Ryusuke Inoue

Tohoku University, Sendai-shi, Miyagi, Japan

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Publications (101)296.37 Total impact

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    ABSTRACT: Background and purpose: Functional capacity is a predictor, as well as a consequence, of stroke. However, little research has been done to examine whether higher-level functional capacity above basic activities of daily living is a predictor of stroke. Methods: We followed 1493 Japanese community-dwelling adults aged ≥60 years (mean age, 70.1 years) who were independent in basic activities of daily living and had no history of stroke. Baseline data were collected using a self-administered questionnaire. Higher-level functional capacity was measured using the total score and 3 subscales (instrumental activities of daily living, intellectual activity, and social role) derived from the Tokyo Metropolitan Institute of Gerontology Index of Competence. Adjusted hazard ratios and 95% confidence intervals were calculated by the Cox proportional hazards model. Results: During a mean follow-up of 10.4 years, 191 participants developed a first stroke. Impaired higher-level functional capacity based on total score of the Tokyo Metropolitan Institute of Gerontology Index of Competence was significantly associated with stroke (hazard ratio, 1.64; 95% confidence interval, 1.15-2.33). Among the 3 subscales, only intellectual activity was significantly associated with stroke (hazard ratio, 1.64; 95% confidence interval, 1.21-2.22). Social role was significantly associated with stroke only among those aged ≥75 years (hazard ratio, 1.78; 95% confidence interval, 1.07-2.98). Conclusions: Impaired higher-level functional capacity, especially in the domain of intellectual activity, was a predictor of stroke, even among community-dwelling older adults with independent basic activities of daily living at baseline. Monitoring of higher-level functional capacity might be useful to detect those at higher risk of developing stroke in the future.
    No preview · Article · Jan 2016 · Stroke
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    ABSTRACT: Japan has often been viewed as an Asian country that possesses a genetically homogenous community. The basis for partitioning the country into prefectures has largely been geographical, although cultural and linguistic differences still exist between some of the districts/prefectures, especially between Okinawa and the mainland prefectures. The Major Histocompatibility Complex (MHC) region has consistently emerged as the most polymorphic region in the human genome, harbouring numerous biologically important variants; nevertheless the presence of population-specific long haplotypes hinders the imputation of SNPs and classical HLA alleles. Here, we examined the extent of genetic variation at the MHC between eight Japanese populations sampled from Okinawa, and six other prefectures located in or close to the mainland of Japan, specifically focusing at the haplotypes observed within each population, and what the impact of any variation has on imputation. Our results indicated that Okinawa was genetically farther to the mainland Japanese than were Gujarati Indians from Tamil Indians, while the mainland Japanese from six prefectures were more homogeneous than between northern and southern Han Chinese. The distribution of haplotypes across Japan was similar, although imputation was most accurate for Okinawa and several mainland prefectures when population-specific panels were used as reference.
    Preview · Article · Dec 2015 · Scientific Reports
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    ABSTRACT: The prognostic significance of white-coat hypertension (WCHT) is controversial, and different findings on self-measured home measurements and 24-h ambulatory monitoring make identifying WCHT difficult. We examined whether individuals with partially or completely defined WCHT, as well as masked hypertension, as determined by different out-of-office blood pressure measurements, have a distinct long-term stroke risk. We followed 1464 participants (31.8% men; mean age, 60.6±10.8 years) in the general population of Ohasama, Japan, for a median of 17.1 years. A first stroke occurred in 212 subjects. Using sustained normal blood pressure (events/n=61/776) as a reference, adjusted hazard ratios for stroke (95% confidence intervals; events/n) were 1.38 (0.82-2.32; 19/137) for complete WCHT (isolated office hypertension), 2.16 (1.36-3.43; 29/117) for partial WCHT (either home or ambulatory normotension with office hypertension), 2.05 (1.24-3.41; 23/100) for complete masked hypertension (both home and ambulatory hypertension with office normotension), 2.08 (1.37-3.16; 38/180) for partial masked hypertension (either home or ambulatory hypertension with office normotension), and 2.46 (1.61-3.77; 42/154) for sustained hypertension. When partial WCHT and partial masked hypertension groups were further divided into participants only with home hypertension and those only with ambulatory hypertension, all subgroups had a significantly higher stroke risk (adjusted hazard ratio ≥1.84, P≤0.04). In conclusion, impacts of partial WCHT as well as partial masked hypertension for long-term stroke risk were comparable to those of complete masked hypertension or sustained hypertension. We need both home and 24-h ambulatory blood pressure measurements to evaluate stroke risk accurately.
    No preview · Article · Nov 2015 · Hypertension
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    ABSTRACT: We aimed to evaluate the hypotensive effect and the time to attain the maximal antihypertensive effect (stabilization time) of 8 mg candesartan/6.25 mg hydrochlorothiazide (HCTZ) combination therapy (combination regimen) and therapy with an increased candesartan dose (12 mg; maximum dose regimen) using home blood pressure (BP) measurements. A prospective, multicenter, open-label, randomized, comparative trial was conducted. Essential hypertensive patients who failed to achieve adequate BP control (systolic BP (SBP) ⩽135 mm Hg) on 8 mg candesartan alone were randomized to two groups: the combination regimen (n=103) and the maximum dose regimen (n=103). Home morning SBP reduction at 8 weeks after randomization was 11.4±1.3 mm Hg in the combination regimen and 7.8±1.2 mm Hg in the maximum dose regimen. The combination regimen provided additional reduction of 4.0 mm Hg (95% confidence interval (CI): 0.8-7.2 mm Hg, P=0.01) in home morning SBP over the maximum dose regimen at 8 weeks after randomization. The maximal antihypertensive effect and stabilization time for home SBP were 9.4 mm Hg and 37.1 days (P<0.0001), respectively, with the combination regimen. The maximum dose regimen decreased home SBP with a very gentle slope, and estimated maximal effect and estimated stabilization time were not significant (P>0.2). The rate of achieving target BP (home morning SBP <135 mm Hg) was significantly higher with the combination regimen than with the maximum dose regimen (52.4 vs. 30.1%, P=0.002). In conclusion, changing from 8 mg candesartan to combination therapy was more effective in reducing home SBP and achieving goal BP more rapidly than increasing the candesartan dose.Hypertension Research advance online publication, 4 June 2015; doi:10.1038/hr.2015.64.
    No preview · Article · Jun 2015 · Hypertension Research
  • Article: PP.31.20
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    ABSTRACT: Objective: The purpose of the present study was to investigate the multi-year seasonal variation in home blood pressure (HBP) among hypertensive patients who were taking antihypertensive medication by applying model-based mathematical approach. Design and method: Hypertension Objective Treatment Based on Measurement by Electrical Devices of Blood Pressure (HOMED-BP) study was a randomized controlled trial to establish the long-term benefit in clinical practice based on self-measured HBP. In the present analysis, hypertensive patients with 52 or more points of weekly-averaged HBP after 1 year from randomization were chosen from the HOMED-BP database. Morning and the evening HBP were separately evaluated. Weekly-averaged systolic and diastolic HBPs were fitted into the following cosine function using nonlinear mixed effect model: HBP = HBP Variation + Other Effects + Intercept HBP Variation = (BPvar/2)*cos {(2[pi]/Tfreq*(W - Tmax)} where BPvar is the maximum-minimum difference in HBP in one cycle of the cosine curve (mmHg), Tfreq is the time requiring one cycle of HBP variation (week), and Tmax is the time when HBP reached for the maximum point at the first time (week) as constants. W denotes the time (week) and W 1-52 means Jan 1st to Dec 31st in the year when each patient was randomized. Other effects included the 2 terms proportional to the defined daily doses (DDD) and the elapsed time from randomization in the HOMED-BP study. Intercept was a constant showing the reference point of HBP variation. Results: From 3518 patients randomized in the HOMED-BP study, 1647 and 1284 eligible patients were selected for the morning and the evening HBP analysis, respectively, and the all cosine function models converged (p < 0.0001). The systolic/diastolic maximum-minimum differences, BPvar, in the morning HBP were 6.6/2.9 mmHg, and those in the evening were 5.5/2.7 mmHg. The time when HBP reached for the maximum point, Tmax, were within 2.6-3.4 weeks. Conclusions: The cosine-curve models appropriately demonstrated the seasonal variation in HBP with 1-year cycle. The highest HBP can be observed in mid-to-late January. Copyright
    No preview · Article · Jun 2015 · Journal of Hypertension
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    Dataset: pgs.13

    Full-text · Dataset · May 2015
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    ABSTRACT: Rapid increases in life expectancy have led to concurrent increases in the number of elderly people living alone or those forced to change living situations. Previous studies have found that poor dietary intake was common in elderly people living alone. However, there have been few studies about the dietary intake in elderly people living in other situations, particularly those living with family other than a spouse (nonspouse family), which is common in Japan. To examine the differences in dietary intake by different living situations in elderly Japanese people. We analyzed the data of 1542 healthy residents in the town of Ohasama aged 60 years and over who had completed self-administered questionnaires. The dietary intake was measured using a validated 141-item food frequency questionnaire. Multiple regression models with robust (White-corrected) standard errors were individually fitted for nutrients and foods by living situation. In men, although the presence of other family was correlated with significantly lower intake of protein-related foods, e.g., legumes, fish and shellfish, and dairy products, these declines were more serious in men living with nonspouse family. Conversely, in men living alone the intake of fruits and vegetables was significantly lower. In women, lower intakes of fruit and protein-related foods were significantly more common in participants living with nonspouse family than those living with only a spouse. These findings revealed that elderly people living alone as well as those living with family other than a spouse had poor dietary intake, suggesting that strategies to improve food choices and skills for food preparation could promote of healthy eating in elderly Japanese people.
    No preview · Article · Apr 2015 · The Journal of Nutrition Health and Aging
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    ABSTRACT: In addition to day-to-day variability in blood pressure (BP) or heart rate (HR), N-terminal pro B-type natriuretic peptide (NT-proBNP) has been reported to be a predictor of cardiovascular disease. Here, we tested the hypothesis that day-to-day BP or HR variability calculated as the intraindividual standard deviation (SD) of home BP or HR is associated with elevated NT-proBNP in a cross-sectional study. Among 664 participants (mean age, 61.9 years; female, 70.5%) from a general Japanese population without a history of heart disease, 86 (13.0%) had NT-proBNP at least 125 pg/ml. Each 1 SD increase in the SD of home systolic BP (SBP) [odds ratio (OR), 1.82; P < .0001) and in the SD of home HR (OR, 1.44; P = 0.008) were significantly associated with the prevalence of NT-proBNP at least 125 pg/ml after adjustment for possible confounding factors including home SBP and HR. Among the four groups defined by the median SD of home SBP and of home HR, the group with higher SDs in home SBP (≥8.0 mmHg) and HR (≥5.0 bpm) had the greatest OR for the prevalence of NT-proBNP at least 125 pg/ml (OR, 4.80; P = 0007 vs. a reference group with lower SDs of home SBP and HR). These results suggest that day-to-day variability in BP and HR may be associated with target-organ damage or complications, which can lead to an elevated NT-proBNP level. An elevated NT-proBNP level may be involved in the prognostic significance of day-to-day variability in BP or HR.
    No preview · Article · Mar 2015 · Journal of Hypertension
  • Masaharu Nakayama · Ryusuke Inoue

    No preview · Article · Jan 2015 · Studies in health technology and informatics
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    ABSTRACT: Numerous factors that affect functional decline have been identified, and personality traits are considered to be an important factor in functional decline risk. The Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG) was developed to measure three higher-level functional capacities, instrumental activities of daily living, intellectual activity, and social roles, in Japanese elderly, which were previously not assessed adequately with existing scales of functional decline. The objective of this study was to explore the effect of personality traits as predictors of higher-level functional decline over a 7-year follow-up in a rural Japanese community. Data on 676 participants (mean 67.1 years) who were free of functional decline and had completed questionnaires at baseline and 7 years later, were analyzed. Demographic characteristics, lifestyle and personality characteristics were obtained from a self-administered questionnaire at baseline. Higher-level functional decline was examined using the subscales of the TMIG at baseline and at a 7-year follow-up examination. Over the 7-year study period, 21.7% of eligible participants reported decline in higher-level functional capacity. After adjustment for putative confounding factors, the traits that were significant predictors of decline in higher-level functional capacity at the 7-year follow-up had higher psychoticism scores [odds ratio (95% confidence interval) 2.12 (1.23-3.66)] and lower extraversion scores [1.89 (1.01-3.56)]. The personality traits of higher psychoticism and lower extraversion were significantly associated with a risk of future functional decline. A better understanding of these personality traits may help identify of at-risk individuals and could help reduce functional decline in older adults.
    No preview · Article · Oct 2014 · The Tohoku Journal of Experimental Medicine
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    ABSTRACT: Background: 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. Methods: From the general population of Ohasama, we obtained plasma renin activity (PRA) and plasma aldosterone concentrations (PACs) for 608 participants (mean age = 57.6 years; 71.4% women) without hypertension at baseline. Using the Cox model, we computed the adjusted hazard ratio (HR) of natural log-transformed ARR (lnARR) for the development of hypertension, defined as blood pressure ≥140/90mm Hg or start of treatment with antihypertensive drugs during follow-up. Results: During a mean follow-up of 6.8 years, 298 participants developed hypertension. The median PRA, PAC, and ARR were 1.2ng/ml/hour, 6.6ng/dl, and 5.5ng/dl per ng/ml/hour, respectively. Each 1 SD increase in lnARR was associated with an increased risk for the development of hypertension in participants overall (HR = 1.18; P = 0.007). In participants with higher sodium intake (median ≥4,102mg/day), a significant association of lnARR with hypertension remained (HR = 1.25; P = 0.009), whereas no significant association was observed in participants with lower sodium intake (P = 0.18). Participants who developed hypertension had significantly lower PRA than those who did not (P = 0.003), despite no differences in PAC (P = 0.91). Conclusions: These results raise the hypothesis that relative aldosterone excess may have a deleterious effect on the development of hypertension by contributing to salt/volume-related hypertension.
    Preview · Article · Jun 2014 · American Journal of Hypertension
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    Full-text · Dataset · May 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.
    Full-text · Article · May 2014 · Journal of the American Society of Nephrology
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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.
    No preview · Article · Apr 2014 · Clinical and Experimental Hypertension
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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.
    Preview · Article · Mar 2014 · Hypertension
  • Masaharu Nakayama · Ryusuke Inoue

    No preview · Article · Jan 2014 · Studies in health technology and informatics
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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.
    Full-text · Article · Nov 2013 · Pharmacogenomics
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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.
    No preview · Article · Sep 2013 · Journal of Hypertension
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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.
    Full-text · Article · Nov 2012 · Hypertension
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    ABSTRACT: Objective: Few studies described the home blood pressure (HBP) in young children. Using intrafamilial correlations of blood pressure as research focus, we assessed the feasibility of HBP monitoring in this age group. Methods: We enrolled 382 mothers (mean age 38.8 years) and singletons (7.0 years) in theTohoku Study of Child Development.We measured their conventional blood pressure (CBP; single reading) at an examination centre. Participants monitored HBP in the morning. We used the OMRON HEM-70801C for CBP and HBP measurement. In a separate group of 84 children (mean age 7.7 years), we compared blood pressure readings obtained by the OMRON monitor and the Dinamap Pro 100, a device approved by FDA for use in children. We used correlation coefficients as measure of intrafamilial aggregation, while accounting for the mothers' age, body mass index, heart rate and smoking and drinking habits and the children's age, height, and heart rate. Results: Mother-offspring correlations were closer (P < or = 0.003) for HBP than CBP for systolic pressure [0.28 (P < 0.0001) vs 0.06 (P = 0.26)] and diastolic pressure [0.28 (P < 0.0001) vs 0.02 (P = 0.65)].The between-device differences (OMRON minus Dinamap) averaged 7.8 +/- 6.0 mmHg systolic and 5.8 +/- 5.5 mmHg diastolic. Conclusions: HBP monitoring is an easily applicable method to assess intrafamilial blood pressure aggregation in young children and outperforms CBP. Validation protocols for HBP devices in young children need revision, because the Korotkoff method is not practicable at this age and there is no agreed alternative reference method.
    No preview · Article · Sep 2012 · Acta cardiologica