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European Journal of Heart Failure 2007 9(2):178-183; doi:10.1016/j.ejheart.2006.06.004
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© 2007 European Society of Cardiology

Acute heart failure associated with high admission blood pressure — A distinct vascular disorder?

Olga Milo-Cottera, Kirkwood F. Adamsb, Christopher M. O'Connora, Nir Urielc, Edo Kaluskic, G. Michael Felkera, Beth Weatherleya, Zvi Veredc and Gad Cottera,*

a Duke University Medical Center and the Duke Clinical Research Institute USA
b The University of North Carolina Chapel Hill, North Carolina, USA
c Assaf-Harofeh Medical Center Zerifin Israel

* Corresponding author. Duke Clinical Research Institute, 2400 Pratt St., Durham NC, 27515, USA. E-mail address: cotte013{at}mc.duke.edu


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 
Background: Although blood pressure (BP) is elevated in patients with acute heart failure (AHF), first admission BP has not been meticulously recorded before treatment in previous studies.

Methods: During three consecutive months, all AHF admissions (335 patients) to a city hospital which provides the sole inpatient medical service for approximately 500,000 people were registered. First BP was recorded before treatment at the first patient encounter in the ambulance or the emergency room.

Results: Mean BP at admission was 164±38/88±22 mm Hg. Mean BP in the highest quartile was 212±22/115±13 mm Hg. Patients with higher baseline BP had higher ejection fraction (highest versus lowest quartile 48±13% vs. 33±14%, p<0.001), less atrial fibrillation (18% vs. 42%, p=0.001) as well as lower mean urea and higher mean haemoglobin. The apparently more favourable baseline characteristics in patients with higher admission BP did not translate into lower morbidity – the rate of worsening heart failure – was not related to admission BP. However, 6 month mortality was lower in patients with higher admission BP (4% vs. 19.3%, p=0.002).

Conclusions: Blood pressure is elevated substantially at the onset of AHF. The different characteristics and outcome of patients admitted with high-BP associated AHF suggest that this presentation may be a specific disorder related to a distinct yet unknown pathophysiological mechanism.

Key Words: Acute heart failure • Blood pressure • Hypertension

Received February 7, 2006; Revised April 28, 2006; Accepted June 14, 2006


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 References
 
Acute heart failure (AHF) is the one of the most common disorders encountered in medical practice, and is associated with a high mortality and morbidity rate despite contemporary therapy [1]. Although, many studies have identified factors which contribute to the pathogenesis and outcome of patients with chronic heart failure, such as neurohormonal activation, reduced ejection fraction and ischaemic aetiology, these prognostic factors do not necessarily have the same importance in AHF [2,3].

Recent results from the ADHERE study suggest that systemic hypertension may be an important and poorly recognized factor in many AHF patients [1]. However, the clinical implications and pathophysiological role of elevated blood pressure in AHF remain poorly understood [4,5]. In our first AHF studies [6-8], we observed that at admission, prior to all treatment, blood pressure in many patients with AHF was markedly elevated. This was followed by a haemodynamic study showing increased systemic vascular resistance (SVR) in association with systemic hypertension in a few patients who developed pulmonary oedema, suggesting, not surprisingly, that vasoconstriction was responsible for the elevated systemic pressure seen in our previous work in acute heart failure. [5,9].

The major goal of the present study was to carefully document the degree of systemic blood pressure elevation in patients with AHF, and to determine the relationship between systemic blood pressure, clinical characteristics and outcomes in patients with AHF. We obtained initial blood pressure readings in a consecutive cohort of patients with AHF, and evaluated the association between elevated BP on admission with baseline characteristics and clinical outcomes.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 References
 
2.1. Setting
The study was performed in the Assaf-Harofeh Medical Center, a community hospital in the south-eastern part of the Tel-Aviv metropolitan area. Assaf-Harofeh is the only hospital serving a geographical area that includes three cities and approximately 500,000 people.

2.2. Patients and methods
The study was approved by the ethical review board of the Assaf-Harofeh Medical Center. During the study period (December 2003 to March 2004) emergency room records were screened for all hospital admissions due to dyspnoea. AHF was diagnosed by the presence of signs of pulmonary congestion on physical examination and chest X-ray. Additional medical data were obtained from patient files and pooled for subsequent statistical analysis. These data included clinical, laboratory and echocardiographic parameters. Importantly for each AHF admission, the chart review included all ambulance and emergency room records. The teams in both settings routinely obtain and document blood pressure, pulse, respiratory rate and oxygen saturation in all patients at first encounter, prior to all treatment. Echocardiographic measures of ejection fraction (EF) were collected from the patients' charts. It is routine practice in our hospital to perform new echocardiographic assessments for all patients who have not had an echo within the 6 months prior to admission. Hence, echocardiographic measurements for most patients were performed either during admission or within 6 months prior to admission. Patients were followed throughout their period of hospitalisation, for recurrent episodes of worsening heart failure and death. In-hospital worsening heart failure was defined as persistent or recurrent symptoms and signs of heart failure that required an increase or initiation of heart failure specific therapy (either intravenous therapy or mechanical or circulatory support).

After discharge, all patients were followed up by telephone at three and six months with meticulous recording of any information related to heart failure admissions and death. If patients could not be contacted directly, additional relevant medical data were obtained from patients' relatives, computerized records from our outpatient clinics, and emergency room records.

2.3. Statistical analysis
Patient characteristics, measures of disease severity, and 6-month outcomes are presented by quartile of admission mean arterial pressure (MAP). MAP was estimated as (admission systolic BP+2*diastolic BP)/3. The rank correlation between admission MAP and each baseline characteristic, with a test that the correlation was zero, are presented. For descriptive purposes, patients were divided into quartiles according to baseline mean arterial blood pressure (MAP). Outcomes were defined as the time to the event or 6 months follow-up if no event occurred. The association between each outcome and MAP was tested using Cox regression models. Proportionality of hazards was assessed by examining plots of log(–log(survival)) and the statistical significance of time-by-MAP interaction terms in the survival models. Linearity in the log was assessed by testing the statistical significance of additional restricted cubic spline terms in the models. P values below 0.05 were statistically significant.


   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 References
 
During the study period a total of 14,144 patients were examined in the emergency room of the hospital, of these 6852 were admitted. All charts from the patients admitted to the hospital were reviewed on a daily basis by the study investigators to check for a possible diagnosis of AHF. From this cohort, 335 patients who met the above-mentioned criteria for AHF were identified.

Mean MAP on initial presentation was 164±38/88±22 mm Hg and 75% of patients had evidence of systemic hypertension (first recorded systolic blood pressure>140 mm Hg). The mean blood pressure in the highest MAP quartile was 212±22/115±13 mm Hg (Table 1).


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  		Table 1 Baseline characteristics and measures of severity at admission according to mean arterial blood pressure quartiles

 
The baseline characteristics, disease severity measures, treatment and outcome by baseline MAP quartiles are presented in Tables 1-3GoGo. MAP was significantly correlated with many key baseline clinical characteristics related to the presence of heart failure. Higher blood pressure was associated with preserved left ventricular ejection fraction, a lower rate of atrial fibrillation as well as lower serum creatinine and BUN and higher haemoglobin and total cholesterol. Notably a few important characteristics at baseline showed a correlation with increased admission MAP-pulse rate, lymphocyte count and serum cholesterol. All these parameters were higher in patients with higher admission MAP.


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  		Table 2 Discharge medications according to admission mean arterial pressure

 


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  		Table 3 Clinical outcome according to admission mean arterial pressure

 
Higher admission BP was not a simple measure of more severe heart failure at admission. There was a strong trend towards a lower rate of mechanical ventilation in patients with higher admission BP, while the rate of persistent or worsening heart failure during the first 24 h was similar (Table 3). Admission oxygen saturation correlated negatively with admission BP (higher saturation in patients with lower BP), however this slight association was mainly driven by higher oxygen saturation in patients with the lowest admission BP (Table 1).

Despite this more favourable risk factor profile, morbidity was not different in patients with higher admission BP. This patient subset commonly exhibited recurrent heart failure during follow-up with an event rate similar to that of patients in the lowest blood pressure quartile. Though the rate of mechanical ventilation at admission was lower in patients with higher admission BP, oxygen saturation was slightly lower at admission. Overall, the rate of persistent or worsening heart failure during the first 24 h of admission was similar in patients with higher and lower admission BP (Table 3). MAP was not significantly associated with the probability of worsening heart failure during 6 months follow-up. In contrast, the 6-month mortality was significantly lower in patients with higher baseline BP — 4% vs. 19%, p=0.002 (Fig. 1).


Figure 01
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  		Fig. 1 Product-limit (Kaplan-Meier) survival probability estimates according to admission mean arterial pressure quartile.

 

   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
References
 
There are three important findings from our study. First, our results suggest that elevated systemic blood pressure is a common phenomenon in patients admitted from the community with acute heart failure. We monitored blood pressure earlier and found the elevation to be greater than described previously in the ADHERE registry. Data on systemic blood pressure from ADHERE represent the first blood pressure recorded in the chart and probably reflect prior treatment [1]. Previous studies enrolling the subset of patients with acute heart failure and severe pulmonary oedema have also suggested that blood pressure may be significantly elevated in many patients with AHF [6-8]. Our findings suggest that a substantial elevation in blood pressure is present in the majority of patients with acute heart failure admitted from a community setting with or without pulmonary oedema. Secondly, our work gives an initial detailed clinical description of the association between systemic blood pressure and the clinical characteristics of patients with acute heart failure. Patients with significant elevation of blood pressure have mostly preserved left ventricular systolic function, less renal insufficiency, lower BUN and higher haemoglobin and serum cholesterol as compared to those with lower blood pressure. Interestingly, medical treatment was generally similar in patients regardless of blood pressure at admission, although digitalis and aldosterone inhibitors were administered more to patients with lower admission blood pressure (and presumably lower EF). It is possible that the need to control blood pressure in the patients with higher admission blood pressure offsets the level of evidence for such treatment in patients with preserved EF (beta blockers) who are more represented in the group with higher admission blood pressure. We observed a trend towards more statin administration in the group with higher admission BP, probably due to the higher levels of cholesterol observed in these patients. Finally, our results provide important information on the relationship between outcomes and admission blood pressure. Consistent with the risk profile from previous studies, patients with elevated blood pressure had much lower mortality at 6 months compared to patients with lower admission blood pressure. However, despite being at low risk for death, patients with elevated blood pressure experience substantial morbidity in the follow-up period. Systemic blood pressure did not predict the risk of worsening heart failure during follow-up or the likelihood of readmission for this problem.

4.1. Implications concerning the pathophysiology of AHF
Our results suggest that elevation of systemic blood pressure represents a new and under-recognized aspect of the pathophysiology of acute heart failure in many patients. Importantly, in the present study, higher admission BP was not a simple measure of more severe heart failure on admission. There was a trend towards a lower rate of mechanical ventilation in patients with higher admission BP, while the rate of persistent or recurrent heart failure in the first 24 h following admission was similar. Systemic hypertension could induce afterload mismatch leading to acute diastolic dysfunction with increased left ventricular filling pressures and attendant increases in pulmonary venous pressure and pulmonary congestion. The findings of Gandhi et al., who examined echocardiographic measures of systolic and diastolic dysfunction in patients admitted with pulmonary oedema associated with high blood pressure, provide important data to support this pathophysiological mechanism [10]. These investigators found no evidence of reduced systolic function or significant mitral regurgitation in a series of patients admitted with pulmonary oedema associated with systemic hypertension. They reported that the only measure that changed significantly from admission to recovery was the E/A ratio which was much improved. This and other findings have led Cleland et al., in a recent editorial to suggest that AHF may be related to an acute deterioration of diastolic function [11].

Additional physiological studies are needed to define the mechanisms responsible for elevated systemic pressure in patients with AHF. Fundamental haemodynamic considerations suggest that vascular derangement, in the form of vasoconstriction or changes in vascular stiffness, may be primarily responsible for the elevation of BP as supported by previous studies in which SVR was significantly increased in patients developing AHF and pulmonary oedema [5,9].

Triggers for changes in vascular tone and compliance remain speculative. First, patients with AHF and higher admission BP have higher left ventricular ejection fraction. In previous studies, heart failure with preserved ejection fraction has been shown to be related to more ventricular and arterial stiffness [12]. This arterial stiffness increases with age [13] paralleling the increased rate of AHF and especially AHF associated with preserved ejection fraction [14]. Hence, increased arterial stiffness leading to a tendency for steeper increases in afterload may be an important contributor to AHF and higher admission BP that is especially common in patients with preserved left ventricular ejection fraction (as suggested by the present study).

Second, inflammatory and neurohormonal activation has previously been observed in many patients with AHF [15-18]. Importantly, in a small study, we observed significant increases in IL-6 and CRP in patients admitted due to AHF, which subsided at 2 months follow up [19]. In the present study, we observed a correlation between admission BP and admission WBC count — i.e., patients with higher admission BP also had higher admission WBC counts. In previous studies, WBC count increases were found to correlate with increased IL 6 and CRP [20] — the same factors we have found to be increased in AHF. These findings may be linked to higher admission BP by the recent intriguing findings of Vlachopoulos et al. [21]. These authors demonstrated that inflammatory activation (by salmonella vaccine) increased arterial stiffness in healthy individuals. It would be tempting to hypothesize that the "missing" pathophysiological mechanism for AHF associated with high admission BP may be acute inflammatory activation (such as intercurrent infection — which has been suggested to be associated with the incidence of AHF) leading to an abrupt increase in arterial stiffness with resultant high BP, afterload mismatch and acute diastolic heart failure.

4.2. Implications for the treatment of AHF
If indeed high BP associated AHF is a specific disorder, it is possible that it requires specific treatment. Importantly, previous studies have suggested that vasodilators are effective in AHF; however, most studies have failed to show a substantial effect. A few small studies have demonstrated that appropriate vasodilation administered immediately, and aimed at a reasonable reduction in BP, was highly effective in improving outcome [8] and was superior to both diuretic therapy and non-invasive ventilation [6,7]. However, since these studies included, by definition, patients with significant respiratory impairment secondary to AHF (oxygen saturation<90%), many physicians would identify this as pulmonary oedema, and hence it is possible that the beneficial effects of this treatment are most important in this scenario. This is in line with the recent European guidelines for the diagnosis and treatment of AHF [22], suggesting that AHF accompanied by high blood pressure commonly presents as pulmonary oedema. However, the findings of the current study expand on this concept by suggesting that high admission blood pressure is a very common phenomenon and possibly an important pathophysiological mechanism in a large number of patients admitted with AHF, probably beyond those presenting with pulmonary oedema. If indeed high BP at admission in patients with AHF relates to a specific pathophysiological mechanism, it is possible that directing treatment development with vasodilators to patients with high BP AHF and administering the treatment early — immediately upon patient encounter, will lead to the development of effective and safe treatments and modes of treatment delivery.

4.3. Potential study limitations
The representativeness of the registry is important for generalizability of the concept that elevated systemic pressure is common in patients with acute heart failure. The study was designed to document initial blood pressure in a cohort of consecutive patients in whom a blood pressure was available very early during presentation and prior to all intervention. Due to the circumstances related to treatment of acute heart failure in the geographic region surrounding the study hospital, it was possible to capture all of the acute heart failure admissions during a pre-defined period of 3 months. The generalizability of the study findings to other geographic areas is uncertain, but the study findings are supported by the ADHERE registry and other datasets.

4.4. Conclusions and hypothesis
Blood pressure is substantially elevated at the onset of AHF in a significant subset of patients. This phenomenon may be under-recognized, since first admission BP is not routinely assessed in clinical studies of AHF. AHF associated with high admission BP may be a specific disorder with specific clinical and pathophysiological mechanisms, requiring new treatment modalities. Additional physiological and clinical studies are required to address these possibilities.


   References
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 

  1. Adams K.F., Fonarow G.C., Emerman C.L., et al. Characteristics and outcomes of patients hospitalized for heart failure in the United States: rationale, design, and preliminary observations from the first 100,000 cases in the Acute Decompensated Heart Failure national Registry (ADHERE). Am Heart J (2005) 149:209–216.[CrossRef][Web of Science][Medline]
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This Article
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Right arrow FREE Full Text (PDF) Freely available
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