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NDT Advance Access originally published online on January 25, 2007
Nephrology Dialysis Transplantation 2007 22(4):1198-1204; doi:10.1093/ndt/gfl732
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© The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Aortic stiffness, left ventricular hypertrophy and weekly averaged blood pressure (WAB) in patients on haemodialysis

Hidekazu Moriya, Takayasu Ohtake and Shuzo Kobayashi

Shonan Kamakura General Hospital—Nephrology, 1202-1, Yamazaki Kamakura Kanagawa 247-8533, Japan

Correspondence and offprint requests to: Hidekazu Moriya, Shonan Kamakura General Hospital—Nephrology, 1202-1, Yamazaki Kamakura Kanagawa 247-8533, Japan. Email: hidekazu.moriya{at}tokushukai.jp



   Abstract
Top
 Abstract
Introduction
 Materials and methods
 Results
 Discussion
 References
 
Background. In haemodialysis (HD) patients, no consensus has been reached with regard to the desired blood pressure (BP) level and when or how BP should be monitored. Moreover, BP variability over a period of 1 week has not been well studied in HD patients.

Methods. The present study is an observational study that comprised 101 HD patients (65 males and 36 females). We used daily home blood pressure (HBP) monitoring to record a total of 20 points of BP over a period of 1 week, including measurements of the wake-up and night BPs; this was in addition to the BP recorded before and after each HD session that occurred three times a week. The average of these 20 BP measurements was defined as the weekly averaged blood pressure (WAB). Finally, we studied the relationship between the WAB and left ventricular hypertrophy (LVH) or aortic stiffness measured by baPWV.

Results. The systolic (142.5 ± 19.5 mmHg) and diastolic (.78.8 ± 9.9 mmHg) WABs were almost consistent with the wake-up BP on the day after the midweek dialysis session (R2 = 0.709 and 0.775, respectively). The WAB showed significant positive correlations with the left ventricular mass index (LVMI) (R = 0.387, P < 0.001) and baPWV (R = 0.226, P < 0.05), whereas the predialysis systolic BP did not show a significant positive correlation with the LVMI.

Conclusion. The WAB is a useful marker for evaluating the BP of HD patients and correlates well with the LVMI or baPWV.

Keywords: blood pressure variability; haemodialysis; hypertension; left ventricular hypertrophy; pulse wave velocity



   Introduction
Top
 Abstract
 Introduction
Materials and methods
 Results
 Discussion
 References
 
Cardiovascular complications are the leading cause of mortality and morbidity in haemodialysis (HD) patients. Hypertension plays an important role in the development of cardiovascular disorders in this population as well as essential hypertensive patients [1,2]. Using various definitions of hypertension, it is estimated that the prevalence of hypertension in HD patients is approximately 75% [3,4]. Charra et al. have found a reduced survival rate in HD patients when the predialysis mean arterial pressure was greater than 99 mmHg [5]. Moreover, London [6] recommends an optimum predialysis blood pressure (BP) of less than 140/90 mmHg for HD patients.

However, some reports showed no linear relationship between elevated BP and poor prognosis in HD patients. In a retrospective study by Duranti et al. [7], no significant difference was found between the survival rates of 168 normotensive and 202 hypertensive patients. Zager et al. [8] found a ‘U-curve’ relationship between systolic BP and mortality in dialysis patients. In a study of 1243 patients in Okinawa, Iseki et al. [9] found that low diastolic BP was associated with a higher death rate. Indeed, London [10] has described the importance of pulse BP. Therefore, the systolic, diastolic or pulse BPs should be clearly differentiated when discussing the importance of hypertension in any cardiovascular disorder in HD patients. Moreover, it is important to clearly define the time point at which the BP is measured. Since the BP of HD patients varies with each HD session due to loss of excess fluid, this factor should also be considered. However, little data is available regarding BP variability. Although Agarwal [11] reported BP monitoring over a period of 2 days, we believe that variability should be monitored throughout the week because of the occurrence of weekly changes in the quantity of excess body fluid at each dialysis session.

In the present study, we used home blood pressure (HBP) monitoring to record a total of 20 points of BP over a period of 1 week, including measurements of the wake-up and night BPs; this was in addition to the BP recorded before and after each HD session that occurred three times a week. We studied the relationship between this variability monitored over a period of 1 week and left ventricular hypertrophy (LVH) or aortic stiffness, using brachial–ankle pulse wave velocity (baPWV). Finally, we want to propose that weekly averaged blood pressure (WAB) can be used to understand the role of BP control on cardiovascular damages in HD patients.



   Materials and methods
Top
 Abstract
 Introduction
 Materials and methods
Results
 Discussion
 References
 
Patients
We included all 125 patients in this cross-sectional study from our haemodialysis centre. Patients were eligible for inclusion when (i) they had no clinical cardiovascular complication during 6 months preceding entry, (ii) they received HD for 3.5–4.0 h during each HD session that occurred three times a week and for more than 6 months at the time of enrollment in this study. Exclusion criteria included patients who had (i) congestive heart failure showed by symptoms and a chest X-ray, (ii) uncontrolled dry weight with blood levels of human atrial natriuretic peptide (hANP) more than 60 pg/ml and a cardiothoracic ratio (CTR) of more than 60% at post-HD and (iii) intradialytic hypotension. Congestive heart failure was diagnosed in cases where a chest X-ray revealed infiltration in the lung with acute or chronic orthopnea. Hypotensive episode was defined as a fall in systolic BP below 100 mmHg or a reduction in systolic BP of 30 mmHg or more associated, with hypotension symptoms requiring an intervention, such as reducing ultrafiltration rate, administering saline infusions, or ending the session early (when hypotension occurred near the end of the session). Chest X-ray and hANP were studied at post-dialysis of the first day of a week. Finally, this cross-sectional study comprised 101 HD patients (65 males and 36 females) in our hospital.

All patients provided their informed consent, and the ethical committee of our hospital approved this study.

Blood pressure monitoring and definition of weekly averaged blood pressure (WAB)
Home BP of patients was monitored at home twice a day for 1 week. Recordings were carried out in a sitting position after at least a 5-min rest by using an automatic device that was based on the cuff-oscillometric method [12]. The subjects and their caregivers were taught by nurses how to measure the BP at home using this device. Validity of the device was confirmed such that the difference between the ausculatory method and the device should be within 5 mmHg in each individual [13]. The two measurement time points were after waking up and before eating and taking medicines and before sleeping at night. During the same week, the BP was measured in the supine position before and after each dialysis session. The BP was measured with automated devices by the same method. The pulse pressure was calculated as follows: Systolic BP – Diastolic BP. The mean BP was calculated as follows:


Formula

We defined the WAB to be an average of 20 points of BP (data of BP recorded at home twice a day for 1 week and that recorded in the hospital twice during each dialysis session that occurred three times a week) and defined that intraday BP variability as the difference between systolic BP after waking up and that before sleeping at night. In patients with antihypertensives, the drugs were given as scheduled.

Left ventricular mass index (LVMI)
Standard two-dimensional guided M-mode echocardiographies were performed on an inter-HD midweek day using a 3.75 MHz transducer in a blinded manner by a member of the study team. The left ventricular mass index (LVMI) was calculated according to the Penn convention: (LVMI g/m2: LVMI = 1.04 x {(LVDd + IVSth + PWth)3 – (LVDd)3} – 13.6 g/m2, where LVDd is the left ventricular end diastolic diameter, IVSth is the interventricular septal thickness, and PWth is the left ventricular posterior wall thicknes). The LVMI was also calculated by dividing the LVM by the body surface area.

Aortic stiffness
Aortic stiffness can be assessed non-invasively by measurement of the baPWV in a blinded manner [14]. Recently, a new and simple device that uses an oscillometric method to measure baPWV has been developed [15]. The baPWV was automatically calculated by a Colin Waveform Analyzer (form PWV/ABI; Colin Co., Ltd., Komaki, Japan). Cuffs were connected to both the plethysmographic and oscillometric sensors and were wrapped around the arm opposite to the AV fistula arm and around both ankles while the patient was in the supine position. Transit time ({Delta}Tba) between the brachial and ankle pulse waves was automatically measured based on the time delay between the feet at the arm and ankle. The distance between arm and ankle was calculated automatically based on the height of the patient (H) and anthropomorphic data for the Japanese population. The path length from the suprasternal notch to the brachium (Lb) and ankle (La) was calculated by using the following equation: Lb = 0.2195 x H (cm) – 2.0734, La = 0.8129 x H (cm) + 12.328. The baPWV was then calculated by using the following equation: baPWV = (La – Lb)/{Delta}Tba. The validity, reproducibility and clinical significance of non-invasive baPWV measurements have been reported elsewhere [15].

Statistical analysis
All data are presented as the mean ± SD. Comparison of group mean values was carried out by the two-tailed paired and unpaired t-test. Univariate and multivariate analysis was performed to observe the correlations between LVMI and several factors. Data was analysed on a personal computer using the StatView 5.0 software for Windows (SAS Institute, Cary, NC), and P < 0.05 was regarded to be significant.



   Results
Top
 Abstract
 Introduction
 Materials and methods
 Results
Discussion
 References
 
The clinical characteristics of the subjects are presented in Table 1. The average age was 68.1 ± 11.8 years (range 40–87 years), and the duration of dialysis therapy was 8.9 ± 5.3 years. Intradialytic hypotension episodes were not found in any patient during the week in which the measurements were performed. Of the 101 patients, 64 patients had been treated with antihypertensive drugs and 36 patients had diabetes mellitus.


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  		Table 1. Patients’ characteristics

 
Variability of blood pressure
As shown in Table 2, the predialysis systolic BP of the first dialysis session (151.3 ± 18.5) over a period of 1 week was significantly higher than that of the other dialysis sessions. The average of the wake-up systolic BP on dialysis days (154.4 ± 21.0) was significantly higher than that on non-dialysis days (142.5 ± 23.6). The BP decreased after dialysis; subsequently, it further decreased at night. Therefore, the BP measured at night during the last dialysis session of the week showed the lowest measured BP values. These changes are also shown in Figure 1. The systolic WAB (sWAB) was 142.5 ± 19.5 mmHg. The diastolic, mean and pulse BPs also showed the same pattern of BP variability as the systolic BP throughout the week. The diastolic, mean and pulse WABs were 78.8 ± 9.9 mmHg, 100.1 ± 11.3 mmHg and 63.8 ± 15.3 mmHg, respectively. The systolic and diastolic WABs were almost completely consistent with the wake-up BP on the day after the middle dialysis session (R2 = 0.709 and 0.775, respectively).


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  		Table 2. BP variability over a period of 1 week

 

Figure 1
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  		Fig. 1. BP variability in HD patients over a period of 1 week is shown. The systolic WAB (sWAB) was 142.5 ± 19.5 mmHg. The pattern of BP variability in diastolic, mean and pulse BPs was the same as that of the systolic BP throughout the week, and the diastolic, mean, and pulse WABs were 78.8 ± 9.9 mmHg, 100.1 ± 11.3 mmHg and 636.8 ± 15.3 mmHg, respectively. Systolic and diastolic WABs were almost completely consistent with wake-up BP on the day after the middle dialysis session (R2 = 0.709 and 0.775, respectively).

 
WAB and damage to target organs
The data are shown in Table 3. The sWAB had a significant positive correlation with the LVMI (r = 0.387, P < 0.001) as shown in Figure 2. Similarly, the mean WAB (r = 0.219, P < 0.05) and pulse WAB (r = 0.387, P < 0.001), with the exception of the diastolic WAB, showed significant positive correlations with the LVMI. Also, the wake-up systolic BP on the day after the middle session, which was almost consistent with sWAB, showed significant correlation with LVMI (Figure 3). When the study population was divided into two groups based on the average sWAB value (142.5 mmHg), the LVMI in patients who showed sWAB values greater than 142.5 mmHg (n = 51) was significantly higher than in patients with sWAB values less than 142.5 mmHg (n = 50). The degree of anaemia or volume status estimated by blood levels of hANP or %CTR was not related to the difference of sWAB level. LVMI only showed the difference between the levels of sWAB as shown in Table 4. Moreover, the LVMI in patients with sWAB values greater than 142.5 mmHg associated with intraday systolic BP variability of less than 25 mmHg (n = 39) was significantly higher than that of patients with sWAB values greater than 142.5 mmHg associated with intraday systolic BP variability of more than 25 mmHg (n = 12) as shown in Figure 4. In the case of sWAB values less than 142.5 mmHg, there was no relationship between the LVMI and intraday BP variability. The predialysis systolic BP was marginally associated with the LVMI (r = 0.204, P = 0.06), whereas the predialysis pulse BP showed a significant correlation with the LVMI (r = 0.252, P < 0.05). The predialysis diastolic or mean BP did not correlate with the LVMI (Table 3). Multivariate analysis including several factors which could affect LVMI showed only sWAB as an independent explanatory factor (Table 5).


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  		Table 3. WAB and predialysis BP and damage to target organs

 

Figure 2
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  		Fig. 2. The sWAB had a significant positive correlation with the LVMI (r = 0.387, P < 0.001).

 

Figure 3
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  		Fig. 3. LVMI showed significant correlation with the wake-up BP on the day after the middle HD session (r = 0.367, P < 0.001).

 

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  		Table 4. Comparison between patients who showed WAB more and less than 142.5 mmHg

 

Figure 4
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  		Fig. 4. The LVMI in patients with sWAB values greater than 142.5 mmHg associated with intraday BP variability of less than 25 mmHg was significantly higher than that of patients with sWAB values greater than 142.5 mmHg associated with intraday BP variability of more than 25 mmHg as shown.

 

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  		Table 5. Univariate and multivariate analysis including several factors which could affect LVMI

 
Regarding aortic stiffness, the baPWV showed a significant positive correlation with the sWAB (r = 0.226, P < 0.05) (Figure 5), mean WAB (r = 0.216, P < 0.05), and pulse WAB (r = 0.294, P < 0.005); however, it did not show a significant correlation with the diastolic WAB. The predialysis systolic BP had a significant positive correlation with baPWV (r = 0.272, P < 0.01). The predialysis pulse BP also showed a positive correlation with the baPWV (r = 0.216, P < 0.05), whereas the predialysis diastolic or pulse BP did not show a significant association (Table 3).


Figure 5
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  		Fig. 5. The baPWV showed a significant positive correlation with sWAB (r = 0.226, P < 0.05).

 
Regarding the post-dialysis BP that included systolic, diastolic, mean and pulse BPs, none of these BP values had a significant association with the LVMI or baPWV.



   Discussion
Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
References
 
In a prospective study in HD patients, Degoulet et al. had shown an association between both systolic and diastolic BPs and cardiovascular mortality [16]. Some reports demonstrated that the BP level itself is a strong determinant of the survival rate in dialysis patients [1,2]. However, there is debate regarding the linear relationship between BP and cardiovascular mortality. In this context, most reports published so far have dealt with only pre- or post-dialysis BP. However, patients with HD have variable body fluid conditions at each dialysis session, thus leading to BP fluctuations. Therefore, we wanted to demonstrate the relationship between BP variability over a period of 1 week and the damage to the target organs due to hypertension. This is because there are 2-day HD-free intervals during average HD sessions that occur three times a week. In this study, we propose a new concept of BP variability over a period of 1 week that is termed WAB. We showed that WAB corresponded to the wake-up BP recorded on the midweek non-dialysis day. Interestingly, the wake-up BP on the midweek non-dialysis day also significantly correlated with LVMI.

In essential hypertensives, the therapeutic guidelines of hypertension were published by the Seventh Report of the Joint National Committee, and a systemic strategy for the evaluation and therapy of hypertension has been established. However, in HD patients, no consensus has been reached with regard to the desired BP level and when or how BP should be monitored. Moreover, BP variability over a period of 1 week has not been well studied in HD patients. Blood pressure is not necessarily well controlled in the majority of HD patients. One of the reasons for this is that when BP is strictly controlled, patients tend to complain of general fatigue at home after HD. Generally, only pre- and post-haemodialysis BP tend to be monitored. We showed that following HD, the BP decreased further at night before sleeping in comparison with the post-dialysis BP. This fact may be an important issue when considering the quality of life of HD patients. However, in uraemic patients, a strong correlation is known to exist between BP elevations during sleep and damage to target organs [17,18].

Recently, time-related physiology has received considerable attention in the field of hypertension, and the diurnal change in BP is important in controlling hypertension. It has been reported that diastolic BP with a standard deviation greater than 15 mmHg increases the incidence of cerebral infarction and hypertensive nephropathy [19]. In this regard, ambulatory blood pressure monitoring (ABPM), which is reported to reflect the damage to target organs more precisely than office blood pressure [20–22], is a useful tool in evaluating BP fluctuations. Agarwal [11] reported that ABPM showed a progressive decrease in BP after dialysis. However, after the first night, the BP rapidly returned to predialysis levels on the following morning without further decrease in BP during the second night. In the present study, the BP did not increase to the predialysis level on the following morning. The difference in the findings of this study and ours may be due to the careful determination of dry weight or due to the ratio of use of antihypertensive drugs; that is 35% and 63.4%, respectively.

Moreover, monitoring the BP for 1 or 2 days in HD patients may be insufficient because HD therapy is usually performed regularly two or three times a week. For this reason, we monitored 20 points of BP over a period of 1 week because use of the automatic ABPM device is tedious in HD patients due to the presence of the AV fistula. Furthermore, it is very difficult to monitor the BP for 7 days in terms of the quality of life. The WAB that we have proposed in this study is useful for evaluating hypertension in HD patients. In the present study, the WAB, not the predialysis or post-dialysis BP, had a significant association with the LVMI, although Agarwal et al. [11] reported that predialysis diastolic BP, rather than predialysis systolic BP, was a better reflection of the respective ambulatory BP. In addition, we showed that the WAB was consistent with the wake-up BP on the day after the midweek dialysis session. In other words, we may be able to use this BP measurement instead of the WAB as the weekly average BP.

Left ventricular hypertrophy is an independent predictor of cardiovascular disease and plays an important role in the mortality of HD patients [23,24]. Needless to say, BP control is extremely important for reducing LVH [17]. Conlon et al. [25] observed a strong correlation between systolic ambulatory BP and predialysis systolic BP and a good correlation between LVH and systolic ambulatory BP or predialysis systolic BP. We demonstrated that LVH was significantly correlated with systolic, mean and pulse WAB. The predialysis systolic and diastolic BPs did not show any correlation with LVMI. Only the predialysis pulse BP showed a significant correlation with the LVMI. Often, HD patients do not have a normal nocturnal decrease in BP, thereby resulting in exposure to LVH [26–30]. In our study, the LVMI in patients with sWAB values greater than 142.5 mmHg associated with intraday BP variability of less than 25 mmHg was significantly higher than that of patients with sWAB values greater than 142.5 mmHg associated with intraday BP variability of more than 25 mmHg. These results show that both BP and less variability are associated with LVH. Continuous high BP may be important in the development of LVH.

Furthermore, we also showed a positive correlation between systolic, mean and pulse WAB and the baPWV. Aortic stiffness may result in a higher pulse BP (difference between systolic and diastolic BP) through Windkessel type hypertension [31]. The pulse pressure is known to be an independent predictor of total mortality in non-diabetic patients on chronic HD [32]. In this context, the pulse WAB had a significantly stronger association with the baPWV than any other type of BP. The present study is observational; therefore, it is unclear whether there is any causal relationship between higher pulse WAB and aortic stiffness.

In conclusion, this study clearly demonstrated that the BP of HD patients showed variability not only over a period of 1 day but also over a period of 1 week. Considering this, WAB is a useful marker in evaluating the BP of HD patients and correlates well with LVMI or baPWV.

Conflict of interest statement. None declared.



   References
Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 

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Received for publication: 10. 5.06
Accepted in revised form: 5.11.06


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R. Agarwal
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