Article, Cardiology

Is epistaxis associated with high blood pressure and hypertension? Propensity score matching study

a b s t r a c t

Objective: We aimed to investigate whether high blood pressure and hypertension are associated with epistaxis. Methods: A retrospective study with a propensity score matching analysis was performed at the emergency de- partments (EDs) of a Tertiary university hospital. The mean blood pressure (BP, systolic and diastolic) and pro- portion of subjects with elevated BP (systolic N120 and/or diastolic N80 mmHg) at presentation were compared between the epistaxis group and matched control group. The proportion of patients with newly diag- nosed hypertension within six months between the two groups was also compared.

Results: A total of 1353 patients with epistaxis and the same number of those with simple lacerations were matched. The mean systolic and Diastolic BPs of the epistaxis group were significantly higher than those of the matched control group (157.1 +- 26.4 and 91.4 +- 17.0 mmHg versus 144.9 +- 32.4 and 84.2 +- 13.5 mmHg) (P b 0.001). The proportion of patients with elevated BP at presentation was also significantly higher in the ep- istaxis group (91.4%) than in the matched control group (86.2%) (P b 0.001). Of the 724 (53.5%) patients without pre-existing hypertension in the epistaxis group, 660 patients were followed, of whom 107 (16.2%) were newly diagnosed with hypertension within 6 months, which was a significantly higher percentage than among the matched controls (4.9%, P b 0.001)

Conclusion: The patients with epistaxis had elevated BP at presentation and a higher proportion of newly diag- nosed hypertension within six months compared to the matched controls.

(C) 2020

Introduction

Epistaxis is one of the most common otolaryngologic emergency symptoms. It has long been thought that hypertension is associated with epistaxis, although this association has caused a longstanding con- troversy [1-11]. Chronic hypertension could affect vasculopathogenesis, including atherosclerosis, endothelium dysfunction and rupture [2], and might increase the risk of epistaxis. Actually, patients with epistaxis commonly present at the emergency department (ED) with Elevated blood pressure (BP) [6,7]. However, these results do not establish a cause-effect relationship between the two conditions because the high BP may be caused by the anxiety-induced adrenergic effect due to bleeding. White coat syndrome may also affect the high BP. In addition, the BP can be affected by the time of the visit to the ED because BP fluc- tuates daily and seasonally [12-18]. We wanted to investigate whether

* Corresponding author at: Department of Emergency Medicine, Guri Hospital, Hanyang University, 153, Gyeongchun-ro(st), Guri-si, GyeongGi-do 471-701 Republic of Korea.

E-mail address: [email protected] (C. Kim).

high BP and hypertension are associated with epistaxis. To remove con- founding factors, we compared the BP values between the patients with epistaxis and those with simple lacerations using the propensity score matching technique.

Materials and Methods

This retrospective study was conducted over a 5-year period from January 2014 to December 2018 at the ED of a tertiary university hospi- tal (48,000 visits annually) in Korea, and it was approved by the Institu- tional Review Board of our institution.

Patient selection

All adult patients (>=18) with spontaneous epistaxis who presented at the ED during the study period were included in this study. Patients with non-spontaneous nosebleeds (nasal trauma) and those with fac- tors that could affect the occurrence of epistaxis (hepatic insufficiency, head and neck cancer, and hemorrhagic disease) were excluded. Study subjects were identified by searching the electronic Order

https://doi.org/10.1016/j.ajem.2019.10.025

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Communication System of our hospital. The demographic data (Patient sex and age), the date and time of the visit to the ED and the BP at pre- sentation were extracted from the search results. The personal disease history, such as hypertension (including taking antihypertensive medi- cation), renal insufficiency, hepatic insufficiency and diabetes mellitus , and the administration of antithrombotic (antiplatelet and anti- coagulant) medication were also collected The predesigned form to col- lect the above information from bleeding patients had already been established before this study.

Those in the control group (with simple lacerations) during the same period were also investigated. In this study, superficial lacerations with little or no visible contamination were defined as simple lacera- tions. Patients with other Associated injuries (fracture, intracranial hem- orrhage, intrathoracic/peritoneal hemorrhage, altered mentality, etc.) were excluded. Prior to data extraction, the coder was carefully trained. He coded the above variables for practice and extracted data from pa- tients for approximately a month. Author CK carefully verified the ex- tracted data, and accurate and consistent coding was established after several modifications.

We additionally investigated how many patients were newly diag-

nosed with hypertension in the six months following the hospital visit in each group. First, a chart review (whether the patient had newly di- agnosed hypertension according to the diagnostic code within six months) was conducted. If there was no record of the patients within those six months in our hospital or the timing of the diagnosis (within 6 months) was not confirmed in the process of chart review, a tele- phone survey was conducted. We asked whether they had hyperten- sion, and if they did, we asked when they were diagnosed with hypertension.

Propensity score matching

To adjust for differences between the epistaxis and simple lac- eration groups, propensity score matching was conducted. The propensity scores for each group were calculated by logistic re- gression based on 8 associated clinical factors, namely, age, sex, administration of antithrombotics, hypertension and other comor- bidities (renal insufficiency, DM), season of visit (spring (March to May), summer (June to August), fall (September to November) or winter (December to February)), time of visit (morning (6:00 to 12:00), afternoon (12:00-18:00), evening (18:00-24:00), and night (24:00-06:00)). Because diurnal and seasonal variations in BP have been reported in several studies [12-18], we thought that time of visit and season could be confounders. A 1:1 matched control group was created.

Main outcome

Mean BP (systolic and diastolic) values were compared between the epistaxis group and matched control group. The proportion of subjects with elevated BP values (systolic N120 mmHg and/or diastolic N80 mmHg) at presentation was also compared between the two groups. We additionally compared the proportion of subjects with newly diagnosed hypertension within six months between the two groups.

Statistical analyses

Student’s t-test was performed to compare the BP at presentation between the epistaxis and control groups using the SPSS statistical package (SPSS Inc., version 24.0 for Windows, Chicago IL, USA). A two- tailed p value b 0.05 was considered statistically significant. The cate- gorical data were analyzed by chi-squared tests.

Results

Demographics and clinical characteristics

Of the 1516 patients searched, 67 patients with hepatic insufficiency were excluded (there were no patients with head and neck cancer or hemorrhagic disease in this study). In the process of chart review, an ad- ditional 96 patients with missing data were excluded. As a result, a total of 1353 patients with spontaneous epistaxis were enrolled; 813 (60.1%) were male, and the mean age was 57.2 +- 16.0 (standard deviation) years. Of the total patients enrolled, 629 (46.5%) had pre-existing hyper- tension, 313 (23.1%) had DM, and 98 (7.2%) had renal insufficiency. Ac- cording to the season, they visited the ED in the spring (392, 29.0%), summer (205, 15.2%), fall (330, 24.4%) and winter (426, 31.5%). A

total of 326 (24.1%) visited the ED in the morning (6:00 to 12:00), 273

(20.2%) visited in the afternoon (12:00-18:00), 471 (34.8%) visited in the evening (18:00-24:00), and the remaining 283 (20.9%) visited at night.

Of the 11,178 patients with simple lacerations, the same number of patients (1353) were matched (1:1) according to the propensity score.

Main outcome

The mean systolic and diastolic BP values in the epistaxis group were

157.1 +- 26.4 and 91.4 +- 17.0 mmHg, respectively, which were signifi- cantly higher than those in the matched control group (144.9 +- 32.4 and 84.2 +- 13.5 mmHg, respectively) (P b 0.001). The proportion of pa- tients with elevated BP at presentation was also significantly higher in the epistaxis group (1237/1353, 91.4%) than in the matched control group (1166/1353, 86.2%) (P b 0.001).

Of the 724 (53.5%) patients without pre-existing hypertension in the epistaxis group, 473 had a medical record longer than six months in du- ration in our hospital, and 61 (8.4%) were recorded as being diagnosed with new hypertension within six months in their medical charts. Al- though, there were an additional 25 patients who had a record of hyper- tension, the timing of their diagnosis could not be confirmed in the chart. Thus, the telephone survey for 276 patients (251 patients without any record in our hospital and 25 without a confirmed diagnostic pe- riod) was conducted. Additionally, 46 (6.4%) were verified as being di- agnosed with new hypertension within six months by telephone survey, and 64 (8.8%) were not contacted by telephone survey. Finally, of the 660 patients followed, 107 (16.2%) were newly diagnosed with hypertension within 6 months.

In the same manner, we confirmed that 31 (4.9%) of the 635 patients who were followed were newly diagnosed with hypertension within 6 months in the control group. A total of 83 (11.5%) patients were lost to follow-up (no medical record and no telephone contact), which was significantly lower than in the epistaxis group (P b 0.001).

Discussion

Many studies have reported a relationship between hypertension and epistaxis [1-11]. Isezuo et al. found a higher proportion of patients with pre-existing hypertension in the epistaxis group (32.3%) than in the control group (7.9%). They also demonstrated that the proportion of patients with elevated BP at presentation was higher in the epistaxis group (87.5%) than in the control group (47.6%), and the epistaxis group also had a significantly higher prevalence of hypertension (45.2%) than did the control group (13.2%) [7]. Herkner et al. reported that patients with active epistaxis had higher BP at presentation than the controls [1]. A recent meta-analysis also demonstrated that hypertension was significantly associated with the risk of epistaxis [5].

On the other hand, several studies have demonstrated the opposite results. Knopfholz et al. evaluated the incidence of epistaxis in hyper- tensive patients according to the stages of hypertension and compared BP during epistaxis episodes to routine BP readings [4]. They concluded

C. Kim et al. / American Journal of Emergency Medicine 38 (2020) 13191321 1321

that epistaxis incidence in Hypertensive patients is not associated with hypertension severity and that patients with epistaxis had similar BP values compared to those without epistaxis. Multiple studies have also supported that there is no association between hypertension and epi- staxis [3,9,10,11,19].

Therefore, although there have been many studies performed, the association between epistaxis and hypertension remains controversial. We believe that the presence of possible confounders, such as age, sex, time of occurrence (Circadian variation and seasonal variation), and ad- ministration of an antithrombotic medication could have affected the results of those studies. In Knopfholz’s study, three groups were matched by only sex and age. They did not consider the effects of other confounders [4]. In Sarhan’s study, they did not match the epi- staxis group with the control group [3]. Although the characteristics of the two groups were not different (sex, age, DM, smoking, history of hy- pertension and administration of antithrombotics) they also did not consider the time of the BP measurement. A diurnal variation in BP has been recognized in several studies [12-15]. The morning BP is usu- ally higher than the nighttime BP; thus, if the time of BP measurement between the epistaxis and control groups was different, this could be a confounder. In addition, the patients in which epistaxis occurred at night were not included in that study because the study was conducted in the ENT clinic during the daytime; thus, they could not show the re- lationship between epistaxis and hypertension during the night. Addi- tionally, seasonal variation could affect the results. It has been shown that the BP in winter is significantly higher than that in summer [16-18]. If the proportion of the control group who visited the clinic in winter was significantly higher than that of the epistaxis group, it could confound the results. In many other studies, these confounders could also have affect the results [9,10,11,19]. In this study, we matched the epistaxis group with the control group using propensity score matching to remove the effects of confounders and verified that the pa- tients with epistaxis had elevated BP values at presentation compared to the matched control group. Kikidis et al. demonstrated that of the nine studies reporting a relationship between epistaxis and hyperten- sion, six studies agreed that the BP of patients with epistaxis was higher than the BP of patients in the control group and higher than the norma- tive values in the general population in their systematic review of the literature [2]; however, this finding cannot fully support a causative re- lationship between epistaxis and hypertension. High BP could be the re- sult and not the cause of epistaxis. The measurement of high BP at presentation does not confirm the diagnosis of hypertension; thus, de- termining the difference in the prevalence of hypertension between the two groups is much more important. Therefore, we compared the proportions of patients with newly diagnosed hypertension between the two groups and verified that a higher proportion of the patients with epistaxis had newly diagnosed hypertension within six months compared to the controls. This might mean there were many patients with epistaxis who had not recognized the presence of hypertension at presentation. The epistaxis might have been the first symptom of their hypertension. This undiagnosed pre-existing hypertension at pre- sentation could have affected the results of the studies that reported a lack of a relationship between epistaxis and pre-existing hypertension [3,4,9,10,11,19].

In conclusion, the patients with epistaxis had elevated BP values at

presentation and a higher proportion of newly diagnosed hypertension within six months compared to the matched controls. Thus, ED physi- cians should be interested in continuous BP management for patients with epistaxis and high BP, even though they may not have pre- existing hypertension.

This study has a limitation because it was conducted using a retro- spective review of medical records and a telephone survey. There were 96 patients excluded due to missing data, although there was a predesigned medical form for collecting the necessary information.

There also might have been recall error during the telephone survey. There were some patients who were lost to follow-up (epistaxis group: 64/724, 8.8% and control group: 83/724, 11.5%). Further prospec- tive studies are needed.

Study approval

This study was approved by the Institutional Review Board of our institution.

Funding source

No external funding was secured for this study.

Financial disclosure

The authors have no financial relationships relevant to this article to disclose.

Declaration of Competing Interest

The authors have no conflicts of interest to disclose.

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