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(Hypertension. 2006;47:62.)
© 2006 American Heart Association, Inc.

Original Articles

Out-of-Hemodialysis-Unit Blood Pressure Is a Superior Determinant of Left Ventricular Hypertrophy

Rajiv Agarwal; Neva J. Brim; Jothiharan Mahenthiran; Martin J. Andersen; Chandan Saha

From the Divisions of Nephrology (R.A., N.J.B., M.J.A.), Cardiology (J.M.), and Biostatistics (C.S.), Department of Medicine, Indiana University School of Medicine, and Richard L. Roudebush VA Medical Center (R.A., N.J.B.), Indianapolis, Ind.

Correspondence to Rajiv Agarwal, VA Medical Center, 111N, 1481 W 10th St, Indianapolis, IN 46202. E-mail ragarwal{at}iupui.edu

	Abstract

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Blood pressures (BPs) obtained in the dialysis unit correlate poorly with ambulatory BP and left-ventricular hypertrophy (LVH). We compared the performance of BP obtained within and outside the dialysis unit as a correlate of LVH. BP was obtained in the dialysis unit using routine and standardized methods and outside the dialysis unit using home and ambulatory BP monitoring in 140 patients (mean age, 56 years; 89 men; 129 blacks; and 59 with diabetes mellitus) on chronic hemodialysis for 3 months. Dialysis unit BP recordings were averaged over 2 weeks, and home BP averaged over 1 week. Ambulatory BP monitoring was performed during an interdialytic interval. Echocardiography was performed immediately after dialysis for the assessment of left-ventricular mass. Left ventricular mass/height^2.7 of >51 g/m² was taken as evidence of LVH. Test performance of various BPs was compared using receiver operating characteristic curves. Average ambulatory BP was 129.7±21.2/73.6±13.1 mm Hg, home BP was 139.4±21.2/79.0±12.5 mm Hg, standardized predialysis BP was 142.1±21.7/74.9±13.3 mm Hg, postdialysis was 120.9±20.8/69.6±12.5 mm Hg, routine predialysis was 145.6±20.7/79.4±13.1 mm Hg, and postdialysis was 132.0±19.3/72.6±11.1 mm Hg. Left ventricular mass/height^2.7 was 59.1±16.5, and 68% had LV hypertrophy. Diastolic BP measured by any technique was not associated with LVH. Routine and standardized measurements of BP were similarly weak correlates of LVH. Systolic BP outside the dialysis unit was a stronger correlate of LVH compared with dialysis unit BP.

Key Words: blood pressure monitoring, ambulatory • blood pressure • hypertrophy • hypertension • cross-sectional studies

	Introduction

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Cohort studies, especially those using total mortality as the outcome, have impeded a rational approach to the management of hypertension in hemodialysis patients. Hypertension is common in hemodialysis patients, the diagnosis of which is rendered difficult because of fluctuation in the level of blood pressure (BP), especially when recommended methods of measurements are not used.^1–3 Thus, a need exists to improve the diagnosis of hypertension in hemodialysis patients. To evaluate such a diagnostic test, 3 approaches are possible. First is to test the strength of association of various methods of BP measurement with "hard" cardiovascular outcomes, such as cardiovascular death, myocardial infarction, and strokes. Second is to correlate various BP measurement techniques with the presence of target organ damage known to be associated with hypertension. Third is to compare the correlation of various BP recordings with ambulatory BP. The first approach requires a long-term follow-up and, although ideal, is more difficult to implement. The third approach is the simplest, but whether ambulatory BP is really a gold standard is uncertain.⁴ The second approach is what we adopted in this study.

Left-ventricular (LV) hypertrophy (LVH) is a well-recognized cardiac manifestation of long-term hypertension–induced target-organ damage.⁵ Which technique of measurement of BP, those obtained in the dialysis unit or those obtained between dialysis such as with home or interdialytic ambulatory BP monitoring, is a better correlate of LVH is currently unknown. Interdialytic ambulatory systolic BP has been linked to cardiovascular mortality in treated hypertensive patients on hemodialysis.⁶ However, averaged dialysis unit BP measurements have failed to show such a relationship.⁷ Furthermore, ambulatory BP monitoring is more reproducible and accurate compared with dialysis unit BP measurements.⁸ These differences between BP measurement methods in their level of accuracy, reproducibility, and correlation with cardiovascular death lends plausibility to the hypothesis that BP measurement methods may confer different risks of target organ damage as measured by LVH in hemodialysis patients. Thus, a technique that better assesses the level of BP should also emerge as a better correlate of LVH. Accordingly, we designed this cross-sectional study to assess the relationship between BP recordings obtained within and outside dialysis unit and echocardiographically determined LVH.

	Methods

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This is a cross-sectional study performed at 1 of the 4 dialysis units in Indianapolis affiliated with Indiana University.

Subjects
Patients 18 years of age who had been on chronic hemodialysis for >3 months and were free of vascular, infectious, or bleeding complication within 1 month were enrolled in the study. Those who missed 2 hemodialysis treatments over 1 month, abused drugs, or had chronic atrial fibrillation or body mass index of 40 kg/m² were excluded. Patients who had a change in dry weight or antihypertensive drugs within 2 weeks were also excluded. Presence or absence of hypertension was not a selection criterion. All of the patients underwent a standard 3-times-a-week dialysis.

Anthropometric and demographic characteristics and antihypertensive medications actually taken by the patient were recorded. Echocardiography was performed by a single echocardiographer immediately after the termination of dialysis. Most echocardiograms were obtained within 1 hour of the end of dialysis treatment.

The study was approved by the Institutional Review Board of Indiana University and Research and Development Committee of the Roudebush VA Medical Center, Indianapolis, and all of the subjects gave written informed consent.

Echocardiograms
2D guided M-mode echocardiograms were performed by a dedicated technician (N.J.B.) immediately after a midweek hemodialysis session with a digital cardiac ultrasound machine (Cypress Acuson, Siemens Medical). The protocol specified recording of 12 cycles of 2D parasternal long- and short-axis LV views with optimal orientation of the cursor beam used to derive additional M-mode recordings. The postdialysis period was selected for echocardiography, because it allows control over volume state of the patient because it is associated with the least intravascular volume. The day after dialysis would be associated with a variable change in the dimension of the ventricular cavity depending on the state of volume expansion and was not chosen for echocardiography. Each patient underwent 6 M-mode measurements of interventricular septal thickness (IVSTd), LV internal diameter (LVIDd), and LV posterior wall thickness (PWT; LVPWd) all in diastole using standards of the American Society of Echocardiography.⁹ LV mass was calculated with a previously validated formula¹⁰:

LV mass was corrected for height^2.7 measured in meters, because it correlates better with long-term outcomes in dialysis patients,¹¹ and recent studies have demonstrated that similar thresholds can be used for blacks and whites.¹² LV mass >51 g/m^2.7 was taken as evidence of LVH. All of the measurements were made over 6 cardiac cycles by a highly skilled echocardiographer (N.J.B.) and confirmed by an experienced cardiologist (J.M.).

Ambulatory BP Monitoring
Ambulatory BP monitoring was performed after the midweek hemodialysis session for 44 hours. Ambulatory BPs were recorded every 20 minutes during the day (6 AM to 10 PM) and every 30 minutes during the night (10 PM to 6 AM) using a Spacelab 90207 ABP monitor (SpaceLabs Medical Inc) in the nonaccess arm, as done previously.¹³ Those patients who had <14 recordings on awake ambulatory BP and <7 recording during the asleep state were excluded from analysis (n=31).¹⁴ A fixed-clock method was also used to define day and night for purposes of ambulatory BP monitoring. Day ambulatory BP was defined as those recordings made between 8 AM and 8 PM and night ambulatory BP as those made between 12 AM and 5 AM.

Dialysis Unit BPs
Dialysis unit BP recordings as measured by the dialysis unit staff before and after dialysis were collected prospectively at the time of the patient visit. These BP recordings were obtained without a specified technique and were averaged over 2 weeks. Thus, each patient had 6 predialysis and 6 postdialysis BP recordings to provide routine dialysis unit BP.

BP was also recorded using a standard technique after at least a 5-minute rest and using a validated oscillometric device (HEM 907, Omron Healthcare) by research nurses trained in this technique. Three readings at each visit were averaged to provide 1 recording. Predialysis and postdialysis recordings were averaged separately over 2 weeks to provide a standardized dialysis unit BP.

Home BP Monitoring
Home BP monitoring was performed over 1 week using a validated self-inflating automatic oscillometric device (HEM 705 CP, Omron Healthcare). Patients were instructed in the use of this monitor and were asked not to share this monitor with others. Patients were asked to record their BP 3 times daily and log this on a chart provided for this purpose. Because this monitor is equipped with a memory and printer, we only used those recordings that were recorded in the memory of the monitor.

Data Analysis
To analyze the sensitivity and specificity of hemodialysis unit BPs in relationship to LV hypertrophy, we generated receiver-operating characteristic (ROC) curves, including area under the curve (AUC) and their 95% CIs.¹⁵ Although several factors, such as anemia, arteriovenous fistula, valvular disease, hyperparathyroidism, poor arterial compliance, and renal failure by itself can cause LVH, independently of hypertension,^16–20 we did not adjust for these variables, because the aim was that of comparing the strength of the association of various BP methods with LVH in the same group of patients. Test performances for various PBs were compared using ROC curves. The presence of LVH was defined as LV mass/height^2.7 of >51 g/m². Least-squares linear regression analysis was performed for each systolic BP obtained by various monitoring techniques and LV mass/height^2.7.

All of the analyses were conducted using SPSS Software version 13.0 (SPSS Inc). ROC curves were compared using Stata 8.0 (Stata Corp). The P values reported are 2-sided and taken to be significant at <0.05.

	Results

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Between September 2003 and February 2005, we recruited 150 patients from 4 dialysis units staffed by the nephrology faculty of Indiana University. Adequate LVM was measured by echocardiographic examination in 141 patients. One patient was excluded because of severe dilated cardiomyopathy after lung transplantation. The remaining 140 are the subject of this report. Thirty-one patients had inadequate ambulatory BP recordings. In 4 patients, the cuff size used for home BP recordings was inappropriately small for the arm circumference; 24 patients recorded <6 home BP readings. Some patients had multiple exclusion criteria. After excluding these patients, 97 patients were available with adequate LVM measurements and adequate hemodialysis unit and nondialysis recordings. These 97 patients served as the sample in which to test the value of BP recordings in relating LVM in a paired fashion.

The clinical characteristics of the 140 patients are shown in Table 1. The population was predominantly black, with limited education and income. However, average volume normalized urea clearance time product (Kt/V), serum albumin, and hemoglobin reflect a generally healthy population. Diabetes mellitus caused end-stage renal disease in 31% of the patients and hypertension in 56%.

View this table: [in this window] [in a new window]   TABLE 1. Clinical Characteristics of the Study Population

Majority of the patients (81%) received antihypertensive drugs, with an average of 2.2 drugs in those who took antihypertensives. ß-Blockers were the most commonly used antihypertensive agent (64%). ACE inhibitors were the next most common class, being used in 41% of the patients.

Table 2 shows the BP taken by various techniques and echocardiographic measurements. The average time of ambulatory BP recordings was 44.8±7 hours. Of the recordings, 82% were successfully obtained, with an average of 97±19 recordings per patient. The average number of home BP recordings was 15±4. Day ambulatory BPs were similar to night ambulatory BPs reflecting the absence of nocturnal decline in most patients. As expected, predialysis BPs were higher than postdialysis BPs. The prevalence of LVH, defined as LV mass >51 g/m^2.7, was 68%. Ambulatory BP was lower than home and predialysis BP but higher that postdialysis standardized BP.

View this table: [in this window] [in a new window]   TABLE 2. BP Recordings and Echocardiographic Measurements

The ROC curves for various systolic BPs are shown in Figure 1. The AUC for routine, standardized, or ambulatory diastolic BPs was not related to LVH, because they all include 0.5 in the 95% CI, indicating no value as a diagnostic test; only home diastolic BP achieved statistical significance (Table 3). However, all of the systolic BPs were related to LVH. BPs obtained in the dialysis unit, regardless of the method or timing of measurement, had similar AUC under the ROC curve and were not significantly different from each other. Table 3 shows that the sensitivities and specificities of various BPs do not share a combination of sensitivity and specificity required in clinical decision making in detecting LVH. For example, 1-week averaged home systolic BP of 126.3 mm Hg has a sensitivity of 80.0% to detect LVH but a specificity of only 50%. Similarly, home BP of 147.2 mm Hg has a specificity of 80% but a sensitivity of only 53.3%.

View larger version (14K): [in this window] [in a new window]   Figure 1. ROC curves of routine and standardized hemodialysis unit systolic BP obtained before and after dialysis, home systolic BP, and interdialytic ambulatory systolic BP. The diagonal dotted line indicates a hypothetical test with no predictive value.

View this table: [in this window] [in a new window]   TABLE 3. BP Thresholds for Diagnosing LVH

AUC of ROC curves were statistically significant for all of the systolic BPs when the analysis was limited to 97 patients who had complete data by all of the methods. ROC curves ordered by AUC were home BP (0.713), ambulatory BP (0.648), predialysis routine (0.643), postdialysis routine (0.643), predialysis standardized (0.641), and postdialysis standardized (0.626). Home systolic BP ROC curves had greater AUC compared with routine predialysis systolic (P=0.055), routine postdialysis systolic (P=0.044), predialysis standardized systolic (P=0.031), and postdialysis standardized systolic BP recordings (P=0.039). Home systolic BP was similar to ambulatory BP recording (P=0.089) in detecting LVH. These relationships are illustrated in Figure 2.

View larger version (14K): [in this window] [in a new window]   Figure 2. ROC curves of routine and standardized hemodialysis unit systolic BP obtained before and after dialysis, home systolic BP, and interdialytic ambulatory systolic BP in patients in whom all data were available for all BPs, allowing paired comparisons. The diagonal dotted line indicates a hypothetical test with no predictive value. The AUC for home BP was similar to ambulatory BPs and superior to hemodialysis unit BPs.

Table 4 shows the results of the regression of systolic BP on height^2.7-corrected LV mass in all of the patients (Table 4A) and in patients where data on BP with all of the monitoring techniques were available in each patient (Table 4B). Routine postdialysis BP obtained in the dialysis unit was not a correlate of height^2.7-corrected LV mass. BP obtained outside the dialysis unit showed a stronger relationship with LVH compared with BP obtained within the dialysis unit. When analysis was limited to patients where complete data were available, only out-of-dialysis-unit PBs remained significant determinants of LV mass (Table 4B). Nonetheless, systolic home or ambulatory BPs were relatively weak determinants of LV mass, accounting only for &10% and &5% of the variance.

View this table: [in this window] [in a new window]   TABLE 4. Relationship Between BP Measurement and Height-Corrected LV Mass

	Discussion

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In stable chronic hemodialysis patients, we found that dialysis unit systolic BP recordings using standardized and routine methods had similar and weak performance at predicting LVH. Out-of-clinic recordings made by 1-week-averaged home BP recordings performed better than dialysis unit BP recordings at detecting LVH.

In a large study, the prevalence of LVH was reported as 74% in 433 dialysis patients, which is slightly higher than the 68% that we found.²¹ The most propitious time for the measurement of LV mass by echocardiography is unknown. A fluctuation in internal diameter in LV cavity can cause large errors in echocardiographically measured LV mass. For this reason, we specified the timing of all echocardiograms as immediately after dialysis. Because LV cavity volume is the least during the immediate postdialysis state, it is possible that we underestimated the true prevalence of LVH. If LV mass was measured the day after dialysis, or different diagnostic criteria used, the results may well be different.

The major finding in our study was that 1-week-averaged home systolic BP was similar to resource-intensive interdialytic ambulatory BP measurements in detecting LVH. That home BP emerged as a determinant of LVH, which was similar to ambulatory BP, even in an educationally disadvantaged population demonstrates that home BP measurement technique is robust and can be readily taught and used, even by hemodialysis patients with less education. The threshold BP for making a diagnosis of LVH should have a combination of both high sensitivity and high specificity. This study shows that none of the BP measurement techniques share these characteristics in detecting LVH. Furthermore, even in the best case scenario, <15% of the variance in LV mass is determined by systolic BP. Thus, BP alone, regardless of the technique, cannot be used in detecting the presence or absence of LVH.

Our data demonstrate that diastolic BP recordings by any technique were not useful in detecting LVH. Systolic hypertension is also more prevalent compared with isolated diastolic hypertension,²² and the results of this study support the notion that the focus of treatment in hemodialysis patients should be on systolic BP control.²³ The poor performance of dialysis unit BP measurements in diagnosing target-organ damage and better performance by out-of-clinic recordings may partly explain the failure of epidemiological studies using dialysis unit BP monitoring techniques to uncover hypertension as a risk factor for cardiovascular disease.^24,25

In 2 previous studies, routine predialysis BP averaged over 4 weeks was found as a determinant of LV mass index, as well as 24-hour ambulatory BP monitoring.^4,26 Our data are at variance with these reports, perhaps because of differences in population characteristics and the way the BP was measured. Whereas we performed 44-hour interdialytic ambulatory BP recording, the previous studies recorded ambulatory BP for 24 hours only.^4,26 In fact, when complete interdialytic ambulatory BP monitoring was performed, predialysis systolic BP was found to be only a weak correlate, postdialysis systolic BP a stronger correlate, and ambulatory systolic BP the strongest correlate of LV mass.²⁷ Also, if fewer readings are obtained in the dialysis unit, ambulatory BP emerges as the better determinant of LV mass.²⁸

Some limitations of our study must be addressed. The majority of the patients in our study were black. Whether these data are applicable to nonblacks is uncertain. Risk factors for LVH include diurnal BP variation.^29,30 We did not analyze diurnal BP variation in this report, because it was not relevant to the comparison of various BP measurement methods and the study design. These will be the subjects of future analyses.

Perspectives
One-week-averaged home systolic BP was similar to interdialytic ambulatory systolic BP and superior to dialysis unit BP measurements in detecting LVH. Diastolic BPs, regardless of the measurement technique, were of little use in detecting LVH. Because home BP monitoring correlates well with LVH in hemodialysis patients and outperforms BP measurements made in the dialysis unit, even when made using standard methods, it should be more widely used in the assessment of hypertension in hemodialysis patients. Home BP monitoring may better clarify the relationship between systolic hypertension and cardiovascular outcomes in hemodialysis patients and improve the ability of clinicians in making a more accurate diagnosis of hypertension.

	Acknowledgments

 
This work was supported by grant number 5RO1-NIDDK062030-03 from the National Institutes of Health. M.J.A. is supported by a National Institutes of Health training grant 5T32-DK062711-02. We would also like to thank the members of the dialysis units at Dialysis Clinics, Inc, Clarian Health, and the Roudebush VA Medical Center and the faculty of the Division of Nephrology who gratefully allowed us to study the patients.

Received September 19, 2005; first decision October 14, 2005; accepted October 27, 2005.

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This Article Abstract Full Text (PDF) All Versions of this Article: 47/1/62    most recent 01.HYP.0000196279.29758.f4v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Agarwal, R. Articles by Saha, C. Search for Related Content PubMed PubMed Citation Articles by Agarwal, R. Articles by Saha, C. Pubmed/NCBI databases Medline Plus Health Information Dialysis Kidney Failure Related Collections Hypertrophy Echocardiography