Cardiac Complications of Hypertensive Emergency: Comparison
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Please note this is a comparison between Version 2 by Peter Tang and Version 1 by Ellen Ngarande.

While mortality in patients with hypertensive emergency has significantly improved over the past decades, the incidence and complications associated with acute hypertension-mediated organ damage have not followed a similar trend. Hypertensive emergency is characterized by an abrupt surge in blood pressure, mostly occurring in people with pre-existing hypertension to result in acute hypertension-mediated organ damage. Acute hypertension-mediated organ damage commonly affects the cardiovascular system, and present as acute heart failure, myocardial infarction, and less commonly, acute aortic syndrome. Elevated cardiac troponin with or without myocardial infarction is one of the major determinants of outcome in hypertensive emergency. 

  • hypertensive emergency
  • epidemiology
  • pathophysiology
  • cardiac acute hypertension-mediated organ damage
  • myocardial injury
  • diagnosis
  • classifications

1. Introduction

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[7][8][17][18],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.
Table 1.
Prevalence of cardiac acute hypertension-mediated organ damage in hypertensive emergencies.

Author, Year, Country

Design

AHF

(%)

AMI (%)

AAS (%)

Cumulative (%)

NIMI (%)

Comments

Fragoulis [6], 2021, Greece

Prospective

58

22.6

2

82.6

NR

National cardiac referral centre registry data. Potential for bias towards cardiac complications.

Rubin [18], 2019, France

Prospective

31

NR

NR

31%

63

Excluded myocardial infarction from their cohorts and 63% had elevated troponin while 83% had left ventricular hypertrophy.

Zampaglione [15], 1996, Italy

Prospective

36.8

12

2

50.8

NR

Cerebral infarction was the most common acute hypertension-mediated organ damage. However, composite of cardiac complications occurred in 50.8%.

Kim [12], 2022, Korea

CS

NR

40.5

NR

40.5

60.4

Focused on prognostic role of cardiac troponin in acute severe hypertension. Elevated (occurred in 41.6%) and detectable (occurred in 36.5%) cardiac troponin associated with higher mortality at 3 years.

Guiga [20], 2017, France

CS

37.4

13.8

1.8

53

NR

Reported higher mortality in hypertensive emergency than hypertensive urgency (12.5 vs. 1.8%).

Salvetti [8], 2021, Italy

2008 data

2015 data

Prospective

34

37.5

25

25

1

0.5

60

63

NR

NR

Excluded resuscitated cardiac arrest and patients requiring urgent cardiac catheterization.

Pacheco [7], 2103, Mexico

Prospective

25.2

59.5

6.3

91

NR

Their cohorts composed of a high-risk group admitted into coronary care unit. Reported high rate of acute coronary syndrome and acute aortic syndrome.

Martin [17], 2004, Brazil

Retrospective

25

13

0

33

NR

Reported unstable angina (5%) separately from myocardial infarction (8%).

Vilela-Martin [21], 2011, Brazil

CS

30.7

25.1

3.5

47.2

NR

Reported unstable angina (12.1%) separately from myocardial infarction (13%).

Nkoke [19], 2020, Cameroon

CS

44.6

3.6

0

48.2

NR

Myocardial infarction occurred in 3.6% of their cohorts. Low rate of detection of myocardial infarction may be related to lack of facilities including low rates of ECG and cardiac troponin assay.

Acosta [22], 2020, USA

Retrospective

NR

1

0

1

15

Assessed acute myocardial injury using serial cardiac troponin assay. Excluded acute coronary syndrome from their cohorts.

Pattanshetty [23], 2012, USA

Retrospective

20.5

11.7

2.3

34.5

NR

Obstructive coronary artery disease present in 76.5% of their cohorts with elevated cardiac troponin that had angiogram.

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.
Figure 1. Summary of the pathophysiologic processes in acute hypertension-mediated organ injury. ACS; acute coronary syndrome; AKI, acute kidney injury; aHMOD, acute hypertension-mediated organ damage; BP, blood pressure; HELLP, hemolysis, elevated liver enzymes, low platelets; NSAID, nonsteroidal anti-inflammatory drug; PRES, posterior reversible encephalopathy syndrome; RAAS, renin–angiotensin–aldosterone system; TMA, thrombotic microangiopathy; VSMC, vascular smooth muscle cell; * Not listed as acute hypertensive target organ damage in guidelines; † presence of retinal exudates, hemorrhage ± papilledema.

4. Specific Cardiac Complications of Hypertensive Emergency

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

Acute hypertension mediated-organ damage

  Acute heart failure/acute pulmonary edema *

  Acute coronary syndrome *

    ST-elevation myocardial infarction

    Non-ST-elevation myocardial infarction

    Unstable angina

  Acute aortic syndrome

    Acute aortic dissection *

    Intramural hemorrhage/hematoma

    Penetrating atherosclerotic aortic ulcer

    Aortic aneurysm

    Aortic rupture

Sub-clinical cardiac target organ injury §

  Acute myocardial injury

* Commonly reported cardiac complications; § Not included as a complication in guidelines.

5. Challenges in Evaluation, Classifications, and Treatment of Cardiac Complications of Hypertensive Emergencies

5.1. Sub-Clinical Acute Target Organ Damage

Based on current guidelines, the measurement of cardiac troponin in patients with hypertensive emergency is recommended only when there are symptoms/features of myocardial ischemia. Asymptomatic/sub-clinical myocardial injury occurs in more than one-third of patients with hypertensive emergency [13] and there is evidence for an increased risk of MACE and poor renal outcome in patients with myocardial injury [50][38]. Notwithstanding, current guidelines on the evaluation of hypertensive emergency do not include assessment of subclinical acute target organ damage/dysfunction. The selective use of cardiac troponin assays can result in missed and mis-diagnoses of atypical acute myocardial infarction (including silent myocardial infarction), and subclinical myocardial injury.

5.2. Nomenclature and Classification

The nomenclature and classification of cardiac complications of hypertensive have not been consistent. Many studies used acute heart failure and acute pulmonary oedema (or cardiogenic pulmonary oedema) interchangeably, whereas some reported the two separately.
The universal definition categorizes myocardial infarction into five types [51][39]. However, most studies on the cardiac complications of hypertensive emergency fall short of defining the different subtypes of ACS or myocardial infarction despite differences in their underlying pathophysiologic mechanisms and outcomes/prognosis. It is unclear as to what proportion of patients with ACS had ST-elevation myocardial infarction, non-ST-elevation myocardial infarction or unstable angina, and it remains debatable as to what extent unstable angina will be considered a true acute hypertension-mediated organ damage as defined in current guidelines.

5.3. Treatment

There are no randomized controlled trials to guide treatment in most cases of hypertensive emergencies, and the choice of medications, as well as the rate and magnitude of BP reduction is mainly based on expert opinion [5]. The ESC Council on hypertension recommends intravenous medications with close hemodynamic monitoring in an intensive care unit, which may not be available in low-resource settings, especially in LMICs. Evidence is emerging for the efficacy of orally administered medications in the treatment of hypertensive emergencies. In one study involving patients with malignant hypertension, the cohorts were treated with sequential administration of oral renin–angiotensin system blockers, calcium blockers, thiazide diuretic and spironolactone as required, without the need for admission into intensive care unit [19]. This cost-effective approach to treatment will appeal to LMICs with limited resources.
Presently, there are no well-validated systems for risk stratification or consensus regarding the best management options for high-risk groups, including patients with subclinical target organ damage. Based on the results of the DEMAND MI study, patients with suspected Type 2 myocardial infarction should be subjected to routine assessment of their coronary arteries (invasive or computed tomography) and be given the benefit of evidence-based treatments to improve outcomes [52][40]. This is, however, based on a single study and there is still a need for further clinical trials including patients with hypertensive emergency, to determine outcomes.

5.4. Biomarkers of Subclinical Myocardial Injury

Cardiac troponin is undoubtedly the best indicator of myocardial injury. However, new biomarkers of myocardial injury are being increasingly identified. Cardiac myosin-binding protein C is a novel biomarker of myocardial injury that is more sensitive and has the advantage of rising and falling more quickly than cardiac troponin [73][41]. This allows for more efficient tracking of the onset and resolution of acute hypertension-mediated organ damage, especially following intervention. Cardiac myosin-binding protein C has not been studied in hypertensive emergencies. It may be worthwhile to explore this and other biomarkers of myocardial injury including cardiac magnetic resonance imaging in the diagnosis of subclinical cardiac acute hypertension-mediated organ damage.

References

  1. Arima, H.; Barzi, F.; Chalmers, J. Mortality patterns in hypertension. J. Hypertens. 2011, 29, S3–S7.
  2. Mills, K.T.; Bundy, J.D.; Kelly, T.N.; Reed, J.E.; Kearney, P.M.; Reynolds, K.; Chen, J.; He, J. Global Disparities of Hypertension Prevalence and Control. Circulation 2016, 134, 441–450.
  3. Berry, K.M.; Parker, W.A.; Mchiza, Z.J.; Sewpaul, R.; Labadarios, D.; Rosen, S.; Stokes, A. Quantifying unmet need for hypertension care in South Africa through a care cascade: Evidence from the SANHANES, 2011–2012. BMJ Glob. Health 2017, 2, e000348.
  4. van den Born, B.-J.H.; Lip, G.Y.; Brguljan-Hitij, J.; Cremer, A.; Segura, J.; Morales, E.; Mahfoud, F.; Amraoui, F.; Persu, A.; Kahan, T.; et al. ESC Council on hypertension position document on the management of hypertensive emergencies. Eur. Heart J. Cardiovasc. Pharmacother. 2019, 5, 37–46.
  5. Mishima, E.; Funayama, Y.; Suzuki, T.; Mishima, F.; Nitta, F.; Toyohara, T.; Kikuchi, K.; Kunikata, H.; Hashimoto, J.; Miyazaki, M.; et al. Concurrent analogous organ damage in the brain, eyes, and kidneys in malignant hypertension: Reversible encephalopathy, serous retinal detachment, and proteinuria. Hypertens. Res. 2021, 44, 88–97.
  6. Fragoulis, C.; Dimitriadis, K.; Siafi, E.; Iliakis, P.; Kasiakogias, A.; Kalos, T.; Leontsinis, I.; Andrikou, I.; Konstantinidis, D.; Nihoyannopoulos, P.; et al. Profile and management of hypertensive urgencies and emergencies in the emergency cardiology department of a tertiary hospital: A 12-month registry. Eur. J. Prev. Cardiol. 2022, 29, 194–201.
  7. Pacheco, H.G.; Victorino, N.M.; Urquiza, J.P.N.; Castillo, A.A.; Herrera, U.J.; Mendoza, A.A.; Manzur, F.A.; de la Cruz, J.L.B.; Sánchez, C.M. Patients with hypertensive crises who are admitted to a coronary care unit: Clinical characteristics and outcomes. J. Clin. Hypertens. 2013, 15, 210–214.
  8. Salvetti, M.; Paini, A.; Colonetti, E.; Tarozzi, L.; Bertacchini, F.; Aggiusti, C.; Stassaldi, D.; Rosei, C.A.; Rosei, E.A.; Muiesan, M.L. Hypertensive emergencies and urgencies: A single-centre experience in Northern Italy 2008–2015. J. Hypertens. 2020, 38, 52–58.
  9. Astarita, A.; Covella, M.; Vallelonga, F.; Cesareo, M.; Totaro, S.; Ventre, L.; Apra, F.; Veglio, F.; Milan, A. Hypertensive emergencies and urgencies in emergency departments: A systematic review and meta-analysis. J. Hypertens. 2020, 38, 1203–1210.
  10. Gonzalez, R.; Morales, E.; Segura, J.; Ruilope, L.M.; Praga, M. Long-term renal survival in malignant hypertension. Nephrol. Dial. Transplant. 2010, 25, 3266–3272.
  11. Cremer, A.; Amraoui, F.; Lip, G.Y.H.; Morales, E.; Rubin, S.; Segura, J.; Van den Born, B.J.; Gosse, P. From malignant hypertension to hypertension-MOD: A modern definition for an old but still dangerous emergency. J. Hum. Hypertens. 2016, 30, 463–466.
  12. Kim, W.; Kim, B.S.; Kim, H.-J.; Lee, J.H.; Shin, J.; Shin, J.-H. Clinical implications of cardiac troponin-I in patients with hypertensive crisis visiting the emergency department. Ann. Med. 2022, 54, 507–515.
  13. Janke, A.T.; McNaughton, C.D.; Brody, A.M.; Welch, R.D.; Levy, P.D. Trends in the Incidence of Hypertensive Emergencies in US Emergency Departments From 2006 to 2013. J. Am. Heart Assoc. 2020, 5, e004511.
  14. Lip, G.Y.H.; Beevers, M.; Beevers, G. The failure of malignant hypertension to decline—A survey of 24 years experience in a multiracial population in England. J. Hypertens. 1994, 12, 1297–1305. Available online: http://search.ebscohost.com/login.aspx?direct=true&db=cmedm&AN=7868878&site=ehost-live&scope=site (accessed on 6 February 2022).
  15. Zampaglione, B.; Pascale, C.; Marchisio, M.; Cavallo-Perin, P. Hypertensive urgencies and emergencies. Prevalence and clinical presentation. Hypertension 1996, 27, 144–147.
  16. Lane, D.A.; Lip, G.Y.H.; Beevers, D.G. Improving Survival of Malignant Hypertension Patients Over 40 Years. Am. J. Hypertens. 2009, 22, 1199–1204.
  17. Martin, J.F.V.; Higashiama, E.; Garcia, E.; Luizon, M.R.; Cipullo, J.P. Hypertensive crisis profile. Prevalence and clinical presentation. Arq. Bras. Cardiol. 2004, 83, 130–131.
  18. Rubin, S.; Cremer, A.; Boulestreau, R.; Rigothier, C.; Kuntz, S.; Gosse, P. Malignant hypertension: Diagnosis, treatment and prognosis with experience from the Bordeaux cohort. J. Hypertens. 2019, 37, 316–324. Available online: https://journals.lww.com/jhypertension/Fulltext/2019/02000/Malignant_hypertension__diagnosis,_treatment_and.13.aspx (accessed on 8 February 2022).
  19. Nkoke, C.; Noubiap, J.J.; Dzudie, A.; Jingi, M.A.; Njume, D.; Teuwafeu, D.; Aseneh, J.; Nkouonlack, C.; Menanga, A.; Kingue, S. Epidemiology of hypertensive crisis in the Buea Regional Hospital, Cameroon. J. Clin. Hypertens. 2020, 22, 2105–2110.
  20. Guiga, H.; Decroux, C.; Michelet, P.; Loundou, A.; Cornand, D.; Silhol, F.; Vaisse, B.; Sarlon-Bartoli, G. Hospital and out-of-hospital mortality in 670 hypertensive emergencies and urgencies. J. Clin. Hypertens. 2017, 19, 1137–1142.
  21. Vilela-Martin, J.F.; Vaz-de-Melo, R.O.; Kuniyoshi, C.H.; Abdo, A.N.R.; Yugar-Toledo, J.C. Hypertensive crisis: Clinical-epidemiological profile. Hypertens. Res. 2011, 34, 367–371.
  22. Acosta, G.; Amro, A.; Aguilar, R.; Abusnina, W.; Bhardwaj, N.; Koromia, G.A.; Studeny, M.; Irfan, A. Clinical Determinants of Myocardial Injury, Detectable and Serial Troponin Levels among Patients with Hypertensive Crisis. Cureus 2020, 12, e6787.
  23. Pattanshetty, D.J.; Bhat, P.K.; Aneja, A.; Pillai, D.P. Elevated troponin predicts long-term adverse cardiovascular outcomes in hypertensive crisis: A retrospective study. J. Hypertens. 2012, 30, 2410–2415.
  24. Beishon, L.C.; Minhas, J.S. Cerebral Autoregulation and Neurovascular Coupling in Acute and Chronic Stroke. Front. Neurol. 2021, 12, 720770.
  25. Strandgaard, S.; Haunsø, S. Why does antihypertensive treatment prevent stroke but not myocardial infarction? Lancet 1987, 330, 658–661.
  26. Westerhof, N.; Boer, C.; Lamberts, R.R.; Sipkema, P. Cross-Talk Between Cardiac Muscle and Coronary Vasculature. Physiol. Rev. 2006, 86, 1263–1308.
  27. van den Born, B.-J.H.; Löwenberg, E.C.; van der Hoeven, N.V.; de Laat, B.; Meijers, J.C.; Levi, M.; van Montfrans, G.A. Endothelial dysfunction, platelet activation, thrombogenesis and fibrinolysis in patients with hypertensive crisis. J. Hypertens. 2011, 29, 922–927.
  28. van den Born, B.-J.H.; Koopmans, R.P.; van Montfrans, G.A. The renin-angiotensin system in malignant hypertension revisited: Plasma renin activity, microangiopathic hemolysis, and renal failure in malignant hypertension. Am. J. Hypertens. 2007, 20, 900–906.
  29. te Riet, L.; van Esch, J.H.M.; Roks, A.J.M.; van den Meiracker, A.H.; Danser, A.H.J. Hypertension: Renin-angiotensin-aldosterone system alterations. Circ. Res. 2015, 116, 960–975.
  30. Rocha, R.; Stier, C.T., Jr.; Kifor, I.; Ochoa-Maya, M.R.; Rennke, H.G.; Williams, G.H.; Adler, G.K. Aldosterone: A Mediator of Myocardial Necrosis and Renal Arteriopathy. Endocrinology 2000, 141, 3871–3878.
  31. Koenig, J.B.; Jaffe, I.Z. Direct Role for Smooth Muscle Cell Mineralocorticoid Receptors in Vascular Remodeling: Novel Mechanisms and Clinical Implications. Curr. Hypertens. Rep. 2014, 16, 427.
  32. Kusche-Vihrog, K.; Jeggle, P.; Oberleithner, H. The role of ENaC in vascular endothelium. Pflügers Arch. Eur. J. Physiol. 2014, 466, 851–859.
  33. Galmiche, G.; Pizard, A.; Gueret, A.; El Moghrabi, S.; Ouvrard-Pascaud, A.; Berger, S.; Challande, P.; Jaffe, I.Z.; Labat, C.; Lacolley, P. Smooth Muscle Cell Mineralocorticoid Receptors Are Mandatory for Aldosterone–Salt to Induce Vascular Stiffness. Hypertension 2014, 63, 520–526.
  34. Tsuda, K. Renin-Angiotensin System and Sympathetic Neurotransmitter Release in the Central Nervous System of Hypertension. Int. J. Hypertens. 2012, 2012, 1–11.
  35. Gustafsson, F. Hypertensive arteriolar necrosis revisited. Blood Press 1997, 6, 71–77.
  36. Kincaid-Smith, P.; McMicheal, J.; Murphy, E.A. The clinical course and pathology of hypertension with papilloedema (malignant hypertension). QJM Int. J. Med. 1958, 27, 117–154.
  37. Olsen, F. Acute hypertensive damage of arterial vessels of the heart. Acta Pathol. Microbiol. Scand. Sect. A Pathol. 1978, 86, 199–200.
  38. Thygesen, K.; Alpert, J.S.; Jaffe, A.S.; Chaitman, B.R.; Bax, J.J.; Morrow, D.A.; White, H.D. and Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth universal definition of myocardial infarction. J. Am. Coll. Cardiol. 2018, 72, 2231–2264.
  39. Bularga, A.; Hung, J.; Daghem, M.; Stewart, S.; Taggart, C.; Wereski, R.; Singh, T.; Meah, M.N.; Fujisawa, T.; Ferry, A.V.; et al. Coronary Artery and Cardiac Disease in Patients with Type 2 Myocardial Infarction: A Prospective Cohort Study. Circulation 2022, 145, 1188–1200.
  40. Neri, E.; Toscano, T.; Papalia, U.; Frati, G.; Massetti, M.; Capannini, G.; Tucci, E.; Buklas, D.; Muzzi, L.; Oricchio, L.; et al. Proximal aortic dissection with coronary malperfusion: Presentation, management, and outcome. J. Thorac. Cardiovasc. Surg. 2001, 121, 552–560.
  41. Marber, M.S.; Mills, N.L.; Morrow, D.A.; Mueller, C. Cardiac myosin-binding protein C as a biomarker of acute myocardial infarction. Eur. Heart J. Acute Cardiovasc. Care 2021, 10, 963–965.
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