Stable Angina

Etiology

The mechanism behind stable angina is the result of a supply-demand mismatch. The myocardial oxygen demand transiently exceeds the myocardial oxygen supply, often leading to symptoms. Several factors contribute to stable angina; the most common etiology is coronary artery stenosis. This is further discussed below in the section titled ‘Pathophysiology.’[2]

Epidemiology

Coronary heart disease impacts over 17 million adults in the United States. Of the 17 million Americans affected, 55% of those are male. It contributes to over 500,000 deaths each year in the US. At age 40 years, the lifetime risk of developing coronary disease is estimated at 49% for men and 32% for women. The incidence of coronary events increases with age, although the male predominance of these events gradually narrows with advancing age.[3] Coronary heart disease/ischemic heart disease is not unique to the US; it is the leading cause of death in adults from low, middle, and high-income countries.[4]

Coronary heart disease can also cause significant debility. This debility can manifest in several ways, 1 of which is angina. Angina affects over 10 million people in the US, with over 500,000 new cases diagnosed each year.[1][3]

Pathophysiology

Simply put, angina results from an imbalance between the myocardial oxygen supply and the myocardial oxygen demand. Understanding the factors that contribute to each of these measures is important.

Endothelial cells line the coronary arteries, regulate vascular tone, and prevent intravascular thrombosis. Any disruption in these 2 functions can lead to coronary heart disease. Multiple mechanisms can result in injury or impairment of the endothelial lining. These mechanisms include, but are not limited to, stress, hypertension, hypercholesterolemia, viruses, bacteria, and immune complexes. Endothelial injury triggers an immune response, leading to fibrous tissue formation. Smooth muscle remodeling/fibrous caps can lead to coronary artery stenosis or even acute coronary syndrome. 

Coronary artery stenosis is the most common cause of myocardial ischemia. During increased myocardial oxygen demand, the stenosis prevents adequate myocardial oxygen supply. Four main factors contribute to oxygen demand: heart rate, systolic blood pressure, myocardial wall tension, and myocardial contractility. In states of increased demand such as illness, stress, and exercise – we rely on the body’s ability to up-regulate myocardial oxygen supply appropriately. 

The 4 main factors contributing to myocardial oxygen supply are coronary artery diameter and tone, collateral blood flow, perfusion pressure, and heart rate. While coronary artery stenosis is the most common, other conditions can lead to a decreased myocardial oxygen supply. These examples include but are not limited to, coronary artery vasospasm, embolism, dissection, and micro-vascular disease.[2][5][6]

When the myocardial oxygen demand exceeds the myocardial oxygen supply, this often manifests with symptoms. Myocardial ischemia stimulates chemosensitive and mechanoreceptive receptors within the cardiac muscle fibers and surrounding the coronary vessels. The activation of these receptors triggers impulses through the sympathetic afferent pathways from the heart to the cervical and thoracic spine. Each spinal level has a corresponding dermatome; the discomfort described by the patient often follows the specific dermatomal pattern.[7][8] It is important to conduct a thorough workup and evaluation to determine the cause of angina in each individual; understanding the etiology allows for medical optimization and appropriate management of risk factors.

History and Physical

Individuals with stable angina often have a subacute versus chronic presentation. It is important to use history and physical as a screening tool to identify high-risk individuals. Routine screening of blood pressure, weight, sleep habits, stress, exercise tolerance, tobacco, alcohol, and illicit drug use should be incorporated.

As previously mentioned, typical angina usually presents as chest discomfort or an anginal equivalent provoked by exertion and alleviated at rest or with nitroglycerin. Anginal equivalents vary, but they are commonly described as shortness of breath, nausea, or fatigue disproportionate to the activity level. 

It is important to distinguish between cardiac and non-cardiac chest discomfort. Discussing the details of the patient’s symptoms further guide this differentiation. Relevant details include the pain's quality, location, influencing factors, timing, and duration.[9]

Typical angina is often described as pressure-like, heaviness, tightness, or squeezing. It most commonly affects a broad area of the chest rather than a specific spot. There may be radiation of the pain, depending on which dermatomes are affected.[10][11] Symptoms are described as more severe with increased demand (ie, walking, lifting, emotional stress, etc). Symptoms generally last 2 to 5 minutes, and relief is experienced when the provoking activity is stopped or the patient takes nitroglycerin.[9] The physical exam is most commonly unremarkable. In the setting of typical angina, you would not expect active ischemia, leading to nonspecific physical exam findings. 

Evaluation

The evaluation of stable angina includes:

• Obtain an electrocardiogram to evaluate for active ischemia or evidence of previous infarction. 
• Obtain a chest x-ray to assist in ruling out noncardiac explanations for chest pain (ie, infection, trauma, pneumothorax, etc)
• Obtain a complete blood count, comprehensive metabolic panel, lipid panel, and troponin. Lab work is important in risk stratification and ruling out noncardiac explanations (ie, anemia, infection, renal disease, etc)
• Use previous work up to risk stratify, consider stress testing versus further coronary evaluation in moderate to high-risk individuals. 

Treatment / Management

Treatment for stable angina is geared toward reducing risk factors for presumed underlying coronary heart disease. An interdisciplinary approach would likely benefit individuals with multiple comorbidities: nutrition, diabetic educator, addiction counselor, and physical and occupational therapy. 

First-line Treatment Includes Lifestyle Modifications

• Tobacco cessation results in the biggest risk reduction. 
  • Cigarette smoking is the leading avoidable cause of premature death. The risk of cardiovascular mortality in current smokers is roughly 2 times that of nonsmokers. Interestingly enough, the risk of cardiovascular mortality in former smokers is roughly equal to that of individuals who have never smoked. That said, it is imperative to continuously encourage smoking cessation regardless of age or duration of smoking history[12]
• Cholesterol reduction
  • Evidence has supported that adherence to the Mediterranean diet (high in vegetables and fruits) reduces the risk of cardiovascular disease.[13]
• Blood pressure control
  • The 2017 AHA/ACC guidelines define hypertension as systolic blood pressure ≥130 mmHg or diastolic pressure ≥80 mmHg.[14] Goal blood pressure is unique to each patient; however, it is important to remember that for each 20/10 mmHg increase in systolic/diastolic blood pressure, evidence has supported a 2-fold increased risk of coronary heart and stroke-related mortality.[15]
• Diabetes mellitus management
  • Weight reduction, increased physical activity, and adequate control of comorbidities are recommended.[16]
• Weight loss
  • Obesity is the second leading modifiable cause of premature death.[17] Weight-loss regimens should be catered to each patient, and the discussion should include lifestyle modifications and surgical options if appropriate. 
• Aerobic exercise
  • An average of 150 minutes of moderate-intensity exercise per week or 75 minutes of high-intensity exercise per week has been shown to decrease overall cardiac risk factors and, in turn, the risk of coronary heart disease.[18]
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Pharmacologic

• Aspirin: Determine the risk of coronary heart disease in each patient. In low-risk individuals, the use of aspirin for primary prevention decreases the risk of nonfatal MI without benefit in all-cause mortality and nonfatal stroke.[19] Risk stratification is important as the use of aspirin comes with an increased risk of major bleeding.[20] Extracranial bleeding is the most common, however daily low-dose aspirin does increase the risk of intracranial hemorrhage as well.[21] As there is no evidence to support a mortality benefit for the use of aspirin in low-risk individuals, the risk of bleeding may outweigh the anticipated benefit. This should be decided on a case-by-case basis. High-risk individuals or individuals with known cardiovascular disease benefit from low-dose daily aspirin. According to the meta-analysis performed by the Antithrombotic Trialists' Collaboration, daily aspirin significantly reduced the risk of nonfatal MI, nonfatal stroke, and vascular death by 22%.[22]
• HMG-CoA reductase inhibitor: Statin therapy in high, moderate, and low-risk primary prevention subjects without clinical evidence of coronary disease has demonstrated a reduction in myocardial infarction, stroke, cardiovascular death, and total mortality.[23]
• ACE-inhibitor/angiotensin receptor blocker (ARB): It may be used in primary prevention to assist in blood pressure control and is recommended in the setting of high-risk individuals or known cardiovascular disease for cardioprotective efforts. The use of ACE inhibitors or ARBs in high-risk individuals has been shown to reduce the risk of cardiovascular and all-cause mortality.[24]
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• Symptom Control
  • Beta-blockers: Beta-blockers have been shown to decrease heart rate, blood pressure, and contractility, leading to decreased myocardial oxygen demand and decreased anginal symptoms.[25]
  • Nitrates: Nitrates relax vascular smooth muscle, leading to dilation of veins primarily; this decreases cardiac preload and, in turn, decreases myocardial oxygen demand, relieving anginal symptoms.[26]
  • Ranolazine: The mechanism of action of this medication is not entirely understood; however, it is FDA-approved for symptom control in stable angina.[27]  
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Differential Diagnosis

Below are several important differential diagnoses to consider (see Image. Types of Angina in the Coronary Artery). Brief details are listed next to each diagnosis to help differentiate from stable angina. Please reference their designated topics for specific details and diagnostic criteria for each differential diagnosis.

Cardiovascular

• Acute coronary syndrome
• Unstable angina: Detailed history is pertinent. Chest pain is less likely to follow a predictable pattern, and the patient may even experience chest pain at rest.
• NSTEMI: Elevated cardiac enzymes with or without EKG changes.
• STEMI: Elevated cardiac enzymes with regional ST elevations were noted on the EKG.
• Myocarditis: Elevated cardiac enzymes with EKG changes.
• Pericarditis: Diffuse ST elevations noted on EKG with or without an elevation in cardiac enzymes. Chest pain is pleuritic and is often relieved by leaning forward. 

Gastrointestinal

• Esophageal spasm: Temporal relationship to meals with or without dysphagia
• Gastroesophageal reflux disease: Temporal relationship to meals

Pulmonary 

• Asthma: Abnormal lung sounds are expected on the exam. Anticipate improvement in symptoms with pulmonary hygiene and inhaled beta-agonists. 
• Chronic obstructive pulmonary disease: Abnormal lung sounds are expected on the exam. Anticipate improvement in symptoms with pulmonary hygiene and inhaled beta-agonists. 
• Pulmonary embolus: Chest pain pleuritic in nature. Typically, the presentation includes tachycardia and hypoxemia.

Musculoskeletal 

• Costochondritis: Chest pain reproducible on the exam. History often reveals recent heavy lifting or exercise.
• Trauma: History reveals the mechanism of trauma. Imaging may reveal fractures.

Prognosis

The prognosis varies depending on the etiology of stable angina. Regardless of the etiology, aggressive risk factor modification is imperative. In individuals with stable angina, screening for increased frequency of symptoms or transition to unstable angina should be routinely performed. 

Complications

The most important complication of stable angina is the possibility of progression to acute coronary syndrome. Risk factor modification and medical optimization should be utilized to decrease risk. These individuals require routine monitoring and attentive primary care providers.