Impact of Volume Status on Blood Pressure and Left Ventricle Structure in Patients Undergoing Chronic Hemodialysis

Abstract

In this study, we aimed to examine the impact of volume status on blood pressure (BP) and on left ventricular mass index (LVMI) in chronic hemodialysis (HD) patients. This study enrolled 74 patients (F/M: 36/38, mean age 53.5 ± 15.3 years, mean HD time 41.5 ± 41 months) that were on HD treatment for at least 3 months. Demographics, biochemical tests, hemogram and C-reactive protein levels, mean interdialytic weight gain (IDWG), mean percentage of ultrafiltration (UF), and intradialytic complications such as hypotension and cramps were determined. Mean values of predialysis and postdialysis BP measurements were recorded a month before echocardiographic examination. On the day after a midweek dialysis session, 24 h ambulatory BP monitoring (ABPM) and echocardiographic examination were made concurrently. The patients were classified into two groups according to volume status: normovolemic (group 1; 14F/24M, mean age 50 ± 16.7 years, mean dialysis time 47.7 ± 47.7 months) and hypervolemic (group 2; 15F/21M, mean age 57.3 ± 12.7 years, mean dialysis time 34.9 ± 32 months). HD duration, IDWG, UF, and interdialytic complication rates were similar between the two groups (p < 0.05). Eleven patients (28.9%) of group 1 and 8 patients (22.2%) of group 2 showed dipper (p = 0.50). Valvular damage was more common in group 2 (p = 0.002). Whereas 33 patients (91.7%) had left ventricular hypertrophy (LVH) in group 2, 21 patients of the group 1 (55.3%) had LVH (p < 0.001). Although LVMI showed a significant positive correlation with cardiothoracic index, predialysis and postdialysis BP, IDWG, UF, daytime and nighttime BP measurements of 24 h ABPM, a significant negative correlation was seen with Kt/V urea and serum albumin levels. In conclusion, increased IDWG and UF and elevated BP are independent predictors of LVH for HD patients. Increased volume status leads to IDWG and elevated BP and eventually causes severe LVMI increases.

• Hemodialysis
• blood pressure
• ABPM
• left ventricular hypertrophy
• hypervolemia

INTRODUCTION

Hypertension is one of the major risk factors for cardiovascular diseases influencing the life expectancy in patients undergoing dialysis as well as in general population. Although patients with renal failure before dialysis showed a hypertension prevalence of 80%, it was reported as 56–86% in the patients undergoing hemodialysis (HD).^1–4

In HD patients, the most important probable mechanism leading to hypertension is positive sodium balance and extracellular fluid accumulation, and there are many studies that report this as the main reason observed in 90–95% of the patients.^5,6 In addition, hypertension is an important cause of left ventricular hypertrophy (LVH) in these patients^7,8 Hypertension is associated with cardiac dilatation, myocardial ischemia, fibrosis, arrhythmia, and increased mass of left ventricular muscle leading to LVH.⁹ LVH is also very common in HD patients and has been shown to be a strong predictor of cardiovascular mortality.^10,11

In this study, the effect of volume status on blood pressure (BP) and on left ventricular muscle mass (LVM) and the factors that may be associated with them in chronic HD patients were evaluated.

MATERIALS AND METHODS

This study enrolled patients on chronic HD treatment for at least 3 months. Demographic data, biochemical test results (serum urea, creatinine, sodium, potassium, calcium, phosphorus, parathormone, and albumin levels), hemogram, and C-reactive protein levels and medical treatments within the last month and mean Kt/V urea and mean urea reduction ratio of the last 3 months were determined from the medical records of the patients.

Based on the medical records, mean interdialytic weight gain (IDWG) (kg/day), mean percentage of ultrafiltration (UF) (the ratio of mean amount of fluid drawn to the dry weight per session), intradialytic hypotension episodes (a fall of 20 mmHg in pre-systolic BP and/or a fall of 10 mmHg in pre-diastolic BP),¹² and the number of sessions for which intradialytic cramp occurred during the last month were recorded.

Mean values of systolic and diastolic BP were calculated from the records of predialysis and postdialysis measurements before and after the last 12 HD sessions. Hypertension was defined as predialysis BP >130/80 mmHg.

On the day after a midweek dialysis session, all patients underwent 24 h ambulatory BP monitoring (ABPM) and echocardiographic examination, concurrently. Twenty-four hours of BP monitoring from the upper portion of the non-fistula-bearing arm was performed by the oscillometer method using a noninvasive ABPM equipment (Spacelabs, Issaquah, WA, USA). Daytime and nighttime BPs were defined as the average values during the awake period (between 6:00 am and 10:00 pm) and during the sleeping period (between 10:00 pm and 6:00 am), respectively. Measurements were done at 15 min intervals during the daytime and at 30 min intervals during the nighttime. “Dippers” were defined as those patients who showed a nighttime decline of 10% or more in the mean BP than the average daytime mean BP. Patients not meeting the dipper criteria were defined as “non-dippers.”

With the echocardiography performed on the same day with 24 h BP monitorization, left atrium diameter (LA), left ventricular systolic and end-diastolic diameter, interventricular septum thickness and left ventricular posterior wall thickness (PWT), and valvular functions and ejection fractions of the patients were measured. LVM was calculated using the formula described by Devereux and Reichek¹³:

LVH was defined as left ventricular mass index [(LVMI (LVM to body surface area)] of >131 g/m² in males and 104 g/m² in females.¹⁴ We described LVH as “severe” when LVMI exceeded 140 and 160 g/m² for females and males, respectively.

The patients were divided in two groups as normovolemic (those with dry weight) and hypervolemic (those exceeding dry weight), according to volume status by evaluating in terms of cardiothoracic index (CTI) (below or above 45%), predialysis BP (below or above 130/80 mmHg), LA (below or above 3.6 cm), and clinical evaluation (pretibial edema, intradialytic hypotension, and cramp episodes). Demographics, biochemical test results, hematologic parameters, intradialytic complications, IDWGs, percentages of UF, 24 h BP monitorization data, and echocardiographic findings were compared between the two groups. The parameters that may be related to left ventricle (LV) muscular mass and hypervolemia were investigated.

All data were recorded using SPSS 12.0 statistical software. Parametric data were expressed as mean ± SD. Whereas t-test was used for the analysis of parametric data, Spearsman and Pearson tests were used for correlation analysis. For the analysis of nonparametric data Mann–Whitney U test was used. In the analyses, p < 0.05 was considered significant.

RESULTS

This study included 74 HD patients; 36 of them were women. Mean age of the patients was 53.5 ± 15.3 (21–92) years and mean duration of HD was 41.5 ± 41 (3–192) months.

Normovolemic group (group 1) included 38 patients, 14 of whom were women. Mean age of the patients was 50 ± 16.7 years and mean duration of HD was 47.7 ± 47.7 months. Most frequent etiologies of end-stage renal disease (ESRD) were hypertension (29%), chronic glomerulonephritis (29%), and diabetes (16%). Mean IDWG was 1.14 ± 0.25 kg/day, and percentage of UF drawn per dialysis session was 4.2 ± 1.0 in this group.

Hypervolemic group (group 2) included 36 patients, 15 of whom were women. Mean age of the patients was 57.3 ± 12.7 years and mean duration of HD was 34.9 ± 32 months. Most commonly observed etiologies of disease in this group were hypertension (44%), diabetes (22%), and chronic glomerulonephritis (14%). For the patients of this group, mean IDWG was 1.2 ± 0.45 kg/day and percentage of UF drawn per dialysis session was 4.75 ± 1.58. There was no significant difference between the two groups in terms of HD duration (p = 0.18). Although IDWG and intradialytic UF percentage were higher in the patients of group 2, this difference was not statistically significant (p = 0.47 and 0.08, respectively).

The groups did not show a significant difference in terms of etiology (p = 0.40). Hemogram and biochemical parameters were found to be similar (Table 1). Whereas half of the patients of group 1 showed intradialytic hypotension and 42% had cramp, 58% of patients developed intradialytic hypotension and 50% of patients developed cramp in group 2. Although intradialytic hypotension and cramp complications were more common in group 2, the difference was not statistically significant (p = 0.47 and 0.49). Whereas only two patients were using antihypertensive drugs (angiotensin converting enzyme (ACE) inhibitor and beta blocker) in group 1, seven patients were using antihypertensive drugs (four patients calcium channel blocker, one patient ACE inhibitor, one patient angiotensin receptor blocker (ARB), and one patient beta blocker) in group 2. Between the two groups, there was no significant difference in the use of antihypertensive drug (p = 0.22).

Table 1.  Laboratory parameters of the patients

	Group 1 (n = 38)	Group 2 (n = 36)	p-Value
Urea (mg/dL)	138 ± 34	125 ± 29	0.08
Creatinine (mg/dL)	8.2 ± 2.3	8.0 ± 2.2	0.65
Calcium (mg/dL)	8.9 ± 1.2	9.1 ± 0.6	0.51
Phosphorus (mg/dL)	4.5 ± 1.0	4.4 ± 1.5	0.68
Parathormone (pg/mL)	391 ± 323	414 ± 430	0.79
Albumin (g/dL)	4.0 ± 0.3	4.0 ± 0.3	0.68
Hemoglobin (g/dL)	11.6 ± 1.4	11.1 ± 17	0.19

For the two groups, predialysis and postdialysis BP and interdialytic 24 h ABPM values are shown in Table 2.

Table 2.  Predialytic, postdialytic, and 24 h ABPM results of both groups

	Group 1 (n = 38)	Group 2 (n = 36)	p-Value
Predialytic SBP (mmHg)	115 ± 15	135 ± 21	<0.001
Predialytic DBP (mmHg)	74 ± 9.7	82 ± 9.8	0.001
Postdialytic SBP (mmHg)	101 ± 12	114 ± 16	<0.001
Postdialytic DBP (mmHg)	66 ± 9.9	72 ± 8.8	0.005
Systolic BP—daytime (mmHg)	125 ± 21	142 ± 26	0.003
Dipper	4.8 ± 7.5	5.7 ± 7.4	0.50
Diastolic BP—daytime (mmHg)	78 ± 14	85 ± 14	0.035
Systolic BP—nighttime (mmHg)	119 ± 23	134 ± 27	0.014
Diastolic BP—nighttime (mmHg)	72 ± 15	78 ± 15	0.08

Note: SBP, Systolic BP; DBP, Diastolic BP.

Regarding 24 h ABPM, 11 patients of group 1 (28.9%) and 8 patients of group 2 (22.2%) showed dipper form. The two groups did not show a significant difference in terms of dipper ratio (p = 0.50).

Based on the data obtained from echocardiography, only four patients (10.5%) of group 1 had valvular damage (all of them had mild mitral insufficiency). However, 15 patients of group 2 (41.7%) had valvular damage (13 of them with various graded mitral insufficiency and/or 4 patients with tricuspid insufficiency, 3 patients with aortic stenosis, and 3 patients with aortic insufficiency). Valvular damage was statistically significantly more frequent in group 2 (p = 0.002). Left ventricular diastolic dysfunction was similar in both groups (p = 0.35).

Twenty-one patients of group 1 (55.3%) had LVH, and 11 of them had severe LVH. Whereas 33 patients of group 2 (91.7%) had LVH, 22 of them had severe form. LVH and severe form were significantly more frequent in the patients of group 2 (p  <  0.001). Echocardiographic data of both groups are shown in Table 3.

Table 3.  Echocardiography results of the patients

	Group 1 (n = 38)	Group 2 (n = 36)	p-Value
Cardiothoracic ratio (%)	42.2 ± 3	49.4 ± 4	<0.001
Left atrium diameter	3.4 ± 0.3	3.7 ± 0.4	0.002
Interventricular septum thickness	1.18 ± 0.29	1.3 ± 0.2	0.062
LV-ED diameter	4.6 ± 0.47	4.9 ± 0.5	0.022
LV posterior wall thickness	1.06 ± 0.23	1.17 ± 0.15	0.021
LV muscular mass index	131 ± 44.9	168 ± 42.7	0.001
EF (ejection fraction)	64 ± 5.5	60 ± 7.9	0.042

Note: LV-ED, left ventricle end diastolic.

We found a significantly positive correlation between LVMI and CTI, IDWG, percentage of UF, predialysis and postdialysis systolic and diastolic BP, and daytime and nighttime systolic and diastolic BP measurements of 24 h ABPM. Negative correlation was found between LVMI and Kt/V urea and serum albumin levels (Table 4). There was no correlation between LVMI and the duration of HD, biochemical and hematologic parameters other than albumin, hypotensive attacks, and cramps.

Table 4.  Parameters associated with left ventricular muscular mass index

	Correlation constant (r)	p-Value
Cardiothoracic index	0.308	0.008
Predialytic systolic BP	0.461	<0.001
Predialytic diastolic BP	0.407	<0.001
Postdialytic systolic BP	0.471	<0.001
Postdialytic diastolic BP	0.408	<0.001
Interdialytic gain of weight	0.253	0.03
Percentage of ultrafiltration	0.279	0.016
Systolic BP—daytime	0.443	<0.001
Diastolic BP—daytime	0.294	0.01
Systolic BP—nighttime	0.443	<0.001
Diastolic BP—nighttime	0.298	0.01
Serum albumin	−0.236	0.04
Kt/V urea	−0.298	0.05

DISCUSSION

Cardiovascular diseases are the main cause of death in chronic renal failure patients. LVH is an important risk factor for cardiovascular morbidity and mortality in chronic HD patients and it is significantly promoted by hypertension. In these patients, LVH is a common finding with an incidence of nearly 75–80% in dialysis patients.^8–11,15 In addition, antihypertensive drug regimen does not prevent the progression of LVH in hypertensive HD patients.^7,8 In this study, whereas incidence of LVH in the normovolemic HD patients was 53%, it was found to be 91% in the hypervolemic (mildly hypertensive) patients.

Hypertension is a major risk factor for cardiovascular disease affecting the life expectancy of the general and also ESRD population. It has been reported that 80% of patients with ESRD manifested hypertension just before beginning chronic dialysis.¹ Increased LV mass in association with nocturnal hypertension has been reported in predialysis and dialysis patients.^16,17

BP may be measured during the predialysis, postdialysis, or interdialytic periods in HD patients. In these patients, there is a conflict about which BP will be taken as the essential parameter for the diagnosis or follow-up of the hypertension. Several studies assessed the prediction that can be attributed to BP levels measured before or after the dialysis session. Postdialysis rather than predialysis BP was found to be independently related to increased mortality.^18,19 Since the development and clinical application of ambulatory BP monitoring (ABPM), various studies have shown that assessing the circadian BP profile is more predictive than office BP readings in estimating cardiovascular risk.^20–22 ABPM has been generally considered as the most accurate method for evaluating BP overload in the general population as well as in HD patients.²³

In a recent study of hypertensive patients with LVH, 24 h ABPM was not superior to nurse-recorded seated BP in terms of associations with treatment-induced changes in LV mass.²⁴ Zoccali et al. also used 24 h ambulatory BP monitoring and reported that it did not add any significant information to the dialysis unit BP.²⁵ The authors concluded that the average of 12 predialysis BPs was as useful as ABPM in the prediction of LVH. Cannella et al. also measured 24 h ABPM, and routine dialysis unit BP averaged over 12 sessions. They reported close correlations for BPs between ABPM and routine BP measurements.²⁶ In our study, we obtained the average of at least 12 consecutive predialysis and postdialysis BP measurements. In addition to daytime and nighttime BPs obtained during the 24 h ABPM, predialysis and postdialysis BPs were found to be correlated with left ventricular mass as well.

Cross-sectional studies in hypertensive patients have, in general, shown only modest correlations between clinic BP and left ventricular mass. However, during the studies performed with ABPM; Amar et al. found a strong relationship of pulse pressure with total mortality.²⁷ Another study from Zocalli's group found that the night/day systolic BP ratio was the sole BP indicator associated with all-cause and cardiovascular mortality.²⁸ The best correlation between left ventricular mass index and BP was seen with ABPM. Systolic BP overload was a unique and independent predictor of LVMI and interventricular septal thickness (both measures of LVH), whereas nighttime ambulatory systolic BP was the best predictor for left ventricular PWT.²⁹

Although the reason of the hypertension that is commonly seen in HD patients is multifactorial, the importance of volume status on BP in HD patients has long been recognized.³⁰ In HD patients, the basis for the occurrence of high predialysis BP can result from a number of factors: changes in extracellular volume (i.e., volume expansion), low compliance to restricted salt intake,³¹ and sympathetic and renin angiotensin overactivation.³² The importance of volume status for the BP was investigated in many studies, and some of them reported that intradialytic changes of pressure were independent from IDWG or intradialytic loss of body weight,^33,34 whereas others state that IDWG or intradialytic loss of body weight shows positive correlation with the BP.^35–37 IDWG and intradialytic UF percentage were found to be higher in our hypervolemic patients. Although this elevation was not significant, we believe that IDWG has an effect on the BP.

In many studies, it was shown that in addition to pressure overload, volume overload may also be an important factor for the development of LVH in dialysis patients. It was found that systolic BP and IDWG are independent determinants of the LVH development.^38,39 Elevated BP caused by volume overload was associated not only with LVH, but also with left atrial dilatation and valvular insufficiency.^40–42 In our patients with hypervolemia, in addition to elevated LVH rate, we also found that 47% of the patients had cardiac valvular insufficiency.

Non-dipping occurs in a variety of conditions and diseases, such as chronic renal failure, sleep apnea, volume overload, nocturia, and those with sympathetic activation.⁴³ Non-dipping is associated with LVH⁴⁴ and increased cardiovascular risk.⁴⁵ In our study, 71% of normovolemic patients and 78% of hypervolemic patients showed non-dipper. However, this difference was not significant.

As a conclusion, elevations of BP measurements obtained by 24 h ABPM, IDWG, and increase of the amount of fluid drawn are independent predictors of the LVH development. For HD patients, sensitive mechanisms play an important role in the maintenance of normovolemia (ideal weight and dry weight). Even slight but continuing increases of volume may lead to elevation of BP and increased LVMI, causing LVH eventually.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.