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Analysis of association between brain natriuretic peptide levels and blood pressure variability

  • Authors:
    • Hisashi Masugata
    • Shoichi Senda
    • Michio Inukai
    • Takashi Himoto
    • Naohisa Hosomi
    • Hiroki Okada
    • Fuminori Goda
  • View Affiliations

  • Published online on: April 25, 2014     https://doi.org/10.3892/etm.2014.1692
  • Pages: 21-24
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Abstract

The present study aimed to investigate the association between plasma brain natriuretic peptide (BNP) levels and systolic blood pressure (SBP) variability over a one‑year period. Blood pressure was measured in 44 patients treated for hypertension (73±9 years old) at an outpatient clinic every one to two months over a one‑year period. The standard deviation (SD) and the coefficient of variation (CV) were calculated to assess SBP variability. Mean SBP was also calculated over the year. Plasma BNP levels were measured at the end of the one‑year period. BNP was found to correlate with mean SBP (r=0.599; P<0.001). However, BNP was not observed to be correlate with either the SD (r=0.219; P=0.153) or the CV (r=0.058; P=0.709) of the SBP. Multiple regression analysis revealed that only the mean values of SBP were independently associated with BNP (β=0.613; P<0.001). Thus, BNP was found to be correlated with mean SBP, but not SBP variability. In conclusion, plasma BNP levels may reflect the average SBP, but not SBP variability over the one‑year period prior to the measurement of BNP in patients with hypertension.

Introduction

Brain natriuretic peptide (BNP), a hormone secreted by ventricular cardiomyocytes in response to pressure overload in the left ventricle (1), reflects the presence of left ventricular hypertrophy in patients with hypertension (2,3). Thus, BNP is used during antihypertensive treatment in order to assess hypertensive cardiac damage (4) and risk stratification (5). Previous studies (6,7) have demonstrated that antihypertensive treatment lowers plasma BNP levels; therefore, BNP levels may be used as a marker of blood pressure control. Therefore, it is hypothesized that may be an association between BNP and mean systolic blood pressure (SBP) during the antihypertensive treatment of patients with hypertension.

Seasonal variation in blood pressure has been reported (815), with blood pressure often higher during the winter than the summer. Previous studies in older adults (16,17) have revealed that a 10 mmHg rise in SBP is associated with an ~10% increase in the risk of mortality from stroke or ischemic heart disease. Thus, seasonal variation in SBP may influence mortality induced by cardiovascular events, including stroke and ischemic heart disease. Visit-to-visit variability in SBP has been established to be a strong predictor of stroke, independent of mean SBP (18,19). Visit-to-visit variability in SBP over a one-year period may reflect seasonal SBP variation. However, the association between seasonal SBP variation and plasma BNP levels in patients with hypertension is yet to be elucidated.

In the present study, it was hypothesized that SBP variability over a one-year period may reflect cardiac damage and may be significantly correlated with plasma BNP levels. In order to evaluate this hypothesis, the association between SBP variability over a one-year period and plasma BNP levels was assessed in patients with hypertension. This association was then compared with the association between mean SBP and BNP levels in these patients.

Material and methods

Subjects and protocol

A total of 44 patients [21 male and 23 female; mean age ± standard deviation (SD), 73±9 years; range, 53–87 years] who had been diagnosed with hypertension at Kagawa University Hospital (Kagawa, Japan), and who had visited the outpatient clinic regularly between September 2012 and August 2013, were included in the present study. Hypertension was defined as SBP ≥140 mmHg and/or diastolic blood pressure (DBP) ≥90 mmHg. Blood pressure was determined using the conventional cuff method. All patients were treated with at least one antihypertensive drug. For at least one year prior to the present study, as well as during the present study, the antihypertensive drug regimens of the patients did not change. Patients with a history of heart failure or evident heart disease were excluded and none of the study subjects had a history of atherosclerotic cardiovascular disease or stroke. Patient blood pressure was measured at an outpatient clinic every one to two months during the study year. At the end of the observation period, blood samples were taken in the morning after an 8-h overnight fast. Total cholesterol, triglycerides, high-density lipoprotein cholesterol, blood urea nitrogen, creatinine, uric acid, hemoglobin, C-reactive protein and glycosylated hemoglobin were measured using standard laboratory techniques. Patients with renal dysfunction whose creatinine levels were ≥1.4 mg/dl were excluded from the present study. The association between plasma BNP levels and various clinical parameters, including blood pressure and laboratory data, were analyzed. This protocol was approved by the Ethics Committee of Kagawa University (Kagawa, Japan). Informed consent was obtained from all participants.

Blood pressure parameters

Patient SBP was measured in the morning at an outpatient clinic. Patients were not instructed as to whether to take their hypertension medication prior to or subsequent to the clinical visit. Upon arrival at the outpatient clinic, patients rested for ≥1 min and SBP was then measured. SBP was measured once, while the patient was seated, by a physician who was trained in using the automated oscillometric sphygmomanometer (HEM-1040; Omron, Kyoto, Japan) and blinded to patient blood examination data. The SD and the coefficient of variation (CV) of the SBP values obtained over the one-year observation period were calculated in order to assess SBP variability. The mean SBP values over the year were also calculated to assess average blood pressure control.

Plasma BNP measurement

Plasma BNP levels were measured at the end of the observation period. In brief, samples were taken by a laboratory using an MI02 Shionogi BNP instrument (Shionogi & Co., Ltd., Osaka, Japan). Each blood sample was collected in an EDTA-2Na-treated blood sampling tube and then centrifuged at a low temperature to separate the plasma for the assay.

Statistical analysis

Data are expressed as the mean ± SD. Statistical analyses were performed using SPSS software, version 18.0 (SPSS, Inc., Chicago, IL, USA). For the comparison of monthly mean values of SBP obtained from the patients over the study period, one-way analysis of variance (ANOVA) was used. Linear regression analysis was performed to analyze the association between plasma BNP levels, blood pressure and other variables. Step-wise multiple regression analysis was performed to identify which blood pressure parameters were independently associated with plasma BNP levels. A value of P<0.05 was considered to indicate statistical significance.

Results

Clinical characteristics of the subjects

The clinical parameters of the study subjects are summarized in Table I. The mean SBP (130±13 mmHg) and DBP (69±6 mmHg) values during the one-year observation were not particularly high, due to the antihypertensive treatments taken by the patients. However, the high mean plasma BNP values (39.0±25.7 pg/ml) indicated the presence of cardiac damage in this group of patients.

Table I

Clinical parameters in patients with hypertension.

Table I

Clinical parameters in patients with hypertension.

ParameterValue
Number (male/female)44 (21/23)
Age (years)73±9
BMI (kg/m2)24.0±3.9
Diabetes (%)20
Dyslipidemia (%)41
Total cholesterol (mg/dl)190±28
HDL cholesterol (mg/dl)52±12
Triglycerides (mg/dl)135±81
BUN (mg/dl)16.3±4.4
Creatinine (mg/dl)0.77±0.22
Uric acid (mg/dl)5.3±1.3
Hb (g/dl)13.2±1.5
CRP (mg/dl)0.13±0.16
HbA1c (%)5.6±0.9
BNP (pg/ml)39.0±25.7
Drug administration
 ARB (%)66
 CCB (%)80
 α-blocker (%)3
 β-blocker (%)30
 Diuretic (%)18
 Statins (%)27
Blood pressure and heart rate over one year
 Mean value of SBP (mmHg)130±13
 Mean value of DBP (mmHg)69±6
 Mean value of HR (beats/min)68±5
SBP variability over one year
 SD of SBP (mmHg)10±3
 CV of SBP (mmHg)0.08±0.02

[i] Data are presented as mean ± SD unless otherwise indicated. BMI, body mass index; HDL, high-density lipoprotein; BUN, blood urea nitrogen; Hb, hemoglobin; CRP, C-reactive protein; HbA1c, glycosylated hemoglobin; BNP, brain natriuretic peptide; ARB, angiotensin II receptor blocker; CCB, calcium channel blocker; SBP, systolic blood pressure; DBP, diastolic blood pressure; HR, heart rate; SD, standard deviation; CV, coefficient of variation.

SBP variability

The variation in SBP over the one-year observation period in all subjects is shown in Table II. The highest levels of SBP were observed in December (135±18 mmHg) and March (135±16 mmHg) and the lowest levels were observed in September (126±14 mmHg). However, no statistically significant differences were identified in the monthly mean values of SBP. The SD of the SBP (10±3 mmHg) in the patients, over the one-year study period indicated large variations in SBP (Table II).

Table II

SBP variability during one-year observation in patients with hypertension.

Table II

SBP variability during one-year observation in patients with hypertension.

MonthSBP (mmHg)
January132±17
February134±18
March135±16
April128±16
May130±15
June130±15
July128±14
August130±18
September126±14
October130±17
November132±17
December135±18

[i] SBP, systolic blood pressure.

Correlation of plasma BNP level with SBP variability and mean SBP

Linear regression analysis was performed to assess the correlation between parameters of SBP variability, mean SBP and plasma BNP levels at the end of the one-year observation period (Table III). Only mean SBP showed a significant correlation (r=0.599, P<0.001) with plasma BNP levels. With regard to the parameters of SBP variability, no significant correlation was observed between plasma BNP levels and the SD or the CV of the SBP. Stepwise multiple regression analysis was performed in order to identify which parameters were independently associated with plasma BNP levels. This revealed that only the mean SBP value (β-coefficient=0.613; P<0.001) was independently associated with plasma BNP levels (Table IV).

Table III

Correlation between BNP and other clinical parameters in patients with hypertension.

Table III

Correlation between BNP and other clinical parameters in patients with hypertension.

ParameterrP-value
Age0.3880.009
BMI−0.1970.200
Diabetes0.0520.735
Dyslipidemia0.0180.907
Total cholesterol−0.2690.078
Triglycerides−0.1210.434
HDL cholesterol0.1350.400
BUN−0.0200.896
Creatinine−0.0260.865
Uric acid0.0100.965
Hb0.0790.610
CRP−0.0500.745
HbA1c−0.1180.450
Drug administration
 ARB0.0020.989
 CCB−0.0060.971
 α-blocker−0.0420.787
 β-blocker−0.0610.695
 Diuretics−0.1520.323
 Statins0.0200.896
Blood pressure and heart rate
 Mean value of SBP0.599<0.001
 Mean value of DBP0.1730.263
 Mean value of HR0.0140.930
 SBP variability
 SD of SBP0.2190.153
 CV of SBP0.0580.709

[i] BMI, body mass index; HDL, high-density lipoprotein; BUN, blood urea nitrogen; Hb, hemoglobin; CRP, C-reactive protein; HbA1c, glycosylated hemoglobin; ARB, angiotensin II receptor blocker; CCB, calcium channel blocker; SBP, systolic blood pressure; DBP, diastolic blood pressure; HR, heart rate; SD, standard deviation; CV, coefficient of variation.

Table IV

Multiple regression analysis of BNP and significantly associated variables.

Table IV

Multiple regression analysis of BNP and significantly associated variables.

Independent variableβ-coefficientt-valueP-value
Mean value of SBP0.6134.717<0.001

[i] F ratio=22.252; r2=0.376. SBP, systolic blood pressure.

Discussion

The present study compared SBP variability and mean SBP over a one-year observation period in order to identify the association between these variables and plasma BNP levels in patients with hypertension. The highest levels of SBP were observed during December and March, whereas the lowest levels were observed during September. These findings suggest the following: i) SBP variability during the one-year period was not correlated with the plasma BNP levels detected at the end of the observation period; ii) mean SBP during the one-year period was correlated with the plasma BNP levels detected at the end of the observation period and iii) only the mean values of SBP were independently associated with plasma BNP levels.

Seasonal variation in blood pressure is a well-established phenomenon (815), with blood pressure being higher during the winter than the summer. In a previous study, we reported that the highest levels of SBP were observed during February and the lowest levels were found during August, in healthy elderly subjects evaluated using home blood-pressure measurements (20). In the present study, the highest levels of SBP were observed in December and March. This represented a slight variation from previous reports (815,20). However, in the present study, SBP was detected at an outpatient clinic and included patients who were receiving treatment for hypertension. These differences in methods of blood pressure detection and study participants may be responsible for the discrepancy between the present and previous studies.

The present study aimed to investigate the association between cardiac damage and SBP variability and mean SBP through detecting plasma BNP levels. BNP was found to be correlated with the mean values of SBP, but not with parameters of SBP variability in treated patients with hypertension. These findings indicate that mean values of SBP rather than SBP variability may be a marker of cardiac damage in treated patients with hypertension. Visit-to-visit variability in SBP (SD of SBP) has been demonstrated to be a strong predictor of stroke, independent of mean SBP (18,19). Therefore, further studies may be required in order to determine whether patients with hypertension who demonstrate high visit-to-visit SBP variability have a high risk of cardiac events, including heart failure and ischemic heart diseases.

The specific mechanism through which plasma BNP levels were found to be associated with mean SBP levels, but not SBP variability, is yet to be elucidated. BNP is a hormone secreted by ventricular cardiomyocytes in response to pressure overload of the left ventricle (1). Increases in plasma BNP levels may occur as a consequence of long periods of high blood pressure. Therefore, in the present study, it may be that the patients with hypertension who exhibited SBP variability did not experience persistent high blood pressure. In using plasma BNP levels to assess cardiac damage, the clinical significance of SBP variability and mean SBP may differ.

In conclusion, plasma BNP levels showed stronger correlation with mean values of SBP than with parameters of SBP variability during a one-year observation period. Therefore, the plasma BNP levels taken at the end of the study year may reflect average SBP control, but not the SBP variability during the study year in patients with hypertension.

References

1 

Nakagawa O, Ogawa Y, Itoh H, et al: Rapid transcriptional activation and early mRNA turnover of brain natriuretic peptide in cardiocyte hypertrophy. Evidence for brain natriuretic peptide as an ‘emergency’ cardiac hormone against ventricular overload. J Clin Invest. 96:1280–1287. 1995.PubMed/NCBI

2 

Charles CJ, Kaaja RJ, Espiner EA, et al: Natriuretic peptides in sheep with pressure overload left ventricular hypertrophy. Clin Exp Hypertens. 18:1051–1071. 1996. View Article : Google Scholar : PubMed/NCBI

3 

Peng Q, Hu W, Su H, Yang Q and Cheng X: Levels of B-type natriuretic peptide in chronic heart failure patients with and without diabetes mellitus. Exp Ther Med. 5:229–232. 2013.PubMed/NCBI

4 

Eguchi K, Matsui Y, Shibasaki S, et al; Japanese Morning Surge Study Group. Changes in self-monitored pulse pressure correlate with improvements in B-type natriuretic peptide and urinary albumin in treated hypertensive patients. Am J Hypertens. 20:1268–1275. 2007. View Article : Google Scholar : PubMed/NCBI

5 

Tanaka Y, Daida H, Imai Y, et al: Morning home blood pressure may be a significant marker of nephropathy in Japanese patients with type 2 diabetes: ADVANCED-J study 1. Hypertens Res. 32:770–774. 2009. View Article : Google Scholar : PubMed/NCBI

6 

Andreadis EA, Georgiopoulos DX, Tzavara CK, et al: Plasma brain natriuretic peptide: a biochemical marker of effective blood pressure management? J Hypertens. 27:425–432. 2009. View Article : Google Scholar : PubMed/NCBI

7 

Ito H, Ishii K, Iwakura K, Nakamura F, Nagano T and Takiuchi S: Impact of azelnidipine treatment on left ventricular diastolic performance in patients with hypertension and mild diastolic dysfunction: multi-center study with echocardiography. Hypertens Res. 32:895–900. 2009. View Article : Google Scholar : PubMed/NCBI

8 

Hata T, Ogihara T, Maruyama A, et al: The seasonal variation of blood pressure in patients with essential hypertension. Clin Exp Hypertens A. 4:341–354. 1982. View Article : Google Scholar : PubMed/NCBI

9 

Woodhouse PR, Khaw KT and Plummer M: Seasonal variation of blood pressure and its relationship to ambient temperature in an elderly population. J Hypertens. 11:1267–1274. 1993. View Article : Google Scholar : PubMed/NCBI

10 

Kristal-Boneh E, Harari G and Green MS: Seasonal change in 24-hour blood pressure and heart rate is greater among smokers than nonsmokers. Hypertension. 30:436–441. 1997. View Article : Google Scholar : PubMed/NCBI

11 

Chifamba J, Mufunda J, Sigola LB, Matenga JA and Sparks HV: Effect of variation in environmental temperature on blood pressure: is it important? Cent Afr J Med. 44:37–40. 1998.PubMed/NCBI

12 

Nakajima J, Kawamura M, Fujiwara T and Hiramori K: Body height is a determinant of seasonal blood pressure variation in patients with essential hypertension. Hypertens Res. 23:587–592. 2000. View Article : Google Scholar : PubMed/NCBI

13 

Sothern RB: Circadian and circannual characteristics of blood pressure self-measured for 25 years by a clinically-healthy man. Chronobiologia. 21:7–20. 1994.PubMed/NCBI

14 

Paschalis-Purtak K, Pucilowska B, Kabat M and Sznajderman M: Clinical evaluation of 24 h ambulatory monitoring of blood pressure under various environmental conditions (home and work versus hospital). Blood Press Monit. 3:289–294. 1998.

15 

Imai Y, Munakata M, Tsuji I, et al: Seasonal variation in blood pressure in normotensive women studied by home measurements. Clin Sci (Lond). 90:55–60. 1996.PubMed/NCBI

16 

Khaw KT, Barrett-Connor E, Suarez L and Criqui MH: Predictors of stroke-associated mortality in the elderly. Stroke. 15:244–248. 1984. View Article : Google Scholar : PubMed/NCBI

17 

Barrett-Connor E, Suarez L, Khaw K, Criqui MH and Wingard DL: Ischemic heart disease risk factors after age 50. J Chronic Dis. 37:903–908. 1984. View Article : Google Scholar : PubMed/NCBI

18 

Rothwell PM, Howard SC, Dolan E, et al: Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension. Lancet. 375:895–905. 2010. View Article : Google Scholar : PubMed/NCBI

19 

Rothwell PM: Limitations of the usual blood-pressure hypothesis and importance of variability, instability, and episodic hypertension. Lancet. 375:938–948. 2010. View Article : Google Scholar : PubMed/NCBI

20 

Kimura T, Senda S, Masugata H, et al: Seasonal blood pressure variation and its relationship to environmental temperature in healthy elderly Japanese studied by home measurements. Clin Exp Hypertens. 32:8–12. 2010. View Article : Google Scholar : PubMed/NCBI

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Spandidos Publications style
Masugata H, Senda S, Inukai M, Himoto T, Hosomi N, Okada H and Goda F: Analysis of association between brain natriuretic peptide levels and blood pressure variability. Exp Ther Med 8: 21-24, 2014.
APA
Masugata, H., Senda, S., Inukai, M., Himoto, T., Hosomi, N., Okada, H., & Goda, F. (2014). Analysis of association between brain natriuretic peptide levels and blood pressure variability. Experimental and Therapeutic Medicine, 8, 21-24. https://doi.org/10.3892/etm.2014.1692
MLA
Masugata, H., Senda, S., Inukai, M., Himoto, T., Hosomi, N., Okada, H., Goda, F."Analysis of association between brain natriuretic peptide levels and blood pressure variability". Experimental and Therapeutic Medicine 8.1 (2014): 21-24.
Chicago
Masugata, H., Senda, S., Inukai, M., Himoto, T., Hosomi, N., Okada, H., Goda, F."Analysis of association between brain natriuretic peptide levels and blood pressure variability". Experimental and Therapeutic Medicine 8, no. 1 (2014): 21-24. https://doi.org/10.3892/etm.2014.1692