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Biomedical subjects

M Kikuya

Publications and source records attributed to M Kikuya.

17 recordsLinked to original sources
PubMed2001

Haplotypes of aldosterone synthase (CYP11B2) gene in the general population of Japan: the Ohasama study.

Since the identification of a chimeric aldosterone synthase which induces mendelian hypertension, polymorphisms in aldosterone synthase (CYP11B2) has been one of major targets for molecular analyses in association with hypertension. To date, four polymorphic variants of CYP11B2, -344T/C at promoter region, a gene conversion in intron 2, 2713A/G (in exon 3) which converts from Lys to Arg at codon 173 (K173R), and 4986T/C (in exon7) which converts from Val to Ala at codon 386 (V386A), have been identified in Caucasian population. Then, linkage disequilibrium between -344T/C polymorphism and a gene conversion in intron 2 or K173R mutation has been described, suggesting the presence of genetic haplotypes in Caucasians. Since the presence of a gene conversion in intron 2 or V386A mutation was still unknown in the Japanese population, all these polymorphisms were examined together to determine the CYP11B2 haplotypes of Japanese, using DNA samples from 1290 participants of the Ohasama study, who represent the general population of a rural community of northern Japan. Molecular analyses demon- strated the presence of a gene conversion of intron 2, but the absence of V386A mutation in Japanese population. The complete linkage disequilibrium between -344T/C polymorphism and K173R mutation was noted. Although -344T allele was linked either with a gene conversion in intron 2 or with normal intron 2, -344C allele was completely linked with normal intron 2. These results indicate the presence of 3 allelic haplotypes of CYP11B2, -344C with normal intron 2 and 173R, -344T with normal intron 2 and 173K, and -344T with converted intron 2 and 173K, in the general Japanese population. The frequency (total 1.0) was 0.35, 0.53, and 0.12, respectively. The presence of allelic haplotypes is considered to be an additional genetic information to individual polymorphism of CYP11B2 to determine the linkage between CYP11B2 polymorphisms and hypertension.

Adult↗
PubMed2001

Factors affecting the difference between screening and home blood pressure measurements: the Ohasama Study.

OBJECTIVE: To establish the factors affecting the difference between screening and home blood pressure measurements. DESIGN: A cross-sectional study. SETTING: General population in a rural Japanese community, Ohasama, Japan. PARTICIPANTS: There were 1,789 community-based subjects aged > or =40 years, for whom blood pressure was measured at screening site (screening blood pressure) and at home (home blood pressure). RESULTS: Multiple stepwise regression analysis of all subjects demonstrated that screening pulse pressure was positively associated with the difference between screening and home blood pressure measurements for systolic blood pressure. Age, the use of antihypertensive medication, and smoking status were negatively associated with the difference between measurements of both systolic and diastolic blood pressure. CONCLUSION: We have demonstrated that age, smoking, antihypertensive medication, and screening pulse pressure are independent predictors of the magnitude of the difference between screening and home blood pressure measurements, suggesting that the necessity to consider these factors, for the detection of the subjects who may be inappropriately treated or misjudged following screening blood pressure measurements.

Adult↗
PubMed2001

Usefulness of home blood pressure measurements in assessing the effect of treatment in a single-blind placebo-controlled open trial.

OBJECTIVES: Reproducibility of home blood pressure measurements (HBP), and the placebo effect on HBP, were examined to establish the number of subjects required in order to observe a significant antihypertensive effect of a drug for a comparative study between placebo and active treatment. METHODS: Reproducibility of HBP (n = 172 for systolic blood pressure and n = 137 for diastolic blood pressure) and the placebo effect on HBP (n = 35 for systolic and n = 42 for diastolic blood pressure) were examined using a semi-automatic electronic device on untreated hypertensive subjects during 21 consecutive days of measurements. From these two studies, the number of subjects required in order to observe a significant antihypertensive drug effect was assessed. In both studies, measurements from the first 3 days were excluded from the analysis. RESULTS: Reproducibility, defined as the difference between the initial 5 day average (days 4-8) and the last 5 day average (days 17-21) was -1.9 +/- 7.0/-1.4 +/- 4.8 mmHg (mean +/- SD), indicating high reproducibility with a minimal regression to the mean effect. A placebo was administered after the 8 day run-in period. The difference between the initial 5 day average (days 4-8) and the last 5 day average (days 17-21) was compared. The mean difference was 1.1 +/- 6.2/0.2 +/- 5.7 mmHg, suggesting that there was a minimal, if any, placebo effect. As determined by the power calculations, based on the standard deviations of the tests for reproducibility and the placebo effect, nine of 13 subjects are required to show that a 9/5 mmHg decrease in systolic HBP/diastolic HBP (50% of estimated effective decrease in systolic HBP/diastolic HBP according to the guidelines for clinical trials in Japan) is statistically significant CONCLUSIONS: The results suggest that the HBP measurement is highly reproducible and that there is a minimal, if any, placebo effect. These characteristics of HBP contribute to minimizing the number of subjects necessary for assessment of antihypertensive drug effects in comparative studies between an active treatment and placebo.

Adult↗
PubMed2001

Aldosterone synthase gene (CYP11B2) C-334T polymorphism, ambulatory blood pressure and nocturnal decline in blood pressure in the general Japanese population: the Ohasama Study.

OBJECTIVE: The C-344T polymorphism in the 5'-flanking region of the aldosterone synthase (CYP11B2) gene has been suggested to be associated with hypertension and disturbed circadian blood pressure (BP) rhythm through its effect on aldosterone synthesis. However, previous findings on this topic have been inconsistent. DESIGN: A cross-sectional study. SUBJECTS AND METHODS: We investigated the CYP11B2 C-344T genotype in 802 subjects, aged 40 and over, in a Japanese community, who gave written informed consent and were monitored for 24 h ambulatory BP. RESULTS: The frequencies of the CC, CT, and TT genotypes in these Japanese subjects were 0.14, 0.44, and 0.42, showing a higher frequency of the T allele (0.64) than in Caucasians. Although there was no significant difference in 24 h ambulatory BP levels among the genotypes, the nocturnal decline in BP was significantly greater in the CC homozygous subjects than in other subjects (P = 0.0065 for systolic and P = 0.031 for diastolic decline in nocturnal BP). Detailed analyses demonstrated that this association was significant only in aged (60 years and over) or male subjects. The prevalence of previous cardiovascular disease was significantly less in these subjects with the CC genotype than in those with the TC and TT genotypes, although age, body mass index, male gender, smoking, use of alcohol and antihypertensive medication did not differ among the three genotypes. There was no significant difference among the three genotypes in biochemical and hormonal parameters. CONCLUSION: Although the C-344 T polymorphism of CYP11B2 did not directly influence the level of 24 h BP, the CC genotype was associated with decreased nocturnal BP in elderly or male Japanese. Since prevalence of previous cardiovascular disease was significantly less in homozygous CC subjects, greater nocturnal BP decline in this genotype appears to be beneficial in the circadian BP rhythm.

Aged↗
PubMed2001

Risk factors and predictors of coronary arterial lesions in Japanese hypertensive patients.

The morbidity rate of coronary artery disease has recently increased in Japan. This is attributable to changes from traditional to more westernized lifestyles. In this study, we therefore examined the risk factors and predictors of coronary arterial lesions in Japanese patients with essential hypertension. Coronary angiography was performed in 109 consecutive essential hypertension patients (57 men and 52 women; 66 +/- 8.0 years of age) with either angina pectoris or atypical chest pain, who were chosen from 485 consecutive hypertensive patients in a hypertension clinic in Sendai, Japan. Coronary arterial stenosis of greater than 50% was defined as significant and used as a dependent variable for the multiple regression analysis. Risk factors were defined as factors confirmed to have a causal relationship with coronary arterial lesions, whereas arteriosclerotic complications and hypertensive target organ damage were defined as predictors. Multiple logistic regression analysis was performed using these parameters as independent variables. Of 109 patients, 25 had a coronary arterial stenosis greater than 50%. A smoking habit (odds ratio (OR): 4.48; 95% confidence interval (CI): 1.13-17.82; p<0.05), hypercholesterolemia (OR: 5.34; 95% CI: 1.52-18.73; p<0.05), and 24-h diastolic blood pressure (OR: 2.33; 95% CI: 1.06-5.16; p<0.05) were significant risk factors, whereas carotid intima-media thickness (OR: 5.85; 95% CI: 1.48-23.2; p<0.05) was a significant predictor of coronary arterial lesion. When two of the major risk factors (a smoking habit, hypercholesterolemia, or impaired glucose tolerance including diabetes mellitus) were clustered in addition to the hypertension, the risk of coronary arterial lesions increased by 6.7 to 10.1 times. These findings indicate that the major risk factors established in Caucasians, i.e., a smoking habit, hypercholesterolemia and blood pressure level, are also risk factors for coronary arterial lesions in Japanese with essential hypertension. The presence of two or more risk factors increases the risk of coronary arterial lesions synergistically in the presence of hypertension.

Aged↗
PubMed2000

Prognosis of isolated systolic and isolated diastolic hypertension as assessed by self-measurement of blood pressure at home: the Ohasama study.

BACKGROUND: Although the clinical significance of systolic-diastolic hypertension and isolated systolic hypertension has been established, the significance of isolated diastolic hypertension has not been fully investigated. OBJECTIVE: To clarify the prognostic significance of isolated systolic and isolated diastolic hypertension as assessed by self-measurement of blood pressure (BP) at home (home BP measurements), which has a better reproducibility and prognostic value than casual BP measurements in the general population. SUBJECTS AND METHODS: We obtained home BP measurements for 1913 subjects aged 40 years or older, then followed up their survival status (mean, 8.6 years). We classified the subjects into the following 4 groups according to their home BP levels: systolic-diastolic hypertension, isolated systolic hypertension, isolated diastolic hypertension, and normotension. The prognostic significance of each type of hypertension for the risk of cardiovascular mortality risk was investigated using a Cox proportional hazards regression model adjusted for possible confounding factors. RESULTS: The risk for isolated systolic hypertension and systolic-diastolic hypertension were significantly higher than the relative hazard for normotension, while isolated diastolic hypertension was associated with no significant increase in risk. Home pulse pressure measurement was also independently associated with an increase in the risk of cardiovascular mortality. CONCLUSIONS: Isolated diastolic hypertension, as assessed by home BP measurements, carried a low risk of cardiovascular mortality, similar to that found in subjects with normotension, suggesting that the prognosis of hypertension would be improved by treatment focused on systolic rather than on diastolic home BP measurements. To our knowledge, this study is the first to demonstrate the clinical significance of pulse pressure as assessed by home BP measurement. Arch Intern Med. 2000;160:3301-3306.

Adult↗
PubMed2000

Prediction of stroke by ambulatory blood pressure monitoring versus screening blood pressure measurements in a general population: the Ohasama study.

OBJECTIVE: To investigate the association between 24 h, daytime and night-time ambulatory blood pressures and first symptomatic stroke, to compare their predictive powers for stroke with that of casual (screening) blood pressure, and to compare the predictive power for stroke between daytime and night-time blood pressures, in a general population in Ohasama, Japan. DESIGN: A prospective cohort study. SUBJECTS AND METHODS: We obtained ambulatory blood pressure on 1,464 subjects aged > or = 40 years without history of symptomatic stroke, then followed-up their stroke-free survival. There were 74 first symptomatic stroke during the follow-up period (mean = 6.4 years). The prognostic significance of blood pressure for stroke risk was examined by a Cox proportional hazards regression model adjusted for possible confounding factors. RESULTS: The non-parametric and parametric analysis indicated that 24-h, daytime and night-time ambulatory blood pressures were linearly related with stroke risk. The likelihood ratio analysis demonstrated that these ambulatory blood pressures were significantly better related to stroke risk than did screening blood pressure, and that daytime blood pressure better predicted stroke risk than did night-time blood pressure. CONCLUSIONS: The present study which prospectively investigated the relation between ambulatory blood pressure and first symptomatic stroke risk in a general population demonstrated that (i) ambulatory blood pressure values were linearly related to stroke risk; (ii) ambulatory blood pressures had the stronger predictive power for stroke risk than did screening blood pressure; and (iii) daytime blood pressure better related to stroke risk than did night-time blood pressure.

Blood Pressure↗
PubMed2000

Chronic unilateral ureteral obstruction represented as renin-dependent hypertension.

A 50-year-old woman developed renin-dependent hypertension immediately after accidental unilateral ureteral ligation during hysterectomy, and the hypertension lasted for 5 months. Surgical release of the obstruction was carried out 157 days after the ligation. Then, her blood pressure was normalized. However, the obstructed kidney showed intensive tubulointerstitial fibrosis and functional recovery was not obtained. This case suggests that the renin-angiotensin system may be upregulated in human kidney during unilateral ureteral obstruction for a long duration.

Atrophy↗
PubMed2000

Prognostic significance of blood pressure and heart rate variabilities: the Ohasama study.

To investigate the association between cardiovascular mortality and short-term variabilities in blood pressure and heart rate, we performed a long-term prospective study of ambulatory blood pressure monitoring in Ohasama, Japan, starting in 1987. We obtained ambulatory blood pressure and heart rate in 1542 subjects >/=40 years of age. Blood pressure and heart rate variabilities were estimated as a standard deviation measured every 30 minutes by ambulatory monitoring. There were 67 cardiovascular deaths during the follow-up period (mean=8.5 years). The Cox proportional hazards model, adjusted for possible confounding factors, demonstrated a significant increase in cardiovascular mortality, with an increase in daytime systolic ambulatory blood pressure variability. A similar trend was observed in daytime diastolic and nighttime ambulatory blood pressures. Cardiovascular mortality rate increased linearly, with a decrease in daytime heart rate variability. Subjects in whom the daytime systolic ambulatory blood pressure variability was larger than third quintile and the daytime heart rate variability was lower than the mean-SD were at extremely high risk of cardiovascular mortality. The blood pressure and heart rate variabilities obtained every 30 minutes by ambulatory blood pressure monitoring were independent predictors for cardiovascular mortality in the general population.

Aged↗
PubMed2000

[Development of the general affect scales].

This study aimed at developing a self-report instrument of general mood states which was brief and easy to administer for Japanese respondents. Four studies were conducted. In Study 1, we administered some existing mood questionnaires in order to select appropriate items from them. Factor analysis using oblique rotation yielded eight factors. Following Study 2 and 3, we developed an instrument called the General Affect Scales with three 8-item subscales: positive affect (PA), negative affect (NA), and calmness (CA). The reliability and the validity of each scale were then investigated. It was shown that the subscales except the CA are highly internally consistent and factorially valid. Finally, these subscales were compared with other mood scales in Study 4.

Adolescent↗
PubMed1999

Characteristics of blood pressure measured at home in the morning and in the evening: the Ohasama study.

OBJECTIVE: To determine the qualitative and quantitative differences of blood pressure measured at home (home measurement) in the morning versus the evening. METHODS: Of 3744 participants, aged 20 years or older in the Ohasama population, more than 14 home measurements in the morning and in the evening, respectively, were obtained in each of 1207 individuals (881 untreated, 56.1 +/- 11.4 years and 326 treated, 66.0 +/- 9.2 years). A casual/screening measurement was also obtained in these individuals. RESULTS: The home measurements in the morning were significantly higher than those in the evening. The bivariate linear regression analysis demonstrated that the difference between diastolic home measurement in the morning and that in the evening increased with an increase in diastolic home measurements. The multiple step-wise linear regression analysis, however, demonstrated that male sex, the use of antihypertensive medication, and SD of home measurements in individuals (blood pressure variability), but not level of home measurements, were positively associated with the difference between home measurement in the morning and that in the evening. The SD of home measurement in the evening in individuals was significantly larger than that in the morning, and the SD in treated individuals was significantly larger than that in untreated individuals. The correlations between casual and home measurements were moderate in untreated individuals (r = 0.509-0.567) but poor in treated subjects (r= 0.223-0.384). The correlations between home systolic measurements in the morning and in the evening were very close in both treated and untreated subjects (r = 0.814-0.902). The correlations between the SD of home measurements in the morning and in the evening were moderate in both treated and untreated individuals (r = 0.585-0.657). CONCLUSIONS: Qualitative and quantitative differences in home blood pressure measurement, due to the differential time of measurement, should be taken into consideration in clinical use of home blood pressure measurements.

Adult↗
PubMed1999

Relationships among blood pressures obtained using different measurement methods in the general population of Ohasama, Japan.

To examine the relationships between casual, ambulatory and home blood pressure measurements in the general population, these measurements were obtained in 1,695 of 3,744 subjects aged 20 yr or older in Ohasama, Japan. Of these 1,695 subjects, 1,207 measured their home blood pressure more than 14 times in each of the morning and evening (881 untreated subjects including normotensives and untreated hypertensives, 56.4 +/- 11.5 yr of age; 326 treated subjects, 66.0 +/- 9.2 yr of age). We analyzed data in these 1,207 subjects, examining the distribution of each measurement, the relationships among measurements, and the factors affecting the blood pressure differences among the measurements. For systolic pressure, the casual measurement was the highest among the methods examined. The daytime ambulatory measurement was significantly higher than morning and evening home measurements. Morning home measurements were significantly higher than those in the evening. For diastolic pressure, however, the morning home measurement was the highest among the methods examined. Short-term pressure variability (standard deviation and variation coefficient of ambulatory measurements) was greater than long-term pressure variability (standard deviation and variation coefficient of home measurements). The pressure variability in treated subjects was greater than that in untreated subjects. The correlation between casual pressure and the other pressures was not as strong (r<0.567). Among the relationships between ambulatory and home measurements, the strongest correlation was observed between the 24-h ambulatory measurement and the morning home measurement (r=0.738) in untreated subjects. The morning home measurement was highly correlated with the evening home measurement (r>0.814). The differences among the methods examined were affected by blood pressure level and age. It should be noted that in elderly and treated subjects, blood pressure measurement using one method does not necessarily correlate with that obtained using the other methods. This information is useful for the estimation of the value of one type of blood pressure measurement from values obtained with other methods.

Adult↗
PubMed1998

Home blood pressure measurement has a stronger predictive power for mortality than does screening blood pressure measurement: a population-based observation in Ohasama, Japan.

OBJECTIVE: To compare the predictive powers of self-measurement of blood pressure at home (home blood pressure measurement) and casual (screening) blood pressure measurement for mortality. DESIGN: A prospective cohort study. SUBJECTS AND METHODS: We obtained home and screening blood pressure measurements for 1789 subjects aged > or = 40 years who were followed up for a mean of 6.6 years. The prognostic significance of blood pressure for mortality was determined by the Cox proportional hazards regression model adjusted for age, sex, smoking status, past history of cardiovascular disease, and the use of antihypertensive medication. RESULTS: When the home blood pressure values and the screening blood pressure values were simultaneously incorporated into the Cox model as continuous variables, only the average of multiple (taken more than three times) home systolic blood pressure values was significantly and strongly related to the cardiovascular mortality risk. The average of the two initial home blood pressure values was also better related to the mortality risk than were the screening blood pressure values. CONCLUSIONS: Home blood pressure measurement had a stronger predictive power for mortality than did screening blood pressure measurement for a general population. This appears to be the first study in which the prognostic significances of home and screening blood pressure measurements have been compared.

Adult↗
PubMed1997

Determinants of circadian blood pressure variation: a community-based study in Ohasama.

We investigated factors affecting the nocturnal decline in blood pressure (BP). A cross sectional study was done in 706 community-based untreated subjects > or = 20 years of age. Screening and ambulatory BPs were measured and the effects of age and the ambulatory BP on the nocturnal decline were examined. Bivariate analysis demonstrated that the magnitude of the decline and the percent decline in the nocturnal BP increased with increase in daytime ambulatory BP and decreased with increase in nighttime ambulatory BP. Although the magnitude of the nocturnal decline in BP increased with increasing daytime BP, the nocturnal BP in hypertensives was still higher than those in normotensives. The magnitude decreased with increasing age in men but not in women, while the percent decline decreased with increasing age in both men and women. Since bivariate analysis demonstrated that the daytime BP, nighttime BP, and standard deviation of the 24-hour BP strongly correlated with the magnitude of the nocturnal decline, these parameters were excluded as independent variables from the multivariate analysis. In the multivariate analysis the nighttime pulse pressure was negatively and daytime pulse pressure was positively associated with the magnitude of the decline and the percent decline in the nocturnal BP. A non-dipping circadian variation was frequently observed in elderly normotensive men but the rate of nondipper was rather low in hypertensive individuals in the general population. A marked dipping pattern was frequently observed in hypertensive women > or = 70 years of age. The nocturnal BP levels in subjects with daytime hypertension are higher than those in subjects with daytime normotension. Therefore, BP must ideally be lowered over 24-hour period in hypertensive subjects. The diminished magnitude of the decline and the decrease in the percent decline in the nocturnal BP in the elderly may be mediated by the disturbed baroreflex function due to the decrease in compliance of large elastic artery. However, in some elderly hypertensive women, excess nocturnal decline in BP is observed. In such subjects, we should take care of the nocturnal BP levels during treatment.

Adult↗