Hypertensive emergencies are potentially life-threatening conditions in which a symptomatic acute rise in BP levels leads to the development of acute organ damage . The term hypertensive urgencies, traditionally used to define a symptomatic rise in BP in the absence of organ damage, should be abandoned in favour of the term ‘uncontrolled hypertension’  as these patients do not require hospitalization. A close outpatient follow-up is recommended to ensure BP control is achieved.
Although both conditions are potentially linked to increased morbidity and mortality, their management remains challenging because of lack of evidence. Firstly, in contrast to the ascertained burden of chronic arterial hypertension, the relative prevalence of hypertensive emergencies and hypertensive urgencies in emergency departments and the frequency of each form of aHMOD remains debated, in part, because of heterogeneous diagnostic criteria and paucity of publications. Moreover, though BP values have a central role in making the diagnosis, it is uncertain if the presence of aHMOD should be suspected solely based on elevated BP levels, and if there is a relationship between presenting symptoms and presence of aHMOD. Lastly, the differences in terms of cardiovascular risk factors between patients presenting with hypertensive emergency and hypertensive urgency are poorly investigated.
Given these uncertainties, we conducted a systematic review and meta-analysis to assess the prevalence of hypertensive emergencies and hypertensive urgencies in emergency departments and the prevalence of each subtype of aHMOD. In addition, through a comparative analysis between hypertensive emergency and hypertensive urgency patients, we sought to investigate the role of BP levels, symptoms and cardiovascular risk factors to predict the presence of aHMOD.
This systematic review and meta-analysis adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement .
We included studies assessing the prevalence of hypertensive emergencies by enrolling consecutive patients presenting to the emergency departments. In order to be considered eligible, the following data had to be reported: definition of hypertensive emergency/hypertensive urgency adopted, BP values at presentation and subtype of aHMOD.
We excluded the following types of publications: studies investigating hypertensive emergencies in pregnant women or in patients 18 years old or less; enrolment taking place in any setting other than the emergency departments or setting not clearly specified; retrospective studies in which the diagnosis of hypertensive emergency was based on International Classification of Diseases codes at discharge.
Data regarding patients with uncontrolled hypertension in the absence of aHMOD (i.e. hypertensive urgencies) were also extracted to perform a comparative analysis of hypertensive emergencies and hypertensive urgencies. Data regarding presenting symptoms were extracted when provided.
Two independent authors (A.A. and M.C.) conducted a comprehensive search without language restrictions trough PubMed, OVID and Web of Science Medline databases from their inception to August 22 2019 using the following search terms: hypertensive emergencies, hypertensive crisis, hypertensive urgencies, malignant hypertension, accelerated hypertension, myocardial ischemia, myocardial infarction, unstable angina, coronary artery disease, hypertensive encephalopathy, posterior reversible encephalopathy, posterior leukoencephalopathy syndrome, intracranial hypertension, pulmonary oedema, heart failure, congestive heart failure, ischemic stroke, intracranial/subarachnoid haemorrhage, haemorrhagic stroke, papilloedema, optic papilla oedema, hypertensive retinopathy, aortic dissection (see text document, Supplement Digital Content 1, http://links.lww.com/HJH/B257, which reports the full search strategy used). The research was extended by a manual review of the references from selected studies.
Two reviewers (A.A. and M.C.) initially screened titles and abstracts and then reviewed the full text of selected publications; a third reviewer (A.M.) concluded controversies. In case of studies conducted by the same research group, we investigated the possibility of overlap of the study sample and if it was confirmed, we considered the most recent one. The following data were extracted from the eligible studies: number of patients admitted for hypertensive emergencies and hypertensive urgencies, number of total emergency department visits, prevalence of each aHMOD, BP levels and symptoms at presentation, clinical characteristics of hypertensive emergency and hypertensive urgency patients (age, sex, cardiovascular risk factors). Figure 1 details the research process.
The first part of the analysis aimed to assess the epidemiology of hypertensive emergencies in terms of: overall prevalence, subtype of aHMOD and relative frequency compared with hypertensive urgencies.
The prevalence of hypertensive emergencies was computed for each study as the number of cases divided by the total number of emergency departments visits over the same time period and expressed as a percentage [95% confidence interval (CI)]. The relative prevalence of each subtype of aHMOD was calculated as the number of cases divided by the total number of patients with hypertensive emergencies. These frequencies were then meta-analysed across studies to calculate the average frequency. The relative frequencies of hypertensive emergency and hypertensive urgency were compared by calculating the odds ratio.
The second part of the analysis involved only publications reporting data for both hypertensive emergency and hypertensive urgency patients. Baseline BP values, age, prevalence of known hypertension and frequency of presenting symptoms were meta-analysed across studies and compared between hypertensive emergencies and hypertensive urgencies. Continuous variables (BP, age) were compared by calculating the mean difference; categorical variables (previously known arterial hypertension, presenting symptoms) were compared by calculating odds ratios (OR).
The proportion of variability explained by true heterogeneity (i.e. between-studies variability) was estimated by calculating the I2 for each analysis. Random-effect models were used because of high heterogeneity of the study samples. All statistical analyses were performed with R software version 3.3  with the Metafor package version 2.1 .
Characteristics of the studies
Eight study samples (five prospective [5–8], three retrospective [9–11]) from seven different publications were included in the final analysis, for a total of 1970 hypertensive emergency patients and 4983 hypertensive urgency patients. The definition of hypertensive emergencies always included the presence of aHMOD, but varied with regard to the BP levels considered, with older studies only considering DBP for inclusion. Five studies [5,6,8,10] were conducted in European countries, one in Thailand  and two in Brazil [7,11]. The characteristics of the studies included in the final analysis are shown in Table 1.
Prevalence of hypertensive emergency and hypertensive urgency
The mean prevalence of hypertensive emergencies was 0.3% [0.14–0.46] whereas the prevalence of hypertensive urgencies was 0.94% [0.29–1.59] (see Figures, Supplemental Digital Content 2 and 3, http://links.lww.com/HJH/B258). Both estimates showed high variability across the different studies, with prevalence ranging between 0.08 and 0.76% for hypertensive emergencies (I2 99.7%) and between 0.24 and 2.4% for hypertensive urgencies (I2 100%). Hypertensive urgencies were more common than hypertensive emergencies in most studies (OR for hypertensive urgencies vs. hypertensive emergencies: 2.5 [1.4–4.3]; Fig. 2).
Prevalence of each subtype of acute hypertension-mediated organ damage
The prevalence of each subtype of aHMOD was assessed separately (see Figures, Supplemental Digital Content 4–9, http://links.lww.com/HJH/B259); the overall prevalence is shown in Fig. 3. Acute pulmonary oedema/heart failure was the most common aHMOD [32%; (28–36); I2 72.6%], followed by ischemic stroke [29%; (23–35); I2 87.9%], acute coronary syndrome [18%; (14–22); I2 83.3%], haemorrhagic stroke [11%; (7–14); I2 86.8%], acute aortic syndrome [2%; (0–5); I2 82.7%] and hypertensive encephalopathy (2%; [0–5]; I2 98.7%). For this latter aHMOD, the prevalence ranged between 0 and 5% in seven studies, up to 17% in the remaining one  (see Figure, Supplemental Digital Content 6, http://links.lww.com/HJH/B259).
SBP and DBP values: comparison between hypertensive emergency and hypertensive urgency
SBP at presentation did not differ between hypertensive emergencies and hypertensive urgencies (1.4 mmHg; [−0.8 to 3.6]; I2 63.1%), whereas DBP was slightly higher in hypertensive emergency patients (2.3 mmHg; CI [0.3–4.3]; I2 78.1%; Figs. 4 and 5).
Symptoms: comparison between hypertensive emergency and hypertensive urgency
In accordance to the current guidelines , we distinguished two groups of presenting symptoms complained by comparison between hypertensive emergency and hypertensive urgency patients: ‘specific symptoms’ (chest pain, dyspnoea, focal neurological symptoms and headache) and ‘nonspecific symptoms’. The main symptoms complained by hypertensive emergency patients were neurological symptoms [35% (0.27–0.42)] and dyspnoea [31% (0.25–0.36)] whereas in hypertensive urgency patients presented more frequently with headache [22% (0.09–0.35)] and ‘nonspecific symptoms’ [48% (0.34–0.62)]. The prevalence of ‘nonspecific symptoms’ in hypertensive emergency patients were 24% [0.14–0.35].
We assessed the predictive value of each symptom with regard to the presence of aHMOD by calculating odds ratios of being diagnosed with hypertensive urgency vs. hypertensive emergency for each presenting symptom. Hypertensive urgencies were more likely in the presence of headache [OR 2.5 (1.4–4.5)] and nonspecific symptoms [OR 3.1 (1.4–6.5)]. Hypertensive urgencies were less likely when patients presented with focal neurological symptoms (OR 0.12 [0.07–0.19]), chest pain (OR 0.43 [0.22–0.83]) and dyspnoea [OR 0.27 (0.13–0.54)]. In Fig. 6, the summary of prevalence and OR of hypertensive emergency and hypertensive urgency symptoms (see Figures, Supplement Digital Content 10–24, http://links.lww.com/HJH/B260, which detail the prevalence and the OR for each symptom).
Cardiovascular risk factors: comparison between hypertensive emergency and hypertensive urgency
The prevalence of known arterial hypertension in hypertensive emergency patients was 82.5% (78.6–86.3) I2 79% whereas in hypertensive urgency patients was 78% [72.5–83.6] I2 94.6% without a statistical difference between the two groups (OR hypertensive emergencies vs. hypertensive urgencies: 0.8 [0.5–1.2]; I2 87.4%). Among hypertensive emergency patients, there was a higher percentage of men (52 vs. 42% for hypertensive urgency), hypertensive urgency patients were on average younger than hypertensive emergency patients by 5.4 years (2.6–8.3) I2 90.4% (see Figures, Supplement Digital Content 25–28, http://links.lww.com/HJH/B261, which detail the analysis of known arterial hypertension and age). No other quantitative analysis was performed because of lack of data.
The current review and meta-analysis was designed to assess the epidemiology of hypertensive emergencies and hypertensive urgencies in emergency departments and the main variables associated with aHMOD.
Across the eight included studies, the combined prevalence of hypertensive emergencies and hypertensive urgencies in emergency departments was approximately 1.2% with hypertensive urgencies being significantly more common than hypertensive emergencies [OR 2.5 (1.4–4.3)]. However, prevalence varied widely across studies (range: 0.08--0.76% for hypertensive emergencies and 0.24--2.4% for hypertensive urgencies). This is at least in part explained by the different definitions of hypertensive emergencies/hypertensive urgencies adopted, making it difficult to assess the contribution of additional variables, such as ethnicity, prevalence of hypertension in the population and ease of access to healthcare. The results of our analysis are similar to those of the largest USA database on hypertensive emergencies (STAT Registry) that estimated a prevalence of 0.2% for hypertensive emergencies .
Acute pulmonary oedema/heart failure was the most common subtype of aHMOD, as previously reported in other retrospective studies [13,14]. Heterogeneity across studies was highest for aortic syndromes and for hypertensive encephalopathy. Although this is partly justified by the rare occurrence of these two forms of organ damage, in the case of hypertensive encephalopathy, we observed a very wide range of prevalence (0--17%) suggesting a lack of uniformity in diagnostic criteria and in the utilization of diagnostic imaging. The growing availability of MRI and newer methods for ocular fundus examination , could improve the detection of this specific aHMOD, otherwise probably underestimated.
In the second part of the analysis, we compared hypertensive emergency and hypertensive urgency patients with respect to their BP levels, symptoms at presentation and baseline characteristics (age, sex, cardiovascular risk factors) to identify variables that could predict the presence of organ damage. Since the definition of uncontrolled hypertension provided in the most recent ESC/ESH consensus document  was not adopted in any of the studies included in the analysis, patients with BP levels above a certain threshold in the absence of organ damage were defined as having a hypertensive urgency. BP levels were overall similar between hypertensive emergency and hypertensive urgency patients. Although a statistically significant difference was found for DBP in favour of hypertensive urgency [2.3 mmHg (0.3–4.3)], the small magnitude of such difference makes this finding irrelevant for clinical practice. This data suggests that, despite the widely known linear association between BP levels and the development of aHMOD , others factors, such as the rate of BP rise, play a more important role in the development of the aHMOD.
In accordance with the current ESC/ESH Guidelines , we distinguished two groups of symptoms at presentation – specific and nonspecific – to assess their predictive value with regard to the presence of organ damage. Seventy-six percent of patients with hypertensive emergency presented with specific symptoms. Chest pain, dyspnoea and focal neurological symptoms were strongly associated with the presence of acute organ damage. By contrast, headache carried a more benign prognosis, making the diagnosis of hypertensive urgency approximately 2.5 times more likely. Nonspecific symptoms were the most common presentation for patients with hypertensive urgency (48%). However, a significant proportion of patients with aHMOD (24%) complained of nonspecific symptoms as well, highlighting the need to perform a comprehensive clinical evaluation and to maintain a low threshold for ordering diagnostic tests in patients with acute hypertensive disorders.
Hypertensive urgency patients were on average younger than hypertensive emergency patients [5.4 years (2.6–8.3)] whereas the prevalence of known arterial hypertension was similar between the two groups. No other cardiovascular risk factors were investigated, because of lack of data. Previous studies [12,13,17], mostly retrospective, identified correlations between known cardiovascular risk factors (diabetes, cardiac diseases, renal insufficiency, smoking, alcohol abuse and nonadherence to antihypertensive therapy ) and hypertensive emergencies.
With the exception of one publication , no data regarding inpatient and outpatient outcomes were available. Previous reports, based on small samples [12,19–21], have shown significant mortality and morbidity for both hypertensive emergencies and hypertensive urgencies.
This study has several limitations. Firstly, as the definitions of hypertensive emergency and hypertensive urgency changed over time, the studies included in our analysis adopted different BP levels as the cut-off for the diagnosis of both hypertensive emergencies and hypertensive urgencies, contributing to the heterogeneity of the results. Secondly, protocols for the evaluation for organ damage were not standardized across studies, and availability of diagnostic tools as well as the definitions of some of the subtypes of aHMOD varied during the study period. Reporting of presenting symptoms was not consistent as well, and some of the publications omitted data on cardiovascular risk factors whose analysis could have better elucidated the different profile of patients with hypertensive emergency and hypertensive urgency.
Lastly, the included publications were heterogeneous with regard to geographical setting, study design and year of publication: three studies were retrospective [9,10,11] and five studies were conducted before the year 2010 [5–8,11]; both aspects increase the heterogeneity of the results because of measured and unmeasured confounding factors. Despite these limitations, this meta-analysis represents the first attempt to quantitatively analyse the epidemiology of hypertensive emergencies and hypertensive urgencies in the emergency department setting and the main predictors of aHMOD.
Our results demonstrate the high prevalence of hypertensive emergencies and hypertensive urgencies in emergency departments, with hypertensive urgencies being significantly more common. BP levels alone do not reliably predict the presence of aHMOD, which should be suspected according to the presenting signs and symptoms. If more comprehensive data became available, a risk stratification tool for patients with acute hypertensive disorders could be developed. Quality publications based on larger populations are needed to gain a deeper knowledge of the epidemiology of acute hypertensive disorders, which will help standardize management and guide decision-making for these conditions.
We acknowledge Dr G. Pinna and Dr C. Pascale for the scientific contribution in the field of hypertensive emergencies.
Conflicts of interest
There are no conflicts of interest.
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* Anna Astarita and Michele Covella are joint first authors.