Study on the Influencing Factors of Blood Pressure Variability in Patients Undergoing Maintenance Hemodialysis
BAI Xiao-hui*, PAN Rong-hua, ZHAO Yan-mei, WU Yue-lu, RUI Guo-hua
Department of Nephrology, Liyang Hospital of Traditional Chinese Medicine, Liyang, Jiangsu, 213300, China
*Corresponding Author:BAI Xiao-hui, E-mail: 13585429026@163.com
Abstract

Objective: To investigate the influencing factors of blood pressure variability (BPV) in patients with maintenance hemodialysis (MHD), so as to improve the patients’ prognosis. Methods: The clinical data of 107 MHD patients were retrospectively analyzed. According to intradialytic systolic pressure (SBP)-BPV, the patients were assigned into high SBP-BPV group (n=52) and low SBP-BPV group (n=55). According to intradialytic diastolic pressure (DBP)-BPV, they were divided into high DBP-BPV group (n=49) and low DBP-BPV group (n=58). The basic characteristics of patients in high and low SBP-BPV groups and DBP-BPV groups were compared, and the influencing factors of both SBP-BPV and DBP-BPV were also analyzed. Results: The differences were statistically significant between high and low SBP-BPV groups by comparison to the age, dry weight, body mass index (BMI), dialysis age, interdialysis weight gain (IDWG) rate, pre-dialysis SBP, albumin (ALB), hemoglobin (Hb), total cholesterol (TC) and calcium-phosphorus product (P<0.05 or P<0.01). The differences were also statistically significant between high and low DBP-BPV groups by comparison to the age, dry weight, BMI, IDWG rate, pre-dialysis SBP and DBP, Hb and calcium-phosphorus product (P<0.05 or P<0.01). Multiple linear regression analysis revealed that SBP-BPV was positively correlated with the age, IDWG rate and pre-dialysis SBP (P=0.002, P=0.001, P=0.006), while negatively with Hb (P=0.021). They were all regarded as independent influencing factors of SBP-BPV. Both IDWG rate and pre-dialysis DBP were positively correlated with DBP-BPV (P=0.019, P=0.004), and could be considered as independent influencing factors of DBP-BPV. Conclusion: Advanced age, increased IDWG%, pre-dialysis high SBP and decreased Hb are independent risk factors of SBP-BPV, and both increased IDWG rate and pre-dialysis high DBP are independent risk factors of DBP-BPV in intradialytic MHD patients. Pre-dialysis patients should positively control the weight gain and blood pressure, and ameliorate the nutritional status to stabilize intradialytic blood pressure, consequently improving the prognosis.

Key words: Blood pressure variability Maintenance hemodialysis Influencing factors; Systolic pressure
Introduction

Maintenance hemodialysis (MHD), a major replacement therapy for end-stage renal disease (ESRD), can prolong the survival time of patients and save their life by means of hemodialysis (HD) or peritoneal dialysis. At the end of 2012, more than 402 000 ESRD patients in the United States received HD therapy [1]. However, the morbidity and mortality in this population mainly result from HD vascular access dysfunction which results in a significant component of the overall health care cost [2]. With the development of medical technology, blood purification techniques are improved dramatically, and the survival time of patients undergoing MHD is prolonged obviously, but the mortality remains alarmingly high, at approximately 15%-20 % per year [3]. Cardiovascular disease is the major fatal cause of patients with chronic renal disease, accounting for approximately 50% of deaths in MHD patients. Nevertheless, increased blood pressure variability (BPV) is the most primary cause for cardiovascular events [4]. In recent years, a few studies[5, 6]have demonstrated that both intradialytic systolic blood pressure (SBP)-BPV and diastolic blood pressure (DBP)-BPV can be considered as the major risk factors of cardiovascular events, and the degree of SBP-BPV is significantly associated with the risk of arteriovenous fistulae (AVF) dysfunction. The clinical data of MHD patients and risk factors related to BPV increase were retrospectively analyzed so as to further investigate the relationship between BPV and HD, and to provide some theoretical evidence for improving the prognosis of patients.

Materials and Methods
Basic characteristics

Totally 107 patients who underwent MHD in Liyang Hospital of Traditional Chinese Medicine were selected. Inclusion criteria: (1) stable dry weight in recent 2 weeks; (2) more than 3 months of MHD (2-3 times per week, 4-5 h per time). Exclusion criteria: (1) acute complications and some acute factors that led to renal insufficiency; (2) secondary hypertension caused by non-chronic renal disease; (3)heart failure, myocardial infarction, arrhythmia, severe heart valvular lesion and congenital heart disease; (4) severe liver, lung and central nervous system diseases; (5) hypoproteinemia, cognitive impairment or mental disorder. There were 59 males and 48 females, respectively. They were 21-73 years old, averagely (58.25± 10.81) years old. Dialysis lasted for 15-46 months, averagely (29.15± 5.30) months. In terms of primary disease, there were 37 cases of diabetic nephropathy (DN), 28 cases of chronic glomerulonephritis (CGN), 15 cases of pyelonephritis, 13 cases of benign nephrosclerosis, 9 cases of polycystic kidney and 5 cases of renal obstruction. They were all approved by the Ethics Committee of Liyang Hospital of Traditional Chinese Medicine, and signed the informed consent form.

Methods

The patients’ blood pressure was measured using electronic sphygmomanometer 5 min before HD, every 30 min in the process of HD and 5 min after HD. The values of both SBP and DBP were recorded. The mean value and standard deviation of SBP and DBP as well as SBP-BPV and DBP-BPV were calculated and expressed by coefficient of dispersion. According to intradialytic SBP-BPV, the patients were assigned into high SBP-BPV group (n=52) and low SBP-BPV group (n=55); According to intradialytic DBP-BPV, they were also divided into high DBP-BPV group (n=49) and low DBP-BPV group (n=58).

On day of HD, peripheral venous blood 5 mL was drawn from patients in fasting state. Blood biochemical indexes were detected using fully automatic biochemical analyzer, including albumin (ALB), hemoglobin (Hb), blood urea nitrogen (BUN), creatinine (Cr), glucose, total cholesterol (TC), triglyceride (TG), phosphorus (P), and calcium (Ca), etc. Both urea clearance index and calcium-phosphorus product were calculated. Meanwhile, the patients’ gender, age, dry weight, body mass index (BMI), dialysis age and interdialysis weight gain (IDWG) rate were also recorded.

Observational indexes

The basic characteristics of patients in all groups were compared, and the influencing factors of both SBP-BPV and DBP-BPV were analyzed.

Statistical analysis

SPSS 19.0 statistical software was used. The enumeration data were compared by χ 2 test and expressed by the percentage. The measurement data were compared by t test and expressed by (ヌ± S). Multiple linear regression analysis was used for analyzing the influencing factors of BPV. P< 0.05 was considered to be statistically significant.

Results
Comparison of the basic characteristics between high and low SBP-BPV groups

The differences were statistically significant between high and low SBP-BPV groups by comparison to the age, dry weight, BMI, dialysis age, IDWG rate, pre-dialysis SBP, ALB, Hb, TC and calcium-phosphorus product (P< 0.05 or P< 0.01) (Table 1).

Table 1 Comparison of the Basic characteristics Between High and Low SBP-BPV Groups (ヌ± S)
Comparison of the basic characteristics between high and low DBP-BPV groups

The differences were statistically significant between high and low DBP-BPV groups by comparison to the age, dry weight, BMI, IDWG rate, pre-dialysis SBP and DBP, Hb and calcium-phosphorus product (P< 0.05 orP< 0.01) (Table 2).

Table 2 Comparison of the Basic Characteristics Between High and Low DBP-BPV Groups (ヌ± S)
Influencing factors of SBP-BPV by multiple linear regression analysis

Multiple linear regression analysis was performed, with gender, age, dry weight, BMI, dialysis age, IDWG rate, pre-dialysis SBP and DBP, ALB, Hb, BUN, Cr, urea clearance index, glucose, TC, TG, P, Ca and calcium-phosphorus product being the independent variables and SBP-BPV being the dependent variable. The results displayed that SBP-BPV was positively correlated with the age, IDWG% and pre-dialysis SBP (P=0.002, P=0.001, P=0.006), while negatively with Hb (P=0.021). They were all regarded as independent influencing factors of SBP-BPV (Table 3).

Table 3 Influencing Factors of SBP-BPV by Multiple Linear Regression Analysis
Influencing factors of DBP-BPV by multiple linear regression analysis

Multiple linear regression analysis was performed, with gender, age, dry weight, BMI, dialysis age, IDWG rate, pre-dialysis SBP and DBP, ALB, Hb, BUN, Cr, urea clearance index, glucose, TC, TG, P, Ca and calcium-phosphorus product being the independent variables and DBP-BPV being the dependent variable. The results showed that both IDWG% and pre-dialysis DBP were positively correlated with DBP-BPV (P=0.019, P=0.004), and could be considered as independent influencing factors of DBP-BPV (Table 4).

Table 4 Influencing Factors of DBP-BPV by Multiple Linear Regression Analysis
Discussion

Hypertension is very common in HD patients, but difficult to be controlled. Pulmonary hypertension has been recently reported as a common symptom in HD patients and a valuable predictor of mortality and cardiovascular events [7]. By assessing the prevalence, treatment, and control of hypertension in a cohort of 2 535 clinically stable, adult HD patients, Agarwal et al. [8] found that hypertension was documented in 86.0% of patients, and was controlled adequately in only 30% of the hypertensive patients. In the remaining patients, hypertension was either untreated (12%) or treated inadequately (58%). Among HD patients in China, the prevalence of hypertension came up to 81.52%, in which the blood pressure was controlled less than 140/90 mmHg in 58.98% of hypertensive patients treated with antihypertensive drugs [9]. As is known to all, sustained hypertension is the major cause of cardiovascular events and mortality, but fluctuation of blood pressure can greatly increase the risk of prognosis [10].

BPV refers to the fluctuation of blood pressure with time, and is defined as either the overall variability during a period of time, such as the standard deviation, or the average of the absolute difference between serial readings like average real variability (ARV) [11]. Fluctuation of blood pressure can seriously damage the organs, and the specific mechanisms are as follows: (1) Increased BPV manifests unstable to tissue perfusions, which can injury vascular endothelial cells; (2) It can increase the apoptosis of myocardial cells, and can activate humoral regulation system, predominantly being renin-angiotensin system (RAS); (3) It is closely associated with inflammatory responses [12, 13]. Recently, BPV has been reported as another independent risk factor for cardiovascular events [11, 14]. The study of Rothwell et al. [15] showed that visit-to-visit variability in SBP and maximum SBP were strong predictors of stroke, independent of mean SBP. Schillaci et al.[16]concluded that short-term variability of 24-hour SBP revealed an independent, although moderate, relation to aortic stiffness in hypertension, and this relationship is stronger with measures of BPV focusing on short-term changes, such as ARV and weighted 24-hour SD. With research deepening in recent years, intradialytic BPV has drawn greater attention. Kuiperset al.[17] found that elevation of intradialytic BPV could significantly increase cardiovascular events so as to affect the medium-term prognosis; the patients with circadian rhythm of blood pressure manifested elevation of intradialytic BPV before blood pressure did not change obviously. These findings suggest that circadian rhythm change of blood pressure may be related to intradialytic BPV. Ye et al. [18] believed that the difference rate of SBP was 14%-17%, and that of DBP was 12%-13% between 3-h HD and 1-h HD; the fluctuation range enlarged with decrease of cardiac index, indicating that elevation of intradialytic BPV is associated with weakened heart function and decreased cardiac index of HD patients.

By comparison to the basic characteristics in all groups, the research results in this study showed that the differences were statistically significant between high and low SBP-BPV groups by comparison to the age, dry weight, BMI, dialysis age, IDWG%, pre-dialysis SBP, ALB, Hb, TC and calcium-phosphorus product; and the differences were also statistically significant between high and low DBP-BPV groups by comparison to the age, dry weight, BMI, IDWG rate, pre-dialysis SBP and DBP, Hb and calcium-phosphorus product, suggesting that both SBP and DBP were under the influence of various clinical factors in intradialytic MHD patients, and their influencing factors were approximately the same, but there were also some differences. Multiple linear regression analysis revealed that SBP-BPV was positively correlated with the age, IDWG rate and pre-dialysis SBP, while negatively with Hb. They were all regarded as independent influencing factors of SBP-BPV. Both IDWG rate and pre-dialysis DBP were positively correlated with DBP-BPV, and could be considered as independent influencing factors of DBP-BPV. These findings demonstrate that IDWG rate is the common independent influencing factor of SBP-BPV and DBP-BPV, and can promote BPV increase to some extent. Dry weight, BMI and IDWG rate can all reflect the condition of body fluid metabolism. If the body fluid is removed insufficiently, the total amount of body fluid will increase to disturb the ion metabolism, consequently leading to elevation of intradialytic BPV [19]. Pre-dialysis SBP has promoting effects on both SBP-BPV and DBP-BPV, and can be an independent influencing factor of intradialytic SBP-BPV, so the change of SBP is more significant. Additionally, Hb decrease is related to the patients’ nutritional status. However, in this study, Hb was only the independent influencing factor of SBP-BPV, indicating that nutritional status might involve in SBP fluctuation directly. The reason is possibly that malnutrition can disturb the levels of serum potassium and sodium [20]. Therefore, in order to improve the prognosis, pre-dialysis patients should positively control the IDWG and blood pressure, correct anemia and electrolyte disturbance, and ameliorate nutritional status to stabilize intradialytic blood pressure.

To sum up, advanced age, increased IDWG rate, pre-dialysis high SBP and decreased Hb are independent risk factors of SBP-BPV, and both increased IDWG rate and pre-dialysis high DBP are independent risk factors of DBP-BPV in intradialytic MHD patients. Pre-dialysis patients should positively control the weight gain and blood pressure, and ameliorate the nutritional status to stabilize intradialytic blood pressure, consequently improving the prognosis.

Declaration

The authors of this manuscript declare that they have no conflict of interest.

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