Abstract-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: nϭ83; cardiac: nϭ85) 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 ϩ1 between-subject SD was associated with increased hazard ratios for cardiovascular (1.27; Pϭ0.002) and stroke mortality (1.41; Pϭ0.0009) but not for cardiac mortality (1.13; Pϭ0.26). Conversely, heart rate variability was associated with cardiovascular (1.24; Pϭ0.002) and cardiac mortality (1.30; Pϭ0.003) but not stroke mortality (1.17; Pϭ0.12). 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. Key Words: epidemiology Ⅲ cerebrovascular disease/stroke Ⅲ population science Ⅲ risk factors Ⅲ blood pressure measurement/monitoring H ome blood pressure measurement is reportedly more reliable than conventional blood pressure measurement, because this approach avoids both observer and regression dilution biases and eliminates the white coat effect. 1 Home blood pressure measurement offers more prognostic significance than office blood pressure 2 and is more indicative of target organ damage. 3 The clinical significance of home blood pressure measurement is primarily produced by multiple measurements of blood pressure. 2 These multiple measurements also provide information on day-by-day blood pressure variability under relatively controlled conditions. 4 Previous studies of ambulatory blood pressure monitoring have highlighted that circadian variation 5 and short-term blood pressure variability 6 can predict cardiovascular events above and beyond traditional risk factors. However, no studies have investigated associations between home blood pressure variability and cardiovascular events. We hypothesized that day-by-day blood pressure variability derived from self-measurement at home would provide further insights into pro...

Outcome-driven recommendations about time intervals during which ambulatory blood pressure should be measured to diagnose white-coat or masked hypertension are lacking. We cross-classified 8237 untreated participants (mean age, 50.7 years; 48.4% women) enrolled in 12 population studies, using ≥140/≥90, ≥130/≥80, ≥135/≥85, and ≥120/≥70 mm Hg as hypertension thresholds for conventional, 24-hour, daytime, and nighttime blood pressure. White-coat hypertension was hypertension on conventional measurement with ambulatory normotension, the opposite condition being masked hypertension. Intervals used for classification of participants were daytime, nighttime, and 24 hours, first considered separately, and next combined as 24 hours plus daytime or plus nighttime, or plus both. Depending on time intervals chosen, white-coat and masked hypertension frequencies ranged from 6.3% to 12.5% and from 9.7% to 19.6%, respectively. During 91 046 person-years, 729 participants experienced a cardiovascular event. In multivariable analyses with normotension during all intervals of the day as reference, hazard ratios associated with white-coat hypertension progressively weakened considering daytime only (1.38; P=0.033), nighttime only (1.43; P=0.0074), 24 hours only (1.21; P=0.20), 24 hours plus daytime (1.24; P=0.18), 24 hours plus nighttime (1.15; P=0.39), and 24 hours plus daytime and nighttime (1.16; P=0.41). The hazard ratios comparing masked hypertension with normotension were all significant (P<0.0001), ranging from 1.76 to 2.03. In conclusion, identification of truly low-risk white-coat hypertension requires setting thresholds simultaneously to 24 hours, daytime, and nighttime blood pressure. Although any time interval suffices to diagnose masked hypertension, as proposed in current guidelines, full 24-hour recordings remain standard in clinical practice.

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)(1989)(1990)(1991)(1992)(1993)(1994)(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. This article was sent to Morris J. Brown, Guest Editor, for review by expert referees, editorial decision, and final disposition. Methods Study DesignAs described in detail elsewhere, 5 from 1988 until 1995, we contacted 4969 individuals who resided in 4 districts of Ohasama, a rural community in Iwate Prefecture, Japan, and who were ≥35 years old. Residents were not eligible if they were not at home during normal working hours (n=1057) or if they were hospitalized (n=166) or incapacitated (n=94). Of the remaining 3652 residents, 3090 (84.6%) participated in baseline and follow-up examinations. The study complies with the Declaration of Helsinki, and the study protocol was approved by the institutional review board of Tohoku University School of Medicine and by the Ohasama Town Government Department of Health. Participants gave written informed consent. We excluded 669 participants from analysis because they had not measured their home blood pressure (n=218), had obtained <5 morning or evening readings (n=322), or because at enrollment they had a history of stroke (n=129). Thus, the number of participants statistically analyzed totaled 2421. Data Collection...

Abstract-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 (Ն40 years) were followed up for an average of 11 years. Key Words: self-measurement Ⅲ home blood pressure Ⅲ stroke Ⅲ general population Ⅲ morning-home blood pressure Ⅲ evening-home blood pressure Ⅲ Ohasama study S elf-measurement of blood pressure (BP) at home (home BP) by individual patients is highly reproducible and reliable and is acknowledged worldwide as a useful clinical tool. [1][2][3][4] We have reported previously the strong predictive power of home BP measurements in the morning for cardiovascular disease mortality and stroke incidence. [5][6][7] It is generally agreed that the prognostic power of home BP is higher than casualscreening BP in accordance with these recent studies. [5][6][7][8] Several guidelines recommended that home BP should be measured both in the morning and in the evening (eg, European Society of Hypertension guidelines based on the German Hypertension League recommendation 9,10 ), and it has been recommended in the 7th Report of the Joint National Committee that the home BP level should be evaluated as the average of all of the BP values measured. 1 Because of circadian BP variation and other latent confounding factors, the characteristics of home BP in the morning (morning BP) and that in the evening (evening BP) must be different. 11,12 Our previous study showed that there was a substantial difference between morning BP and evening BP. 11 Moreover, antihypertensive medications were reported to affect circadian BP variation. 13 Although morning BP values have a high predictive power, little is known about the predictive value of evening BP. Bobrie et al 8 demonstrated that the home BP, which was averaged from the morning BP and evening BP readings, had good prognostic value among elderly (Ն60 years) hypertensive patients. However, the clinical significance of the home BP in the evening versus that in the morning was unclear. The purpose of the present study is to evaluate the clinical significance of evening BP as well as morning BP for prediction of stroke incidence using data derived from the Ohasama study, a long-term cohort study in the northern part of Japan.

Although a growing body of evidence suggests a link between diabetes and cancer, it is not clear whether diabetes independently increases the risk of cancer. We conducted a comprehensive assessment of the association between pre-existing diabetes and total and site-specific cancer risk based on a pooled analysis of eight cohort studies in Japan (>330 000 subjects). We estimated a summary hazard ratio by pooling study-specific hazard ratios for total and site-specific cancer by using a random-effects model. A statistically increased risk was observed for cancers at specific sites, such as colon (hazard ratio; HR = 1.40), liver (HR = 1.97), pancreas (HR = 1.85) and bile duct (HR = 1.66; men only). Increased risk was also suggested for other sites, and diabetes mellitus was associated with an overall 20% increased risk in total cancer incidence in the Japanese population. The association between these two diseases has important implications for reiterating the importance of controlling lifestyle factors and may suggest a possible strategy for cancer screening among patients with diabetes. Studies continuously investigating the risk factors for diabetes are also important. (Cancer Sci 2013; 104: 1499-1507 I n Japan, as in other countries, the increasing prevalence of diabetes presents a serious public health problem. The estimated numbers of persons with diabetes in 1997, 2002 and 2007 were 6.9 million (prevalence 5.5%), 7.4 million (prevalence 5.4%) and 8.9 million (prevalence 7.1%), respectively.( 1) A growing body of evidence suggests a link between diabetes and cancer. A recent meta-analysis showed that people with diabetes are at elevated risk for cancers of the liver,biliary tract,pancreas, (4) stomach,colorectum, (6) kidney,bladder, (8) breast (9) and endometrium, (10) but at decreased risk for prostate cancer.(11) Research suggests that hyperinsulinemia acting through aberrations in the insulin-like growth factor pathways or steroid hormone metabolism is involved in mitogenic actions. However, whether diabetes independently increases the risk of these cancers or whether cancer and diabetes simply share common risk factors, such as obesity or physical inactivity, is not clear; many of the studies included in the meta-analysis did not necessarily control for other lifestyle factors. Moreover, evidence from other cancer sites and the impact of diabetes on total cancer have not been elucidated completely. (12)(13)(14) In the present study, we conducted a comprehensive assessment of the association between pre-existing diabetes and total and site-specific cancer by means of a pooled analysis of eight cohort studies in Japan (>330 000 subjects). Patients and MethodsStudy population. In 2006, the Research Group for the Development and Evaluation of Cancer Prevention Strategies in Japan initiated a pooling project using original data from major cohort studies to evaluate the association between lifestyle and major forms of cancer and mortality in Japanese people. The following a priori inclusion criteria were set f...

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. provided. 7 Thus, it can be hypothesized that home BP can better predict future cognitive decline than conventional BP.One of the clinically significant aspects of home BP measurements is produced by the multiple BP measurements. 6 These multiple home BP measurements can also produce day-to-day BP variability that is calculated from the SD of home BP. Our previous studies demonstrated that high day-to-day BP variability was associated with an increased risk of cardiovascular mortality, independent of home BP values, and other risk factors. 8,9 However, no studies have investigated the associations of day-to-day BP variability with cognitive impairment.The objectives of this prospective study were to examine and to confirm the stronger predictive power of home BP values for cognitive decline than conventional BP and to compare the predictive power of the averaged home BP and the day-to-day home BP variability for cognitive decline. Methods DesignThis report was part of the Ohasama study, a community-based BP measurement project ongoing since 1987. Socioeconomic and demographic characteristics of this region and details of the study have been described previously. 5,6 Study PopulationOf the remaining 2400 eligible individuals, 1436 participated in the baseline examination, and 1396 gave informed consent for follow-up analyses. Of these, the total number of participants included in the present analyses was 48...

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.

High BP at different times of day were associated with different subtypes of cerebrovascular and cardiovascular mortality risk.