Michihiro Satoh

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.

Acute and Subacute Effects of the Great East Japan Earthquake on Home Blood Pressure Values

To the Editor: The Great East Japan Earthquake hit northeast Japan at 2:46 pm on March 11, 2011, resulting in >20 000 dead or missing persons. Previous studies demonstrated that an increased incidence of cardiovascular disease was prolonged until a few months after the Hanshin-Awaji earthquake.1,2 This could be explained by increased blood viscosity attributed to diminished water intake, by activation of the coagulation system, and especially by elevated blood pressure (BP).2 However, in most previous studies, BP was measured by office BP, which is influenced by observer bias and the so-called white-coat effect. The self-measured BPs in the morning at home (home BP) measurements are reportedly more reliable than office BP, avoid both observer and regression dilution biases, and can provide information on daily BP under relatively controlled conditions. Thus, in an outpatient clinic located in Sendai, which is one of the devastated cities in northeastern Japan, we surveyed changes in home BP before and after the earthquake in hypertensive patients who have measured their home BP customarily. We obtained home BP in 142 hypertensive patients whose treatment status of hypertension or antihypertensive drugs …

Ambulatory Versus Home Versus Clinic Blood Pressure The Association With Subclinical Cerebrovascular Diseases: The Ohasama Study

The usefulness of ambulatory, home, and casual/clinic blood pressure measurements to predict subclinical cerebrovascular diseases (silent cerebrovascular lesions and carotid atherosclerosis) was compared in a general population. Data on ambulatory, home, and casual/clinic blood pressures and brain MRI to detect silent cerebrovascular lesions were obtained in 1007 subjects aged ≥55 years in a general population of Ohasama, Japan. Of the 1007 subjects, 583 underwent evaluation of the extent of carotid atherosclerosis. Twenty-four–hour, daytime, and nighttime ambulatory and home blood pressure levels were closely associated with the risk of silent cerebrovascular lesions and carotid atherosclerosis (all P<0.05). When home and one of the ambulatory blood pressure values were simultaneously included in the same regression model, each of the ambulatory blood pressure values remained a significant predictor of silent cerebrovascular lesions, whereas home blood pressure lost its predictive value. Of the ambulatory blood pressure values, nighttime blood pressure was the strongest predictor of silent cerebrovascular lesions. The home blood pressure value was more closely associated with the risk of carotid atherosclerosis than any of the ambulatory blood pressure values when home and one of the ambulatory blood pressure values were simultaneously included in the same regression model. The casual/clinic blood pressure value had no significant association with the risk of subclinical cerebrovascular diseases. Although the clinical indications for ambulatory blood pressure monitoring and home blood pressure measurements may overlap, the clinical significance of each method for predicting target organ damage may differ for different target organs.

Factors Associated With Day-By-Day Variability of Self-Measured Blood Pressure at Home: The Ohasama Study

BACKGROUND We previously reported that high day-by-day blood pressure (BP) variability derived from self-measured BP at home (home BP) predicted cardiovascular mortality over and beyond other risk factors. The objective of this study is to clarify the determinants of the day-by-day home-BP variability. METHODS We conducted a cross-sectional community survey in 1,215 inhabitants (female gender 59%, mean age 62 years) of Ohasama, Japan. The subjects measured their BP and heart rate once every morning and once every evening for 4 weeks. The day-by-day BP variability and heart rate variability were defined as within individual standard deviation of all home BP and heart rate, respectively. We also considered coefficient of variation (CV). These parameters in the morning and those in the evening were calculated separately. RESULTS The level and standard deviation of home systolic/diastolic BP (SBP/DBP) in the morning were 123.4 +/- 15.1/75.7 +/- 9.0 mm Hg and 8.6 +/- 3.1/5.8 +/- 2.0 mm Hg. Multivariate linear regression analysis demonstrated that older age, female gender, elevated home BP, low home heart rate, and elevated home heart rate variability were significant determinants of elevated home-BP variability. In addition to these factors, alcohol intake and sedentary lifestyle were also determinants of elevated home-BP variability in the evening. CONCLUSIONS Day-by-day home-BP variability was associated with home BP, alcohol intake or sedentary lifestyle. Whether modifying these factors would reduce BP variability and whether such reduction would lead to better outcomes needs further study.

Day-to-Day Variability in Home Blood Pressure Is Associated With Cognitive Decline The Ohasama Study

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.

Association of (pro)renin receptor gene polymorphisms with lacunar infarction and left ventricular hypertrophy in Japanese women: the Ohasama study

Recent studies have revealed that (pro)renin receptor ((P)RR), a newly identified member of the renin–angiotensin system, is associated with organ damage that occurs with cardiovascular disease. We investigated the association of genetic polymorphisms in the (P)RR gene with lacunar infarction, white matter hyperintensity and left ventricular hypertrophy (LVH) in a Japanese general population recruited from the Ohasama study, a Japanese cohort study. A total of 779 subjects (men=250 and women=529) were recruited. For the association study, we selected three polymorphisms: −782A>G (rs2968915), intervening sequence (IVS)5+169C>T (rs5918007) and +1513A>G (rs6609080). In women, the prevalence of lacunar infarction and LVH was significantly higher in subjects with the +1513GG genotype than in those with the AA or AG genotypes (lacunar infarction: P=0.01, LVH: P=0.003). Plasma renin activity (PRA) levels in women with the GG genotype were significantly lower than in women with the AA or AG genotypes (P=0.01). Multiple logistic regression analysis adjusted for confounding factors demonstrated that +1513A>G polymorphism was significantly and independently associated with the risk of lacunar infarction (trend P=0.03) and LVH (trend P=0.003). In men, there were no significant differences in lacunar infarction, LVH or PRA levels among the three genotypes. The polymorphism of the (P)RR gene +1513A>G is associated with lacunar infarction and LVH in Japanese women. These results suggest that (P)RR has a role in organ damage in humans.

Global Cardiovascular and Renal Outcomes of Reduced GFR

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.

Night-time blood pressure is associated with the development of chronic kidney disease in a general population: the Ohasama Study.

Objective: Ambulatory blood pressure (BP) is reportedly associated with target organ damage. However, whether ambulatory BP carries prognostic significance for the development of chronic kidney disease (CKD) has not been confirmed. Method: We measured ambulatory BP in 843 participants without CKD at baseline from a general Japanese population and examined the incidence of CKD defined as positive proteinuria or an estimated glomerular filtration rate (eGFR) less than 60 ml/min per 1.73 m2 at health checks. The association between baseline ambulatory BP and CKD incidence was examined using the Cox proportional hazard regression model adjusted for sex, age, BMI, habitual smoking, habitual alcohol consumption, diabetes mellitus, hypercholesterolemia, a history of cardiovascular disease, antihypertensive medication, eGFR at baseline, the number of follow-up examinations, and the year of the baseline examination. Results: The mean age of the participants averaged 62.9 ± 8.1 years, 71.3% were women and 23.7% were under antihypertensive medication. During a median follow-up of 8.3 years, 220 participants developed CKD events. The adjusted hazard ratios for CKD in a 1-standard deviation increase in daytime and night-time SBP were 1.13 [95% confidence interval (CI) 0.97–1.30] and 1.21 (95% CI 1.04–1.39), respectively. When night-time and daytime BP was mutually adjusted into the same model, only night-time BP persisted as an independent predictor of CKD. Conclusion: Night-time BP is a better predictor of CKD development than daytime BP in the general population. Ambulatory BP measurement is considered useful for evaluating the risk of progression to CKD.

Home blood pressure level, blood pressure variability, smoking, and stroke risk in Japanese men: the Ohasama study.

BACKGROUND Hypertension and smoking independently contribute to the risk of stroke. Our objective was to investigate home blood pressure (HBP) levels, day-by-day BP variability, and smoking in the prediction of stroke in Japanese men. METHODS In this study, 902 men (mean age, 58.6 years) without a past history of stroke were evaluated. HBP was measured once every morning for 4 weeks. Day-by-day BP variability was defined as within-subject standard deviations (SD) of HBP. Smoking history was obtained from a standardized questionnaire. Hazard ratios (HRs) for stroke were examined by Cox regression model, with adjustment for possible confounders. RESULTS During 13.1 years (median) of follow-up, 89 cerebral infarctions, 28 intracranial hemorrhages, and six other strokes occurred. Systolic HBP levels (HR = 1.59 per 14.6 mm Hg increase, P < 0.0001) and variability (HR = 1.26 per 3.1 mm Hg increase, P = 0.03) of +1 between-subject SD were significantly associated with cerebral infarction. The relationship between HBP and cerebral infarction differed with smoking status (interaction P = 0.021 and 0.017 for systolic level and variability, respectively). In analyses stratified according to smoking, systolic level (HR = 1.78, P < 0.0001) and variability (HR = 1.38, P = 0.006) were significantly associated with cerebral infarction in ever smokers (N = 511), but not in never smokers (N = 391; P ≥ 0.6 for both). No significant association was found between smoking and the risk of intracranial hemorrhage. CONCLUSIONS In ever smokers, both HBP levels and variability are significantly associated with the risk of cerebral infarction. Our findings further validate the benefit of smoking cessation in preventing cardiovascular disease (CVD), especially cerebral infarction.

Predictive power of home blood pressure and clinic blood pressure in hypertensive patients with impaired glucose metabolism and diabetes.

Objectives: We evaluated the predictive power of home blood pressure and clinic blood pressure based on the long-term cardiovascular outcome in hypertensive patients with and without impaired glucose metabolism (IGM). Method: The multicentre Hypertension Objective Treatment Based on Measurement by Electrical Devices Blood Pressure trial (HOMED-BP) involved 3080 patients (50.5% women; mean age 59.7 years) with a baseline, untreated home/clinic blood pressure as well as follow-up, on-treatment blood pressure. Of those, 979 had IGM and 475 of these patients had diabetes. We applied Cox regression pooling all participants in a cohort analysis in which IGM and normal glucose metabolism (NGM) were separated. Results: During median 5.45 years follow-up, cardiovascular events occurred in 48 patients with IGM and 53 patients with NGM. Baseline home SBP significantly predicted cardiovascular outcome among IGM group [hazard ratio 1.68, 95% CI 1.26–2.26, P = 0.0005]. On-treatment home blood pressure was a significant predictor for cardiovascular risk even after the further adjustment of baseline blood pressure level (P ⩽ 0.027), whereas on-treatment clinic blood pressure was not in NGM group (P ≥ 0.37). The event rate in IGM was approximately two times higher than that in NGM (9.95 vs. 4.88 per 1000 patient-years), resulted to the low 5-year number needed to treat in IGM patients [83 vs. 121 for 1–SD (13.1 mmHg) home SBP reduction, and 62 vs. 104 for 1–SD (9.5 mmHg) home DBP reduction). Conclusion: The present findings suggest that long-term cardiovascular risk in IGM patients should be assessed based on home blood pressure, not on clinic blood pressure.