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Hypertension. Author manuscript; available in PMC Mar 1, 2011.
Published in final edited form as:
PMCID: PMC2825286
NIHMSID: NIHMS172864

Blood pressure and mortality among hemodialysis patients

Abstract

Blood pressure measured before and after dialysis does not agree well with those recorded outside the dialysis unit. Whether recordings obtained outside the dialysis unit are of greater prognostic value than blood pressure obtained just before and after dialysis remains incompletely understood. Among 326 patients on long-term hemodialysis, blood pressure was self-measured at home for one week, over an interdialytic interval by ambulatory recording and before and after dialysis over two weeks. Over a mean follow up of 32 (SD 20) months, 102 patients died (31%) yielding a crude mortality rate of 118/1000 patient years. Systolic but not diastolic blood pressure was found to be of prognostic importance. Multivariate-adjusted and unadjusted analyses showed increasing quartiles of ambulatory and home systolic blood pressure to be associated with all-cause mortality (adjusted hazard ratios for increasing quartiles of ambulatory: 2.51, 3.43, 2.62 and for home blood pressure: 2.15, 1.7, 1.44). Mortality was lowest when home systolic BP was between 120–130 mm Hg and ambulatory systolic blood pressure was between 110–120 mmHg. Blood pressure recorded before and after dialysis were not statistically significant (p=0.17 for predialysis and p=0.997 for postdialysis) in predicting mortality. Out-of-dialysis unit blood pressure measurement provided superior prognostic information compared to BP within the dialysis unit (likelihood ratio test, p<0.05).

Conclusions

Out-of-dialysis-unit blood pressure among hemodialysis patients is prognostically more informative than that recorded just before and after dialysis. Therefore the management of hypertension among these patients should focus on blood pressure recordings outside the dialysis unit.

Keywords: Home blood pressure, ambulatory blood pressure, prognosis, end-stage renal disease

Introduction

Hypertension is common among patients with chronic kidney disease and often remains poorly controlled in hemodialysis patients 1. Recently, a large cohort study found that the variability of BP within patients was at least as great as variability seen between patients2. BP obtained in the dialysis unit by technicians and nurses without attention to detail differ strikingly from BP obtained using standard methods. Nearly half the systolic BP are more than 10 mm Hg different from routine BP when standard methods of measurements are used 3. BP obtained before and after dialysis, even if obtained using standardized methods, agree poorly with interdialytic ambulatory BP 4, 5. Furthermore, even standardized BP recordings cannot be used to predict the presence or absence of left ventricular hypertrophy 6. In contrast, BP obtained outside the dialysis unit, whether obtained by interdialytic automatic BP measurement or self-measured BP at home is useful in diagnosing left ventricular hypertrophy 6. Thus dialysis unit measurement is only distantly related to ambulatory BP or target organ damage. This poor relationship calls into question the use of BP obtained before and after dialysis for the diagnosis and treatment of hypertension among patients on hemodialysis 7.

Large cohort studies have found that lower systolic BP obtained before or after dialysis is a determinant of mortality 8, 9. On the other hand, a higher ambulatory BP is associated with increased mortality among hemodialysis patients 10. More recently, home and ambulatory BP recordings were found to be of prognostic value 11. Yet, almost all hypertension management in dialysis units utilizes dialysis unit BP. For treating hypertension, even the national guidelines recommend the use of BP obtained in the dialysis unit 12. The recommendation is possibly because studies that have delineated the relationship between out-of-dialysis-unit BP measurement with outcomes are limited in size.

This study examines the hypothesis that out-of-dialysis-unit BP measurement will be of greater prognostic significance compared to BP recorded just before and after dialysis. The purpose of this report was to evaluation the presence, strength and shape of the relationship between BP measured using different modalities (home, ambulatory and dialysis unit) and all-cause mortality among hemodialysis patients.

Methods

Participants

The cross-sectional data on part of this cohort has previously been reported 5, 6. Patients 18 years or older who had been on chronic hemodialysis for more than 3 months, and were free of vascular, infectious or bleeding complications within one month of recruitment who were dialyzed three times a week dialysis at one of the four dialysis units in Indianapolis affiliated with Indiana University were enrolled in the study. Those who missed two hemodialysis treatments or more over one month, abused drugs, had chronic atrial fibrillation or body mass index of 40 kg/m2 or more were excluded. Patients who had a change in dry-weight or antihypertensive drugs within 2 weeks were also excluded. 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 subjects gave written informed consent.

Measurements

Ambulatory BP Monitoring

Ambulatory BP monitoring was performed either after the first or mid-week hemodialysis session for 44 hours. Ambulatory BP was 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 ambulatory blood pressure monitor (SpaceLabs Medical Inc, Redmond, WA, USA) in the non-access arm, as reported previously 13. Awake and sleep readings were calculated for each patient by self-reported sleep and wake times by means of a diary. Even limited number of ambulatory BP are useful for prognostic purposes in the general population, therefore we did not exclude any patients based on the number of ambulatory BP recordings 14.

Dialysis Unit Blood Pressures

The “reverse epidemiology” of hypertension and mortality among dialysis patients has been described using BP measured in the dialysis unit using oscillometric technique and without adherence to standardized BP measurement methods. To reflect this practice and allow comparisons with larger cohorts, BP was measured by routine oscillometric technique in the dialysis unit. Accordingly, dialysis unit BP recordings were obtained by the dialysis unit staff using the sphygmomanometer equipped with hemodialysis machines without a specified technique and were averaged over two weeks surrounding the ambulatory BP measurement. Thus, each patient had six pre-dialysis and six post-dialysis BP recordings to provide routine dialysis unit BP.

Home BP Monitoring

Home BP monitoring was performed over one week using a validated self-inflating automatic oscillometric device (HEM 705 CP or 790 IT, Omron Healthcare, Bannockburn, IL). Patients were instructed in the use of this monitor and asked not to share this monitor with others. Patients were asked to record their BP three times daily—on waking up, between noon and 6 PM and at bedtime—and log this on a chart provided for this purpose. In some participants, home BP was recorded twice daily in triplicate for 4 days after the mid-week dialysis. The average of all readings by day was taken as those representing the overall home BP. Since this monitor is equipped with a memory and printer, we used only those recordings that were recorded in the memory of the monitor.

Outcomes

All cause mortality was the primary focus of our study and this outcome was available in every patient. Patients were censored on the date that they had the last dialysis visit if they were transplanted or left the dialysis unit.

Data Analysis

Kaplan-Meier survival curves were created and the log-rank test performed to test the equality of survival by quartiles of BP. Cox proportional hazards regression was used to determine the significance and strength of association of factors associated with mortality outcomes. The proportionality assumption was tested both by evaluating the log minus log plot as well as by testing the Schoenfield residuals. Initially, model fits for mortality were compared between BP without adjustment. To directly compare the BP types (home vs ambulatory) on their impact on all-cause mortality the hazards ratio for each BP type and the nested model was compared with the likelihood ratio test. We then created multivariate adjusted models. Adjustments were made for the following variables: age, ethnicity, sex, diabetes mellitus, cardiovascular disease, antihypertensive medications, serum albumin, hemoglobin, and dialysis vintage. Adjusted hazard ratios were calculated with continuous covariates (age, albumin, hemoglobin, dialysis vintage) at their group means and categorical variables treated as present between quartiles of BP. To ascertain the BP level associated with the best survival, restricted cubic splines of BP were generated and the association of these splines with mortality was tested using the Cox model.

All analyses were conducted using Stata 11.0 (Stata Corp, College Station, TX). The P values reported are two-sided and taken to be significant at <0.05.

Results

Between September 2003 and September 2009, 326 patients from four dialysis units staffed by the nephrology faculty of Indiana University, Indianapolis were recruited. The study flow is outlined in Figure 1. Most patients were excluded because of absence of ambulatory BP recordings; only 2 patients were dropped because ambulatory BP recording was inadequate.

Figure 1
Study flow diagram.

The clinical characteristics of patients by quartiles of systolic ambulatory BP are shown in Table 1. The population was predominantly black with average age of 55 years. All patients were on three times weekly dialysis and were prescribed a dialysis time of about 4 hours and blood flow rate of 400 mL/min. Serum albumin and hemoglobin reflect the general hemodialysis population. Cardiovascular disease defined as previous history of myocardial infarction, coronary bypass surgery or angioplasty, or stroke was present in 33% patients. Majority (74%) of the patients received antihypertensive drugs; beta-blockers were used in about half, and ACE inhibitors or angiotensin receptor blockers in two-thirds. As expected, those who were in the upper quartiles of hypertension also took more antihypertensive drugs.

Table 1
Clinical characteristics of the study population by Quartiles of 44-hour ambulatory systolic BP

Median follow up was 29 months (inter-quartile range 16 – 48 months) with the longest follow up of 6 years. During this follow up period 102 (31%) patients died. The crude mortality rate was 118/1000 patient-years.

Figure 2 shows the Kaplan-Meier survival curves depicting the relationship between all-cause mortality and quartiles of blood pressure measured using ambulatory or BP measurements. A significant relationship between increasing levels of systolic blood pressure and all cause mortality was seen with home (Figure 3) and ambulatory blood pressure. On the other hand, dialysis unit BP recordings were of no prognostic importance.

Figure 2
Kaplan Meier survival curves for ambulatory systolic BP and mortality. The log rank test demonstrated a significant difference in survival between quartiles of ambulatory systolic BP.
Figure 3
Kaplan Meier survival curves for home systolic BP and mortality. The log rank test demonstrated a significant difference in survival between quartiles of ambulatory systolic BP.

Table 2 shows the relationship between BP and mortality outcomes by quartiles of systolic ambulatory BP and home BP. The relationship between quartiles of systolic BP obtained by various methods and the hazard ratio for all-cause mortality showed a strong relationship for ambulatory and less strong relationship for home BP measurements. No such relationship between dialysis-unit BP and mortality was seen (model chi2 4.97, p=0.17 for predialysis and model chi2 0.04, p=0.997 for postdialysis). The relationship between BP and mortality was limited to systolic BP; no such relationship was demonstrated for diastolic BP. The relationship between wake and sleep BP and mortality was similar to that seen for overall 44-hour ambulatory systolic BP (Table 3).

Table 2
Hazard Ratios for all-cause mortality by quartiles of ambulatory or home systolic BP
Table 3
Hazard Ratios for all-cause mortality by quartiles of wake and sleep ambulatory systolic BP

Time on dialysis (dialysis vintage) significantly influenced survival. In case of ambulatory systolic BP, the hazard ratio per year on dialysis was 1.066 (p=0.002). In case of home systolic BP, the hazard ratio per year on dialysis was 1.048 (p=0.019). Prevalent cardiovascular disease also influenced survival (for ambulatory HR 1.69, p = 0.017; for home HR 1.62, p=0.031) as did ethnicity (for ambulatory HR for blacks 0.41, p=0.013; for home HR for blacks 0.48, p=0.037; whites being the reference group).

To directly compare dialysis-unit BP with out-of-dialysis unit BP 3 models were created. Model 1 was created with quartiles of all 4 types of BP: ambulatory, home, pre-dialysis and post-dialysis. Two nested models were next generated. Model 2 contained only quartliles of dialysis unit BP and Model 3 contained only out-of-dialysis unit BP. The two nested models (Models 2 and 3) were compared to the model with all 4 types of BP (Model 1) using the likelihood ratio test. Model 2 was inferior to Model 1 (likelihood ratio test, p=0.009) but Model 3 was similar to Model 1 (likelihood ratio test, p=0.3). Models containing ambulatory and home BP showed similar fits by the likelihood ratio test.

Figure 4 shows the non-linear nature of the relationship between BP and mortality seen for ambulatory and home BP measurements and outcomes. In general, systolic ambulatory BP associated with least mortality was between 110–120 mmHg. The “best” systolic home BP was between 120–130 mmHg.

Figure 4
Non-linear relationship of systolic BP obtained outside the dialysis unit and subsequent mortality over up to 6 years. The best outcome was seen when ambulatory systolic BP was between 110–120 mmHg and home systolic BP was between 120–130 ...

Discussion

The results of this study demonstrate the following: 1) the prognostic information of BP measurements obtained in outside the dialysis unit either by the patient or by an automatic monitor is greater than that obtained in the dialysis unit; 2) the prognostic information is nearly all contained in the systolic component of BP, rather than the diastolic component; 3) the relationship of BP to mortality is independent of conventional and unconventional cardiovascular risk factors (Table 2); and 4) the relationship of BP recordings and mortality followed a W-shaped curve for out of dialysis unit recordings (Figure 4).

Patients who were recently hospitalized or sick were excluded. Thus, patients who may have been more hypotensive were not studied. Thus this study differed in its recruitment criteria compared to epidemiologic studies which have analyzed all patients in the dialysis unit regardless of their level of illness. These large cohort studies report a consistently higher mortality for lower blood pressures and do not find increase in mortality for increasing level of BP 8, 9. Perhaps this may be due to a stronger signal of low BP for mortality reflecting the poor health of these patients 8. Similar to what has been reported by large cohort studies utilizing dialysis unit measurements, we found a higher mortality among patients in the lowest quartile of home and ambulatory BP. However, in sharp contrast to the cohort studies, out-of-dialysis-unit BP recordings demonstrated a clear trend of increasing all-cause mortality among patients in increasing home or ambulatory BP quartiles. These findings suggest that BP recorded outside the dialysis unit may contain greater prognostic information compared to BP measured in the dialysis unit 15.

Three studies using ambulatory BP monitoring in hemodialysis patients support the notion that ambulatory BP and mortality are strongly related. Among 57 treated French hypertensive hemodialysis patients, Amar et al 10 reported that at follow-up of 34 ± 20 months, 10 patients died of cardiovascular causes. Nocturnal systolic BP was associated with increased risk of cardiovascular death (risk ratio 1.41 95% CI 1.08 to 1.84). The largest study to date among hemodialysis patients reporting the relationship between 24-hour ambulatory BP and cardiovascular outcomes comprised of 168 patients16. Among these non-diabetic patients without pre-existing cardiovascular events Tripepi et al reported the ratio of the average systolic BP during the night and day (night/day systolic ratio) used to indicate the nocturnal fall in BP or the dipping phenomenon was associated with all-cause and cardiovascular mortality on both univariate and multivariate analyses. In contrast to Tripepi et al, this study included blacks (who had a lower mortality compared to whites) and those with cardiovascular disease (who had a higher mortality as expected). A previous report by Alborzi et al reported that ambulatory BP was of greater prognostic value compared to dialysis unit BP recordings but these analyses were unadjusted for cardiovascular risk factors 11. An important aspect of the current report is that the effect of ambulatory and home BP on survival persisted even after adjusted for cardiovascular disease as well as conventional and non-conventional cardiovascular risk factors for mortality. Furthermore, the current study extends the above reports to a cohort nearly twice as large as the largest study reported to date and with a longer follow up.

The present study found that home systolic BP threshold for optimal survival was 10 mmHg higher than ambulatory systolic BP. When compared to ambulatory systolic BP among hemodialysis patients, home systolic BP is on average 12.2 mmHg higher 5. Thus it is not surprising to find a higher threshold for optimal outcome with home systolic BP. A shorter follow up from a subgroup of this cohort has also reported a link between increased home BP to mortality among long-term hemodialysis patients 11. The results of this study are also consistent with previously published cohort studies examining the influence of home BP with clinic BP among patients without kidney disease 17, 18. Similarly, compared to clinic BP among patients with CKD not on dialysis, the risk for ESRD is increased to a greater extent when home BP recordings are considered 19.

The W-shaped relationship for home BP and mortality was unexpected. A similar though less pronounced W-pattern was discernable for ambulatory BP. It is possible that when home BP (or ambulatory BP) were found to be high, patients were treated leading to a subsequent improvement in survival. Thus, treatment with antihypertensive medications (that may have a cardioprotective effect) or dry-weight reduction may modify the relationship of the initial measurement of BP and the final outcome. Given that the analysis is limited to a single occasion of BP measurement the time dependent relationships cannot be explored.

There are several possibilities why out-of-dialysis-unit measurements may have provided better prognostic information. First, multiple blood pressure measurements over the course of the day, as done with home or ambulatory blood pressure monitoring, can average out the troughs and peaks in BP swings which pre-dialysis and post-dialysis BP recordings are unable to provide 20. Second, dialysis unit blood pressures are influenced by the white coat effect – elevated BP only in the dialysis setting — which is less pronounced with home blood pressures and eliminated by ambulatory blood pressure monitoring 21. Third, masked hypertension—elevated BP at home but normal in the dialysis unit—is potentially detected with home BP monitoring and ambulatory blood pressure monitoring and may be of prognostic significance 22. Finally, blood pressures sampled from a broader pool of situations may make them more representative of the person’s typical blood pressure 14

There are several strengths and limitations of our work. Our study was largely limited to black people and we excluded certain patients such as those with morbid obesity and atrial fibrillation due to difficulties with accurate blood pressure assessment in this group. Whether the same results would hold in people of other ethnicities and of broader clinical characteristics is not known and will require verification in future cohorts. Although this is the largest study among dialysis patients reported to date, the sample size of our study was still relatively small. Some strengths of our study are as follows: 1) by testing cubic splines, we could test the threshold of BP associated with a better prognosis, instead of using arbitrary definitions of normotension and hypertension which are debatable in the hemodialysis population; 2) the home blood pressure monitor we used was a validated device equipped with a memory device and printer, so there was a mechanism in place to confirm the authenticity of the patient reports 23.

Perspective

Dialysis unit blood pressures neither predict target organ damage 6 nor all-cause mortality in relatively healthy dialysis patients. Thus, in dialysis patients more so than in the general population, blood pressure measurement and treatment should occur with recordings made outside the clinic. The results of the study support the view of a BP being important for prognostication of mortality even after adjustment for non-conventional risk factors. We cannot imply causality in a cohort study; however, this study may offer some guidelines with respect to BP goals. Self-measured systolic BP of approximately 120–130 mm Hg and of approximately 110–120 mm Hg by ambulatory BP are associated with the best prognosis. These thresholds may be used to test the hypothesis if controlling hypertension in hemodialysis patients using out of dialysis unit blood pressure recordings would make a difference to cardiovascular mortality 24.

Acknowledgments

Source of Funding: NIH 2R01-DK062030-06A109

Footnotes

Disclosures: None

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