Abstract
This study aimed to investigate the relationship between nondipper pulse rate (PR) and hypertensive target organ damage. Ambulatory blood pressure monitoring was conducted in 940 high‐risk Japanese patients enrolled in the Japan Morning Surge Home Blood Pressure Study. Nondipper PR was defined as (awake PR−sleep PR)/awake PR <0.1. The authors measured the patients' brain natriuretic peptide (BNP) and left ventricular mass index (LVMI). The nondipper PR group (n=213) had a significantly higher prevalence of high BNP (≥35 pg/mL, 39.9% vs 26.1%; P<.001) than the dipper PR group (n=727). LVMI was significantly higher in the nondipper PR patients compared with the dipper PR patients among the women (mean LVMI: 111.3±32.4 vs 104.2±26.7 g/m2, P=.03) but not the men (mean LVMI: 117.6±32.0 vs 117.2±33.1 g/m2, P=.92). In conclusion, the nondipper PR was associated with cardiac overload.
1. Introduction
In recent years, several reports have shown that a decrease in the nocturnal blood pressure (BP) decline (ie, nondipper BP) is related to cardiovascular (CV) events.1, 2, 3 There are also several reports on the relationship between the nondipper pulse rate (PR) and CV events in hypertensive patients.4, 5, 6 Our previous study demonstrated a significant synergetic interaction of the nondipper PR with nondipper BP for CV events.6
Although some reports have shown a relationship between nondipper BP and hypertensive target organ damage,7, 8 it remains unclear whether the nondipper PR is associated with hypertensive target organ damage. Measurements of target organ damage such as brain natriuretic peptide (BNP), left ventricular mass index (LVMI), brachial‐ankle pulse wave velocity (baPWV), and urinary albumin‐creatinine ratio (UACR) are surrogate markers for predicting CV events.9, 10, 11 Decreased levels of these markers are significantly related to a decrease in the rate of CV events.12 It is thus important for us to evaluate hypertensive target organ damage.
We hypothesized that the nondipper PR in treated hypertensive patients may be associated with hypertensive target organ damage, and that the relationship between the nondipper PR and hypertensive target organ damage may be strengthened by nondipper BP. In the present study, we investigated the association between abnormal diurnal variations of PR and hypertensive target organ damage in high‐risk Japanese patients from the Japan Morning Surge‐Home Blood Pressure (J‐HOP) study, which is much closer to the actual clinical setting.
2. Methods
2.1. Patients
This study was performed as part of the J‐HOP study.13 The recruitment of the patients for the J‐HOP study was consecutively conducted from January 2005 to May 2012, by 75 doctors at 71 institutions (45 primary practices, 22 hospital‐based outpatient clinics, and four specialized university hospitals) throughout Japan.13 The ethics committee of the internal review board of the Jichi Medical University School of Medicine, Tochigi, Japan, approved the protocol. The study protocol was registered on the clinical trials registration site: University Hospital Medical Information Network Clinical Trials Registry (UMIN‐CTR): #UMIN000000894. Written informed consent was obtained from all patients who were enrolled in the study.
Briefly, the J‐HOP study is a prospective observational study conducted to evaluate the predictive values of home BP for CV events in Japanese patients with any of the following CV risk factors: hypertension, diabetes mellitus, hyperlipidemia, smoking (including those with chronic obstructive pulmonary disease), chronic renal disease, atrial fibrillation, metabolic syndrome, and sleep apnea syndrome.
2.2. BP measurements
Clinic BPs were measured using a validated upper‐arm cuff oscillometric BP device (HEM‐5001, Medinote, Omron Healthcare, Kyoto, Japan)14 according to Japanese Society of Hypertension 2004 guidelines.15 This device automatically takes three measurements at 15‐second intervals after a measurement button is pressed once. All recorded BP parameters were stored along with the time information. The clinic BP values were obtained using the average of six readings from two clinic visits by each patient. The patients were instructed to take their morning medication as usual on the days they attended the clinic. Ambulatory BP monitoring was performed on a weekday with an automatic system that recorded the wearer's BP and PR every 30 minutes for 24 hours. Nondipper BP was defined as (awake systolic BP−sleep systolic BP)/awake systolic BP <0.1. Nondipper PR status was defined as (awake PR−sleep PR)/awake PR <0.1 according to a previous report.4
2.3. Echocardiographic measurements and pulse wave velocity
Echocardiography was performed at each participating institute. Echocardiography was performed by a trained technician and the results were checked by a trained echocardiologist. Two‐dimensional M‐mode or B‐mode images were obtained using an ultrasound machine according to the guidelines of the American Society of Echocardiology (ASE) and the European Association of Echocardiography (EAE). Left ventricular mass was obtained using the formula validated by the ASE: left ventricular mass = 0.8 (1.04 ([diastolic left ventricular dimension + diastolic posterior wall diameter + diastolic interventricular septal diameter]3 − [diastolic left ventricular dimension]3)) + 0.6 g. The left ventricular mass index (LVMI) was calculated as left ventricular mass / body surface area. These measurements and definitions were based on the guidelines of the ASE and EAE.16
The baPWV was measured by the volume plethysmographic method with previously validated equipment (form pulse wave velocity/ankle brachial index; Omron Healthcare). We used the mean of the right and left baPWV values for the analysis. We obtained 788 LVMI and 862 baPWV values from the total patient series.
2.4. Blood and urine examinations
Blood and urine samples were collected upon each patient's hospital arrival in the morning in a fasting state at enrollment and at the end of the study. The blood samples were centrifuged at 3000g for 15 minutes at room temperature. Plasma/serum samples after separation and urine samples were stored at 4°C in refrigerated containers and sent to a commercial laboratory (SRL, Tokyo) within 24 hours. All assays were performed within the next 24 hours at this single laboratory center. The UACR was measured using an immunoturbidity kit (AutoWako Microalbumin; Wako Pure Chemical Industries, Osaka, Japan). The plasma level of BNP (MI02 Shionogi BNP; Shionogi, Osaka, Japan) was measured by using a chemiluminescent enzyme.17 The intracoefficients of variation were 0.5% for urinary albumin and 1.9% for BNP. We defined the high BNP group as patients with a BNP level ≥35 pg/mL. 18
2.5. Statistical analyses
Data are presented as means (±standard deviation) or percentages. Because the distribution of the plasma BNP levels and UACR values was highly skewed, it was expressed as the median value together with the 25th and 75th percentiles (25%, 75%) and log‐transformed before the statistical analysis. The comparison between groups was based on the χ2 test of independence for categorical variables and analysis of variance for continuous variables. We performed one‐way analysis of variance to detect differences among groups. We performed analysis of covariance to detect the differences among groups after adjustment for significant covariates, and the Bonferroni test was used for multiple pairwise comparisons.
The association between BNP and nondipper PR was assessed by multiple linear regression after adjusting for covariates (age, sex, body mass index [BMI], dyslipidemia, diabetes mellitus, sleep systolic BP, and sleep PR in model 1; age, sex, BMI, dyslipidemia, diabetes mellitus, sleep systolic BP, sleep PR, and nondipper BP in model 2). The odds ratios and 95% confidence intervals of BNP ≥35 pg/mL were calculated by multiple logistic regression analyses after adjustments for these covariates. Associations/differences with a P value <.05 (two‐tailed) were considered significant. All statistical analyses were performed with IBM SPSS Statistics version 22 software (Chicago, IL).
3. Results
The characteristics of the enrolled patients according to their PR dipping patterns are shown in Table 1. The patients with a nondipper PR were significantly older (67.3±10.4 years vs 64.8±11.5 years, P=.004), were taking a significantly higher number of antihypertensive agents (2.2±1.1 vs 1.9±0.9, P<.001), and were significantly more likely to be using a β‐blocker (33.3% vs 12.1%, P<.001) compared with patients with a dipper PR.
Table 1.
Baseline characteristics according to PR dipping pattern
| Dipper PR (n=727) | Nondipper PR (n=213) | P Value | |
|---|---|---|---|
| Age, y | 64.8±11.5 | 67.3±10.4 | .004 |
| Male, % | 44.7 | 49.3 | .17 |
| Body mass index, kg/m2 | 24.6±3.5 | 24.3±3.2 | .39 |
| Current smoker, % | 11.6 | 9.4 | .38 |
| Hypertension, % | 96.3 | 94.3 | .21 |
| Dyslipidemia, % | 36.3 | 37.1 | .83 |
| Diabetes, % | 17.4 | 19.7 | .43 |
| Antihypertensive agents, No. | 1.9±0.9 | 2.2±1.1 | <.001 |
| Calcium channel blocker, % | 64.0 | 64.8 | .83 |
| Angiotensin‐converting enzyme inhibitors, % | 7.4 | 10.8 | .12 |
| Angiotensin II receptor blockers, % | 63.3 | 64.3 | .78 |
| β‐Blocker, % | 12.1 | 33.3 | <.001 |
| Loop diuretic, % | 1.2 | 2.3 | .24 |
| Thiazide, % | 32.6 | 32.4 | .96 |
| Clinic SBP, mm Hg | 139±15 | 140±15 | .79 |
| Clinic DBP, mm Hg | 81±11 | 78±11 | .004 |
| Clinic PR, beats per min | 72±11 | 69±12 | <.001 |
| 24‐h SBP, mm Hg | 130±12 | 130±12 | .86 |
| 24‐h DBP, mm Hg | 77±9 | 75±8 | .01 |
| 24‐h PR, beats per min | 68±8 | 67±9 | .08 |
| Awake SBP, mm Hg | 135±13 | 134±13 | .84 |
| Awake DBP, mm Hg | 80±10 | 78±9 | .02 |
| Awake PR, beats per min | 73±9 | 68±10 | <.001 |
| Sleep SBP, mm Hg | 120±14 | 119±15 | .64 |
| Sleep DBP, mm Hg | 70±9 | 68±9 | .004 |
| Sleep PR, beats per min | 59±7 | 65±9 | <.001 |
Abbreviations: DBP, diastolic blood pressure; PR, pulse rate; SBP systolic blood pressure.
The values of clinic diastolic BP, 24‐hour diastolic BP, awake diastolic BP, and sleep diastolic BP were significantly lower in the nondipper PR group compared with the dipper PR group. However, these differences were not significant after adjusting for age. The BNP levels were significantly higher in the nondipper PR group compared with the dipper PR group (median BNP: 20.5 pg/mL vs 18.3 pg/mL, P<.001; Figure 1A). The group of patients with a nondipper PR (n=213) had a significantly higher percentage of higher BNP levels (≥35 pg/mL, 39.9% vs 26.1%; P<.001) than those with a dipper PR (n=727). (Figure 1B). The difference of LVMI was not statistically significant (mean LVMI: 114.3±32.8 g/m2 vs 110.2±30.0 g/m2, P=.12; Figure 2A). The baPWV and UACR values were similar in the two groups (mean baPWV: 1661±310 cm/s vs 1642±332 cm/s, P=.48; median UACR: 13.7 mg/g Cr vs 12.9 mg/g Cr, P=.65) (Figure 2B,C).
Figure 1.
Pulse rate (PR) dipping patterns and brain natriuretic peptide (BNP; A) levels and the percentage of BNP ≥35 pg/mL (B). Data are presented as median values (25%, 75%). *P<.001.
Figure 2.
Pulse rate (PR) dipping patterns and left ventricular mass index (LVMI; A), brachial‐ankle pulse wave velocity (baPWV; B), and urinary albumin‐creatinine ratio (UACR; C). Data are presented as means (±standard deviation) or median values (25%, 75%). N.S. indicates not significant
Because the BNP and LVMI were significantly different between the men and women in the present study (median BNP: 16.3 pg/mL vs 21.0 pg/mL, P=.001; mean LVMI: 117.5±32.2 g/m2 vs 105.7±28.1 g/m2, P<.001), we analyzed BNP and LVMI separately in men and women. The BNP level in patients with nondipper PR was higher than that in patients with dipper PR in both sexes (male: median BNP 19.9 pg/mL vs 15.5 pg/mL, P=.002; female: median BNP 27.2 pg/mL vs 21.4 pg/mL, P=.02). The LVMI was significantly higher in the nondipper PR patients compared with the dipper PR patients among the women (mean LVMI: 111.3±32.4 g/m2 vs 104.2±26.7 g/m2, P=.03) but not the men (mean LVMI: 117.2±33.1 g/m2 vs 117.6±32.0 g/m2, P=.92) (Figure S1).
We divided the patients into four groups according to the dipping patterns of BP and PR: dipper BP and dipper PR, dipper BP and nondipper PR, nondipper BP and dipper PR, and nondipper BP and nondipper PR. The characteristics of these four groups are summarized in Table S1. The patients with nondipper BP and nondipper PR had the highest age, the highest number of antihypertensive agents used, and the highest rate of β‐blocker administration. As shown in Figure 3A, the patients' BNP levels increased incrementally and significantly (P for trend <.001) (median BNP): dipper BP and dipper PR, 15.6; dipper BP and nondipper PR, 19.4; nondipper BP and dipper PR, 23.0; nondipper BP and nondipper PR, 30.9 pg/mL.
Figure 3.
Brain natriuretic peptide (BNP) levels (A) and the percentage of BNP ≥35 pg/mL (B) according to blood pressure (BP) and pulse rate (PR) dipping patterns. Data are shown as median values (25%, 75%). *P<.05. **P<.01. ***P<.001.
In the multiple linear regression analysis, the nondipper PR was independently associated with log‐transformed BNP (β=0.166, P<.001) after adjusting for age, sex, BMI, dyslipidemia, diabetes, sleep systolic BP, sleep PR, and nondipper BP (Table 2). The nondipper PR was associated with log‐transformed BNP independent of nondipper BP.
Table 2.
Multivariate analysis for log‐transformed brain natriuretic peptide
| Model 1 | Model 2 | |||
|---|---|---|---|---|
| β | P Value | β | P Value | |
| Age | 0.396 | <.001 | 0.393 | <.001 |
| Male | −0.073 | .01 | −0.074 | .009 |
| Body mass index | −0.052 | .075 | −0.051 | .080 |
| Dyslipidemia | −0.022 | .44 | −0.022 | .44 |
| Diabetes | 0.043 | .13 | 0.043 | .14 |
| Sleep SBP | 0.107 | <.001 | 0.097 | .003 |
| Sleep PR | −0.246 | <.001 | −0.245 | <.001 |
| Nondipper PR | 0.166 | <.001 | 0.166 | <.001 |
| Nondipper BP | – | – | 0.022 | .50 |
Abbreviations: BP, blood pressure; PR, pulse rate; SBP systolic blood pressure.
The prevalence of patients with high BNP levels (BNP >35 pg/mL) was 21% in the dipper BP and dipper PR group, 35% in the dipper BP and nondipper PR group, 33% in the nondipper BP and dipper PR group, and 46% in the nondipper BP and nondipper PR group (Figure 3B). We calculated the odds ratio of BNP ≥35 pg/mL using multiple logistic regression analyses after adjustments for covariates. The odds ratio of nondipper PR was 2.60 (95% confidence interval, 1.76–3.84; P<.001) after adjusting for age, sex, BMI, dyslipidemia, diabetes mellitus, sleep systolic BP, sleep PR, and nondipper BP (Table 3).
Table 3.
Multiple logistic regression analysis for BNP ≥35 pg/mL
| Model 1 | Model 2 | |||
|---|---|---|---|---|
| Odds Ratio (95% CI) | P Value | Odds Ratio (95% CI) | P Value | |
| Age (10 years) | 2.37 (2.00–2.83) | <.001 | 2.35 (1.97–2.81) | <.001 |
| Male | 0.88 (0.64–1.22) | .44 | 0.88 (0.63–1.21) | .42 |
| Body mass index | 0.98 (0.93–1.03) | .37 | 0.98 (0.93–1.03) | .38 |
| Dyslipidemia | 1.03 (0.74–1.43) | .87 | 1.03 (0.74–1.44) | .85 |
| Diabetes | 1.22 (0.83–1.86) | .29 | 1.23 (0.82–1.85) | .31 |
| Sleep SBP (10 mm Hg) | 1.22 (1.09–1.36) | .001 | 1.19 (1.04–1.35) | .01 |
| Sleep PR (10 beats per min) | 0.54 (0.43–0.67) | <.001 | 0.54 (0.44–0.68) | <.001 |
| Nondipper PR | 2.60 (1.75–3.82) | <.001 | 2.60 (1.76–3.84) | <.001 |
| Nondipper BP | – | – | 1.17 (0.82–1.68) | .39 |
Abbreviations: BNP, brain natriuretic peptide; BP, blood pressure; CI, confidence interval; PR, pulse rate; SBP, systolic blood pressure.
We speculate that the patients' β‐blocker usage may confound the association between BP and PR dipping pattern with target organ damage; therefore, we analyzed the patients after the exclusion of those taking β‐blockers. The BNP in patients with nondipper PR was higher than that in patients with dipper PR (median BNP 17.4 pg/mL vs 16.7 pg/mL, P=.046). In the multiple linear regression analysis, nondipper PR was independently associated with log‐transformed BNP (β=0.11, P=.001) after adjusting for age, sex, BMI, dyslipidemia, diabetes, systolic BP during sleep, PR during sleep, and nondipper BP (Table S2). The patients' BNP levels gradually increased according to the dipping patterns of BP and PR (median BNP: dipper BP and dipper PR, 14.3; dipper BP and nondipper PR, 16.4; nondipper BP and dipper PR, 22.2; nondipper BP and nondipper PR, 25.6 pg/mL; P for trend <.001 [Figure S2]). In women, the LVMI in patients with nondipping PR was higher than in those with dipping PR, but the difference was not significant (mean LVMI: 109.4±27.4 g/m2 vs 103.9±26.7 g/m2, P=.13). In men, the difference was also not significant (P=.56).
We also analyzed BNP and LVMI by quartile analysis of the dipping rate of PR: (awake PR–sleep PR)/awake PR. The highest dipping rate (awake PR–sleep PR)/awake PR group (Q1) was PR >21.1%, the dipping rate of PR in the second group (Q2) ranged from 15.9% to 21.1%, the dipping rate of PR in the third group (Q3) ranged from 10.8% to 15.8%, and the dipping rate of PR in the fourth group (Q4) was ≤10.7%. The BNP in Q4 was significantly higher than that in the other group (Q1–Q3) (median BNP 20.7 vs 18.2, P<.001). The LVMI in Q4 was also significantly higher than that in the other groups (Q1–Q3) (mean LVMI: 115.0±33.3 g/m2 vs 109.9±29.6 g/m2, P=.045).
4. Discussion
In the present study, nondipper PR pattern was independently associated with BNP level. Moreover, nondipper PR was also independently associated with LVMI among women. On the other hand, nondipper PR was not associated with UACR or pulse wave velocity. The present study is the first to show that the nondipping pattern of diurnal PR might be associated with cardiac overload. In the present study, we excluded patients with atrial fibrillation and heart failure (HF) because of the influence of heart rate.
In addition, in a subsample of our patients who were not taking β‐blockers, the nondipper PR was still associated with BNP. We were thus able to clarify the association between abnormal diurnal variations of PR and hypertensive target organ damage in high‐risk Japanese patients from the J‐HOP study, which is much closer to the actual clinical setting.
The nondipper PR pattern was independently associated with BNP in our patient series. BNP is not only a surrogate maker for target organ damage but also a predictor of CV events. In an analysis of patients from the Framingham Offspring Study, Wang and colleagues11 showed that a high BNP level was an independent predictor of CV events or mortality. In a study of a Japanese general population, high BNP was also an independent predictor of congestive HF and mortality.19 The nondipper PR pattern may therefore present a high risk of CV events.
In the present study, the nondipper PR pattern was not only independently associated with BNP in the women but also with LVMI. LVMI has been reported to be a more powerful predictor of CV events than BNP.20 HF with a preserved ejection fraction is more common in women than in men. Women who have HF with a preserved ejection fraction were more likely to be older and hypertensive.21 Therefore, especially among elderly women who have hypertension, nondipper PR assessed by ambulatory BP monitoring would be useful to help predict the risk of HF with a preserved ejection fraction.
The reason for the disagreement in the results for BNP and LVMI is unclear. Nondipper PR might not reflect structural change but rather may indicate an increase in hemodynamic stress in response to LV. In the present study, LVMI was assessed in only a small number of patients, and thus further studies will be needed to clarify the association between nondipper PR and cardiac damage.
The nondipper PR pattern was independently associated with a high BNP level after adjusting for covariates such as nondipper BP in this study. Both dipper BP with nondipper PR and nondipper BP with nondipper PR were associated with high BNP levels. Even among these patients, because patients with nondipper BP and nondipper PR had the highest BNP levels, there might be a high prevalence of potential HF. In our previous study, we observed a significant synergetic interaction of nondipper PR with nondipper BP for CV events.6 These patients might be at an especially high risk for CV events.
In contrast, nondipper PR was not associated with UACR or pulse wave velocity. Nondipper BP is well‐known to be associated with a risk for damage to all target organs (brain, heart, and kidneys) compared with dipper BP.22 In their study, Cuspidi and colleagues23 reported that a nondipper PR pattern was not correlated with any parameter of subclinical organ damage. In our study, a nondipper PR pattern was not correlated with UACR or baPWV, but was associated with BNP. Thus, the present study is the first to show that the nondipping pattern of diurnal PR might be associated with cardiac overload.
The nondipper PR pattern might be explained by a pathology of HF. In patients with potential HF, because of the increased venous return in the supine position, the heart rate might be increased as an acute reaction. Moreover, after 1 to 3 hours in the horizontal position, there is a redistribution of blood volume from the lower extremities and splanchnic beds to the heart. In normal individuals, this has little effect, but in individuals with potential HF, it might cause a decrease in the nocturnal heart rate decline.
Heart rate during sleep is generally lower than during the daytime.24 As with BP, circadian heart rate changes are diminished or lost in conditions with a sympathetic‐parasympathetic imbalance. Some studies have shown that cardiac parasympathetic control might be defective in patients with HF.25, 26 A relationship between the decline of parasympathetic nerve activity and left ventricular diastolic dysfunction has also been described.27 A possible reason for this is that the high BNP level in patients with a nondipper PR might be a reflection of left ventricular diastolic dysfunction. The nondipper PR pattern may thus indicate potential HF. However, an association between elevated sympathetic nerve activity and higher UACRs has been shown.28 This may be one of the reasons why the nondipper PR pattern in treated hypertensive patients is associated with cardiac damage but not renal damage.
A definition of (awake PR–sleep PR)/awake PR <0.1 as the cutoff level for nondipper PR status might be considered somewhat arbitrary. However, we confirmed that BNP was significantly higher in the lowest quartile compared with other quartiles, and LVMI was also significantly higher in the lowest quartile compared with the other quartiles. An adequate cutoff value for nondipper PR should be discussed.
4.1. Study limitations
First, because this was a cross‐sectional study, our present findings do not allow us to determine the causal relationship between BNP levels and nondipper PR. Second, although nondipper PR may closely reflect an autonomic nerve imbalance, we did not assess reliable parameters for autonomic nervous system function. Third, nondipper PR pattern might be influenced by β‐blocker use. However, we obtained the same result after the exclusion of patients who were taking β‐blockers. Finally, the increase of LVMI in women with nondipper PR was observed by post hoc analysis, and this sex difference should be tested in different cohorts. In this study, the lack of an association between nondipper PR and LVMI may have been due to the small number of patients. Thus, further prospective studies will be needed to clarify the association between nondipper PR and LVMI.
5. Conclusions
Nondipper PR pattern was associated with BNP level, but it was not associated with UACR or baPWV in high‐risk Japanese patients. Particularly in women, nondipper PR pattern was also associated with LVMI. The association between nondipper PR and cardiac overload may explain the subsequent CV events.
Conflict of interest
K. Kario has received research grants from Teijin Pharma, Ltd.; Novartis Pharma K.K.; Takeda Pharmaceutical Co., Ltd.; Omron Healthcare Co., Ltd.; and Fukuda Denshi, and honoraria from Mochida Pharmaceutical Co., Ltd.; Takeda Pharmaceutical Co., Ltd.; Daiichi Sankyo Co., Ltd.; and Sumitomo Dainippon Pharma Co., Ltd. The other authors have no conflicts of interest to report.
Supporting information
Oba Y, Kabutoya T, Hoshide S, Eguchi K, Kario K. Association between nondipper pulse rate and measures of cardiac overload: The J‐HOP Study. J Clin Hypertens. 2017;19:402–409. doi: 10.1111/jch.12975
Funding information
This study was financially supported, in part, by a grant from the 21st Century Center of Excellence Project run by Japan's Ministry of Education, Culture, Sports, Science and Technology (to K. Kario); a grant from the Foundation for Development of the Community (Tochigi, Japan); a grant from Omron Healthcare Co., Ltd; a Grant‐in‐Aid for Scientific Research (B) (21390247) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, 2009 to 2013; and funds from the MEXT‐Supported Program for the Strategic Research Foundation at Private Universities, 2011 to 2015 Cooperative Basic and Clinical Research on Circadian Medicine (S1101022). Funding sponsors had no role in designing or conducting this study; in the collection, management, analysis, or interpretation of the data; in the preparation of the article; or in the decision to submit the article for publication.
References
- 1. Fagard RH, Thijs L, Staessen JA, Clement DL, De Buyzere M, De Bacquer DA. Night‐day blood pressure ratio and dipping pattern as predictors of death and cardiovascular events in hypertension. J Hum Hypertens. 2009;23:645–653. [DOI] [PubMed] [Google Scholar]
- 2. Verdecchia P, Porcellati C, Schillaci G, et al. Ambulatory blood pressure. An independent predictor of prognosis in essential hypertension. Hypertension. 1994;24:793–801. [DOI] [PubMed] [Google Scholar]
- 3. Ingelsson E, Björklund‐Bodegård K, Lind L, Arnlöv J, Sundström J. Diurnal blood pressure pattern and risk of congestive heart failure. JAMA. 2006;295:2859–2866. [DOI] [PubMed] [Google Scholar]
- 4. Ben‐Dov IZ, Kark JD, Ben‐Ishay D, Mekler J, Ben‐Arie L, Bursztyn M. Blunted heart rate dip during sleep and all‐cause mortality. Arch Intern Med. 2007;167:2116–2121. [DOI] [PubMed] [Google Scholar]
- 5. Eguchi K, Hoshide S, Ishikawa J, et al. Nocturnal nondipping of heart rate predicts cardiovascular events in hypertensive patients. J Hypertens. 2009;27:2265–2270. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Kabutoya T, Hoshide S, Ishikawa J, Eguchi K, Shimada K, Kario K. Effect of pulse rate and blood pressure dipping status on the risk of stroke and cardiovascular disease in Japanese hypertensive patients. Am J Hypertens. 2010;23:749–755. [DOI] [PubMed] [Google Scholar]
- 7. Hoshide S, Kario K, Hoshide Y, et al. Associations between nondipping of nocturnal blood pressure decrease and cardiovascular target organ damage in strictly selected community‐dwelling normotensives. Am J Hypertens. 2003;16:434–438. [DOI] [PubMed] [Google Scholar]
- 8. Kario K, Matsuo T, Kobayashi H, Imiya M, Matsuo M, Shimada K. Nocturnal fall of blood pressure and silent cerebrovascular damage in elderly hypertensive patients. Advanced silent cerebrovascular damage in extreme dippers. Hypertension. 1996;27:130–135. [DOI] [PubMed] [Google Scholar]
- 9. Munakata M, Konno S, Miura Y, Yoshinaga K, J‐TOPP Study Group . Prognostic significance of the brachial‐ankle pulse wave velocity in patients with essential hypertension: final results of the J‐TOPP study. Hypertens Res. 2012;35:839–842. [DOI] [PubMed] [Google Scholar]
- 10. Pikula A, Beiser AS, DeCarli C, et al. Multiple biomarkers and risk of clinical and subclinical vascular brain injury: the Framingham Offspring Study. Circulation. 2012;125:2100–2107. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Wang TJ, Larson MG, Levy D, et al. Plasma natriuretic peptide levels and the risk of cardiovascular events and death. N Engl J Med. 2004;350:655–663. [DOI] [PubMed] [Google Scholar]
- 12. Roughton RW, Frampton CM, Yandle TG, Espiner EA, Nicholls MG, Richards AM. Treatment of heart failure guided by plasma aminoterminal brain natriuretic peptide (N‐BNP) concentrations. Lancet. 2000;355:1126–1130. [DOI] [PubMed] [Google Scholar]
- 13. Ishikawa J, Haimoto H, Hoshide S, et al. An increased visceralsubcutaneous adipose tissue ratio is associated with difficult‐to‐treat hypertension in men. J Hypertens. 2010;28:1340–1346. [DOI] [PubMed] [Google Scholar]
- 14. Eguchi K, Kuruvilla S, Ogedegbe G, Gerin W, Schwartz JE, Pickering TG. What is the optimal interval between successive home blood pressure readings using an automated oscillometric device? J Hypertens. 2009;27:1172–1177. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15. Ogihara T, Kikuchi K, Matsuoka H, et al. The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2009). Hypertens Res. 2009;32:3–107. [PubMed] [Google Scholar]
- 16. Lang RM, Bierig M, Devereux RB, et al. Recommendations for chamber quantification. Eur J Echocardiogr. 2006;7:79–108. [DOI] [PubMed] [Google Scholar]
- 17. Hoshide S, Yano Y, Haimoto H, et al. Morning and evening home blood pressure and risks of incident stroke and coronary artery disease in the Japanese general practice population: the Japan morning surge‐home blood pressure study. Hypertension. 2016;68:54–61. [DOI] [PubMed] [Google Scholar]
- 18. Ponikowski Piotr, Voors Adriaan A, Anker Stefan D, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2016;37:2129–2200. [DOI] [PubMed] [Google Scholar]
- 19. Nakamura M, Tanaka F, Onoda T, et al. Gender‐specific risk stratification with plasma B‐type natriuretic peptide for future onset of congestive heart failure and mortality in the Japanese general population. Int J Cardiol. 2010;143:124–129. [DOI] [PubMed] [Google Scholar]
- 20. Levy D, Garrison RJ, Savage DD, et al. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med. 1990;322:1561–1566. [DOI] [PubMed] [Google Scholar]
- 21. Zsilinszka R, Shrader P, DeVore AD, et al. Sex differences in the management and outcomes of heart failure with preserved ejection fraction in patients presenting to the emergency department with acute heart failure. J Card Fail. 2016;22:781–788. doi: 10.1016/j.cardfail.2015.12.008. [DOI] [PubMed] [Google Scholar]
- 22. Kario K, Shimada K, Pickering TG. Abnormal nocturnal blood pressure falls in elderly hypertension: clinical significance and determinants. J Cardiovasc Pharmacol. 2003;41:S61–S66. [PubMed] [Google Scholar]
- 23. Cuspidi C, Meani S, Negri F, Valerio C, Sala C, Mancia G. Is blunted heart rate decrease at night associated with prevalent organ damage in essential hypertension? Blood Press Monit. 2011;16:16–21. [DOI] [PubMed] [Google Scholar]
- 24. Verdecchia P, Schillaci G, Borgioni C, et al. Adverse prognostic value of a blunted circadian rhythm of heart rate in essential hypertension. J Hypertens. 1998;16:1335–1343. [DOI] [PubMed] [Google Scholar]
- 25. Arsenos P, Gatzoulis KA, Gialernios T, et al. Elevated nighttime heart rate due to insufficient circadian adaptation detects heart failure patients prone for malignant ventricular arrhythmias. Int J Cardiol. 2014;172:e154–e156. [DOI] [PubMed] [Google Scholar]
- 26. Eckberg DL, Drabinsky M, Braunwald E. Defective cardiac parasympathetic control in patients with heart disease. N Engl J Med. 1971;285:877–883. [DOI] [PubMed] [Google Scholar]
- 27. Arora R, Krummerman A, Vijayaraman P, et al. Heart rate variability and diastolic heart failure. Pacing Clin Electrophysiol. 2004;27:299–303. [DOI] [PubMed] [Google Scholar]
- 28. Mena‐Martín FJ, Martín‐Escudero JC, Simal‐Blanco F, et al. Influence of sympathetic activity on blood pressure and vascular damage evaluated by means of urinary albumin excretion. J Clin Hypertens (Greenwich). 2006;8:619–624. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials