Kei Asayama

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 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.

Prognosis of white-coat and masked hypertension: International Database of HOme blood pressure in relation to Cardiovascular Outcome.

Home blood pressure monitoring is useful in detecting white-coat and masked hypertension and is recommended for patients with suspected or treated hypertension. The prognostic significance of white-coat and masked hypertension detected by home measurement was investigated in 6458 participants from 5 populations enrolled in the International Database of HOme blood pressure in relation to Cardiovascular Outcomes. During a median follow-up of 8.3 years, 714 fatal plus nonfatal cardiovascular events occurred. Among untreated subjects (n=5007), cardiovascular risk was higher in those with white-coat hypertension (adjusted hazard ratio 1.42; 95% CI [1.06–1.91]; P=0.02), masked hypertension (1.55; 95% CI [1.12–2.14]; P<0.01) and sustained hypertension (2.13; 95% CI [1.66–2.73]; P<0.0001) compared with normotensive subjects. Among treated patients (n=1451), the cardiovascular risk did not differ between those with high office and low home blood pressure (white-coat) and treated controlled subjects (low office and home blood pressure; 1.16; 95% CI [0.79–1.72]; P=0.45). However, treated subjects with masked hypertension (low office and high home blood pressure; 1.76; 95% CI [1.23–2.53]; P=0.002) and uncontrolled hypertension (high office and home blood pressure; 1.40; 95% CI [1.02–1.94]; P=0.04) had higher cardiovascular risk than treated controlled patients. In conclusion, white-coat hypertension assessed by home measurements is a cardiovascular risk factor in untreated but not in treated subjects probably because the latter receive effective treatment on the basis of their elevated office blood pressure. In contrast, masked uncontrolled hypertension is associated with increased cardiovascular risk in both untreated and treated patients, who are probably undertreated because of their low office blood pressure.Home blood pressure monitoring is useful in detecting white-coat and masked hypertension and is recommended for patients with suspected or treated hypertension. The prognostic significance of white-coat and masked hypertension detected by home measurement was investigated in 6458 participants from 5 populations enrolled in the International Database of HOme blood pressure in relation to Cardiovascular Outcomes. During a median follow-up of 8.3 years, 714 fatal plus nonfatal cardiovascular events occurred. Among untreated subjects (n=5007), cardiovascular risk was higher in those with white-coat hypertension (adjusted hazard ratio 1.42; 95% CI [1.06–1.91]; P =0.02), masked hypertension (1.55; 95% CI [1.12–2.14]; P <0.01) and sustained hypertension (2.13; 95% CI [1.66–2.73]; P <0.0001) compared with normotensive subjects. Among treated patients (n=1451), the cardiovascular risk did not differ between those with high office and low home blood pressure (white-coat) and treated controlled subjects (low office and home blood pressure; 1.16; 95% CI [0.79–1.72]; P =0.45). However, treated subjects with masked hypertension (low office and high home blood pressure; 1.76; 95% CI [1.23–2.53]; P =0.002) and uncontrolled hypertension (high office and home blood pressure; 1.40; 95% CI [1.02–1.94]; P =0.04) had higher cardiovascular risk than treated controlled patients. In conclusion, white-coat hypertension assessed by home measurements is a cardiovascular risk factor in untreated but not in treated subjects probably because the latter receive effective treatment on the basis of their elevated office blood pressure. In contrast, masked uncontrolled hypertension is associated with increased cardiovascular risk in both untreated and treated patients, who are probably undertreated because of their low office blood pressure. # Novelty and Significance {#article-title-34}

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.

Prediction of Stroke by Self-Measurement of Blood Pressure at Home Versus Casual Screening Blood Pressure Measurement in Relation to the Joint National Committee 7 Classification: The Ohasama Study

Background and Purpose— To compare the predictive power of self-measured home blood pressure (HBP) and casual blood pressure (CBP) for stroke risk in relation to the Joint National Committee 7 (JNC-7) classification. Methods— HBP and CBP measurements were taken in 1702 subjects (≥40 years) without a history of stroke, who were followed up for an average of 11 years. Subjects were classified into 4 groups on the basis of either HBP or CBP, according to the JNC-7 criteria: group 1 (HBP <115/75 mm Hg; CBP <120/80 mm Hg); group 2 (115/75≤HBP<135/85 mm Hg; 120/80≤CBP<140/90 mm Hg); group 3 (135/85≤HBP<150/95 mm Hg; 140/90≤CBP<160/100 mm Hg); and group 4 (HBP≥150/95 mm Hg; CBP ≥160/100 mm Hg). Groups 2, 3, and 4 were further divided into 2 subgroups (a and b): those without and with cardiovascular disease risks, respectively. The risk of the first stroke in these groups was examined by the Cox hazards model adjusted for age and sex. Results— The stroke risk in groups 3b and 4b (defined by HBP and CBP) was 2 to 5× higher than that in group 1 with significant differences. The risk in groups 2a, 3a, and even 4a was not significantly different from that in group 1 by the CBP-based classification, but the risk in group 4a was significantly higher than that in group 1 by the HBP-based classification, which also showed a stepwise increase in risk from groups 2a to 4a. Conclusions— The JNC-7 classification had a stronger predictive power using HBP-based classification compared with CBP-based classification, suggesting the usefulness of HBP in the management of hypertension.

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.