Cardiovascular disease is the most common cause of mortality. Each year it accounts for 30% of deaths worldwide and 38.5% in the United States and Western Europe [1]. Although the incidence of cardiovascular disease is decreasing in high-income countries due to education and advancement in medical therapy, it is rapidly rising in middle- and low-income countries as they become increasingly industrialized and urbanized [1]. Acute coronary syndrome (ACS) is a spectrum of unstable cardiovascular disease that includes unstable angina (UA), non-ST-elevation myocardial infarction (NSTEMI), and ST-elevation myocardial infarction (STEMI), and is often the initial clinical presentation for coronary artery disease (CAD). The major risk factors for ACS include tobacco abuse, family history of CAD, advanced age, hypertension, hyperlipidemia, and diabetes mellitus.

This chapter focuses on the management of ACS in patients with diabetes. Diabetics are more likely than nondiabetics to experience ACS, and diabetes is an independent predictor for mortality in ACS. Diabetics are also more likely to develop complications of ACS and its management such as heart failure and bleeding. With a few exceptions, the management of ACS is similar in patients with and without diabetes. In patients with diabetes, management does not differ between patients who are insulin dependent and patients who do not require insulin. Although intensive treatment of hyperglycemia, dyslipidemia, and hypertension can reduce cardiovascular and microvascular events in diabetics by as much as 50%, diabetes remains a major risk factor for ACS [2].

The initiating event in ACS is rupture or erosion of an atherosclerotic plaque within the coronary endothelium. This exposes the lumen of the coronary artery to subendothelial matrix, leading to the activation of platelets and eventual thrombus formation. ACS is a dynamic process, during which there is cyclical transition among partial vessel occlusion, complete occlusion, and reperfusion. In UA, plaque rupture results in severe obstruction of coronary blood flow and subsequent ischemic symptoms, at times associated with electrocardiographic ST depressions or T-wave inversions without elevation of cardiac biomarkers. NSTEMI is defined by obstruction that leads to infarction without electrocardiographic ST elevation. Plaque rupture that results in complete and prolonged coronary artery occlusion usually leads to ST elevation and subsequent myocardial infarction.

Classically, patients with ACS present with substernal chest pain characterized as “vice-like” or “pressure.” The pain often radiates to the left shoulder or jaw, but can radiate to the right arm, back, neck, and/or epigastrium. Associated symptoms include nausea, vomiting, diaphoresis, palpitations, dyspnea, dizziness, and/or confusion. The chest discomfort associated with STEMI is usually more severe than the discomfort experienced with UA/NSTEMI. Also, chest pain in the setting of STEMI is less likely to be relieved by nitroglycerine. Atypical symptoms or silent ischemia (with associated symptoms such as cardiac dysrhythmias or heart failure) are more common in diabetics, women, and the elderly. Appropriate therapy for ACS is dependent on early recognition of symptoms by the patient, as delayed medical evaluation can result in cardiogenic shock and sudden cardiac death. While physical examination is unlikely to aid in the diagnosis of ACS, it is important in risk stratification, excluding alternate diagnoses, and determining whether mechanical complications of myocardial infarction (MI) are present.

Other diagnoses that cause chest pain can be mistaken for ACS. Gastrointestinal disorders such as gastroesophageal reflux disease (GERD), esophageal spasm, and esophageal hyperalgesia can mimic ischemic chest pain. GERD and CAD can coexist, and it is not uncommon for patients with ACS to mistake their symptoms as reflux. Given this, it is prudent to exclude ACS before proceeding with further evaluation for gastrointestinal disease.

Acute pericarditis causes pleuritic chest pain that is worse when supine and relieved by sitting up and leaning forward. It is usually associated with diffuse ST-segment elevation and concomitant PR-segment depression. If there is myocardial involvement (myocarditis), the cardiac biomarkers may be elevated and transthoracic echocardiogram (TTE) may reveal a regional wall motion abnormality. It can be distinguished from acute MI by the lack of reciprocal ST depression. Also, the ST elevations in acute pericarditis are usually concave, as opposed to the convex ST elevations seen in acute MI.

Aortic dissection typically causes sharp, tearing chest pain with radiation to the back. It is often most severe at onset, as opposed to ischemic chest pain, the severity of which increases over time. Aortic dissection is usually distinguished from ACS based on symptoms, though physical examination can assist in the diagnosis. Examination in patients with aortic dissection may reveal a difference between right and left upper extremity blood flow, detected by comparing the pulse and blood pressure. The diastolic murmur of aortic insufficiency may also be present. If the aorta is enlarged, the chest radiograph will show a widened mediastinum. A TTE may reveal the dissection flap, but the diagnosis is usually made by transesophageal echocardiogram (TEE), computerized tomography (CT), or magnetic resonance imaging (MRI).

Acute onset of pleuritic chest pain and shortness of breath in the absence of pathology on chest radiography suggests pulmonary embolism (PE). The ECG most often shows sinus tachycardia, but may demonstrate right ventricular strain. Although cardiac biomarkers can be slightly elevated with acute PE, TTE can be performed to rule out a left ventricular wall motion abnormality and identify right ventricular dysfunction.

With the exception of reperfusion timing, patients across the spectrum of ACS are managed similarly. The major difference is that STEMI patients need emergent reperfusion, whereas patients with UA and NSTEMI can be risk stratified to early coronary angiography or conservative management. The following discussion will include medical management and reperfusion strategies in patients with ACS. The management of patients with and without diabetes is similar, with a few exceptions that will be discussed below.