Left untreated, hypertension can lead to target organ disease in the cardiovascular system and also within the cerebrovascular system, peripheral vascular system, kidneys, and/or eyes; it can eventually lead to consequences such as stroke, transient ischemic attacks, peripheral artery disease, chronic kidney disease, and retinopathy. Figure 26.1 illustrates the generally accepted continuum of hypertensive disease and, specifically, its effects on the myocardium. The primary goal of treatment for hypertension is to reduce the blood pressure to a level below that which was used to diagnose the condition; however, these thresholds have been recently debated in the literature. In addition, the role that an individual’s race plays in the development of hypertension is rightfully gaining more research and clinical attention, e.g., African Americans develop hypertension earlier in life and have higher average blood pressures than Caucasians [10]. Recent guidelines account for this difference and contain specific recommendations for black and non-black patients [11].

The highly anticipated and debated Eighth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC8) outlines nine recommendations for the management of hypertension based on evidence published exclusively from randomized controlled trials [11]. While continuing to endorse a hypertension goal of <140/90 mmHg for patients less than 60 years old, the new recommendations relax to some extent the previously published goals if patients are ≥60 years old (new goal: <150/90 mmHg), have diabetes, or have chronic kidney disease (new goal: <140/90 mmHg for both) [9]. Since the release of these JNC8 guidelines, a number of other groups such as the American Society of Hypertension (ASH) , European Society of Hypertension, and the National Institute for Health and Clinical Excellence have reaffirmed recommendations of a blood pressure goal of <140/90 mmHg for all patients, providing an exception that it may be appropriate to target a blood pressure of <150/90 in patients over 80 years old [12–14]. For example, ASH delineates staging of hypertension (e.g., prehypertension versus hypertension) and blood pressure goals based on age and comorbid conditions. They recommend that the general population and patients with diabetes, kidney disease, and coronary artery disease should attempt to achieve a blood pressure of <140/90 mmHg but recommend <150/90 mmHg for patients over 80 years old and a diastolic goal of <90 mmHg for patients less than 50 years old [12]. Despite this controversy and uncertainty in optimal blood pressure targets, the ultimate goal of hypertension prevention and management is to prevent disease progression and reduce overall morbidity and mortality.

Lifestyle modifications are considered as a key component in the treatment regimen for patients with hypertension. Modifications such as smoking cessation, weight loss, increased physical activity, and decreased sodium intake have all been shown to have profound effects on lowering blood pressure and improving overall health [9, 11–14]. Medications of choice for managing hypertension have also changed with the release of recent guidelines. The JNC8 guidelines indicate that an angiotensin-converting enzyme (ACE) inhibitor (or angiotensin receptor blocker [ARB]), a dihydropyridine calcium channel blocker , and thiazide-type diuretics are considered “first-line” therapy options for such patients [11]. Selection of an antihypertensive will also be determined by patient race (black or non-black) and/or whether the patient has a concomitant condition. In following JNC8 recommendations, additional considerations should be determined relative to patients with various races, diabetes mellitus, and/or chronic kidney disease; however, other organizations such as ASH consider the presence of other compelling indications for selection of medication or combination of medications (Table 26.4). Indeed, beta-blockers are no longer a preferred agent unless the patient has a compelling indication. For example, for those patients with hypertension and coronary artery disease, a beta-blocker plus an ACE inhibitor may be warranted. Lastly, if blood pressure therapeutic goals are not achieved with a single agent, a second or third antihypertensive may need to be added.

The proper and immediate management for acute coronary syndrome is pivotal in preventing the progression of myocardial tissue damage. Aside from early recognition and response, goals of therapy are to remove the precipitating factor(s) causing the ischemia and to minimize irreversible damage from occurring to the myocardial tissue. Importantly, patients are at a higher risk of death or worsening myocardial infarction if they have prolonged ischemic symptoms, clinical and ECG findings, and/or elevated biochemical cardiac markers [17, 18].

After an initial stratification of risks for the determination of the planned intervention (i.e., percutaneous coronary intervention, or PCI), patients with unstable angina/NSTEMI should undergo a medical therapy regimen that includes: (1) rapid vasodilation with nitroglycerin; (2) supplemental oxygen to achieve a goal arterial oxygen saturation >90 %; (3) morphine sulfate for pain and agitation control; (4) beta-blockade in patients without contraindications (e.g., bradycardia, lung disease, or hemodynamic decompensation); (5) correction of serum potassium and magnesium levels as indicated; (6) antihyperlipidemia treatment, (e.g., with a statin either initially or upon discharge for lipid management); (7) arrhythmia management, both atrial and ventricular; and (8) an ACE inhibitor for blood pressure control and prevention of myocardial injury progression [16]. In addition to this regimen, antiplatelet and anticoagulation therapy should be initiated immediately. Antiplatelets include aspirin and adenosine diphosphate P2Y₁₂ protein receptor blocker such as clopidogrel, prasugrel, or ticagrelor; these are drugs of choice, and a glycoprotein IIb/IIIa receptor antagonist can be considered if ischemia persists or if a patient is deemed at high risk for immediate death or severe complications. If revascularization with PCI is performed, dual antiplatelet therapy (e.g., aspirin and clopidogrel) is typically indicated for at least one year post-procedure. In some settings dual antiplatelet therapy may also be indicated for medical management in the absence of PCI. In other words, the decision to use an anticoagulant agent in the setting of unstable angina/NSTEMI depends on whether the patient undergoes reperfusion therapy with PCI. Currently, the common anticoagulation options include: heparin, unfractionated or low molecular weight (e.g., enoxaparin), direct thrombin inhibitors (e.g., bivalirudin), or factor Xa inhibitors (e.g., fondaparinux) [16, 18].

It is imperative to achieve myocardial reperfusion of STEMI patients in a timely manner, to salvage as much viable myocardium as possible. The preferred method of myocardial reperfusion is PCI [19]. Fibrinolytic pharmacologic therapy (tissue plasminogen activator, streptokinase, or urokinase) is an alternative option for patients being first treated in a non-PCI-capable hospital, with expected transport delays exceeding 120 min [16, 17]. The timing of reperfusion therapy is essential in achieving the highest survival benefit; it has the most impact on infarct size and preservation of left ventricular function. For example, the goal of first medical contact (FMC) to PCI time is 90 min with initial presentation to a PCI-capable center and 120 min with initial presentation to a non-PCI-capable center necessitating transport to a PCI-capable center. In cases where PCI is not feasible, a goal time to initiation of fibrinolytic therapy is within 30 min after a diagnosis of STEMI. After reperfusion efforts, continued management is achieved through routine measures listed above, including oxygen, nitroglycerin, aspirin, analgesia, statin, beta-blocker, and an ACE inhibitor [17]. Aldosterone antagonists are also recommended after STEMI in patients who develop heart failure.

Heart failure is a progressive disease in which initial compensatory mechanisms will eventually become themselves detrimental to the patient (Fig. 26.2). Therefore, pharmacologic treatment is aimed at those neurohormonal mechanisms, such as the renin-angiotensin-aldosterone system and sympathetic nervous system, which mediate the progression of the disease. Goals of therapy include: (1) improving quality of life, (2) reducing HF symptoms and hospitalizations, and (3) prolonging overall survival.

In the past, treatment decisions were largely guided by NYHA classification; however, in recent years they are increasingly determined by ACCF/AHA disease staging (Table 26.6) [22]. Management of HF begins with correcting any factors (e.g., infection or nonsteroidal anti-inflammatory drugs) and addressing comorbid conditions (e.g., sleep-disordered breathing) that may be contributing to the progression of the disease. After underlying conditions have been improved or corrected, efforts are made to follow guideline-directed medical therapy (GDMT) in order to realize the mortality and morbidity benefits demonstrated in reported clinical trials. To date, ACE inhibitors and beta-blockers remain the cornerstones of GDMT and are proven to provide significant morbidity and mortality benefits [25–29]. Initial doses for each agent are very low and titrated as tolerated over 3–6 months, until goal doses are reached (Tables 26.7). In circumstances where a patient has a contraindication or experiences an adverse event with an ACE inhibitor, an ARB may be substituted as a means to retain mortality benefits [30]. Aldosterone antagonists have a role in decreasing mortality and hospitalization rates in patients with class III and IV heart failure [31]. The vasodilators hydralazine and isosorbide dinitrate, given in combination, are recommended for the management of black patients with NYHA III and IV on GDMT and for patients with contraindications to ACE inhibitors or ARBs [32]. Other agents such as diuretics and digoxin can also be given for symptom relief and to reduce subsequent hospitalizations. Currently, loop diuretics are the most potent class of clinically used diuretics and are the mainstay in volume control for HF pharmacotherapy. In all such patients, fluid status is an important monitoring parameter; for example, fluid retention can blunt the response of ACE inhibitors and increase beta-blocker adverse events, whereas fluid depletion can increase the risk of renal insufficiency. Importantly, both electrolyte levels and kidney function need to be monitored regularly when these agents are used in combination. Recently, cardiac resynchronization therapy (CRT) is a nonpharmacologic strategy that has been shown to reduce mortality and hospitalization rates in patients with class III or IV heart failure, who are already receiving optimal medical management [23]. Implantable cardioverter defibrillators (ICDs) may be used in selected individuals for the primary prevention of sudden cardiac death [33]. For more information on these technologies, the reader is referred to Chap. 30.