Introduction
Hypertensive urgency is a marked elevation in blood pressure without evidence of target organ damage, such as pulmonary edema, cardiac ischemia, neurologic deficits, or acute renal failure. Specific cutoffs have been proposed, such as systolic blood pressure greater than 180 mmHg or diastolic blood pressure greater than 110 mmHg, but these are arbitrarily derived numbers that have not been associated with short-term morbidity or mortality.[1][2] Given this, some have proposed reserving the term hypertensive urgency for patients with severely elevated blood pressure and significant risk factors for progressive end-organ damage such as congestive heart failure or chronic kidney disease. However, hypertensive urgencies are associated with a higher incidence of adverse cardiovascular events over the long term and warrant a nuanced approach focused on ensuring better blood pressure control, reducing catalysts for marked elevations of blood pressure, and reliably following up with primary care providers.[3]
Etiology
Register For Free And Read The Full Article
- Search engine and full access to all medical articles
- 10 free questions in your specialty
- Free CME/CE Activities
- Free daily question in your email
- Save favorite articles to your dashboard
- Emails offering discounts
Learn more about a Subscription to StatPearls Point-of-Care
Etiology
The etiology of acute elevations is variable. Noncompliance with antihypertensive therapy, use of sympathomimetics, and thyroid dysfunction are among the many possible causes of hypertensive urgencies. Even anxiety and pain may cause acute elevations in blood pressure and require a different treatment strategy.
Falsely elevated blood pressure due to poor equipment or technique is another potential etiology of elevated blood pressure readings that should be evaluated and remedied.[4][5]
Pseudohypertension, a falsely elevated blood pressure reading due to sclerotic or calcified arteries that do not collapse during inflation of a blood pressure cuff, is another possible cause of elevated blood pressure readings. Pseudohypertension should be considered in patients presenting without symptoms suggestive of end-organ dysfunction but with markedly elevated blood pressure despite seemingly aggressive management.[6]
Epidemiology
About 30% of American adults have hypertension.[7] The prevalence of hypertension worldwide is around 31%, which means over 1.3 billion people.[8][9][10] Among these, 1% to 2% will suffer from a hypertensive crisis in their lifespan, a term that encompasses both hypertensive urgencies and emergencies. Studies on the epidemiology of acute hypertensive crises are limited, possibly due to difficulties in parsing out when a patient's symptoms are related to their blood pressure versus some other cause. Obesity, female gender, history of cardiovascular disease, diabetes, smoking, and, most importantly, noncompliance with antihypertensive medications are some of the risk factors associated with acutely elevated blood pressure.[11]
Males are more likely to suffer a hypertensive crisis as opposed to females. It is more common in older patients and people of Afro-Caribbean origin.[12][13][14]
Pathophysiology
The pathophysiology of hypertension is complicated and not fully understood. At baseline, perfusion of cardiac, renal, and brain tissue is tightly autoregulated by varying mechanisms. With chronic hypertension, the cerebral perfusion curve shifts to the right, accommodating a higher baseline blood pressure while maintaining a steady cerebral perfusion pressure.[15]
The rapidity of blood pressure elevation is presumed to be an important factor in causing end-organ damage. Severe acute elevations are likely related to an influx of humoral vasoconstrictors, resulting in elevated systemic vascular resistance. The increased vascular wall stress and associated endothelial injury result in increased vascular permeability, activation of coagulation factors and platelets, and fibrin deposition. Continued endothelial damage and fibrinoid necrosis result in ischemia, which then leads to the further release of vasoactive mediators and further injury.[16]
Pressure natriuresis and the activation of the renin-angiotensin system result in volume depletion, often leading to further vasoconstriction. Systemic vasoconstriction causes impaired blood flow to vital organs, leading to end-organ injury, which, although unrelated to hypertensive urgency, is the hallmark of hypertensive crisis.[17]
History and Physical
The history and physical exam for patients with markedly elevated blood pressure should focus on determining whether or not the patient has signs of target organ damage. Symptoms warranting further evaluation include a headache, dizziness, shortness of breath, chest pain, vomiting, or vision changes.
The physical exam starts with an accurate blood pressure reading, with a properly-sized cuff placed on a bare upper arm. If a properly-sized cuff is not available due to large arm circumference, wrist measurement may be the most accurate but should be interpreted with caution due to lack of data compared to invasive measurements. Blood pressure should be measured in both the lying and the standing position (to assess volume depletion). It should also be taken in both arms as a significant difference between both arms may indicate aortic dissection.[18]
Other physical exam signs should be carefully evaluated. Signs of heart failure, such as elevated jugular venous distention, rales on lung auscultation, or a gallop on heart auscultation, indicate that the patient may be actively experiencing a hypertensive emergency rather than urgency. A detailed neurologic exam, including cerebellar testing, is also essential to rule out central nervous system impairment. Finally, fundoscopy showing papilledema may be a significant finding mandating more aggressive therapy.[19]
The history and physical examination establish the nature, gravity, and management of the hypertensive crisis. Therefore, the history should revolve around the presence of end-organ damage, the circumstances leading to hypertension, and any identifiable cause.
The severity and duration of the patient’s preexisting hypertension should be assessed, as well as their medication history. The details of antihypertensive treatment and compliance, the use of over-the-counter options such as sympathomimetic agents, and the use of illicit drugs, for instance, cocaine, are crucial points of the medication history. Additionally, it is essential to elicit information regarding the presence or absence of previous end-organ dysfunction, especially renal and cerebrovascular disease. In women, determining the date they had their last menstrual period is important, as hypertension affects 10% of pregnancies.[20]
Evaluation
No routine evaluation for hypertensive urgencies exists. The goal is to rule out target organ damage.[21] If the history and physical suggest that this may be present, lab testing or imaging such as metabolic panels, urinalysis, electrocardiogram, chest X-ray, and brain computed tomography may be useful.
Obtain electrolyte levels, blood urea nitrogen, and creatinine levels to assess renal function. A dipstick urinalysis to see if there is hematuria or proteinuria and urine microscopy to detect red blood cells/casts must also be performed.[22] A complete blood cell count and peripheral smear should be carried out to out-rule microangiopathic anemia. A pregnancy test, toxicology screen, and endocrine testing may be done, as indicated. Imaging should be guided by the clinical presentation. Chest radiography and electrocardiography are indicated if there are clinical signs of pulmonary edema or chest pain. Patients with a neurologic abnormality should be assessed initially with a head computed tomography scan, with further imaging studies guided by the clinical presentation.[23]
Patients at high risk for rapidly evolving target organ damage warrant particular caution, such as those with chronic congestive heart failure, chronic kidney disease, coronary artery disease, or a history of stroke. While there is little data to guide specific evaluation in such patients, a lower threshold to obtain lab testing, electrocardiography, or imaging should be considered.
Pregnant patients with elevated blood pressure also require extra caution. In these patients, especially in the absence of preexisting hypertension, preeclampsia can ensue at lower blood pressure levels than in hypertensive emergencies. In the absence of a history of hypertension, especially if the patient complains of potentially worrisome symptoms such as a headache, vision changes, or abdominal pain, lab testing should be obtained, including complete blood count, hepatic function panel, and lactic dehydrogenase.[24]
Treatment / Management
At least one incident of increased blood pressure occurs in about 3%-45% of adult patients during their attendance in the emergency department. The basic principle in establishing the essential emergency department care of hypertensive patients is the occurrence of end-organ dysfunction.[25] Mainly, patients present to the emergency department with high blood pressure; however, only a small percentage of patients will actually require emergency treatment. Providers must always remember a critical point while managing a patient with any degree of blood pressure elevation, and that is to manage the patient and not the number.
The foremost goal of the emergency provider is to establish which patients with acutely raised blood pressure are exhibiting clinical evidence of end-organ damage and need immediate intravenous treatment.[26] On the other hand, patients presenting with acutely raised blood pressure, such as systolic more than 200 mmHg or diastolic more than 120 mmHg, with no symptoms and whose blood pressure stays persistently elevated to this level at the time of discharge should be commenced on medical therapy. They should also have a close follow-up in the outpatient clinics, with a reduction in blood pressure over hours or days.[25][26][27](B3)
The treatment for hypertensive urgency is to ensure better long-term blood pressure control.[21][28][29] Emphasizing the need for compliance with medications and close primary care follow-up is paramount. Patients without symptoms or signs of target organ damage have not been shown to benefit from aggressive antihypertensive therapy in the acute setting. Rapid lowering of blood pressure in these patients offers no benefit. It carries the theoretical risk of causing relative hypotension and end-organ hypoperfusion, especially in those individuals who have longstanding severely elevated blood pressure. However, it may be beneficial to start these patients on oral antihypertensives with the goal of lowering the blood pressure slowly over 24 to 48 hours. Little data directly address what specific agent is ideal in this situation. More importantly, a close follow-up within a week with a primary care provider should be scheduled to ensure improved blood pressure control and to initiate or titrate medications as needed.(A1)
Severe elevation in the blood pressure of pregnant women should be managed immediately to prevent end-organ damage.[30] Women with preexisting hypertension who become pregnant or intend to become pregnant must be transitioned to nifedipine, methyldopa, and/or labetalol during the course of pregnancy. Pregnant women should not be given angiotensin-converting enzyme inhibitors (ACEIs), angiotensin-receptor blockers, and direct renin inhibitors.[31](A1)
Pharmacotherapy
Optimal pharmacotherapy is reliant upon the particular organ at risk, as stated below. In patients presenting with hypertensive crises, antihypertensive medication has been observed to be effective in acutely reducing blood pressure.
Sodium nitroprusside is a commonly prescribed medication. It is short-acting and can be titrated minute to minute as per the response. However, patients should have constant monitoring in HDU/ICU.
Labetalol, an alpha- and beta-blocker, has been shown to be very beneficial in managing a hypertensive crisis. It is particularly preferred in acute dissection and end-stage renal disease. Doses as 10 to 20 mg boluses may be administered, or they may be given as an IV infusion at 1 mg/min until the desired blood pressure is achieved.
Fenoldopam is a peripheral dopamine receptor agonist, and it is given as an IV dose of 0.1 µg/kg/min to be titrated every 15 minutes.
Clevidipine is a dihydropyridine calcium channel blocker administered intravenously for rapid and precise blood pressure reduction. Initial IV infusion of clevidipine is commenced at 1 to 2 mg/hour to be titrated according to the response.
Differential Diagnosis
The differential diagnoses of hypertensive urgency include but are not limited to the following:
- Anxiety disorders
- Apnea
- Cocaine-related cardiac myopathy
- Heart failure
- Hyperthyroidism
- Hypertrophic cardiomyopathy
- Myocardial infarction
- Primary aldosteronism
- Hemorrhagic stroke
- Ischemic stroke
Prognosis
Patients with hypertensive urgency are at increased risk for long-term morbidity and mortality. The one-year mortality for those experiencing an episode of hypertensive urgency is approximately 9%. Untreated hypertension is notorious for increasing mortality risk and is often described as a silent killer.
The long-term prognosis of patients with hypertensive urgencies or emergencies is not favorable. A retrospective study done on 670 adults who presented with severely raised blood pressure showed that 57.5% suffered from hypertensive emergencies. 98% of patients with hypertensive emergency and 23.2% with hypertensive urgency were hospitalized. Median survival was found to be 14 days for those who had neurovascular emergencies and 50 days for patients who had cardiovascular emergencies.[32]
Complications
Patients with hypertensive urgency should be treated appropriately; if not, they can progress to hypertensive emergency with end-organ damage. Long-term complications associated with uncontrolled hypertension include:
Deterrence and Patient Education
Patients with hypertensive urgency are advised lifestyle changes, and these include:
Pearls and Other Issues
- Hypertensive urgency is an acute, severe elevation in blood pressure without signs or symptoms of end-organ damage.
- Proposed blood pressure levels indicating hypertensive urgency are arbitrary and not associated with short-term morbidity and mortality.
- The focus should be on symptoms of end-organ damage in the patient's history, including chest pain, shortness of breath, headache, neurologic deficits, and vision changes.
- Caution is advised in pregnant patients with hypertension. Preeclampsia can ensue at lower blood pressure levels than expected in other hypertensive emergencies.
- Treat the patient, not the number. For example, rapidly bringing down blood pressure in a patient without end-organ damage may result in relative hypoperfusion and harm the patient rather than help.
Enhancing Healthcare Team Outcomes
Patients with hypertensive urgency are best managed by an interprofessional team that includes a cardiologist, internist, nephrologist, specialty cardiac nurse, pharmacist, and ophthalmologist. The key is to educate the patient on medication compliance. Patients without symptoms or signs of target organ damage have not been shown to benefit from aggressive antihypertensive therapy in the acute setting. Rapid lowering of blood pressure in these patients offers no benefit and carries the theoretical risk of causing relative hypotension and end-organ hypoperfusion, especially in those individuals who have longstanding severely elevated blood pressure. However, it may be beneficial to start these patients on oral antihypertensives with the goal of lowering the blood pressure slowly over 24 to 48 hours.
The primary care providers, nurses, and pharmacists should educate the patient on the importance of a healthy lifestyle that includes discontinuing smoking, maintaining a healthy body weight, and regular exercise. Any concerns noted by a care team member should immediately be communicated to the appropriate practitioners for remediation. Accurate patient records are essential, as they keep the entire team informed regarding the patient's status and progress. This interprofessional care model will help drive improved patient outcomes. [Level 5]
References
Frei SP, Burmeister DB, Coil JF. Frequency of serious outcomes in patients with hypertension as a chief complaint in the emergency department. The Journal of the American Osteopathic Association. 2013 Sep:113(9):664-8. doi: 10.7556/jaoa.2013.032. Epub [PubMed PMID: 24005086]
Level 2 (mid-level) evidenceLevy PD, Mahn JJ, Miller J, Shelby A, Brody A, Davidson R, Burla MJ, Marinica A, Carroll J, Purakal J, Flack JM, Welch RD. Blood pressure treatment and outcomes in hypertensive patients without acute target organ damage: a retrospective cohort. The American journal of emergency medicine. 2015 Sep:33(9):1219-24. doi: 10.1016/j.ajem.2015.05.036. Epub 2015 May 30 [PubMed PMID: 26087706]
Level 2 (mid-level) evidenceVlcek M, Bur A, Woisetschläger C, Herkner H, Laggner AN, Hirschl MM. Association between hypertensive urgencies and subsequent cardiovascular events in patients with hypertension. Journal of hypertension. 2008 Apr:26(4):657-62. doi: 10.1097/HJH.0b013e3282f4e8b6. Epub [PubMed PMID: 18327073]
Pickering TG, Hall JE, Appel LJ, Falkner BE, Graves J, Hill MN, Jones DW, Kurtz T, Sheps SG, Roccella EJ, Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Recommendations for blood pressure measurement in humans and experimental animals: Part 1: blood pressure measurement in humans: a statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Hypertension (Dallas, Tex. : 1979). 2005 Jan:45(1):142-61 [PubMed PMID: 15611362]
Level 3 (low-level) evidenceIrving G, Holden J, Stevens R, McManus RJ. Which cuff should I use? Indirect blood pressure measurement for the diagnosis of hypertension in patients with obesity: a diagnostic accuracy review. BMJ open. 2016 Nov 3:6(11):e012429. doi: 10.1136/bmjopen-2016-012429. Epub 2016 Nov 3 [PubMed PMID: 27810973]
Kleman M, Dhanyamraju S, DiFilippo W. Prevalence and characteristics of pseudohypertension in patients with "resistant hypertension". Journal of the American Society of Hypertension : JASH. 2013 Nov-Dec:7(6):467-70. doi: 10.1016/j.jash.2013.05.006. Epub 2013 Jul 10 [PubMed PMID: 23849622]
Level 2 (mid-level) evidenceHajjar I, Kotchen TA. Trends in prevalence, awareness, treatment, and control of hypertension in the United States, 1988-2000. JAMA. 2003 Jul 9:290(2):199-206 [PubMed PMID: 12851274]
Mills KT, Bundy JD, Kelly TN, Reed JE, Kearney PM, Reynolds K, Chen J, He J. Global Disparities of Hypertension Prevalence and Control: A Systematic Analysis of Population-Based Studies From 90 Countries. Circulation. 2016 Aug 9:134(6):441-50. doi: 10.1161/CIRCULATIONAHA.115.018912. Epub [PubMed PMID: 27502908]
Level 1 (high-level) evidenceKearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet (London, England). 2005 Jan 15-21:365(9455):217-23 [PubMed PMID: 15652604]
Bloch MJ. Worldwide prevalence of hypertension exceeds 1.3 billion. Journal of the American Society of Hypertension : JASH. 2016 Oct:10(10):753-754. doi: 10.1016/j.jash.2016.08.006. Epub 2016 Sep 19 [PubMed PMID: 27660007]
Saguner AM, Dür S, Perrig M, Schiemann U, Stuck AE, Bürgi U, Erne P, Schoenenberger AW. Risk factors promoting hypertensive crises: evidence from a longitudinal study. American journal of hypertension. 2010 Jul:23(7):775-80. doi: 10.1038/ajh.2010.71. Epub 2010 Apr 15 [PubMed PMID: 20395943]
Alshami A, Romero C, Avila A, Varon J. Management of hypertensive crises in the elderly. Journal of geriatric cardiology : JGC. 2018 Jul:15(7):504-512. doi: 10.11909/j.issn.1671-5411.2018.07.007. Epub [PubMed PMID: 30364798]
Waldron FA, Benenson I, Jones-Dillon SA, Zinzuwadia SN, Adeboye AM, Eris E, Mbadugha NE, Vicente N, Over A. Prevalence and risk factors for hypertensive crisis in a predominantly African American inner-city community. Blood pressure. 2019 Apr:28(2):114-123. doi: 10.1080/08037051.2019.1568183. Epub 2019 Jan 22 [PubMed PMID: 30669866]
Hyman DJ, Pavlik VN. Characteristics of patients with uncontrolled hypertension in the United States. The New England journal of medicine. 2001 Aug 16:345(7):479-86 [PubMed PMID: 11519501]
Kessler CS, Joudeh Y. Evaluation and treatment of severe asymptomatic hypertension. American family physician. 2010 Feb 15:81(4):470-6 [PubMed PMID: 20148501]
Marik PE, Varon J. Hypertensive crises: challenges and management. Chest. 2007 Jun:131(6):1949-62 [PubMed PMID: 17565029]
Taylor DA. Hypertensive Crisis: A Review of Pathophysiology and Treatment. Critical care nursing clinics of North America. 2015 Dec:27(4):439-47. doi: 10.1016/j.cnc.2015.08.003. Epub 2015 Sep 26 [PubMed PMID: 26567490]
Um SW, Ohle R, Perry JJ. Bilateral blood pressure differential as a clinical marker for acute aortic dissection in the emergency department. Emergency medicine journal : EMJ. 2018 Sep:35(9):556-558. doi: 10.1136/emermed-2018-207499. Epub 2018 Jul 18 [PubMed PMID: 30021832]
Tajunisah I, Patel DK. Malignant hypertension with papilledema. The Journal of emergency medicine. 2013 Jan:44(1):164-5. doi: 10.1016/j.jemermed.2011.05.042. Epub 2011 Aug 4 [PubMed PMID: 21820265]
Level 3 (low-level) evidenceToo GT, Hill JB. Hypertensive crisis during pregnancy and postpartum period. Seminars in perinatology. 2013 Aug:37(4):280-7. doi: 10.1053/j.semperi.2013.04.007. Epub [PubMed PMID: 23916027]
Wolf SJ, Lo B, Shih RD, Smith MD, Fesmire FM, American College of Emergency Physicians Clinical Policies Committee. Clinical policy: critical issues in the evaluation and management of adult patients in the emergency department with asymptomatic elevated blood pressure. Annals of emergency medicine. 2013 Jul:62(1):59-68. doi: 10.1016/j.annemergmed.2013.05.012. Epub [PubMed PMID: 23842053]
Handler J. Hypertensive urgency. Journal of clinical hypertension (Greenwich, Conn.). 2006 Jan:8(1):61-4 [PubMed PMID: 16407692]
Rodriguez MA, Kumar SK, De Caro M. Hypertensive crisis. Cardiology in review. 2010 Mar-Apr:18(2):102-7. doi: 10.1097/CRD.0b013e3181c307b7. Epub [PubMed PMID: 20160537]
Sibai BM. Diagnosis and management of gestational hypertension and preeclampsia. Obstetrics and gynecology. 2003 Jul:102(1):181-92 [PubMed PMID: 12850627]
Arbe G, Pastor I, Franco J. Diagnostic and therapeutic approach to the hypertensive crisis. Medicina clinica. 2018 Apr 23:150(8):317-322. doi: 10.1016/j.medcli.2017.09.027. Epub 2017 Nov 24 [PubMed PMID: 29174704]
Ipek E, Oktay AA, Krim SR. Hypertensive crisis: an update on clinical approach and management. Current opinion in cardiology. 2017 Jul:32(4):397-406. doi: 10.1097/HCO.0000000000000398. Epub [PubMed PMID: 28306673]
Level 3 (low-level) evidenceSlovis CM, Reddi AS. Increased blood pressure without evidence of acute end organ damage. Annals of emergency medicine. 2008 Mar:51(3 Suppl):S7-9. doi: 10.1016/j.annemergmed.2007.11.005. Epub 2008 Jan 11 [PubMed PMID: 18191294]
Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, Clement D, Coca A, De Simone G, Dominiczak A, Kahan T, Mahfoud F, Redon J, Ruilope L, Zanchetti A, Kerins M, Kjeldsen S, Kreutz R, Laurent S, Lip GYH, McManus R, Narkiewicz K, Ruschitzka F, Schmieder R, Shlyakhto E, Tsioufis K, Aboyans V, Desormais I, List of authors/Task Force members:. 2018 Practice Guidelines for the management of arterial hypertension of the European Society of Hypertension and the European Society of Cardiology: ESH/ESC Task Force for the Management of Arterial Hypertension. Journal of hypertension. 2018 Dec:36(12):2284-2309. doi: 10.1097/HJH.0000000000001961. Epub [PubMed PMID: 30379783]
Level 1 (high-level) evidenceChobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ, Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Heart, Lung, and Blood Institute, National High Blood Pressure Education Program Coordinating Committee. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension (Dallas, Tex. : 1979). 2003 Dec:42(6):1206-52 [PubMed PMID: 14656957]
Level 1 (high-level) evidenceOlson-Chen C, Seligman NS. Hypertensive Emergencies in Pregnancy. Critical care clinics. 2016 Jan:32(1):29-41. doi: 10.1016/j.ccc.2015.08.006. Epub 2015 Oct 6 [PubMed PMID: 26600442]
Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, DePalma SM, Gidding S, Jamerson KA, Jones DW, MacLaughlin EJ, Muntner P, Ovbiagele B, Smith SC Jr, Spencer CC, Stafford RS, Taler SJ, Thomas RJ, Williams KA Sr, Williamson JD, Wright JT Jr. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2018 Oct 23:138(17):e484-e594. doi: 10.1161/CIR.0000000000000596. Epub [PubMed PMID: 30354654]
Level 1 (high-level) evidenceGuiga 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. Journal of clinical hypertension (Greenwich, Conn.). 2017 Nov:19(11):1137-1142. doi: 10.1111/jch.13083. Epub 2017 Sep 3 [PubMed PMID: 28866866]
Dubow J, Fink ME. Impact of hypertension on stroke. Current atherosclerosis reports. 2011 Aug:13(4):298-305. doi: 10.1007/s11883-011-0187-y. Epub [PubMed PMID: 21626308]
Kitiyakara C, Guzman NJ. Malignant hypertension and hypertensive emergencies. Journal of the American Society of Nephrology : JASN. 1998 Jan:9(1):133-42 [PubMed PMID: 9440098]
Abdulrahman H, van Dalen JW, den Brok M, Latimer CS, Larson EB, Richard E. Hypertension and Alzheimer's disease pathology at autopsy: A systematic review. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2022 Nov:18(11):2308-2326. doi: 10.1002/alz.12707. Epub 2022 Jun 27 [PubMed PMID: 35758526]
Level 1 (high-level) evidenceRuivo JA, Alcântara P. [Hypertension and exercise]. Revista portuguesa de cardiologia : orgao oficial da Sociedade Portuguesa de Cardiologia = Portuguese journal of cardiology : an official journal of the Portuguese Society of Cardiology. 2012 Feb:31(2):151-8. doi: 10.1016/j.repc.2011.12.012. Epub 2012 Jan 10 [PubMed PMID: 22237005]
Virdis A, Giannarelli C, Neves MF, Taddei S, Ghiadoni L. Cigarette smoking and hypertension. Current pharmaceutical design. 2010:16(23):2518-25 [PubMed PMID: 20550499]
Level 3 (low-level) evidence