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The role of real-world data, collected from clinical practice rather than clinical trials, has become increasingly important for investigating real-life situations, such as treatment effects. In Japan, evidence on hypertension, cardiovascular diseases, and kidney diseases using real-world data is increasing. These studies are mainly based on "the insurer-based real-world data" collected as electronic records, including data from health check-ups and medical claims such as JMDC database, DeSC database, the Japan Health Insurance Association (JHIA) database, or National Databases of Health Insurance Claims and Specific Health Checkups (NDB). Based on the insurer-based real-world data, traditional but finely stratified associations between hypertension and cardiovascular or kidney diseases can be explored. The insurer-based real-world data are also useful for pharmacoepidemiological studies that capture the distribution and trends of drug prescriptions; combined with annual health check-up data, the effectiveness of drugs can also be examined. Despite the usefulness of insurer-based real-world data collected as electronic records from a wide range of populations, we must be cautious about several points, including issues regarding population uncertainty, the validity of cardiovascular outcomes, the accuracy of blood pressure, traceability, and biases, such as indication and immortal biases. While a large sample size is considered a strength of real-world data, we must keep in mind that it does not overcome the problem of systematic error. This review discusses the usefulness and pitfalls of insurer-based real-world data in Japan through recent examples of Japanese research on hypertension and its association with cardiovascular or kidney disease., (© 2024. The Author(s).)

Background: Previous observational studies have shown similarities in cardiometabolic risk factors between spouses. It is still possible that this result reflects the age similarity of spouses rather than environmental factors of spouses (e.g. cohabitation effect). To clarify the importance of mate cardiometabolic risk factors for similarity of environmental factors, it is necessary to examine whether they are observed in random male-female pairs while maintaining the age of the spousal pairs. This study aimed to determine whether the similarities found between spousal pairs for cardiometabolic risks were also observed between random male-female pairs., Methods: This cross-sectional study included 5,391 spouse pairs from Japan; data were obtained from a large biobank study. For pairings, women of the same age were randomly shuffled to create new male-female pairs of the same age as that of the original spouse pairs. Similarities in cardiometabolic risk factors between the random male-female pairs were analysed using Pearson's correlation or age-adjusted logistic regression analyses., Results: The mean ages of the men and women were 63.2 and 60.4 years, respectively. Almost all cardiometabolic risk factors similarities were not noted in cardiometabolic risk factors, including the continuous risk factors (anthropometric traits, blood pressure, glycated haemoglobin level, and lipid traits); lifestyle habits (smoking, drinking, and physical activity); or diseases (hypertension, type 2 diabetes mellitus, and metabolic syndrome) between the random male-female pairs. The age-adjusted correlation coefficients ranged from - 0.007 for body mass index to 0.071 for total cholesterol. The age-adjusted odds ratio (95% confidence interval) for current drinkers was 0.94 (0.81 - 1.09); hypertension, 1.07 (0.93 - 1.23); and type 2 diabetes mellitus, 1.08 (0.77 - 1.50)., Conclusion: In this study, few similarities in cardiometabolic risk factors were noted among the random male-female pairs. As spouse pairs may share environmental factors, intervention strategies targeting lifestyle habits and preventing lifestyle-related diseases may be effective., (© 2022. The Author(s).)

A diminished nocturnal decline in blood pressure (BP) represents a risk factor for cardiovascular disease. To define daytime and nighttime ambulatory BP, clock time-dependent methods are used when information on diary-based sleeping time is unavailable. We aimed to compare fixed-clock intervals with diary records to identify nocturnal BP declines as a predictor of long-term cardiovascular risk among the general population. Data were obtained from 1714 participants with no history of cardiovascular disease in Ohasama, Japan (mean age, 60.6 years; 64.9% women). We defined extreme dippers, dippers, non-dippers, and risers as nocturnal systolic BP decline ≥20%, 10-19%. 0-9%, and <0%, respectively. Over a mean follow-up period of 17.0 years, 206 cardiovascular deaths occurred. Based on diary records, multivariable-adjusted hazard ratios (HRs) for cardiovascular death compared with dippers were 1.24 (95% confidence interval [CI], 0.82-1.87) in extreme dippers, 1.21 (0.87-1.69) in non-dippers, and the highest HR of 2.31 (1.47-3.62) was observed in risers. Using a standard fixed-clock interval (daytime 09:00-21:00; nighttime 01:00-06:00), a nighttime 2 h-early shifted fixed-clock (daytime 09:00-21:00; nighttime 23:00-04:00), or a nighttime 2 h-late shifted fixed-clock (daytime 09:00-21:00; nighttime 03:00-08:00), the HR (95%CI) in risers compared with dippers was 1.57 (1.08-2.27), 2.02 (1.33-3.05), or 1.29 (0.86-1.92), respectively. Although use of diary records remains preferable, the standard and nighttime 2 h-early shifted fixed-clock intervals appear feasible for population-based studies.

The burden of premature death and health loss from ESRD is well described. Less is known regarding the burden of cardiovascular disease attributable to reduced GFR. We estimated the prevalence of reduced GFR categories 3, 4, and 5 (not on RRT) for 188 countries at six time points from 1990 to 2013. Relative risks of cardiovascular outcomes by three categories of reduced GFR were calculated by pooled random effects meta-analysis. Results are presented as deaths for outcomes of cardiovascular disease and ESRD and as disability-adjusted life years for outcomes of cardiovascular disease, GFR categories 3, 4, and 5, and ESRD. In 2013, reduced GFR was associated with 4% of deaths worldwide, or 2.2 million deaths (95% uncertainty interval [95% UI], 2.0 to 2.4 million). More than half of these attributable deaths were cardiovascular deaths (1.2 million; 95% UI, 1.1 to 1.4 million), whereas 0.96 million (95% UI, 0.81 to 1.0 million) were ESRD-related deaths. Compared with metabolic risk factors, reduced GFR ranked below high systolic BP, high body mass index, and high fasting plasma glucose, and similarly with high total cholesterol as a risk factor for disability-adjusted life years in both developed and developing world regions. In conclusion, by 2013, cardiovascular deaths attributed to reduced GFR outnumbered ESRD deaths throughout the world. Studies are needed to evaluate the benefit of early detection of CKD and treatment to decrease these deaths., (Copyright © 2017 by the American Society of Nephrology.)

Objective: To assess the present status of clinical care for postpartum patients with hypertensive disorders of pregnancy (HDP) in Japan., Methods: We conducted a nationwide questionnaire survey of obstetricians, internists and hypertension specialists and analyzed 686 valid responses., Results: Though HDP is widely known as a risk factor for subsequent hypertension and cardiovascular disease, over one-third of obstetricians terminated their postpartum follow-up of HDP patients without referring them to other departments., Conclusion: It is important to establish an effective referral system, whereby patients with HDP can be smoothly transferred to primary care or a specialist physician after childbirth for long-term monitoring and management of blood pressure.

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.

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.

Background: To clarify whether the double product (DP) (product of systolic blood pressure (SBP) and pulse rate (PR)) at rest based on home blood pressure (HBP) measurement has prognostic value for mortality., Methods: HBP data of 2,583 participants from a Japanese general population (40% men) ≥35 years of age (mean, 59 years) without a history of cardiovascular disease (CVD) were obtained. The prognostic significance for a 1,000 mm Hg × beats/min elevation in the DP was determined by Cox proportional hazard regression analysis. The association between mortality and the DP was compared to that between mortality and the SBP or the PR using the likelihood ratio (LR) test., Results: During a mean follow-up of 12.0 years, 454 total deaths, 153 CVD deaths (85 cardiac diseases, 68 strokes), and 301 non-CVD deaths occurred. The DP was positively and significantly associated with total, CVD, cardiac, stroke, and non-CVD mortality. The LR test showed that the DP was more strongly associated with total mortality, mortality from cardiac disease, and non-CVD than SBP. Similarly, the DP was more strongly associated with total death, CVD death, and death from stroke than PR., Conclusions: The home DP was significantly associated with mortality, and the LR test indicated that the association between the DP and mortality would be stronger than that between mortality and SBP or PR. These findings are preliminary, and further study is needed to confirm the usefulness of the DP in risk stratification.

The aim of this study was to investigate how frequent ambulatory blood pressure (ABP) readings need to be obtained to reproduce the ambulatory arterial stiffness index (AASI) and pulse pressure (PP) without loss of information. We compared concordance from full and reduced ABP recordings. We recorded 24-h ABP at 30-min intervals in 1542 residents of Ohasama, Japan (baseline age, 40-93 years; 63.4% women). We randomly excluded up to 16 readings per recording or we selected readings at fixed 1- or 2-h intervals. Using full recordings as reference, we computed for the reduced recordings repeatability coefficient by Bland and Altman's approach. By Cox regression, we also calculated multivariate-adjusted hazard ratios for cardiovascular mortality. The median number of ABP readings per recording was 46. Randomly excluding more readings reduced the concordance of AASI, but not PP. Selecting blood pressure readings at 1- or 2-h intervals produced mean values of AASI and PP, which significantly differed from those in full recordings. During follow-up (median, 13.3 years) 126 cardiovascular deaths occurred. Across quartiles, AASI significantly predicted cardiovascular mortality in a U-shaped manner. AASI lost its prognostic significance when the number of randomly excluded readings increased from 8 to 16 or when the interval between readings was 1 h or longer. Compared with PP, AASI is less reproducible when the number of readings in ABP decreases, but this does not affect the predictive accuracy of AASI for cardiovascular mortality, until the median number of readings per ABP recording is less than ∼35., (© 2011 The Japanese Society of Hypertension All rights reserved)

The introduction of 24-h ambulatory blood pressure (BP) monitoring has enabled BP evaluations at specific times of the day. Associations between diurnal BP variation and cardiovascular prognosis have been investigated in the Ohasama study, which is an epidemiological survey of hypertension using ambulatory and home BP monitoring that has been ongoing since 1985 in the general population of Ohasama, a town located in northern Japan. A diminished nocturnal decline in systolic BP was associated with a greater common carotid intima-media thickness as well as a higher risk of cardiovascular morbidity and mortality, especially the risk for cerebral infarction. The consumption of large amounts of alcohol was associated with a higher morning pressor surge. A large nocturnal decline in BP and a large morning pressor surge were both associated with a risk of cerebral hemorrhage. Ambulatory BP monitoring provides not only static, but also dynamic information about BP that should be considered to ensure effective management of hypertension and cardiovascular diseases.

Previous studies on the prognostic significance of the morning blood pressure surge (MS) produced inconsistent results. Using the International Database on Ambulatory Blood Pressure in Relation to Cardiovascular Outcome, we analyzed 5645 subjects (mean age: 53.0 years; 54.0% women) randomly recruited in 8 countries. The sleep-through and the preawakening MS were the differences in the morning blood pressure with the lowest nighttime blood pressure and the preawakening blood pressure, respectively. We computed multivariable-adjusted hazard ratios comparing the risk in ethnic- and sex-specific deciles of the MS relative to the average risk in the whole study population. During follow-up (median: 11.4 years), 785 deaths and 611 fatal and nonfatal cardiovascular events occurred. While accounting for covariables and the night:day ratio of systolic pressure, the hazard ratio of all-cause mortality was 1.32 (95% CI: 1.09 to 1.59; P=0.004) in the top decile of the systolic sleep-through MS (>or=37.0 mm Hg). For cardiovascular and noncardiovascular death, these hazard ratios were 1.18 (95% CI: 0.87 to 1.61; P=0.30) and 1.42 (95% CI: 1.11 to 1.80; P=0.005). For all cardiovascular, cardiac, coronary, and cerebrovascular events, the hazard ratios in the top decile of the systolic sleep-through MS were 1.30 (95% CI: 1.06 to 1.60; P=0.01), 1.52 (95% CI: 1.15 to 2.00; P=0.004), 1.45 (95% CI: 1.04 to 2.03; P=0.03), and 0.95 (95% CI: 0.68 to 1.32; P=0.74), respectively. Analysis of the preawakening systolic MS and the diastolic MS generated consistent results. In conclusion, a MS above the 90th percentile significantly and independently predicted cardiovascular outcome and might contribute to risk stratification by ambulatory blood pressure monitoring.

Background: Resting heart rate can predict cardiovascular disease mortality or all-cause mortality. Because of the effect of the alert reaction, heart rates measured out-of-office should have better predictive power than those obtained at clinics. However, only a few studies have described the relationship between heart rate measured by ambulatory blood pressure monitoring devices and cardiovascular disease prediction., Methods: We studied 1444 individuals from the Japanese general population who did not have a history of cardiovascular diseases including arrhythmia. We used multiple adjusted Cox proportional hazards to calculate the mortality risk of daytime heart rate, night-time heart rate, and the day-night heart rate dip ratio [day-night heart rate dip ratio = (daytime heart rate--night-time heart rate)/daytime heart rate x 100]., Results: After 12 years of follow-up, 101, 195, and 296 participants died due to cardiovascular diseases, noncardiovascular diseases, and all causes, respectively. As shown by others, neither daytime nor night-time heart rate predicted cardiovascular disease mortality, whereas both predicted noncardiovascular disease mortality. The day-night heart rate dip ratio was significantly related to all-cause mortality. When night-time heart rate and day-night heart rate dip ratio were simultaneously included into the same Cox model, only night-time heart rate significantly and independently predicted all-cause mortality (relative hazard per 10 bpm increase = 1.29, 95% confidence interval, 1.07-1.54)., Conclusion: Night-time heart rate value seems to have the most important predictor of all-cause mortality among ambulatory heart rate parameters in this population.

The prognostic significance of morning surge in blood pressure (BP) remains obscure because the findings of the four prospective studies available [ambulatory BP monitoring (ABPM) substudy of the Syst-Eur trial, the Jichii Medical School ABPM-wave1 study, the Bordeaux hypertensive cohort study, and the Ohasama study] have generated conflicting results partly because of small number of events and differences in definitions, measurement conditions, target outcomes, and study populations. A large morning surge was associated with a significantly lower risk of total cardiovascular events in the Syst-Eur study. On the contrary, a large morning surge was associated with a significantly higher risk of total stroke events in the Jichii Medical School ABPM-wave1 study, and of total cardiovascular events in the Bordeaux hypertensive cohort study. The Ohasama study found that a large morning surge was not associated with the risk of total stroke events, but rather with a significantly higher risk of cerebral hemorrhage. More prospective studies or meta-analyses are required to better elucidate the prognostic significance of the morning surge in BP.

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.

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.

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 >or=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.

Background: Recently, the advantages of self-measurement of blood pressure (BP) at home have been recognized. The same advantages could also be applicable to resting heart rate (HR) values assessed at home using a device designed for home BP measurement. However, there have been no studies investigating whether home HR values predict the risk of cardiovascular disease mortality. We therefore investigated the usefulness of HR values in predicting cardiovascular mortality using a device that allowed self-measurement of BP and HR at home., Methods: The association between the home-measured resting HR and the 10-year risk of cardiovascular mortality was examined in 1780 Japanese individuals >/=40 years of age who had no significant arrhythmias. A Cox proportional hazards model that adjusted for major risk factors was used., Results: An increase of 5 beats/min in the morning home HR measurement was associated with a 17% increase in the risk of cardiovascular mortality (95% confidence interval 5% to 30%). This relationship was also statistically significant after adjustment for home BP values. Even when home-measured systolic BP was within the normal range (<135 mm Hg), subjects with HR >/=70 beats/min had a higher risk of cardiovascular mortality (relative hazard 2.16, 95% confidence interval 1.21 to 3.85) than those with normal systolic BP and HR values., Conclusions: Self-measurement of HR at home, together with self-measurement of BP, is a simple method of providing useful clinical information for assessing cardiovascular risk.