Authors

• Lucija Bilinovac — Medicinski fakultet Sveučilišta u Zagrebu, Zagreb, Hrvatska — ORCID: 0000-0002-0206-2884
• Iva Kurjaković — Medicinski fakultet Sveučilišta u Zagrebu, Zagreb, Hrvatska — ORCID: 0000-0002-6988-7303
• Jurica Vuković — Klinička bolnica Merkur, Zagreb, Hrvatska — ORCID: 0000-0003-3727-5457
• Juraj Jug — Medicinski fakultet Sveučilišta u Zagrebu, Zagreb, Hrvatska — ORCID: 0000-0002-3189-1518
• Martina Lovrić-Benčić — Medicinski fakultet Sveučilišta u Zagrebu, Zagreb, Hrvatska — ORCID: 0000-0001-8446-6120
• Ingrid Prkačin — Medicinski fakultet Sveučilišta u Zagrebu, Zagreb, Hrvatska — ORCID: 0000-0002-5830-7131

Abstract

Hypertensive crisis is defined as systolic pressure higher than 180 mmHg or diastolic pressure higher than 120 mmHg and can be the first manifestation of arterial hypertension. In a hypertensive emergency there is evidence of organ damage in addition to severe blood pressure elevation, while in hypertensive urgency there is no organ damage. Patients with hypertensive crisis require thorough clinical assessment to exclude secondary causes of arterial hypertension. Pulse wave velocity is the measure of arterial stiffness which is directly connected to cardiovascular risk and hypertension-mediated organ damage. The aim of this study was to show the measurement of arterial stiffness in an emergency room setting as a noninvasive method of assessing cardiovascular risk in patients with hypertensive urgency. Arterial stiffness was measured for all patients with a noninvasive method using the Agedio B900 device operating on the principle of oscillometry. This study showed that the patients presenting to the Emergency Room with hypertensive urgency had higher pulse wave velocity values when compared with the reference range and to patients with resistant hypertension. Noninvasive measurement of arterial stiffness is a novel method in the diagnostic algorithm for patients with hypertensive crisis.

Keywords

pulse wave velocity, hypertensive crisis, hypertensive urgency

DOI

Full Text

Arterial hypertension is one of the main risk factors for morbidity and mortality worldwide. (1) Approximately 40% of the population older than 25 have high blood pressure, which accounts for around one billion people, and 1% of those patients will develop hypertensive crisis. (2, 3) Hypertensive crisis is defined by systolic blood pressure values over 180 mmHg or diastolic blood pressure values higher than 120 mmHg. It can develop de novo or as a complication of existing primary or secondary arterial hypertension. Hypertensive crisis can be divided into hypertensive urgency (HU) and hypertensive emergency (HE) regarding target organ damage. Hypertensive emergency includes damage to the cardiovascular, renal, and/or cerebrovascular system in addition to high blood pressure values. In hypertensive urgency, end organ damage is not present. The exact mechanism of hypertensive crisis is unknown. It is believed that the sudden elevation in blood pressure in hypertensive crisis comes from a sudden increase of systemic vascular pressure, which is connected to the action of humoral vasoconstrictors leading to intimal proliferation and fibrinoid necrosis of the blood vessel wall. (3) According to the ESC (European Society of Cardiology) and ESH (European Society of Hypertension) guidelines from 2018, arterial stiffness is recognized as a risk factor for development of hypertension-mediated organ damage (HMOD) with a pulse wave velocity (PWV) >10 m/s. (4) PWV is considered one of the most important clinical parameters for evaluation of cardiovascular risk and vascular adaptability and for follow up after the treatment. Although most commercially available PWV measuring devices offer regional estimates of arterial stiffness (measured between two vessels), local measurement offers a more precise evaluation of the condition of the arteries considering the difference between structure of the arteries. The trend in cardiovascular monitoring is shifting from invasive technologies towards noninvasive ones. (5) The population of patients with resistant hypertension is known to be a high-risk group in which arterial stiffness is recognized as a marker of increased risk. (6) Today’s hypertension guidelines suggest PWV measurement in order to determine the best candidates for renal denervation procedures. Pulse wave velocity is a predictor of total cardiovascular mortality, which associates PWV with diminished response on renal denervation procedure. (7, 8) Increased PWV was found in elderly patients with isolated systolic hypertension and diabetes mellitus. (7) Patients with hypertensive crisis could have increased PWV and vascular age compared with the reference values, just like the population of patients with resistant hypertension, who are known to be a high-risk group in which arterial stiffness is recognized as a marker of increased cardiovascular risk. (6) The aim of this study was to evaluate the measurement of pulse wave velocity in the emergency room as a noninvasive method of assessing cardiovascular risk in patients with hypertensive urgency. ## Patients and Methods This study included 23 patients who presented to the emergency room of the Clinic for Internal Diseases of the University Hospital “Merkur” in Zagreb over the course of 3 inconsecutive months in 2018/2019, who were included in a study of diagnosing hypertensive emergency approved by the Ethics Committee of the University Hospital “Merkur”. Patients whose pulse wave velocity was measured had hypertensive urgency. The study included patients with newly diagnosed hypertension and HU, patients with earlier diagnosed hypertension and HU, and patients with resistant hypertension and HU. After being admitted to the emergency room, three consecutive measurements of blood pressure were performed for all patients and oral antihypertensive therapy was given. Most patients were given 30 or 60 mg of urapidil or a fixed combination of oral antihypertensives (ACE inhibitor + calcium channel blocker). After the patients were informed about participating in a clinical study and gave their informed consent, pulse wave velocity was measured. The device used for measuring pulse wave velocity was the Agedio B900 Pulse Wave Analysis System (Germany). The device works on the principle of oscillometry. It includes a cuff, which comes in three different sizes – small, medium, and large, depending on the size of the arm which is measured in advance, the measuring device itself, and an Apple iPad with a software that shows the results. It allows for brachial blood pressure and arterial stiffness to be measured in a single procedure. Arterial stiffness is quantified as PWV and expressed in m/s. (9) The clinician inputs additional patient data such as age, sex, body weight, and height into the device. After the measurement the device produces two reports, one for the patient, containing the estimated vascular age, and one for the clinician, with hemodynamic parameters: central blood pressure, pulse pressure, mean arterial pressure, and augmentation index. (9) Arithmetic mean and standard deviation were used to present the data which followed normal distribution, and median value was used for the rest. The data were analyzed using parametric and nonparametric tests (Student’s t-test, Mann-Whitney U test). Pearson’s correlation coefficient was calculated to determine correlation. The program used for statistical analysis was MS Excel. ## Results Average age of patients was 64.0±10.76 years. 61.87% were women (14 patients) and 39.13% were men (9 patients). Female patients were older than male patients (F 67.00±10.52 years, M 59.33±9.92 years, p=0.05). The most common signs and symptoms the patients presented with were headache (30%), epistaxis (18%), chest pain (17%), dyspnea (15%), psychomotor agitation (10%), cardiac arrhythmias (6%), and paresthesia (4%). Average brachial systolic blood pressure was 190.87±9.61 mmHg, i.e. higher than 180 mmHg, which is a criterion for hypertensive crisis. Average brachial diastolic pressure was 108.91±16.23 mmHg. Average central systolic blood pressure was 155.34±19.61 mmHg, and average central diastolic blood pressure was 102.86±17.14 mmHg (**Table 1**). ### TABLE 1: Blood pressure and pulse wave velocity values in patients with hypertensive crisis. | **N** | **Age (years)** | **BBP sys. mmHg** | **BBP dias. mmHg** | **CBP sys. mmHg** | **CBP dias. mmHg** | **PWV (m/s)** | **Vascular age** | **Sex** | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | 1 | 61 | 182 | 74 | 134 | 77 | 9.6 | 9 | M | | 2 | 56 | 182 | 95 | 159 | 101 | 9.4 | 9 | M | | 3 | 58 | 195 | 105 | 153 | 110 | 9.3 | 9 | M | | 4 | 68 | 200 | 120 | 154 | 108 | 11.0 | 9 | M | | 5 | 48 | 180 | 130 | 153 | 122 | 8.1 | 9 | M | | 6 | 53 | 212 | 130 | 140 | 112 | 8.5 | 8 | M | | 7 | 48 | 192 | 136 | 156 | 122 | 8.2 | 9 | M | | 8 | 63 | 180 | 90 | 152 | 80 | 10.3 | 9 | F | | 9 | 73 | 186 | 92 | 156 | 94 | 11.9 | 9 | F | | 10 | 82 | 203 | 96 | 181 | 102 | 15.0 | 9 | F | | 11 | 75 | 180 | 100 | 146 | 100 | 11.8 | 9 | F | | 12 | 77 | 180 | 100 | 130 | 67 | 12.4 | 9 | F | | 13 | 69 | 190 | 100 | 141 | 85 | 10.7 | 8 | F | | 14 | 53 | 190 | 110 | 114 | 81 | 7.3 | 0 | F | | 15 | 61 | 201 | 115 | 120 | 94 | 10.0 | 3 | F | | 16 | 66 | 212 | 121 | 188 | 128 | 12.1 | 9 | F | | 17 | 77 | 185 | 129 | 160 | 104 | 12.9 | 9 | F | | 18 | 51 | 197 | 126 | 179 | 127 | 9.6 | 7 | F | | 19 | 63 | 187 | 110 | 169 | 113 | 10.9 | 8 | M | | 20 | 76 | 188 | 108 | 166 | 111 | 12.9 | 9 | F | | 21 | 66 | 192 | 86 | 185 | 91 | 11.8 | 8 | F | | 22 | 49 | 185 | 122 | 167 | 126 | 8.9 | 5 | F | | 23 | 79 | 191 | 110 | 170 | 111 | 13.7 | 9 | M | [†] BBP – brachial blood pressure, CBP- central blood pressure, sys. - systolic, dias. – diastolic. Values of PWV were higher than reference values for their age in all patients, averaging at 10.71±1.96 m/s. Student’s t-test showed a statistically significant difference between PWV measured in men and women (M 9.85±1.78, F 11.26±1.94; p=0.05). Other values that were measured did not show statistically significant difference. The median value of increased vascular age compared with biological age of patients was 7.91±2.27 years. PWV values show positive correlation with age (r=0.9461, p<0.0001). Central systolic blood pressure showed a weak positive correlation with PWV (r=0.4659, p=0.025). Other compared variables showed no statistically significant correlation. ## Discussion The primary factor affecting the stiffness of the arterial wall is aging, which was also confirmed by the results of this study. Difference in pulse wave velocity between men and women in this study can therefore be explained by the higher age at which women present with hypertensive urgency. Average values of PWV measured in this pilot study were higher than 10 m/s, which is a borderline value for HMOD. (4) The PWV itself is a marker of increased cardiovascular risk and can be used to divide patients into groups based on the therapy they need, whether that be monotherapy, fixed combination therapy, or triple therapy for hypertension. Since a part of the patients included in this study presented with HU as a first manifestation of AH without an earlier diagnosis of AH, measuring PWV as a parameter which changes over a longer period allows for the assessment of cardiovascular status for these patients. Patients with hypertensive urgency as well as those with hypertensive emergency have an increased risk for another episode of uncontrolled blood pressure elevation in the six months following presentation. (10) Regular follow-up and optimizing their antihypertensive therapy is therefore necessary in these patients. Measuring PWV is an additional parameter in such follow-up because it can be affected by long-term control of blood pressure. The patients in this study had a significantly higher mean value of PWV than the patients with resistant hypertension included in another study conducted at the University Hospital “Merkur”. Mean values of PWV in patients with resistant hypertension were 8.84 m/s. The same measuring device was used in that study, allowing for a direct comparison. (6) This finding is in accordance with the hypothesis that the speed at which blood pressure rises is more important than the duration of hypertension for the occurrence of vascular injury. (10, 11) After measuring office blood pressure, patients were given oral antihypertensives and their PWV was measured. It is necessary to measure PWV within 24 hours from blood pressure measurement to establish the diagnosis of hypertensive crisis. From the data it was visible that PWV remained elevated despite therapy. However, the method of measuring arterial stiffness is still not the first choice in an emergency since it takes more time than the classical blood pressure measurement. (12) Further advancements in technology can lead to improvement in this area, making the noninvasive measuring of PWV a widespread test in emergency room, together with blood pressure measurement. ## Conclusion Patients presenting to the emergency room with hypertensive urgency have elevated values of PWV compared with reference values and compared with patients with resistant hypertension. Although hypertensive urgency does not imply target organ damage, patients have increased cardiovascular risk, which is directly connected to PWV. Additional research is required on the long-term predictive value of PWV measured during hypertensive crisis.

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