Taku Obara

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.

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.

Prediction of Stroke by Home “Morning” Versus “Evening” Blood Pressure Values: The Ohasama Study

Predictive power of self-measured blood pressure at home (home BP) for cardiovascular disease risk has been reported to be higher than casual-screening BP. However, the differential prognostic significance of home BP in the morning (morning BP) and in the evening (evening BP), respectively, has not been elucidated. In the Ohasama study, 1766 subjects (≥40 years) were followed up for an average of 11 years. The predictive power for stroke incidence of evening BP was compared with that of morning BP as continuous variables. The Cox regression model demonstrated that evening BP and morning BP predicted future stroke risk equally. Subjects were also assigned to 1 of 4 categories based on home BP. In this analysis, stroke risk in morning hypertension ([HT] morning BP ≥135/85 mm Hg and evening BP <135/85 mm Hg; relative hazard (RH): 2.66; 95% CI:1.64 to 4.33) and that in sustained HT(morning BP and evening BP ≥135/85 mm Hg; RH: 2.38; 95% CI: 1.65 to 3.45) was significantly higher than that in normotension (morning BP and evening BP <135/85 mm Hg). The risk in morning HT was more remarkable in subjects taking antihypertensive medication (RH: 3.55; 95% CI: 1.70 to 7.38). Although the risk in evening HT (morning BP <135/85 mm Hg and evening BP ≥135/85 mm Hg) was higher than that in normotension, the differences were not significant. In conclusion, morning BP and evening BP provide equally useful information for stroke risk, whereas morning HT, which indicates HT specifically observed in the morning, might be a good predictor of stroke, particularly among individuals using anti-HT medication.

Isolated uncontrolled hypertension at home and in the office among treated hypertensive patients from the J-HOME study.

Objectives To evaluate the current status of blood pressure (BP) control as measured at home and in the office, as well as to clarify and compare the prevalence and characteristics of isolated uncontrolled hypertension as measured at home (home hypertension) and in the office (office hypertension). Design A cross-sectional study. Setting Primary care offices in Japan. Participants A sample of 3400 patients with essential hypertension (mean age, 66 years; males, 45%) receiving antihypertensive treatment. Results Overall, the mean home systolic BP (SBP)/diastolic BP (DBP) was 140/82 mmHg, and the mean office SBP/DBP was 143/81 mmHg. Of the 3400 subjects, 19% had controlled hypertension (home SBP/DBP < 135/85 mmHg and office SBP/DBP < 140/90 mmHg), 23% had isolated uncontrolled home hypertension (home SBP/DBP ≥ 135/85 mmHg and office SBP/DBP < 140/90 mmHg), 15% had isolated uncontrolled office hypertension (home SBP/DBP < 135/85 mmHg and office SBP/DBP < 140/90 mmHg), and 43% had uncontrolled hypertension (home SBP/DBP ≥ 135/85 mmHg and office SBP/DBP ≥ 140/90 mmHg). Compared to controlled hypertension, factors associated with isolated uncontrolled home hypertension included obesity, relatively higher office SBP, habitual drinking, and the use of two or more prescribed antihypertensive drugs. Compared to uncontrolled hypertension, factors associated with isolated uncontrolled office hypertension included female gender, lower body mass index, and relatively lower office SBP. Conclusions The use of all four, three of four, or all three predictive factors might be useful for the clinician to suspect isolated uncontrolled home or office hypertension.

Detection of carotid atherosclerosis in individuals with masked hypertension and white-coat hypertension by self-measured blood pressure at home: the Ohasama study.

Objective To investigate carotid atherosclerosis in individuals with masked hypertension (MHT) and white-coat hypertension (WCHT) in a general population. Methods Self-measurement of blood pressure at home (HBP) and casual blood pressure (CBP) measurements were recorded in 812 individuals aged at least 55 years (mean 66.4 years) from the general Japanese population. The intima–media thickness (IMT) of the near and far wall of both common carotid arteries was measured and averaged. The relationships between carotid atherosclerosis (IMT and plaque) and the four blood pressure groups (sustained normal blood pressure: HBP < 135/85 mmHg, CBP < 140/90 mmHg; WCHT: HBP < 135/85 mmHg, CBP ≥ 140/90 mmHg; MHT: HBP ≥ 135/85 mmHg, CBP < 140/90 mmHg; sustained hypertension: HBP ≥ 135/85 mmHg, CBP ≥ 140/90 mmHg) were examined using multivariate analysis adjusted for possible confounding factors. Results Adjusted IMT in individuals with sustained hypertension [0.77 mm; 95% confidence interval (CI) 0.75 to 0.79 mm] and MHT (0.77 mm; 95% CI 0.73 to 0.80 mm) was significantly greater than in those with sustained normal blood pressure (0.71 mm; 95% CI 0.69 to 0.72 mm) and WCHT (0.72 mm; 95% CI 0.71 to 0.74 mm) (P < 0.0001). The odds ratios for the presence of plaques in all four groups were similar to the trends in IMT. Conclusions Our findings imply that CBP measurements alone are insufficient to distinguish individuals at high risk of carotid atherosclerosis from those at low risk. However, these individuals do have distinct HBP measurements, suggesting that HBP measurement could become a valuable tool for predicting carotid atherosclerosis.

Cardiovascular outcomes in the first trial of antihypertensive therapy guided by self-measured home blood pressure

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.

Prognostic significance of night-time, early morning, and daytime blood pressures on the risk of cerebrovascular and cardiovascular mortality: the Ohasama Study.

Objective To clarify whether high blood pressure (BP) at a particular time of day is associated with cerebrovascular and cardiovascular mortality risk. Methods Cerebrovascular and cardiovascular mortality in 1360 individuals aged 40 years and older in Ohasama, Japan, was followed for an average of 10.6 years. We used 2-h moving averages of the BP (a total of 24 average BP measurements for two consecutive hours based on four BP readings taken every 30 min) to compare the predictive power of BP taken during a 24-h period given the same number of measurements. The associations between cerebrovascular and cardiovascular mortality risk and the 2-h moving averages of systolic blood pressure (2 h-SBP) recorded over 24 h were analysed using a Cox proportional hazards model after adjusting for possible confounding factors. Results The total cerebrovascular and cardiovascular mortality risk was significantly associated with elevated 2 h-SBP recorded during the night and early morning periods. Haemorrhagic stroke mortality was significantly associated with elevated daytime 2 h-SBP. Cerebral infarction mortality and heart disease mortality were significantly associated with elevated night-time 2 h-SBP. Conclusion High BP at different times of day were associated with different subtypes of cerebrovascular and cardiovascular mortality risk.

Home Blood Pressure Variability as Cardiovascular Risk Factor in the Population of Ohasama

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.