Atsuhiro Kanno

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.

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.

Serum Magnesium, Ambulatory Blood Pressure, and Carotid Artery Alteration: The Ohasama Study

BACKGROUND To investigate the associations of 24-h ambulatory blood pressure (ABP) and serum magnesium level (sMg) with risk of carotid artery alteration in a general population. METHODS sMg and ABP, monitored every 30 min, were measured in 728 subjects (mean age, 67 years) from the Japanese general population. The extent of carotid artery alteration was evaluated according to mean common carotid intima-media thickness (IMT) and the presence of focal carotid plaque. To determine the association of sMg and carotid artery alteration, analysis of covariance (ANCOVA) (for adjusted mean IMT) or multiple logistic regression analysis (for odds ratio (OR) for the presence of carotid plaques) was used. RESULTS Lower sMg was significantly associated with mean IMT (P = 0.004) and risk of ≥2 carotid plaques (P = 0.03) after adjusting for possible confounding factors, including 24-h ABP (systolic), creatinine clearance (Ccr) (estimated using the Cockcroft-Gault equation), and serum minerals (sodium, potassium, calcium, and inorganic phosphorus). Even when 24-h ABP values were within normal range (<130/80 mm Hg), lower sMg levels (<2.2 mg/dl) were significantly associated with mean IMT (P = 0.007) and risk of ≥2 carotid plaques (OR, 2.14; 95% confidence interval, 1.18-3.85; P = 0.01). CONCLUSIONS Both 24-h ABP and lower sMg were closely and independently associated with risk of carotid artery alteration. Further investigations are needed to examine the relationship between sMg levels and the incidence of cardiovascular disease.

Stroke Risk in Treated Hypertension Based on Home Blood Pressure: the Ohasama Study

BACKGROUND Several observational studies have shown that treated hypertensives are characterized as having worse prognosis than nonhypertensives. However, there is little evidence based on home blood pressure (home BP) measurement. We compare the risk of stroke between untreated individuals and those taking antihypertensive medication based on home BP and casual-screening BP (casual BP) in the general population. METHODS The study included 1,690 untreated and 700 treated subjects aged >or=35 years. We measured home BP and casual BP at the beginning of the study. The risk of first stroke was examined by using the Cox proportional hazards model. RESULTS During 11.9 years of follow-up, we observed 242 first-time stroke cases. Treated subjects had significantly higher risk for stroke than untreated subjects based on home BP (relative hazard (RH) = 1.48) as well as on casual BP (RH = 1.78), adjusted for systolic BP values and characteristics. When subjects were classified into six categories based on BP (optimal, normal, high normal, and grade 1-3 hypertension), RHs in treated hypertensives linearly increased (trend P < 0.01) based on home BP. However, there was no consistent association for casual BP (trend P: not significant) in treated subjects. Stroke risk was linearly increased regardless of the BP information source in untreated subjects (home BP: trend P < 0.01, casual BP: trend P < 0.01). CONCLUSION The results suggest a strong association between elevated home BP and increased risk of stroke. Home BP is a better tool to assess stroke risk, especially in treated hypertensives.

Association of environmental tobacco smoke exposure with elevated home blood pressure in Japanese women: the Ohasama study.

Objective Only a few of numerous epidemiological studies have demonstrated a positive association between environmental tobacco smoke (ETS) exposure and blood pressure (BP), despite experimental studies showing such a positive association. The association between home blood pressure (HBP) and ETS exposure was investigated in the general population. Methods Five hundred and seventy-nine nonsmoking Japanese women were enrolled. The participants were classified into four categories according to their responses to a self-administered questionnaire: unexposed women (non-ETS), women exposed at home [ETS(home)], at the workplace/other places [ETS(work/other)] and at home and at the workplace/other places [ETS(both)]. Variables were compared using analysis of covariance adjusted for age, marital status, body mass index, diabetes mellitus, stroke, heart disease, hyperlipidemia, alcohol intake, salt intake and activity levels. Results In participants without antihypertensive medication, systolic morning HBP in ETS(both) was 4 mmHg higher than that in non-ETS (116.8 ± 1.01 vs. 113.1 ± 1.08 mmHg, P = 0.02) and systolic morning HBP in ETS(home) and systolic evening HBP in ETS(both) were 3 mmHg higher than those in non-ETS (116.2 ± 1.07 vs. 113.1 ± 1.08 mmHg, P = 0.04; and 115.3 ± 1.02 vs. 111.9 ± 1.09 mmHg, P = 0.03, respectively). In participants with antihypertensive medication, ETS exposure status was not significantly associated with increased HBP levels. Conclusions A positive association between HBP levels and ETS exposure was confirmed. HBP measurement is recommended in population-based studies investigating the effects of ETS exposure. ETS exposure may increase BP, thereby synergistically contributing to unfavorable cardiovascular outcomes along with other deleterious effects of ETS.

Association of Kidney Dysfunction with Silent Lacunar Infarcts and White Matter Hyperintensity in the General Population: The Ohasama Study

Background: No previous study has investigated the association of kidney dysfunction with silent lacunar infarcts and white-matter hyperintensity (WMH) independent of ambulatory blood pressure (BP). Methods: A cross-sectional study involving 1,008 participants (mean age 66 years) from a general population of Ohasama, Japan, was conducted. Calculated creatinine clearance (CCr) was estimated using the Cockcroft-Gault equation. In continuous and categorical analyses, the association between CCr and the prevalence of silent lacunar infarcts and WMH was investigated. Silent lacunar infarcts and WMH were detected on MRI. Multiple logistic regression analysis adjusted for 24-hour ambulatory BP, sex, age, body mass index, smoking and drinking status, antihypertensive medication, and histories of hypercholesterolemia, diabetes mellitus and heart disease was performed. Results: On univariate analysis, decreased CCr (continuous variable) and CCr <60 ml/min/1.73 m2 (categorical variable) were significantly associated with lacunar infarcts and WMH. After adjustment, each 1-standard-deviation decrease in CCr (odds ratio = 1.22; p = 0.036) and CCr <60 ml/min/1.73 m2 (odds ratio = 1.68; p = 0.007) was significantly associated with a high prevalence of lacunar infarcts. Even when 24-hour ambulatory BP was within the normal range (<130/80 mm Hg), CCr <60 ml/min/1.73 m2 was associated with a high prevalence of lacunar infarcts (odds ratio = 1.62; p = 0.047). CCr <60 ml/min/1.73 m2 and 24-hour ambulatory BP had additive effects on lacunar infarcts. After the same adjustment, the association between CCr and WMH was not significant. Conclusions: CCr is closely associated with lacunar infarcts, suggesting that kidney dysfunction in the elderly is an independent risk factor or predictor for silent lacunar infarcts.

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.

Stroke Risk of Blood Pressure Indices Determined by Home Blood Pressure Measurement The Ohasama Study

Background and Purpose— The purpose of this prospective cohort study was to investigate associations between stroke and blood pressure (BP) indices (systolic BP [SBP], diastolic BP [DBP], mean BP, and pulse pressure [PP]) determined by home BP measurement. Methods— Associations between stroke and BP indices were examined in a rural Japanese population. Home BP data of 2369 subjects (40% men) ≥35 years of age (mean, 59 years) without a history of stroke were obtained. Associations between stroke and each index were determined using Cox proportional hazards regression and the likelihood ratio (LR) test. Results— During follow-up (mean, 11.7 years), 238 strokes occurred. The LR test showed that SBP and mean BP were significantly more strongly associated with total and ischemic stroke than DBP and PP (LR &khgr;2 ≥9.3, P<0.01 for SBP/mean BP, LR &khgr;2 ≤3.8, P≥0.05 for DBP/PP). SBP tended to be more strongly associated with total/ischemic stroke than mean BP (LR &khgr;2=3.8, P=0.05 for SBP, LR &khgr;2 ≤0.2, P>0.6 for mean BP). PP tended to be slightly more strongly associated with ischemic stroke than DBP (LR &khgr;2=7.5, P<0.01 for DBP, LR &khgr;2=9.3, P<0.01 for PP), whereas DBP was significantly more strongly associated with hemorrhagic stroke than PP (LR &khgr;2=9.2, P<0.01 for DBP, LR &khgr;2=2.5, P=0.01 for PP). Conclusion— PP obtained from home BP measurements was weakly associated with stroke, whereas SBP showed the strongest association. Additionally, DBP and PP may be associated with different stroke types.

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.

Pre-hypertension as a significant predictor of chronic kidney disease in a general population: the Ohasama Study

BACKGROUND Hypertension is associated with an increased risk of development of chronic kidney disease (CKD). However, it is unclear whether pre-hypertension is related to the incidence of CKD. METHODS The incidence of CKD defined as positive proteinuria or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m(2) was examined in 2150 inhabitants without pre-existing CKD from the general Japanese population. The association of blood pressure and CKD incidence was examined using a Cox regression model adjusted for age, sex, habitual smoking and drinking, obesity, history of cardiovascular disease, diabetes mellitus or hypercholesterolemia, eGFR at baseline, number of follow-up examinations and year of baseline examination. Participants were categorized according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. RESULTS Participants were categorized into normotension (n = 586, 27.3 % ), pre-hypertension (n = 815, 37.9 % ), Stage 1 hypertension (n = 386, 18.0 % ) and Stage 2 hypertension (n = 363, 16.9 % ). During a mean follow-up of 6.5 years (14 023 person-years), 461 incidences of CKD were recorded. Compared to normotension, adjusted hazard ratios of CKD were significantly higher for pre-hypertension (1.49, P < 0.003), Stage 1 (1.83, P < 0.001) and Stage 2 (2.55, P < 0.001) hypertension. The population-attributable fraction of pre-hypertension (12.1 % ) was considered to be compatible to that of Stage 1 (8.6 % ) and Stage 2 (14.9 % ) hypertension. CONCLUSION This was the first study to demonstrate that pre-hypertension was significantly associated with an increased risk of CKD and was one of the considerable causes of CKD in the general population.