Takuo Hirose

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.

Association of (Pro)renin Receptor Gene Polymorphism With Blood Pressure in Japanese Men: The Ohasama Study

BACKGROUND Recent studies have revealed that (pro)renin receptor ((P)RR), a newly identified member of the renin-angiotensin system (RAS), is associated with blood pressure regulation in animals. However, there is no information on (P)RR in humans. We investigated the association of (P)RR gene polymorphisms with blood pressure in a Japanese population. METHODS Subjects (n = 1,112) were recruited from participants in the Ohasama study, a Japanese cohort study. For the association study, we selected three polymorphisms: -782A>G (rs2968915), intervening sequence (IVS)5+169C>T (rs5918007), and +1513A>G (rs6609080). Because the (P)RR gene is on the X chromosome, men (n = 357) and women (n = 755) were analyzed separately. RESULTS In men, 24-h systolic blood pressure (SBP) and diastolic blood pressure (DBP) values, daytime SBP and DBP values, and nighttime SBP and DBP values were significantly higher in IVS5+169T allele carriers than C allele carriers. Multiple regression analysis showed that IVS5+169C>T was significantly and independently related to ambulatory blood pressure (ABP). IVS5+169C>T was not associated with casual blood pressure (CBP) in men. In women, there were no significant differences in blood pressure values among the three genotypes of IVS5+169C>T. This polymorphism had no significant association with any other clinical characteristic. -782A>G was weakly associated with ABP in men. +1513A>G was not associated with blood pressure values in either men or women. CONCLUSIONS We demonstrated for the first time that polymorphism of the (P)RR gene IVS5+169C>T is associated with ABP in Japanese men. This association suggests that (P)RR has a role in blood pressure regulation.

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.

Predictive value of ambulatory heart rate in the Japanese general population: the Ohasama study.

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 × 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.

Seasonal trends of blood pressure during pregnancy in Japan : the Babies and their Parents' Longitudinal Observation in Suzuki Memorial Hospital in Intrauterine Period study

Objective Blood pressure (BP) increases both in winter and in the last trimester of pregnancy. Some interaction seems to exist between season and gestational age. The present study observed home BP values during pregnancy with adjustment for seasonal variation and gestational age. Methods We observed 10 353 home BP measurements from 101 normal pregnant women attending a maternity hospital in Japan. Home BP values were examined by mixed linear model adjusting for meteorological data and gestational age. Results The lowest home BP values were observed in the second trimester [mean (±standard deviation) systolic/diastolic BP, 101.8 ± 7.9/59.8 ± 5.8 mmHg at gestational week 20]. In the last trimester, home BP values gradually increased and the values after gestational week 26 were significantly higher than those at gestational week 20 (110.1 ± 9.7/66.8 ± 7.7 mmHg at gestational week 40). A 10°C increase in daily minimum outdoor temperature was associated with a mean reduction of 2.5/2.5 mmHg (Δ systolic BP/Δ diastolic BP: 95% confidence interval, 2.3/2.4 to 2.6/2.7 mmHg) in home BP with adjustment for gestational age. The largest and smallest estimated home BP changes during pregnancy were 12.8/12.5 and 3.1/3.0 mmHg in pregnant woman who delivered in January and July, respectively. Conclusion Interactions among BP, season and gestational age should be considered when evaluating BP in pregnant women. Risks associated with high BP might be underestimated in pregnant woman in summer who will deliver in winter.

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.

Gene expression of (pro)renin receptor is upregulated in hearts and kidneys of rats with congestive heart failure

Recent studies have revealed that (pro)renin receptor ((P)RR), a newly identified member of the renin-angiotensin system, was associated with organ damage in the kidney. However, there has been little information for (P)RR in hearts. To investigate the regulation of (P)RR in heart failure, we examined the expression of (P)RR in hearts and kidneys of rats with congestive heart failure (CHF) due to coronary ligation by quantitative RT-PCR and immunohistochemistry. Significantly increased levels of (P)RR mRNA were found in the atrium, right ventricle, non-infarcted part of left ventricle, infarcted part of left ventricle and kidney of CHF rats, when compared with sham operated rats (about 1.6-fold, 1.4-fold, 1.6-fold, 1.7-fold and 1.5-fold, respectively). Expression levels of mRNAs encoding renin and angiotensinogen in these heart and kidney tissues were also increased in the CHF rats. Immunohistochemistry showed positive (P)RR immunostaining in the myocardium, the renal tubular cells, and vascular smooth muscle and endothelial cells in the heart and the kidney. The renal tubular cells were more intensely immunostained in CHF rats than in sham operated rats. These findings suggest that the expression of (P)RR is increased in the hearts and kidneys of rats with heart failure, and that (P)RR may contribute to heart failure.

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.

Expression of (pro)renin receptor in human kidneys with end-stage kidney disease due to diabetic nephropathy.

(Pro)renin receptor ((P)RR), a specific receptor for renin and prorenin, is a 350 amino-acid protein with a single transmembrane domain and may play important pathophysiological roles in diabetic nephropathy. The aim of the present study is to clarify the expression of (P)RR in the kidney with end-stage renal disease due to diabetic nephropathy. The kidney tissues were obtained at autopsy from patients with and without Type 2 diabetes mellitus (n=5 without diabetes mellitus; and n=8 with diabetes mellitus). Immunocytochemistry showed that (P)RR was mainly expressed in the tubular cells and collecting duct cells of the kidney without diabetic nephropathy. Cells in glomeruli were very weakly and sporadically immunostained for (P)RR. Vascular smooth muscle cells and endothelial cells were very weakly or were not immunostained for (P)RR. Adipocytes in the adipose tissue around the kidney were positively immunostained for (P)RR. Immunostaining pattern of (P)RR in the kidney with diabetic nephropathy was similar to that without diabetic nephropathy. However, most notably, (P)RR immunostaining in the tubular cells and collecting duct cells was clearly and frequently more strongly observed in the kidney with diabetic nephropathy up to the end-stage renal disease. The present study has raised the possibility that (P)RR expressed in the diabetic kidney may play a pathophysiological role in angiotensin I generation and renal fibrosis found in end-stage renal disease.