to fewer associated side effects. The most commonly used selective beta-1 blockers are metoprolol, atenolol, and bisoprolol.
Calcium channel blockers (CCBs) consist of three sub-classes namely, dihydropyridines (e.g., nifedipine), phenylalkylamines (e.g., verapamil) and modified benzothiazepines (e.g., diltiazem). The beneficial anti-anginal effects of CCB include: reduction in the afterload consequent to systemic vasodilation as well as epicardial vessel vasodilation, enhancement of the coronary collateral flow with subsequent sub-endocardial perfusion due to the inhibition of calcium influx via L-type channels. Long-acting calcium channel blockers are an effective antianginal agent and are considered to be the first choice in post-MI patients with a contraindication to beta-blocker. Long-acting CCBs are also specifically used to control symptoms in patients with vasospastic angina. However short-acting CCBs, such as nifedipine, are avoided due to an increased risk of myocardial infarction and mortality.
Nicorandil has both, anti-anginal effects due to nitrate-like and ATP-sensitive potassium channel activating properties and provides cardio-protective effects as well. Therefore, nicorandil usage in addition to standard  anti-anginal therapy may be indicated in patients who are intolerant to beta-blocker therapy or in whom CCB monotherapy or combination therapy CCB is unsuccessful.
Ranolazine is a one of the newer FDA approved anti-anginal medication for management of chronic stable angina. Perhexiline is another anti-anginal, primarily used in Australia and New Zealand, being studied for use in the United States and UK. In patients with chronic stable angina, other effective agents with anti-anginal and anti-ischemic properties are ivabradine, trimetazidine and molsidomine.

### ACEI/RAAS Blockers
Patients diagnosed with syndrome X and hypertension may have microvascular angina characterized by a reduced coronary vasodilator reserve and increased sympathetic drive. ACE inhibition in such patients may attenuate sympathetic coronary vasoconstriction, normalize thallium perfusion defects and reduce exercise-induced ischemia with subsequent increased myocardial oxygen supply. Based on the recent AHA and ESC guidelines, the recommended goal blood pressure in patients with atherosclerotic coronary vascular disease is less than 130/80 mm Hg.

### Anti-lipid Agents
Statins by inhibiting HMG-CoA reductase subsequently reduce serum cholesterol levels and have been shown to be effective in the primary prevention of various hyperlipidemias and secondary prevention of ischemic heart disease. The most commonly used statins are simvastatin, atorvastatin, pravastatin and rosuvastatin. The incidence of major cardiovascular mortality was reduced by 30% with the use of simvastatin and pravastatin in patients with coronary artery disease and therefore may be used for both primary and secondary prevention. However, there are no trials specifically performed on patients with stable angina but they form a significant portion in other major trials studying the efficacy of lipid-lowering drugs on the overall mortality from cardiovascular events. In patients with low HDL and high triglycerides as an adjunctive to statin therapy, fibrates or niacin may be used.

## Revasularization
The goal of the treatment of chronic stable angina is to reduce the symptoms, delay the progression of atherosclerosis, and prevent cardiovascular events. In order to achieve these goals, lifestyle modifications and medical therapy are the first line treatment. Revascularization is done to increase survival in specific conditions where the stenosis of the coronary arteries is anatomically and functionally significant and the symptoms are refractory to medical therapy. There are currently two well-established revascularization approaches for the treatment of chronic stable angina caused by coronary atherosclerosis: CABG and PCI. Since the introduction of coronary artery bypass surgery in 1967 and percutaneous transluminal coronary angioplasty (PTCA) in 1977, research has supported the effective usage of both strategies for treatment of patients with chronic stable angina. However, as with any treatment method, both methodologies have weaknesses. The choice between PCI and CABG is based upon anatomy and other factors such as left ventricular function and the presence or absence of diabetes. In general, PTCA is reserved for single or some cases of two vessel disease, while CABG is reserved for patients with two or three vessel disease or left main disease. With the availability of drug-eluting stents, PCI is increasingly being performed for many lesions including more complex ones.

### PCI
Percutaneous coronary intervention for coronary artery disease first began in 1977, as a valuable mode of revascularization, wherein at the point of coronary stenosis a catheter-borne balloon is inflated to relieve the stenosis.

### CABG
Coronary artery bypass surgery, also coronary artery bypass graft (CABG, pronounced "cabbage") surgery, and colloquially heart bypass or bypass surgery is a surgical procedure performed to relieve angina and reduce the risk of death from coronary artery disease. Arteries or veins from elsewhere in the patient's body are grafted to the coronary arteries to bypass atherosclerotic narrowings and improve the blood supply to the coronary circulation supplying the myocardium (heart muscle). This surgery is usually performed with the heart stopped, necessitating the usage of cardiopulmonary bypass; techniques are available to perform CABG on a beating heart, so-called "off-pump" surgery.

### PCI vs Medical Therapy
An increased risk of mortality and morbidity is associated with untreated coronary artery disease. The main aim of therapy in patients with chronic stable angina is to alleviate symptoms, delay the progression of atherosclerosis, reduce the incidence of adverse coronary events and improve prognosis. This may be achieved with either initial medical therapy or with initial revascularization that includes percutaneous coronary intervention or coronary artery bypass grafting. Medical therapy alleviates symptom and improves prognosis; however, on the contrary, revascularization procedures provide symptomatic relief but generally does not improve mortality.

### CABG vs Medical Therapy
It is well established that revascularization with CABG has shown to provide better symptomatic relief and improved survival rates in comparison to medical therapy in some patients with stable angina. However, the long term benefit of CABG is limited by the progression of atherosclerosis in other unbypassed vessels and stenosis of the graft itself.

### PCI and CABG vs Medical Therapy
The Mass and Mass-II trials directly compared the effect of medical therapy, CABG and PCI for the management of chronic stable angina. However, there are a few reservations to the application of results from these studies as they did not include the current optimal strategies of therapy.

### PCI vs CABG
PCI and CABG have become the standard of care in the management of patients with symptomatic coronary artery disease. Patients with multi-vessel disease, the overall mortality and freedom from myocardial infarction appear to be similar in both the treatment strategies; however, the need for repeat revascularization is significantly higher in patients who initially underwent PCI secondary to a higher incidence of restenosis.

## Alternative Therapies for Refractory Angina

### Transmyocardial Revascularization (TMR)
As the survival of patients with primary coronary events continue to increase, the number of patients presenting with refractory ischemia despite maximal medical therapy and unsuitable for further traditional revascularization techniques also continues to rise. Transmyocardial revascularization (TMR) is one of the emerging techniques that has been studied in many randomized trials and has shown to reduce the incidence of recurrent angina, increase exercise tolerance time and improve quality of life. TMR can be performed using either a laser beam or a percutaneous approach. However, only laser TMR is currently FDA approved.

### Spinal Cord Stimulation (SCS)
In patients with refractory angina, spinal cord stimulation (SCS) is used to provide analgesia in the region of radiation of anginal-pain with the help an implanted device consisting of a stimulating electrode tip that extends into the dorsal epidural space, usually at the C7-T1 level.

### Enhanced External Counter Pulsation (EECP)
Enhanced external counter pulsation (EECP) is another alternative therapy in the management of refractory angina. Most data from observational studies have demonstrated significant improvement in the exercise tolerance and reduction in the frequency of anginal symptoms as well as the use of nitroglycerin among patients treated with EECP.

## Discharge Care

### Patient Follow-Up
Ongoing follow-up of the patient with chronic stable angina is necessary to monitor symptoms and to optimize antianginal therapy. It is generally recommended that these patients be evaluated every 4-6 months during first year of diagnosis/initiation of therapy and annually thereafter.  Based upon clinical judgement, if the patient is poorly responsive to therapy, if the episodes are severe or frequent, or if the patient is fragile with multiple co-morbidities, they may need to be seen more frequently.
During a follow-up visit, the patient should be asked about the frequency and severity of their anginal symptoms, their level of exercise capacity, whether they have been able to modify his/her risk factors, how well they are tolerating and complying with the therapy and whether he/she has developed new illnesses or co-morbidities.

### Rehabilitation
Cardiac rehabilitation, also called cardiac rehab (CR), is a medically supervised program to help cardiac patients recover quickly and improve their overall well being. The main goal of rehabilitation is to help patients understand their disease and inculcate a regimen to stabilize and reduce, or even reverse the progression of cardiovascular disease. Cardiac rehab is often divided into phases that involve monitored exercise, counseling, emotional support, and education about lifestyle changes to reduce the risks of heart problems. It also helps reverse limitations experienced by patients who have suffered the adverse patho-physiologic and psychological consequences of cardiac events, thus, also helping patients to return to work early. Traditionally, cardiac rehabilitation has been provided to lower-risk patients who could exercise without physical limitations. However, rapid evolution in the management of CAD has now changed the demographics of the patients, so that, even patients with recent revascularization can be candidates for rehabilitation training.

## Secondary Prevention

### Smoking Cessation
The 1989 Surgeon Generals report, which assessed numerous case-control and cohort studies, reported that smoking increased cardiovascular disease mortality by 50%. Cigarette smoking, likely due to the hemodynamic consequences of sympathetic neural stimulation and systemic catecholamine release, plays an important role in the pathogenesis of coronary artery disease. Cigarette smoking also forms a major risk factor for acute cardiovascular events as it relates to an associated increase in blood coagulability. Hence, cigarette smoking is an important reversible risk factor in the pathogenesis of CAD and cessation of which improves prognosis and is associated with a substantial decrease in the risk of mortality. In patients with stable angina pectoris, nicotine replacement therapy has shown to be potentially beneficial despite the associated cardiovascular risks of nicotine, such as increase in heart rate with a small rise in blood pressure. Nicotine replacement therapy may be initiated as early as 23 days after acute myocardial infarction or cardiac arrhythmias.  Additionally, nicotine patches have been used successfully in high-risk patients without any adverse effects such as aggravation of MI or arrhythmia.

### Weight Management
Obesity is directly associated with the development of coronary artery disease (CAD) risk factors such as: hypertension, diabetes, reduced levels of HDL-C and elevated levels of triglyceride. Research has demonstrated that CAD risk factors contribute to a strong, graded, J-shaped univariable relationship between BMI and cardiovascular disease mortality. This increased mortality, when adjusted for age, self-reported smoking status, total cholesterol, and systolic blood pressure, maintained significant hazard ratios. Hence, in obese patients with CAD, weight reduction and/or dietary interventions may be warranted to reduce the incidence of above-mentioned risk factors and prevent future coronary events. Weight reduction is strongly recommended in patients with a BMI greater than 30 kg/m2 and in patients with increased waist circumference (greater than 102 cms for men and 89 cms for women), characteristic of truncal obesity. Based on the plasma lipid abnormalities, adequate dietary modification may also be indicated.

### Physical Activity
Based on an individual's ability to exercise and severity of the symptoms, physical activity may be indicated as a treatment. As a treatment, increased physical activity has demonstrated improvements in an individual's sustained exercise duration, reduced the frequency of symptoms and also provided beneficial effects on blood pressure, diabetes and the overall lipid profile. Before the initiation of an exercise regimen, an exercise test is indicated as a useful guide to assess the level of tolerance.

### Lipid Management
In patients with established coronary artery disease, the recommended goal for total cholesterol is 130 mg/dl and LDL-C is 100 mg/dl, while the HDL-C and triglyceride concentrations serve as preferred markers for risk assessment. In patients with CAD, a fasting lipid-profile may be repeated at 5 year intervals to assess the overall risk of cardiovascular mortality and morbidity. Based on the individuals lipid abnormalities, necessary dietary interventions and/or lipid-lowering agents are suggested to prevent the risk of future coronary events. A Mediterranean diet consisting of fruits, vegetables, lean meat and fish has also been shown to be beneficial. Omega-3 fatty acid supplementation may be indicated in patients with stable angina for secondary prevention, as it has been shown to reduce elevated triglycerides and also reduce the risk of sudden cardiac death. Fish consumption once a week has also been associated with reduced risk of mortality from coronary artery disease and, for this reason, is strongly recommended.

### BP Control
The risk of progression of atherosclerosis is proportional to the increase in elevated blood pressure, hyperglycemia and dyslipidemia. Therefore, the control of hypertension, hyperglycemia and other features of metabolic syndrome deserves special attention in the prevention of mortality and morbidity due to coronary artery disease. In patients with established CAD, concomitant diabetes and/or renal dysfunction, the blood pressure goal is 130/80-85 and the decision to lower blood pressure depends on the total cardiovascular risk and the extent of target organ damage. Close monitoring and lifestyle changes may be indicated in low-risk patients without documented target organ damage. However, in high-risk patients with a sustained SBP of 140 mm Hg and/or DBP 90 mm Hg, the goal is to lower blood pressure less than 140/90 with the help of combined drug therapy and life style modification. Anti-hypertensive therapies that have shown to significantly reduce cardiovascular mortality and morbidity in patients with coronary artery disease include diuretics, beta-blockers, ACEIs, ARBs and calcium channel blockers.

### Diabetes Control
Diabetes is one of the major modifiable risk factors for coronary artery disease. Maintaining a good glycemic control has been demonstrated to delay the disease progression in patients with impaired glycemic control and further prevent microvascular complications. In type 1 diabetics, appropriate insulin therapy and concomitant dietary modification may be required. However, in patients with type 2 diabetes, a multi-factorial intervention involving increased physical activity, weight reduction, dietary modification and/or drug therapy has shown to reduce the risk of overall cardiovascular and microvascular events by approximately 50%.