A prospective study of the physician effect on blood pressure in renal-transplant recipients

G. V. Ramesh Prasad, Michelle M. Nash and Jeffrey S. Zaltzman

Division of Nephrology, Department of Medicine, St Michael's Hospital, Toronto, Canada



   Abstract
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Background. Physician presence results in elevated blood pressure (BP) in the general population. The determinants of this phenomenon in renal-transplant recipients are not known.

Methods. We prospectively evaluated BP changes with physician presence in 231 stable adults with graft survival >=1 year. A nurse measured timed sitting BP by Korotkoff phase I and V sounds before physician entry, during physician presence and upon exit. The haemoglobin, creatinine, weight, immunosuppressive drug dosage and/or level, and anti-hypertensive medication profile were recorded. Paired Student's t-test with Bonferroni correction and multiple linear regression analysis were used to examine BP changes. Characteristics of patients with change in mean arterial BP >=+10 mmHg (n=55, ‘high’) were compared with those with change <=+5 mmHg (n=132, ‘low’) by chi-square or Wilcoxon rank sum test as appropriate. A group of 100 recipients served as controls in whom BP was measured thrice without physician presence on any occasion. A multivariate analysis was performed for the combined groups controlling for physician entry as a predictor variable.

Results. In the study group, systolic BP (mean±SE) rose by 4.2±0.8, diastolic BP by 3.5±0.5 and mean arterial BP by 3.5±0.5 mmHg in physician presence. The BP returned to baseline with exit (P<0.001 for each). Higher haemoglobin and creatinine demonstrated a trend towards influencing the physician-induced rise in diastolic BP. The ‘high’ sub-group demonstrated a shorter time to the second BP measurement in physician presence (P=0.03) and a trend towards morning measurements (P=0.08). In the control group, systolic BP declined by 3.2±0.9 mmHg from the first to the second measurement, with a further decline of 2.4±0.6 mmHg from the second to third measurements. Diastolic BP did not change. In the combined multivariate analysis, physician entry was an independent predictor of BP change (P=0.0001).

Conclusions. Renal-transplant recipients demonstrate a significant physician effect on BP despite adequate experience with post-transplant clinic visits and BP-altering medication. This population deserves further evaluation through ambulatory BP monitoring.

Keywords: blood pressure; physician effect; post-transplant hypertension; white-coat effect; white-coat hypertension



   Introduction
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
The observation that blood pressure (BP) readings taken in a physician's office are higher than home readings was first made more than 60 years ago [1]. Of the potential factors that exist in an office environment, physician presence when BP is recorded exerts a major influence on the measurement obtained [2]. This so-called ‘white-coat effect’ has been demonstrated in both normotensive and hypertensive subjects in the general population [3]. It affects the decision to diagnose hypertension as well as to pursue further investigation and treatment [4], and often leads to the use of ambulatory BP monitoring. Amongst various populations, renal-transplant recipients constitute a group at high risk of hypertension [5]. However, the risk factors of hypertension that operate in renal-transplant recipients differ from those operating in the general population [6]. In this prospective study we therefore sought to define the prevalence and determinants of the physician effect on BP in stable outpatient renal-transplant recipients and to characterize the factors that influence BP variability in the office setting for this population.



   Subjects and methods
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
The nephrology division at St Michael's Hospital provides care to a steadily increasing population of approximately 700 adult single-organ renal-transplant recipients. Over a 14 month period, successive eligible recipients from this group were enrolled in the study at the start of their usual clinic visit after providing informed consent. Recipients were eligible for inclusion if they had intact native kidneys, graft survival >1 year, stable renal function that was defined as no acute rejection episodes in the preceding 6 months and fluctuation of the serum creatinine (SCr) of <10% over that period, and were taking stable doses of at least one immunosuppressive medication.

Systolic BP (SBP) and diastolic BP (DBP) recordings were performed in a standardized manner in our clinic, with measurements made in both supine and sitting positions at the start of the visit, using a mercury sphygmomanometer by Korotkoff phase I and V sounds. For the study, the sitting BP reading was utilized; recipients with an orthostatic drop in SBP of more than 10 mmHg were determined to be clinically unstable and requiring increased medical attention, and were thus excluded from further analysis. The first BP measurement was made by the registered nurse 2 min after the patient entered the examination room, and before the physician entered the room. During the encounter the nurse engaged the patient in conversation. The physician then entered the room, engaging the sitting patient in casual conversation during the first 2 min while the nurse made the second BP measurement with the cuff in the same position on the arm at the end of that time period. After the physician left the room, the nurse obtained a third BP measurement 2 min later. The time at which each BP measurement was taken was recorded. The mean arterial BP (MAP) was estimated using the formula: MAP=DBP+1/3 (SBP–DBP). Additional variables that were collected included the haemoglobin (Hb), SCr, weight, use of cyclosporin (CsA) or tacrolimus (Tac), the dose of prednisone and the anti-hypertensive medication profile. For the purposes of the study, hypertension was defined as the use of at least one anti-hypertensive drug. A ‘physician effect’ was arbitrarily defined as being present when a change in MAP of >=+10 mmHg occurred upon physician entry in to the room.

Differences in BP during each of the three clinic situations (before physician entered the room to during physician presence, and the latter to after physician left the room) were compared using a paired Student's t-test. To assess the impact of other influences on the change in clinic BP with physician presence besides the white-coat effect, a multiple linear regression analysis was performed that included possible predictors of post-transplant hypertension. In a further analysis, characteristics of a defined sub-group of study group recipients with a change in mean BP of >=+10 mmHg were compared to those of a sub-group with a rise of <=+5 mmHg, eliminating those with changes of >+5 but <10 mmHg, using a chi-square test for categorical variables and a Wilcoxon rank sum test for continuous variables.

In a separate control group of 100 recipients, BP was measured in an identical manner on three occasions, with a standardized time interval of 10 min between measurements 1 and 2, and 5 min between measurements 2 and 3. BP comparisons were performed in a similar manner. Finally, for the entire group (study and control) a multivariate analysis utilizing physician presence as an independent variable and including significant predictors of BP, controlling for time-to-measurement was performed. A two-tailed P-value of <0.05 was considered significant. The Statistical Package for the Social Sciences (SPSS®) was used for all analyses. The Research Ethics Board at St Michael's Hospital approved the protocol for this study.



   Results
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
A total of 231 single-organ renal allograft recipients were enrolled in the physician-effect arm of the study, and 100 recipients in the control arm. Their demographic characteristics are given in Table 1Go. The two groups were similar, except that lower mean cyclosporin levels and prednisone doses were found in the control group.


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Table 1.  Demographic features of study (n=231) and control groups (n=100)

 
The entry of the physician into the examination room resulted in a significant rise in SBP, DBP and MAP. Likewise, upon the exit of the physician from the room, there was a decline in all three BP parameters to baseline (Table 2Go, Figures 1AGo and 2AGo). The difference between these BP changes was highly significant (P<0.001 for each). The time interval between measurements 1 and 2 was 11.4±7 min (range 1–55) while that between measurements 2 and 3 was 6.5±3 min (range 1–25), although each measurement was taken at 2 min after the nurse's or physician's entry or exit.


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Table 2.  Blood pressure values depending on physician presence in the examination room in the study group (n=231) and control group (n=100)

 


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Fig. 1.  Group-averaged SBP prior to physician entry (SBP 1), during physician presence (SBP 2) and after physician exit (SBP 3) for the study group are shown, along with the corresponding values in the control group where all readings were taken in physician absence (mean and 95% CI, mmHg).

 


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Fig. 2.  Group-averaged DBP prior to physician entry (DBP 1), during physician presence (DBP 2) and after physician exit (DBP 3) for the study group are shown, along with the corresponding values in the control group where all readings were taken in physician absence (mean and 95% CI, mmHg).

 
Possible independent predictors of post-transplant hypertension were included in multiple linear regression models separately utilizing each change in BP parameter (SBP, DBP, MAP) as the dependent variable. While the Hb (P=0.01) and SCr (P=0.03) exhibited a trend towards significance in predicting change in DBP and the Hb (P=0.06) possibly for change in MAP, no other factor had a substantial influence. Notably, known influences on BP such as weight (P=0.39), age (P=0.93) or prednisone dose (P=0.66) were insignificant in the multivariate model for change in MAP or the other BP parameters.

Fifty-five patients (24%) exhibited a rise in the MAP of >=+10 mmHg upon entry of the physician in to the room. When the study group was divided in to three sub-groups based on the change in MAP with physician presence [low=<=+5 mmHg (n=132), medium=+5 to +10 mmHg (n=44), high=>=+10 mmHg (n=55)], the time to the second BP measurement was less in the ‘high’ than in the ‘low’ sub-group (12.2±8 vs 9.8±6 min, P=0.03). In addition, there was a trend towards a greater representation of morning measurements in the ‘high’ group (P=0.08). No other significant differences between the groups were found.

In the control group, on the other hand, there was a statistically significant decline in the SBP between measurements 1 and 2 (P=0.0001), and a continuing decline between measurements 2 and 3 (P=0.0001). However, no decline in the DBP was noted (Figures 1BGo and 2BGo). The MAP difference did not attain significance between measurements 1 and 2 (P=0.08), but did so between measurements 1 and 3 (P=0.001). Moreover, while there was no significant difference in systolic BP and MAP between the study and control groups at measurement 1, the BP was significantly higher at measurements 2 and 3 in the study group compared to the control group (Table 2Go).

In the multivariate analysis normalizing for time-to-measurement and including physician entry in to the room as an independent variable, change in BP was influenced by physician presence (P=0.0001), but not by any other variable, including time-to-second BP measurement (P=0.41).



   Discussion
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
This study is the first to describe systematically the magnitude and determinants of the physician effect on BP in the post-renal-transplantation situation. Since physician systolic pressures are ~10 mmHg higher than those taken by a nurse [7], we chose a similar definition to define a clinically significant BP effect. Approximately one-quarter of stable outpatient renal-transplant recipients demonstrated a rise in MAP of >=+10 mmHg when a physician entered the examination room, a rise that was abolished upon physician exit. The level of Hb, SCr, time of day of the measurement and the time interval between measurements were found to possibly influence this change in BP. The role of these factors in BP variability, either collectively or individually, cannot be determined with certainty from this study. Notably, factors such as age, gender, time since transplant, immunosuppressive or anti-hypertensive medication and weight failed to predict a change in BP with physician presence. The BP changes seen are most probably related to the presence of the physician, since a rise was seen with physician presence in the study group, while in fact a decline in BP was seen in the control group.

White-coat hypertension occurs in ~20% of patients with mild hypertension [8], although estimates vary between 12 and 52% depending on the definition used [9]. While it is mostly a condition of older adults [10], it is also present in pregnant women [11] and children [12]. Conversation with a physician raises BP [13] as does suggesting verbally that a rise in BP is likely to happen [14]. The importance of this white-coat effect may extend to the daily management of renal-transplant recipients, although this has not been evaluated prospectively. Renal-transplant recipients are particularly prone to developing hypertension due to factors such as their own native kidney disease, cyclosporin and corticosteroid exposure [15], donor hypertension and advancing age [15], impaired renal allograft function [16], and acute rejection [17]. Post-transplant hypertension is known to be associated with poor long-term renal allograft outcome [18,19]. It is also associated with increased cardiovascular morbidity, and influences patient survival as well [17]. Most of these associative studies have utilized casual BP measurements, which are probably adequate for analyses at the population level but not for managing individual patients, when a more complete understanding of the determinants of the BP measurement obtained in the clinic is required.

This study does have some limitations. The BP measurements were performed in a busy clinic situation, designed to adhere as closely as possible to a real-life situation. A white-coat effect induced by the nurse cannot be excluded; this study only confirms a differential superimposed effect induced by the physician compared to the nurse [7], and which may also explain the lesser magnitude of the change observed compared to the observations of Mancia et al. [3].

In summary, we have demonstrated that stable renal-transplant recipients are susceptible to a physician effect on BP despite being adequately experienced with post-transplant clinic visits. Although not surprising, hypertension was present in most individuals (93%) in this cohort, a large number (24%) demonstrated a significant additional physician-induced rise in BP. In routine assessment of renal-transplant recipients, it is thus advisable to obtain BP readings when the physician is not present. Further studies of BP variation in this group of patients are warranted. This study provides a simple method for selecting renal-transplant recipients for future prospective evaluation through ambulatory BP measurements.



   Acknowledgments
 
The investigators gratefully acknowledge the contributions of Maureen Connelly RN, Jennie Huckle RN, Galo Meliton RN and Fernanda Shamy RN in obtaining the BP measurements.

Conflict of interest statement. None declared.



   Notes
 
Correspondence and offprint requests to: Dr G. V. Ramesh Prasad, Division of Nephrology, St Michael's Hospital, 61 Queen Street East, 9th Floor, Toronto, Ontario M5C 2T2, Canada. Email: prasadr{at}smh.toronto.on.ca Back



   References
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 

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Received for publication: 25. 5.02
Accepted in revised form: 3.12.02





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