Junichiro Hashimoto

Prognostic significance of the nocturnal decline in blood pressure in individuals with and without high 24-h blood pressure: the Ohasama study.

Objective To examine the relationship between the normal nocturnal decline in blood pressure and the risk of cardiovascular mortality in individuals with and without high 24-h blood pressure values. Methods We obtained 24-h ambulatory blood pressure readings from 1542 residents of Ohasama, Japan, who were aged 40 years or more and were representative of the Japanese general population. We then followed up their survival for a mean of 9.2 years. The relationship was analysed using a Cox proportional hazards model adjusted for possible confounding factors. Results There was a linear relationship between the nocturnal decline in blood pressure and cardiovascular mortality. On average, each 5% decrease in the decline in nocturnal systolic/diastolic blood pressure was associated with an approximately 20% greater risk of cardiovascular mortality. There were no significant interactions for the risk between 24-h systolic/diastolic blood pressure values and continuous values for the nocturnal decline in blood pressure (P for interaction > 0.6). Even when 24-h blood pressure values were within the normal range (< 135/80 mmHg, average 118/69 mmHg), diminished nocturnal decreases in systolic/diastolic blood pressure were associated with an increased risk of cardiovascular mortality. Conclusions This is the first study to demonstrate that a diminished nocturnal decline in blood pressure is a risk factor for cardiovascular mortality, independent of the overall blood pressure load during a 24-h period, in the general population.

Ambulatory Blood Pressure and 10-Year Risk of Cardiovascular and Noncardiovascular Mortality: The Ohasama Study

The objective of this study was to elucidate the long-term prognostic significance of ambulatory blood pressure. Ambulatory and casual blood pressure values were obtained from 1332 subjects (872 women and 460 men) aged ≥40 years from the general population of a rural Japanese community. Survival was then followed for 14 370 patient years and analyzed by a Cox hazard model adjusted for possible confounding factors. There were 72 cardiovascular deaths during the 10.8-year follow-up. The relationship between 24-hour systolic blood pressure and the cardiovascular mortality risk was U-shaped in the first 5 years, then changed to J-shaped over the rest of the 10.8-year follow-up. After censoring the first 2 years of data, the risk flattened until it again increased for the fifth quintile of 24-hour systolic blood pressure for the 10.8-year follow-up period. For 24-hour diastolic blood pressure, the J-shaped relationship remained unchanged, regardless of follow-up duration and censoring. Ambulatory systolic blood pressure values consistently showed stronger predictive power for cardiovascular mortality risk than did casual systolic blood pressure in the 10.8-year follow-up data, whereas such relationships became more marked after censoring the first 2 years. When nighttime and daytime systolic blood pressure values were simultaneously included in the same Cox model, only nighttime blood pressure significantly predicted the cardiovascular mortality risk for the 10.8-year follow-up data. We conclude that the relationship between ambulatory systolic blood pressure and cardiovascular mortality is not U-shaped or J-shaped, and that nighttime blood pressure has better prognostic value than daytime blood pressure.

Prognostic Significance for Stroke of a Morning Pressor Surge and a Nocturnal Blood Pressure Decline: The Ohasama Study

There is continuing controversy over whether the pattern of circadian blood pressure (BP) variation that includes a nocturnal decline in BP and a morning pressor surge has prognostic significance for stroke risk. In this study, we followed the incidence of stroke in 1430 subjects aged ≥40 years in Ohasama, Japan, for an average of 10.4 years. The association between stroke risk and the pattern of circadian BP variation was analyzed with a Cox proportional hazards model after adjustment for possible confounding factors. There was no significant association between total stroke risk and the nocturnal decline in BP (percentage decline from diurnal level) or between total stroke risk and the morning pressor surge. The cerebral infarction risk was significantly higher in subjects with a <10% nocturnal decline in BP as compared with subjects who had a ≥10% nocturnal decline in BP (P=0.04). The morning pressor surge was not associated with a risk of cerebral infarction. On the other hand, an increased risk of cerebral hemorrhage was observed in subjects with a large morning pressor surge (≥25 mm Hg; P=0.04). Intracerebral hemorrhage was also observed more frequently in extreme dippers (those with a ≥20% nocturnal decline in BP) than dippers (those with a 10% to 19% decline; P=0.02). A disturbed nocturnal decline in BP is associated with cerebral infarction, whereas a large morning pressor surge and a large nocturnal decline in BP, which are analogous to a large diurnal increase in BP, are both associated with cerebral hemorrhage.

Day-by-Day Variability of Blood Pressure and Heart Rate at Home as a Novel Predictor of Prognosis: The Ohasama Study

Day-by-day blood pressure and heart rate variability defined as within-subject SDs of home measurements can be calculated from long-term self-measurement. We investigated the prognostic value of day-by-day variability in 2455 Ohasama, Japan, residents (baseline age: 35 to 96 years; 60.4% women). Home blood pressure and heart rate were measured once every morning for 26 days (median). A total of 462 deaths occurred over a median of 11.9 years, composing 168 cardiovascular deaths (stroke: n=83; cardiac: n=85) and 294 noncardiovascular deaths. Using Cox regression, we computed hazard ratios while adjusting for baseline characteristics, including blood pressure and heart rate level, sex, age, obesity, current smoking and drinking habits, history of cardiovascular disease, diabetes mellitus, hyperlipidemia, and treatment with antihypertensive drugs. An increase in systolic blood pressure variability of +1 between-subject SD was associated with increased hazard ratios for cardiovascular (1.27; P=0.002) and stroke mortality (1.41; P=0.0009) but not for cardiac mortality (1.13; P=0.26). Conversely, heart rate variability was associated with cardiovascular (1.24; P=0.002) and cardiac mortality (1.30; P=0.003) but not stroke mortality (1.17; P=0.12). Similar findings were observed for diastolic blood pressure variability. Additional adjustment of heart rate variability for systolic blood pressure variability and vice versa produced confirmatory results. Coefficient of variation, defined as within-subject SD divided by level of blood pressure or heart rate, displayed similar prognostic value. In conclusion, day-by-day blood pressure variability and heart rate variability by self-measurement at home make up a simple method of providing useful clinical information for assessing cardiovascular risk.

How many times should blood pressure be measured at home for better prediction of stroke risk? Ten-year follow-up results from the Ohasama study

Objective To determine the optimum number of blood pressure self-measurements taken at home (home blood pressure) in relation to their predictive value for stroke risk. Methods We obtained more than 14 measurements of home blood pressure from 1491 people aged ⩾ 40 years without a history of stroke in the general population in Japan, and followed them up after a mean period of 10.6 years. The prognostic significance of blood pressure for stroke risk was examined using the Cox proportional hazards regression model, which was adjusted for possible confounding factors. Results The predictive value of home blood pressure increased progressively with the number of measurements, showing the highest predictive value with the average of whole measurements (mean = 25 measurements, 35% increase in the risk of stroke per 10 mmHg elevation in blood pressure). The initial home blood pressure values (one measurement) showed a significantly greater relation with stroke risk than conventional blood pressure values (mean of two measurements) (19/8% increase in the risk of stroke per 10 mmHg elevation in initial home/conventional systolic blood pressure values, respectively). Conclusions There was no threshold for the number of home blood pressure measurements within the range of 1–14 measurements for increasing the predictive power of stroke risk, suggesting that as many measurements as possible, preferably more than 14 measurements, is recommended for better prediction of stroke risk. It should be emphasized that home blood pressure has a stronger predictive power than does conventional blood pressure, even for a lower number of measurements.

Ambulatory blood pressure of adults in Ohasama, Japan.

We performed a cross-sectional study in a small town in northern Japan to evaluate the distribution, reference values, and daily variation in ambulatory blood pressure. A total of 705 subjects (229 men aged 61.3 +/- 13.4 years [mean +/- SD] and 476 women aged 57.5 +/- 13.3 years; 41.1% of the regional adult population, n = 1716), including those treated with antihypertensive drugs (n = 231, 66.5 +/- 9.5 years) as well as untreated subjects (n = 474, 55.0 +/- 13.5 years), participated in the study. Both ambulatory and screening blood pressures were measured in 659 subjects. Ambulatory blood pressure was measured with an automatic device (Colin ABPM-630). The 24-hour ambulatory blood pressure in the total population was 121.7 +/- 13.0/71.1 +/- 7.6 mm Hg (95th percentile value [95%] = 146/85 mm Hg). The corresponding value in the untreated subjects was 119.4 +/- 12.5/70.1 +/- 7.4 mm Hg (95% = 144/83 mm Hg). The 24-hour average ambulatory blood pressure was 118.0 +/- 11.1/69.4 +/- 6.8 mm Hg (95% = 139/81 mm Hg) in subjects identified as normotensive by their screening blood pressure (n = 448, 57.2 +/- 13.1 years) and 133.6 +/- 14.2/78.9 +/- 8.8 mm Hg in those identified as hypertensive by their screening blood pressure (n = 73, 63.1 +/- 10.6 years). Based on the mean+SD of the 24-hour ambulatory blood pressure in the normotensive subjects by their screening blood pressure (129/76 mm Hg), the 24-hour ambulatory blood pressures in 25 (34.2%) of these 73 hypertensive subjects by screening blood pressure were below this level. Nine (2%) of 448 normotensive subjects by screening blood pressure were above the mean+2 SDs (140/83 mm Hg) of the 24-hour ambulatory blood pressure in the normotensive group by screening blood pressure. Ambulatory and screening blood pressures increased with age. The age-dependent increase in ambulatory blood pressure was less apparent in men. The 24-hour average pulse rate decreased with age. The daily variation in ambulatory blood pressure (standard deviation) increased with age, whereas that of pulse rate decreased with age. Increases in blood pressure variation were observed in nighttime and daytime blood pressure values. The differences between day versus night ambulatory blood pressures decreased with age in men but not in women.(ABSTRACT TRUNCATED AT 400 WORDS)

Characteristics of a community-based distribution of home blood pressure in Ohasama in northern Japan.

Objective: To evaluate the distribution, reference values and day-to-day variation of blood pressure of untreated subjects measured at home Design: Cross-sectional study of a cohort Setting: General community in northern Japan Subjects: Blood pressure was measured in 871 subjects (mean±SD age 46.0±19.5 years, range 7-98, constituting 38.7% of the local population of Uchikawama region, Ohasama) who were not receiving antihypertensive medication Methods: Subjects measured their own blood pressure at home at least three times (mean±SD 19.718.4) each morning using a semi-automatic oscillometric blood pressure measuring device. Screening blood pressure was measured once. Main outcome measures: Distribution of home blood pressure in the study population as a whole and with respect to age and sex, and the distribution of day-to-day variation of home blood pressure were determined Results: Mean home blood pressure was 117.3±13.4/69.3±9.7mmHg (95% confidence interval 116.4-118.2/68.7-70.0). The 95th centile value was 143/85 mmHg, mean + SD 131/79 mmHg and mean + 2SD 144/89 mmHg. Mean screening blood pressure was 126.2 ±18.9/72.1 ±11.7 mmHg (95th centile 159/92 mmHg). Age- and sex-specific 95th centile values as well as mean±SD were obtained. Mean + SD, mean + 2SD and the 95th centile values obtained as reference upper limits of home blood pressure from subjects identified as normotensive by screening blood pressure (n=707) were 125/77, 137/86 and 134/83 mmHg, respectively. Home blood pressure increased gradually with increasing age in both men and women, although blood pressure was significantly higher in men until 50 years of age. Day-to-day variation of home systolic blood pressure also increased with age Conclusions: Since the distribution of home blood pressure values was affected by age and sex, age- and sex-matched reference values for home blood pressure should be established. Home blood pressure values in elderly subjects should be evaluated carefully, since these exhibit greater day-to-day variation

Central Pulse Pressure and Aortic Stiffness Determine Renal Hemodynamics: Pathophysiological Implication for Microalbuminuria in Hypertension

A significant link has been reported between aortic stiffening and renal microvascular damage, but the underlying mechanism remains poorly understood. We hypothesized that alterations in central and renal hemodynamics are responsible for this link. In 133 patients with hypertension, pressure waveforms were recorded on the radial, carotid, femoral, and dorsalis pedis arteries with applanation tonometry to estimate the aortic pressures and aortic (carotid-femoral) and peripheral (carotid-radial and femoral-dorsalis pedis) pulse wave velocities. Flow-velocity waveforms were recorded on the renal segmental arteries with duplex ultrasound to calculate the resistive index (RI) as [1 − (end-diastolic velocity/peak systolic velocity)] and on the femoral arteries to calculate the reverse/forward flow index and diastolic/systolic forward-flow ratio. Albuminuria was defined as urinary albumin/creatinine ratio ≥30 mg/g of creatinine. The renal RI (mean: 0.65±0.07) was strongly correlated (P<0.001) with the aortic pulse pressure (r=0.62), incident pressure wave (r=0.55), augmented pressure (r=0.49), and aortic pulse wave velocity (r=0.51), although not with the mean arterial pressure or peripheral pulse wave velocities. The correlations remained highly significant after consideration of confounders including age, cholesterol, hemoglobin A1c, and glomerular filtration rate. The renal RI was inversely correlated with the femoral reverse and diastolic forward flow indices. Both aortic pulse pressure and renal RI correlated with the urinary albumin/creatinine ratio independent of confounders. Each 0.1 increase in renal RI was associated with a 5.4-fold increase in the adjusted relative risk of albuminuria. In conclusion, increased aortic pulse pressure causes renal microvascular damage through altered renal hemodynamics resulting from increased peripheral resistance and/or increased flow pulsation.

Ambulatory Arterial Stiffness Index and 24-Hour Ambulatory Pulse Pressure as Predictors of Mortality in Ohasama, Japan

Background and Purpose— Ambulatory arterial stiffness index (AASI) and pulse pressure (PP) are indexes of arterial stiffness and can be computed from 24-hour blood pressure recordings. We investigated the prognostic value of AASI and PP in relation to fatal outcomes. Methods— In 1542 Ohasama residents (baseline age, 40 to 93 years; 63.4% women), we applied Cox regression to relate mortality to AASI and PP while adjusting for sex, age, BMI, 24-hour MAP, smoking and drinking habits, diabetes mellitus, and a history of cardiovascular disease. Results— During 13.3 years (median), 126 cardiovascular and 63 stroke deaths occurred. The sex- and age-standardized incidence rates of cardiovascular and stroke mortality across quartiles were U-shaped for AASI and J-shaped for PP. Across quartiles, the multivariate-adjusted hazard ratios for cardiovascular and stroke death significantly deviated from those in the whole population in a U-shaped fashion for AASI, whereas for PP, none of the HRs departed from the overall risk. The hazard ratios for cardiovascular mortality across ascending AASI quartiles were 1.40 (P=0.04), 0.82 (P=0.25), 0.64 (P=0.01), and 1.35 (P=0.03). Additional adjustment of AASI for PP and sensitivity analyses by sex, excluding patients on antihypertensive treatment or with a history of cardiovascular disease, or censoring deaths occurring within 2 years of enrollment, produced confirmatory results. Conclusions— In a Japanese population, AASI predicted cardiovascular and stroke mortality over and beyond PP and other risk factors, whereas in adjusted analyses, PP did not carry any prognostic information.

Clinical evaluation of semiautomatic and automatic devices for home blood pressure measurement: comparison between cuff-oscillometric and microphone methods.

The accuracy and reliability of blood pressure (BP) values were evaluated by comparing values obtained with eight automatic or semiautomatic devices designed for home BP measurement (four microphone devices based on the Korotkoff-sound technique and four cuff-oscillometric devices) with those obtained by the auscultatory method, using a standard mercury sphygmomanometer. Systolic blood pressure (SBP) values obtained using the microphone devices coincided well with those obtained by the auscultatory method. However, these devices produced a certain proportion of errors in the measurement of diastolic blood pressure (DBP), sometimes resulting in recordings at least 25mmHg higher than those obtained by the standard method. The most frequent causes of this phenomenon were an auscultatory (silent) gap and a weak Korotkoff sound after phase IV. A microphone device using a condenser microphone built into the manometer displayed comparatively good acoustic characteristics for determining DBP. All cuff-oscillometric devices demonstrated minimal mean differences and a constant s.d. of mean difference for DBP, with no great differences from the auscultatory method. However, mean differences and s.d.s in SBP measurements using cuff-oscillometric devices were relatively greater than those obtained using some of the microphone devices. Furthermore, the direction of the mean differences in measurements from those obtained with the auscultatory method differed. The error in relation to the auscultatory method tended to be reproducible in the same subjects with both the microphone and the cuff-oscillometric devices. These results indicate that practitioners should select the most appropriate method and/or device by taking into account the factors which may cause measurement error in relation to the auscultatory method in each subject, and should then evaluate, at least once, the difference in BP values obtained using the auscultatory method and using the device. In future, home blood pressure measurement devices for determination of SBP should employ a microphone method, while a method which combines a microphone with a cuff-oscillometric device, thereby compensating for the disadvantage of the Korotkoff-sound signal with the pulse wave signal, should be recommended for measurement of DBP.