Systemic hypertension is the most prevalent non-communicable disease and remains the leading preventable cause of premature death globally, accounting for more than 50% of cases of myocardial infarction, heart failure, and stroke [1]. Since 1990, the number of people living with systemic hypertension has doubled across the world, with low- and middle-income-countries (LMICs) accounting for most of this increase. Globally, there were roughly 1.4 billion people with systemic hypertension in 2010, and this is projected to exceed 1.6 billion by the year 2025 [2]. Approximately 1.04 billion (75%) of the global population of people with hypertension reside in LMICS [2]. South Africa has a hypertension prevalence of 35% and has the highest burden of uncontrolled hypertension amongst countries of sub-Saharan Africa [3]

The most common acute complication of systemic hypertension leading to emergency room visits is hypertensive emergency. Hypertensive emergencies represent a heterogenous group of disorders characterized by (1) acute severe blood pressure (BP) elevation, often ≥180/120 mmHg, (2) acute hypertension-mediated organ damage, and (3) the need for a prompt but contextual, system-specific lowering of the BP to avert catastrophic outcomes [4]. The organs commonly affected by acute hypertension-mediated organ damage include the heart and aorta, brain, kidneys, and retina. Concurrent occurrence of acute hypertension-mediated organ damage in multiple organs has been demonstrated, suggesting a common pathophysiologic mechanism across vascular beds [5]. Patients with severe BP elevation without evidence of acute hypertension-mediated organ damage are categorized as having hypertensive urgency, and this, along with hypertensive emergency, constitutes the syndrome of hypertensive crisis. However, the European Society of Cardiology (ESC) Council on hypertension recently proposed replacing the term hypertensive urgency with “uncontrolled hypertension”, therefore rendering the umbrella term hypertensive crisis (hitherto used to describe hypertensive emergency and hypertensive urgency) unnecessary [4].

Cardiac complications are the most prevalent acute hypertension-mediated organ damage in hypertensive emergencies. The three major cardiac acute hypertension-mediated organ damage syndromes include acute heart failure/cardiogenic pulmonary oedema, acute coronary syndrome (ACS), and less commonly, acute aortic syndrome (primarily acute aortic dissection) ^[6][7][8][9][6,7,8,9]. Mortality in hypertensive emergency is substantially elevated, especially among patients admitted into coronary care units when compared to patients without hypertensive emergencies [10]. One of the prognostic factors for major adverse cardiac events (MACE) and cerebrovascular events in patients with hypertensive emergency is raised cardiac troponin levels, with or without proven ACS ^[11][12][11,12].

2. Epidemiology

Although the availability of effective and well-tolerated antihypertensive medications has significantly improved outcomes in patients with hypertensive emergencies, the incidence remains unchanged ^[13][14][13,14]. An estimated 2–3% of hypertensive patients will develop hypertensive emergency in their lifetime ^[15][16][15,16]. Data on gender differences in patients with hypertensive emergency have been inconsistent, with some studies showing a predominance of males ^{[7][8][17][18]}[7,8,17,18], and others showing comparable prevalence in males and females ^[6][15][19][6,15,19]. Similarly, reports of age distribution compared with patients having acute severe hypertension without acute hypertension-mediated organ damage has been contradictory [9]. Studies report a varying prevalence of cardiac acute hypertension-mediated organ damage, depending on demographics and comorbidities, among others; however, cardiac involvement predominates in most of the studies, with a cumulative prevalence ranging from 3.6 to 91% (Table 1). Reasons for this marked variation in prevalence include: (1) selection bias due to preferential referrals to specialized centers; (2) variation in the exclusion criteria applied; (3) selective use of cardiac troponin assays resulting in underdiagnosis of atypical cases of myocardial infarction; (4) the non-inclusion of patients managed at primary and secondary care levels without referral to tertiary centers where most of the studies were carried out. A recent systematic review reported a composite prevalence of 52% for cardiac involvement in patients with hypertensive emergencies [9]. Epidemiology of the different cardiac acute hypertension-mediated organ damage is further discussed in the section for specific cardiac complications of hypertensive emergency.

AAS, acute aortic syndrome; AHF, acute heart failure; AMI, acute myocardial infarction; CS, cross-sectional; NIMI, non-ischemic myocardial injury; NR, not reported; USA, United State of America.

3. Pathophysiology

The exact pathophysiologic mechanisms of hypertensive emergency remain incompletely understood. However, a sudden rise in BP serves as a common denominator underlying the various forms of acute hypertension-mediated organ damage, and most hypertensive emergencies occur in people with pre-existing hypertension [4]. Although triggers for the surge in BP are also not clearly understood, nonadherence to antihypertensive medications, stress, and increased salt intake have been identified as major risk factors [6]. Three intrinsically interwoven processes operating in concert play an important role in the pathophysiology. These include the failure of vascular autoregulation, endothelial dysfunction, and activation of the renin angiotensin aldosterone system (RAAS). The principal function of vascular autoregulation is to ensure uninterrupted blood flow to vital organs during fluctuations in BP and perfusion pressure, and this is accomplished via the appropriate modification of the peripheral vascular resistance (PVR) ^[24][25][24,25]. Vascular resistance is constantly modified by metabolic, myogenic, and endothelial modulators acting in concert [26]. During increased BP and perfusion pressure, vascular resistance increases to mitigate hyper perfusion-induced organ injury, while in the face of hypotension and reduced perfusion pressure, vasodilation results in reduced vascular resistance to maintain flow to vital organs. In hypertensive emergency, a surge in BP and increased intravascular shear stress results in the disruption of vascular autoregulation and endothelial damage. This causes increased vascular permeability, perivascular oedema, exposure of subendothelial contents to circulating blood, and thrombogenesis [27]. The ensuing microvascular damage and thrombotic occlusion results in hemolysis, hypoperfusion, release of cytokines and proinflammatory molecules, ischemia, and activation of the RAAS ^[27][28][27,28]. Heightened activation of the RAAS and increased levels of angiotensin II is nearly ubiquitous in patients with hypertensive emergency and correlates with the extent of microvascular damage [28]. Angiotensin II is a potent mediator of vasoconstriction, inflammation, endothelial dysfunction, remodeling, and vascular fibrosis, and stimulates the secretion of aldosterone [29]. In addition to its principal role of volume expansion and BP maintenance, aldosterone causes cardiovascular and renal inflammation, fibrosis, and remodeling [30]. Recent studies demonstrated the expression of mineralocorticoid receptors in endothelial and vascular smooth muscle cells, resulting in aldosterone-induced vascular inflammation, fibrosis, and remodeling, as well as vascular smooth muscle cell hypertrophy and proliferation ^[31][32][33][31,32,33]. RAAS also exerts stimulatory effects on the cerebral sympathetic nervous system and potentiates the release of norepinephrine [34]. Increased levels of norepinephrine are associated with natriuresis, volume contraction, and the activation of RAAS, thus, establishing a vicious cycle. Fibrinoid necrosis of small muscular arteries and arterioles, characterized by medial smooth muscle cell necrosis and the focal deposition of proteinaceous material occurs in malignant hypertension, a form of hypertensive emergency [35]. This is succeeded by proliferative endarteritis, characterized by intimal thickening, hyperplasia of the intimal fibroblasts, generation of collagen fibers, and atrophy of the media. Fibrinoid necrosis and proliferative endarteritis are considered the histological hallmark (but not pathognomonic) of malignant hypertension, and both may result in impaired perfusion and ischemia [35]. These changes have been demonstrated in various organs including the kidney, brain, intestine, and pancreas [36]. In one proof-of-concept study, the intravenous injection of angiotensin II in an experimental model of hypertension resulted in increased endothelial permeability and necrosis of cardiac myocytes and intramyocardial arterioles, with sparing of the epicardial coronary arteries [37]. The constellation of pathophysiologic events described above does not occur in any preferential order, but rather, evolves concurrently in a variety of sequences with overlaps and widespread involvement of the vascular beds across various organs. The combined effects of autoregulatory failure, endothelial dysfunction and RAAS activation establishes a vicious cycle of BP elevation and progressively worsening acute hypertension-mediated organ damage. A summary of the pathophysiological mechanisms is presented in Figure 1.

4. Specific Cardiac Complications of Hypertensive Emergency

The different cardiac complications of hypertensive emergency are presented in Table 2.