Ryusuke Inoue

Tohoku University, Japan

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Publications (88)255.28 Total impact

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    ABSTRACT: In cross-sectional studies, the aldosterone-to-renin ratio (ARR) has been reported to be associated with hypertension under conditions of higher sodium intake. The objective of this prospective study was to investigate the association between ARR and the development of hypertension in community residents stratified by dietary sodium intake.
    American journal of hypertension. 06/2014;
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    ABSTRACT: Tissue damage by oxidative stress is a key pathogenic mechanism in various diseases, including AKI and CKD. Thus, early detection of oxidative tissue damage is important. Using a tRNA-specific modified nucleoside 1-methyladenosine (m1A) antibody, we show that oxidative stress induces a direct conformational change in tRNA structure that promotes subsequent tRNA fragmentation and occurs much earlier than DNA damage. In various models of tissue damage (ischemic reperfusion, toxic injury, and irradiation), the levels of circulating tRNA derivatives increased rapidly. In humans, the levels of circulating tRNA derivatives also increased under conditions of acute renal ischemia, even before levels of other known tissue damage markers increased. Notably, the level of circulating free m1A correlated with mortality in the general population (n=1033) over a mean follow-up of 6.7 years. Compared with healthy controls, patients with CKD had higher levels of circulating free m1A, which were reduced by treatment with pitavastatin (2 mg/d; n=29). Therefore, tRNA damage reflects early oxidative stress damage, and detection of tRNA damage may be a useful tool for identifying organ damage and forming a clinical prognosis.
    Journal of the American Society of Nephrology 05/2014; · 8.99 Impact Factor
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    ABSTRACT: Although an association between high blood pressure and cognitive decline has been reported, no studies have investigated the association between home blood pressure and cognitive decline. Home blood pressure measurements can also provide day-to-day blood pressure variability calculated as the within-participant SD. The objectives of this prospective study were to clarify whether home blood pressure has a stronger predictive power for cognitive decline than conventional blood pressure and to compare the predictive power of the averaged home blood pressure with day-to-day home blood pressure variability for cognitive decline. Of 485 participants (mean age, 63 years) who did not have cognitive decline (defined as Mini-Mental State Examination score, <24) initially, 46 developed cognitive decline after a median follow-up of 7.8 years. Each 1-SD increase in the home systolic blood pressure value showed a significant association with cognitive decline (odds ratio, 1.48; P=0.03). However, conventional systolic blood pressure was not significantly associated with cognitive decline (odds ratio, 1.24; P=0.2). The day-to-day variability in systolic blood pressure was significantly associated with cognitive decline after including home systolic blood pressure in the same model (odds ratio, 1.51; P=0.02), whereas the odds ratio of home systolic blood pressure remained positive, but it was not significant. Home blood pressure measurements can be useful for predicting future cognitive decline because they can provide information not only on blood pressure values but also on day-to-day blood pressure variability.
    Hypertension 03/2014; · 6.87 Impact Factor
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    ABSTRACT: Abstract Based on ambulatory blood pressure (BP) monitoring, the aldosterone-to-renin ratio (ARR) has been reported to be associated with a diminished nocturnal decline in BP, generally referred to as a "non-dipping" pattern. The objective of this cross-sectional study was to investigate the association between ARR and the non-dipping pattern based on home BP measurements. This study included 177 participants ≥55 years from the general population of Ohasama (mean age: 67.2 years; 74.6% women); no patient was receiving antihypertensive treatment. The median plasma renin activity (PRA), plasma aldosterone concentration (PAC) and ARR were 0.8 ng/mL/h, 8.1 ng/dL and 9.7 ng/dL per ng/mL/h, respectively. Each 1 SD increase in log-transformed (ln) ARR was significantly associated with the prevalence of the non-dipping pattern after adjustments for possible confounding factors including home morning systolic BP (odds ratio, 1.45; p = 0.049). However, no significant associations of PRA or PAC with the non-dipping pattern were observed (p ≥ 0.2). When participants were divided into four groups according to median levels of home morning and night-time systolic BPs, the group with a higher home morning systolic BP (≥128.4 mmHg) with a higher home night-time systolic BP (≥114.4 mmHg) had the greatest ARR levels (ANCOVA p = 0.01). These results support the hypothesis that relative aldosterone excess may be related to a non-dipping pattern in a general population and suggest that a non-dipping pattern can be accurately observed by home BP measurements.
    Clinical and Experimental Hypertension 01/2014; 36(2):108-14. · 1.28 Impact Factor
  • Masaharu Nakayama, Ryusuke Inoue
    Studies in health technology and informatics 01/2014; 205:1257.
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    ABSTRACT: Background: Patients with mild-to-moderate essential hypertension in the HOMED-BP trial were randomly allocated to first-line treatment with a calcium channel blocker (CCB), angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB). Methods: We recruited 265 (93 for CCB, 71 for ACEI and 101 for ARB) patients who completed the genomic study. Home blood pressure was measured for 5 days off-treatment before randomization and for 5 days after 2-4 weeks of randomized drug treatment. Genotyping was performed by 500K DNA microarray chips. The blood pressure responses to the three drugs were analyzed separately as a quantitative trait. For replication of SNPs with p < 10(-4), we used the multicenter GEANE study, in which patients were randomized to valsartan or amlodipine. Results: SNPs in PICALM, TANC2, NUMA1 and APCDD1 were found to be associated with CCB responses and those in ABCC9 and YIPF1 were found to be associated with ARB response with replication. Conclusion: Our approach, the first based on high-fidelity phenotyping by home blood pressure measurement, might be a step in moving towards the personalized treatment of hypertension. Original submitted 29 April 2013; Revision submitted 14 August 2013.
    Pharmacogenomics 11/2013; 14(14):1709-21. · 3.86 Impact Factor
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    ABSTRACT: Ambulatory blood pressure (BP) is reportedly associated with target organ damage. However, whether ambulatory BP carries prognostic significance for the development of chronic kidney disease (CKD) has not been confirmed. We measured ambulatory BP in 843 participants without CKD at baseline from a general Japanese population and examined the incidence of CKD defined as positive proteinuria or an estimated glomerular filtration rate (eGFR) less than 60 ml/min per 1.73 m at health checks. The association between baseline ambulatory BP and CKD incidence was examined using the Cox proportional hazard regression model adjusted for sex, age, BMI, habitual smoking, habitual alcohol consumption, diabetes mellitus, hypercholesterolemia, a history of cardiovascular disease, antihypertensive medication, eGFR at baseline, the number of follow-up examinations, and the year of the baseline examination. The mean age of the participants averaged 62.9 ± 8.1 years, 71.3% were women and 23.7% were under antihypertensive medication. During a median follow-up of 8.3 years, 220 participants developed CKD events. The adjusted hazard ratios for CKD in a 1-standard deviation increase in daytime and night-time SBP were 1.13 [95% confidence interval (CI) 0.97-1.30] and 1.21 (95% CI 1.04-1.39), respectively. When night-time and daytime BP was mutually adjusted into the same model, only night-time BP persisted as an independent predictor of CKD. Night-time BP is a better predictor of CKD development than daytime BP in the general population. Ambulatory BP measurement is considered useful for evaluating the risk of progression to CKD.
    Journal of Hypertension 09/2013; · 4.22 Impact Factor
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    ABSTRACT: Blood pressure variability based on office measurement predicts outcome in selected patients. We explored whether novel indices of blood pressure variability derived from the self-measured home blood pressure predicted outcome in a general population. We monitored mortality and stroke in 2421 Ohasama residents (Iwate Prefecture, Japan). At enrollment (1988-1995), participants (mean age, 58.6 years; 60.9% women; 27.1% treated) measured their blood pressure at home, using an oscillometric device. In multivariable-adjusted Cox models, we assessed the independent predictive value of the within-subject mean systolic blood pressure (SBP) and corresponding variability as estimated by variability independent of the mean, difference between maximum and minimum blood pressure, and average real variability. Over 12.0 years (median), 412 participants died, 139 of cardiovascular causes, and 223 had a stroke. In models including morning SBP, variability independent of the mean and average real variability (median, 26 readings) predicted total and cardiovascular mortality in all of the participants (P≤0.044); variability independent of the mean predicted cardiovascular mortality in treated (P=0.014) but not in untreated (P=0.23) participants; and morning maximum and minimum blood pressure did not predict any end point (P≥0.085). In models already including evening SBP, only variability independent of the mean predicted cardiovascular mortality in all and in untreated participants (P≤0.046). The R(2) statistics, a measure for the incremental risk explained by adding blood pressure variability to models already including SBP and covariables, ranged from <0.01% to 0.88%. In a general population, new indices of blood pressure variability derived from home blood pressure did not incrementally predict outcome over and beyond mean SBP.
    Hypertension 11/2012; · 6.87 Impact Factor
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    ABSTRACT: This study investigated the association between breastfeeding and both self-measured home blood pressure (HBP) and conventional blood pressure (CBP) in 7-year-old Japanese children. We obtained data pertaining to breastfeeding and blood pressure for 377 mother-offspring pairs from the Tohoku Study of Child Development, which is a prospective birth cohort study. Information on breastfeeding and other factors were obtained from parental questionnaires during the follow-up period. Based on the duration of breastfeeding as a major source of nutrition, mother-offspring pairs were divided into short-term (mean, 5.1 months) and long-term (mean, 11.3 months) breastfeeding groups. At the age of 7 years (84.4±1.8 months), each child's blood pressure was measured. The HBP in the long-term breastfeeding (LBF) group (92.8 mm Hg systolic/55.0 mm Hg diastolic) was significantly lower (P=0.006/0.03) than in the short-term breastfeeding group (94.5/56.3 mm Hg); however, there were no significant differences in the CBP measurements between the short- and LBF groups. Using multiple regression analysis, the duration of breastfeeding (greater than 8 months) was more strongly associated with HBP (P=0.01/0.06) than with CBP (P=0.4/0.8). Furthermore, the adjusted R-squared values for HBP (0.25/0.12) tended to be higher than those for CBP (0.07/0.04). These findings were independent of the birth weight. In conclusion, breastfeeding has a protective effect against elevated blood pressure even in young children, and subtle, but important, differences were precisely detected by self-measurements performed at home.Hypertension Research advance online publication, 6 September 2012; doi:10.1038/hr.2012.128.
    Hypertension Research 09/2012; · 2.79 Impact Factor
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    ABSTRACT: Hypertension guidelines recommend blood pressure self-measurement at home (HBP), but no previous trial has assessed cardiovascular outcomes in hypertensive patients treated according to HBP. The multicenter Hypertension Objective Treatment Based on Measurement by Electrical Devices of Blood Pressure (HOMED-BP; 2001-2010) trial involved 3518 patients (50% women; mean age 59.6 years) with an untreated systolic/diastolic HBP of 135-179/85-119 mm Hg. In a 2 × 3 design, patients were randomized to usual control (125-134/80-84 mm Hg (UC)) vs. tight control (<125/<80 mm Hg (TC)) of HBP and to initiation of drug treatment with angiotensin converting enzyme inhibitors, angiotensin receptor blockers or calcium channel blockers. During follow-up, a computer algorithm automatically generated treatment recommendations based on HBP. At the last follow-up (median 5.3 years), TC patients used more antihypertensive drugs than UC patients (1.82 vs. 1.74 defined daily doses, P=0.045) and had a greater HBP reduction (21.3/13.1 mm Hg vs. 22.7/13.9 mm Hg, P=0.018/0.020), but they less frequently achieved the lower HBP targets (37.4 vs. 63.5%, P<0.0001). The primary end point, cardiovascular death plus stroke and myocardial infarction, occurred in 25 UC and 26 TC patients (hazard ratio, 1.02; 95% confidence interval, 0.59-1.77; P=0.94). Rates were similar (P0.13) in the three drug groups. In all patients combined, the risk of the primary end point independently increased by 41% (6-89%; P=0.019) and 47% (15-87%; P=0.0020) for a 1-s.d. increase in baseline (12.5 mm Hg) and follow-up (13.2 mm Hg) systolic HBP. The 5-year risk was minimal (1%) if on-treatment systolic HBP was 131.6 mm Hg or less. HOMED-BP proved the feasibility of adjusting antihypertensive drug treatment based on HBP and suggests that a systolic HBP level of 130 mm Hg should be an achievable and safe target.Hypertension Research advance online publication, 16 August 2012; doi:10.1038/hr.2012.125.
    Hypertension Research 08/2012; · 2.79 Impact Factor
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    ABSTRACT: Clinicians often need access to electronic information resources that answer questions that occur in daily clinical practice. This information generally comes from publicly available resources. However, clinicians also need knowledge on institution-specific information (e.g., institution-specific guidelines, choice of drug, choice of laboratory test, information on adverse events, and advice from professional colleagues). This information needs to be available in real time. This study characterizes these needs in order to build a prototype hospital information system (HIS) that can help clinicians get timely answers to questions. We previously designed medical knowledge units called Medical Cells (MCs). We developed a portal server of MCs that can create and store medical information such as institution-specific information. We then developed a prototype HIS that embeds MCs as links (MCLink); these links are based on specific terms (e.g., drug, laboratory test, and disease). This prototype HIS presents clinicians with institution-specific information. The HIS clients (e.g., clinicians, nurses, pharmacists, and laboratory technicians) can also create an MCLink in the HIS using the portal server in the hospital. The prototype HIS allowed efficient sharing and use of institution-specific information to clinicians at the point of care. This study included institution-specific information resources and advice from professional colleagues, both of which might have an important role in supporting good clinical decision making.
    Journal of Medical Systems 08/2012; 37(4):9956. · 1.78 Impact Factor
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    ABSTRACT: Hypertension and smoking independently contribute to the risk of stroke. Our objective was to investigate home blood pressure (HBP) levels, day-by-day BP variability, and smoking in the prediction of stroke in Japanese men. In this study, 902 men (mean age, 58.6 years) without a past history of stroke were evaluated. HBP was measured once every morning for 4 weeks. Day-by-day BP variability was defined as within-subject standard deviations (SD) of HBP. Smoking history was obtained from a standardized questionnaire. Hazard ratios (HRs) for stroke were examined by Cox regression model, with adjustment for possible confounders. During 13.1 years (median) of follow-up, 89 cerebral infarctions, 28 intracranial hemorrhages, and six other strokes occurred. Systolic HBP levels (HR = 1.59 per 14.6 mm Hg increase, P < 0.0001) and variability (HR = 1.26 per 3.1 mm Hg increase, P = 0.03) of +1 between-subject SD were significantly associated with cerebral infarction. The relationship between HBP and cerebral infarction differed with smoking status (interaction P = 0.021 and 0.017 for systolic level and variability, respectively). In analyses stratified according to smoking, systolic level (HR = 1.78, P < 0.0001) and variability (HR = 1.38, P = 0.006) were significantly associated with cerebral infarction in ever smokers (N = 511), but not in never smokers (N = 391; P ≥ 0.6 for both). No significant association was found between smoking and the risk of intracranial hemorrhage. In ever smokers, both HBP levels and variability are significantly associated with the risk of cerebral infarction. Our findings further validate the benefit of smoking cessation in preventing cardiovascular disease (CVD), especially cerebral infarction.
    American Journal of Hypertension 06/2012; 25(8):883-91. · 3.67 Impact Factor
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    ABSTRACT: The aldosterone-to-renin ratio (ARR) is used to screen for primary aldosteronism and could be an index for salt sensitivity. The association between ARR and the development of chronic kidney disease (CKD) is completely unknown. A longitudinal observational study involving 689 participants from a general Japanese population (mean age 58.2 years; 68.5% women) who did not have CKD and were not receiving antihypertensive medication at baseline was conducted. The estimated glomerular filtration rate (eGFR) was calculated from serum creatinine levels, and CKD was defined as eGFR less than 60 ml/min per 1.73 m(2) and/or dipstick-positive proteinuria. The associations of baseline plasma renin activity (PRA), plasma aldosterone concentration, and ARR with the development of CKD were examined using Cox proportional hazard regression analysis adjusted for sex, age, BMI, smoking, drinking, history of hypercholesterolemia, diabetes mellitus, and cardiovascular disease, SBP, and baseline eGFR. During a mean 9.1-year follow-up, 118 participants developed CKD. A 1 standard deviation increment in the natural log-transformed (ln) ARR was positively associated with the incidence of CKD (hazard ratio 1.29, P = 0.012). LnPRA showed an inverse association (hazard ratio 0.76, P = 0.007). Meanwhile, plasma aldosterone concentration was not associated with CKD. Individuals who developed CKD had significantly lower baseline PRA (0.97 vs. 1.14 ng/ml per h; P = 0.03) and higher baseline ARR levels [66.6 vs. 56.8 (pg/ml)/(ng/ml per h); P = 0.02] than those who did not. Lower PRA and higher ARR were associated with the development of CKD in a general population, suggesting that they are independent predictors of CKD.
    Journal of Hypertension 05/2012; 30(8):1632-8. · 4.22 Impact Factor
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    ABSTRACT: The hypotensive effect and the time to attain the maximum antihypertensive effect (stabilization time) of losartan/hydrochlorothiazide (HCTZ) combination therapy and therapy with a maximal dose of angiotensin II receptor blockers (ARBs) in patients who failed to achieve adequate blood pressure (BP) control on a medium-dose of ARBs were compared by analyzing exponential decay functions using daily serial morning home BP measurements. Essential hypertensive patients treated with a medium dose of ARB, in whom a target home SBP (135 mmHg) was not achieved, were randomized into two groups: a combination group (n = 110) and a maximal-dose ARB group (n = 111). The combination therapy provided additional reduction of 5.2 mmHg [95% confidence interval (CI) 1.8 to 8.5 mmHg, P = 0.003] in home SBP over the maximal-dose ARB therapy in 8 weeks after randomization. A greater reduction in the home SBP values was seen in the combination group than in the maximal-dose ARB group from the second day after randomization on the basis of a linear mixed model. The maximum antihypertensive effect and stabilization time for home SBP were 10.9 ± 5.0 mmHg and 7.3 ± 29.7 days, respectively, in the combination group, whereas the corresponding values in the maximal-dose ARB group were 7.9 ± 2.6  mmHg and 122.3 ± 42.7 days, respectively, on the basis of a nonlinear mixed model. Changing from a medium dose of ARB monotherapy to combination therapy was more effective in the reduction of home SBP and achieved goal BP more rapidly than increasing the ARB dose. Home BP measurement is a useful tool for characterizing the antihypertensive effects of drugs.
    Journal of Hypertension 05/2012; 30(7):1478-86. · 4.22 Impact Factor
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    ABSTRACT: Hypertension is associated with an increased risk of development of chronic kidney disease (CKD). However, it is unclear whether pre-hypertension is related to the incidence of CKD. The incidence of CKD defined as positive proteinuria or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m(2) was examined in 2150 inhabitants without pre-existing CKD from the general Japanese population. The association of blood pressure and CKD incidence was examined using a Cox regression model adjusted for age, sex, habitual smoking and drinking, obesity, history of cardiovascular disease, diabetes mellitus or hypercholesterolemia, eGFR at baseline, number of follow-up examinations and year of baseline examination. Participants were categorized according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. Participants were categorized into normotension (n = 586, 27.3 % ), pre-hypertension (n = 815, 37.9 % ), Stage 1 hypertension (n = 386, 18.0 % ) and Stage 2 hypertension (n = 363, 16.9 % ). During a mean follow-up of 6.5 years (14 023 person-years), 461 incidences of CKD were recorded. Compared to normotension, adjusted hazard ratios of CKD were significantly higher for pre-hypertension (1.49, P < 0.003), Stage 1 (1.83, P < 0.001) and Stage 2 (2.55, P < 0.001) hypertension. The population-attributable fraction of pre-hypertension (12.1 % ) was considered to be compatible to that of Stage 1 (8.6 % ) and Stage 2 (14.9 % ) hypertension. This was the first study to demonstrate that pre-hypertension was significantly associated with an increased risk of CKD and was one of the considerable causes of CKD in the general population.
    Nephrology Dialysis Transplantation 04/2012; 27(8):3218-23. · 3.37 Impact Factor
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    ABSTRACT: Aldosterone is thought to have deleterious effects on the cardiovascular system. The aldosterone-to-renin ratio (ARR) is more reproducible than aldosterone levels alone and could be an index for inappropriate aldosterone secretion or activity. We previously reported the apparent relation between ARR and hypertension in subjects with high sodium intake. This prospective study investigated the risk of ARR for a first stroke in a general population stratified by sodium intake. We obtained plasma renin activity (PRA) and plasma aldosterone concentrations (PAC) for 883 participants aged ≥ 35 years not receiving antihypertensive treatment in the general population of Ohasama (mean age: 59.0 ± 11.3 years; 65.6% women). Over a mean of 10.9 follow-up years, 45 strokes occurred. The median PRA, PAC, and ARR were 1.2 ng/ml/h, 6.4 ng/dl, and 5.3 ng/dl per ng/ml/h, respectively. Using Cox regression, we computed hazard ratios adjusted for sex, age, body mass index (BMI), and systolic blood pressure. No association between logARR and stroke was observed in subjects overall. However, in subjects with high sodium intake (≥ median of 4,058 mg/day (salt equivalent, 10.5 g/day)), each 1 s.d. increase in logARR was associated with an increased hazard ratio for stroke (hazard ratio: 1.49, P = 0.04). No significant association was observed in subjects with low sodium intake (P = 0.7). When we repeated all the analyses using logPRA or logPAC, no significant associations were found. These results suggest that high ARR, that is, relative aldosterone excess, is a predictor for stroke under conditions of high sodium intake.
    American Journal of Hypertension 04/2012; 25(7):777-83. · 3.67 Impact Factor
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    ABSTRACT: The target home blood pressure (BP) levels for antihypertensive treatment have not been fully investigated. We estimated home BP values that corresponded to the referential values of casual screening of BP using reduced major axis (RMA) regression for data from untreated and treated individuals in a general population. The study included 2651 participants (778 treated) aged 20 years or above. The relationships between casual BP and home BP were examined using RMA regression to consider measurement errors. We calculated estimated home BP values that corresponded to casual BP using the regression equations. Although casual BPs and home BPs were significantly correlated (all: P<0.0001), the coefficients of determination in multiple regression were higher in untreated individuals than those in treated ones. When RMA regression was applied between casual BP (x) and morning home BP (y), the equations were expressed as y=0.78x+26.55 (systolic BP) and y=0.84x+14.34 (diastolic BP) in treated individuals and y=0.79x+19.29 (systolic BP) and y=0.85x+9.94 (diastolic BP) in untreated ones. The estimated home BPs corresponded to 140/90 mmHg of casual BP: 135.8/89.8 mmHg (morning), 132.2/86.6 mmHg (evening), and 133.9/87.8 mmHg (average) in treated individuals and 129.2/86.7 mmHg (morning), 127.8/84.8 mmHg (evening), and 128.2/85.2 mmHg (average) in untreated individuals. We estimated the referential values of home BP in treated hypertensives using a regression model; however, further intervention studies on home BP are needed to clarify the target treatment goals of home BP.
    Blood pressure monitoring 03/2012; 17(3):89-95. · 1.62 Impact Factor
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    ABSTRACT: To clarify whether the double product (DP) (product of systolic blood pressure (SBP) and pulse rate (PR)) at rest based on home blood pressure (HBP) measurement has prognostic value for mortality. HBP data of 2,583 participants from a Japanese general population (40% men) ≥35 years of age (mean, 59 years) without a history of cardiovascular disease (CVD) were obtained. The prognostic significance for a 1,000 mm Hg × beats/min elevation in the DP was determined by Cox proportional hazard regression analysis. The association between mortality and the DP was compared to that between mortality and the SBP or the PR using the likelihood ratio (LR) test. During a mean follow-up of 12.0 years, 454 total deaths, 153 CVD deaths (85 cardiac diseases, 68 strokes), and 301 non-CVD deaths occurred. The DP was positively and significantly associated with total, CVD, cardiac, stroke, and non-CVD mortality. The LR test showed that the DP was more strongly associated with total mortality, mortality from cardiac disease, and non-CVD than SBP. Similarly, the DP was more strongly associated with total death, CVD death, and death from stroke than PR. The home DP was significantly associated with mortality, and the LR test indicated that the association between the DP and mortality would be stronger than that between mortality and SBP or PR. These findings are preliminary, and further study is needed to confirm the usefulness of the DP in risk stratification.
    American Journal of Hypertension 02/2012; 25(5):568-75. · 3.67 Impact Factor
  • Nephrology Dialysis Transplantation. 01/2012; 27(suppl 2):ii121-ii132.

Publication Stats

885 Citations
255.28 Total Impact Points

Institutions

  • 2006–2014
    • Tohoku University
      • • Graduate School of Pharmaceutical Sciences
      • • Department of Pharmacology
      Japan
  • 2012
    • University of Oxford
      Oxford, England, United Kingdom
    • University of Leuven
      • Division of Hypertension and Cardiovascular
      Louvain, Flanders, Belgium
    • Universitair Ziekenhuis Leuven
      • Department of Cardiovascular diseases
      Leuven, VLG, Belgium
    • Nihon University
      Edo, Tōkyō, Japan
  • 2011
    • National Cancer Center, Japan
      • Research Center for Cancer Prevention and Screening
      Edo, Tōkyō, Japan
  • 2008
    • The Jikei University School of Medicine
      Edo, Tōkyō, Japan
    • Shiga University of Medical Science
      • Department of Health Science
      Ōtu, Shiga, Japan
  • 2007–2008
    • Tohoku Pharmaceutical University
      Japan