Proposal of reference value for day-to-day blood pressure variability based on two outcomes: the Ohasama study.

BACKGROUND: This study aimed to propose reference values for day-to-day home blood pressure (BP) variability that align with the established hypertension threshold of home BP for the risk of two different outcomes: cardiovascular mortality and cognitive decline. METHODS: This prospective study was conducted in Ohasama town, Japan, with 1212 participants assessed for cardiovascular mortality risk (age: 64.7 years, 33.6% men). Additionally, 678 participants (age: 62.7 years, 31.1% men) were assessed for cognitive decline risk (Mini-Mental Scale Examination score <24). The within-individual coefficient of variation of home morning SBP (HSBP) was used as the index of day-to-day BP variability (%). Adjusted Cox regression models were used to estimate the HSBP-CV values, which provided the 10-year outcome risk at an HSBP of 135 mmHg. RESULTS: A total of 114 cardiovascular deaths and 85 events of cognitive decline (mean follow-up:13.9 and 9.6 years, respectively) were identified. HSBP and HSBP-coefficient of variation (HSBP-CV) were associated with increased risks for both outcomes, with adjusted hazard ratios per 1-standard deviation increase of at least 1.25 for cardiovascular mortality and at least 1.30 for cognitive decline, respectively. The adjusted 10-year risks for cardiovascular mortality and cognitive decline were 1.67 and 8.83%, respectively, for an HSBP of 135 mmHg. These risk values were observed when the HSBP-CV was 8.44 and 8.53%, respectively. CONCLUSION: The HSBP-CV values indicating the 10-year risk of cardiovascular mortality or cognitive decline at an HSBP of 135 mmHg were consistent, at approximately 8.5%. This reference value will be useful for risk stratification in clinical practice.

Association between an Antioxidant-Rich Japanese Diet and Chronic Kidney Disease: The Ohasama Study.

AIMS: Although physiological effects of hydrophilic- (H-) and lipophilic- (L-) antioxidant capacities (AOCs) are suggested to differ, the association of an antioxidant-rich diet and chronic kidney disease (CKD) incidence has not been examined. We therefore explored the association between the H- or L-AOC of a whole Japanese diet and CKD risk in a general population. METHODS: A total of 922 individuals without CKD (69.2% women; mean age, 59.5 years old) from Ohasama Town, Japan, were examined. CKD incidence was defined as the presence of proteinuria and/or an estimated glomerular filtration rate (eGFR) of ＜60 ml/min/1.73 m2. Consumption of H-/L-AOC was determined based on the oxygen radical absorbance capacity in a specially developed Japanese food AOC database. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for new-onset CKD using a Cox proportional hazards model. RESULTS: During the median follow-up of 9.7 years, 137 CKD incidents were recorded. After adjusting for potential confounding variables, the highest quartile of L-AOC was significantly associated with a 51% reduced CKD risk among only women. An increased L-AOC intake was more effective in preventing eGFR reduction than in preventing proteinuria in women. These associations were not seen for H-AOC intake in both sexes and L-AOC intake in men. CONCLUSIONS: A high intake of lipophilic antioxidants may be associated with a reduced CKD risk. The balance between dietary antioxidant intake and pro-oxidants induced by unhealthy lifestyles may be crucial for preventing future kidney deterioration.

Characteristics and Risk of Diabetes in People With Rare Glucose Response Curve During an Oral Glucose Tolerance Test.

CONTEXT: Existing differences in persons with lower 30- or 60-minute plasma glucose (PG) levels during 75-g oral glucose tolerance test (OGTT) than fasting PG remain unclear. OBJECTIVE: To clarify the characteristics of persons whose PG levels decrease after glucose administration during OGTT and their risk of incidence of diabetes in a Japanese general population. METHODS: In this cohort study, a total of 3995 men and 3500 women (mean age 56.7 years) without diabetes were classified into 3 groups: (1) PG at both 30 and 60 minutes ≥ fasting PG; (2) PG at 30 minutes ≥ fasting PG and PG at 60 minutes < fasting PG; (3) PG at 30 minutes < fasting PG. The characteristics and the risk of diabetes onset were analyzed using ordered logistic regression and Cox proportional hazard regression, respectively. RESULTS: Among 7495 participants, the numbers of individuals in the group 1, 2, and 3 were 6552, 769, and 174, respectively. The glucose response curve of the group 3 was boat shaped. Group 3 had the youngest age, lowest percentage of men, and best health condition, followed by groups 2 and 1. Among 3897 participants analyzed prospectively, 434 developed diabetes during the mean follow-up period of 5.8 years. The hazard ratio for diabetes onset in the group 2 was 0.30 with reference to the group 1. No-one in group 3 developed diabetes. CONCLUSION: People with lower 30-minute PG than fasting PG tended to be women, young, healthy, and at low risk of diabetes onset.

Self-measured home blood pressure highlights cardiovascular risk in women: the HOMED-BP study.

No studies examined sex differences in relation to the prognostic significance of self-measured home blood pressure (HBP). We compared the predictive power for the risk of cardiovascular events in 1547 women and 1516 men with hypertension using HBP captured at treatment-free baseline and during on-treatment follow-up, based on the Hypertension Objective Treatment Based on Measurement by Electrical Devices of Blood Pressure (HOMED-BP) study. To express the change in risk for the composite cardiovascular endpoint associated with a 1-SD increase in HBP at baseline or on treatment, we derived multivariable-adjusted hazard ratios (HR) based on a Cox regression model. Over a median follow-up of 7.3 years, 100 composite events occurred, including 40 events in women. In women, systolic HBP both at baseline and on-treatment showed significant risk increment (at baseline: HR per 1-SD increment, 1.62; 95% confidence interval [CI], 1.17-2.24. on-treatment: HR, 1.74; 95% CI, 1.32-2.29). However, systolic HBP at baseline did not predict cardiovascular events in men (P = 0.25). On-treatment HBP was significantly associated with cardiovascular risk (P ≤ 0.012) irrespective of sex. Nevertheless, the point estimate of HR for systolic HBP in men (1.33) was less than that in women (1.74), and the interaction of sex with 1 SD-increase in systolic HBP in cardiovascular risk was significant irrespective of baseline (P = 0.039) or follow-up (P = 0.040) measurement when they were mutually adjusted. The increase in cardiovascular risk with the systolic HBP was steeper in women than in men for both baseline and on-treatment. The current findings unveil the importance of the control of systolic HBP, especially in women. Clinical Trial Registration: UMIN Clinical Trial Registry ( http://www.umin.ac.jp/ctr ), Unique identifier: C000000137.

Associations of Dental Health With the Progression of Hippocampal Atrophy in Community-Dwelling Individuals: The Ohasama Study.

BACKGROUND AND OBJECTIVES: Although tooth loss and periodontitis have been considered risk factors of Alzheimer disease, recent longitudinal researches have not found a significant association with hippocampal atrophy. Therefore, this study aimed to clarify a longitudinal association between the number of teeth present (NTP) and hippocampal atrophy dependent on the severity of periodontitis in a late middle-aged and older adult population. METHODS: This study included community-dwelling individuals aged 55 years or older who had no cognitive decline and had undergone brain MRI and oral and systemic data collection twice at 4-year intervals. Hippocampal volumes were obtained from MRIs by automated region-of-interest analysis. The mean periodontal probing depth (PD) was used as a measure of periodontitis. Multiple regression analysis was performed with the annual symmetric percentage change (SPC) of the hippocampal volume as the dependent variable and including an interaction term between NTP and mean PD as the independent variable. The interaction details were examined using the Johnson-Neyman technique and simple slope analysis. The 3-way interaction of NTP, mean PD, and time on hippocampal volume was analyzed using a linear mixed-effects model, and the interaction of NTP and time was examined in subgroups divided by the median mean PD. In all models, dropout bias was adjusted by inverse probability weighting. RESULTS: Data of 172 participants were analyzed. The qualitative interaction between NTP and the mean PD was significant for the annual SPC in the left hippocampus. The regression coefficient of the NTP on the annual SPC in the left hippocampus was positive (B = 0.038, p = 0.026) at the low-level mean PD (mean -1 SD) and negative (B = -0.054, p = 0.001) at the high-level mean PD (mean +1 SD). Similar results were obtained in the linear mixed-effects model; the interaction of NTP and time was significant in the higher mean PD group. DISCUSSION: In a late middle-aged and older cohort, fewer teeth were associated with a faster rate of left hippocampal atrophy in patients with mild periodontitis, whereas having more teeth was associated with a faster rate of atrophy in those with severe periodontitis. The importance of keeping teeth healthy is suggested.

Determinants of double product: a cross-sectional study of urban residents in Japan.

BACKGROUND: The current study aimed to investigate the determinants of high double product (DP) by evaluating the association between resting DP, which is calculated as systolic blood pressure (SBP) multiplied by heart rate (HR), and blood test results and lifestyle factors. METHODS: This research included 973 participants in the baseline survey of the KOBE study, which included a cohort of urban residents. The possible DP determinants were identified by examining the association between lifestyle factors and laboratory findings and DP by analyzing covariance adjusted for sex and age. Logistic regression analysis was performed with high DP (SBP × HR ≥ 9145 mmHg beats/min or quintile according to sex) as outcome and DP determinants as independent variables. RESULTS: Age, hematocrit, and gamma-glutamyl transferase (log) level were positively associated with a high DP in both men and women. In addition, a high DP was positively associated with Homeostatic Model Assessment for Insulin Resistance score in women alone. Meanwhile, the amount of exercise was negatively associated with a high DP in men alone. CONCLUSIONS: High DP values at rest were associated with insulin resistance, gamma-glutamyl transferase, and the amount of exercise in participants without underlying disease.

The long-term reproducibility of the white-coat effect on blood pressure as a continuous variable from the Ohasama Study.

There is little information about the reproducibility of the white coat effect, which was treated as a continuous variable. To investigate a long-term interval reproducibility of the white-coat effect as a continuous variable. We selected 153 participants without antihypertensive treatment (men, 22.9%; age, 64.4 years) from the general population of Ohasama, Japan, to assess the repeatedly measured white-coat effect (the difference between blood pressures at the office and home) in a 4-year interval. The reproducibility was assessed by testing the intraclass correlation coefficient (two-way random effect model-single measures). The white-coat effect for systolic/diastolic blood pressure slightly decreased by 0.17/1.56 mmHg at the 4-year visit on average. The Bland-Altman plots showed no significant systemic error for the white-coat effects (P ≥ 0.24). The intraclass correlation coefficient (95% confidence interval) of the white-coat effect for systolic blood pressure, office systolic blood pressure, and home systolic blood pressure were 0.41 (0.27-0.53), 0.64 (0.52-0.74), and 0.74 (0.47-0.86), respectively. Change in the white-coat effect was mainly affected by a change in office blood pressure. Long-term reproducibility of the white-coat effect is limited in the general population without antihypertensive treatment. The change in the white-coat effect is mainly caused by office blood pressure variation.

Offering on-site mammography in workplaces improved screening rates: Cluster randomized controlled trial.

OBJECTIVES: Despite evidence of breast cancer screening efficacy, the screening rate has remained less than 50% in Japan. This study aimed to evaluate the effect of an environmental approach offering on-site mammography in workplaces. METHODS: Supermarket stores were randomly assigned into two groups, the intervention group (leaflet and mammography) and the control group (leaflet). From May to July 2018, participants in the intervention group were given a leaflet informing them of the subsidies for breast cancer screening and offered the opportunity to have mammography in their workplaces. Participants in the control group were given the same leaflet, but had to arrange their own screening outside the workplace. The primary outcome was the breast cancer screening rate in 2018. The odds ratio (OR) and 95% confidence interval (CI) for having screening in the intervention group compared with the control group were estimated using multilevel logistic regression. RESULTS: We analyzed data from 1624 participants (mean age 53 years) from 25 supermarket stores (intervention: 8 stores, control: 17 stores). Among participants who had not attended screening in the previous year, the screening rate was 7% in the control group and 53% in the intervention group, with an adjusted OR (95% CI) of 14.22 (8.97-22.54). The effect was greater in those who had never attended screening before. CONCLUSION: In a worksite-based cluster randomized controlled trial in Japanese supermarket stores, an environmental approach offering mammography in workplaces substantially increased the breast cancer screening rate within 1 year (UMIN000030465).

Association Between Ambulatory Blood Pressure and Risk of Home Hypertension in a Normotensive Population: The Ohasama Study.

BACKGROUND: We investigated the association between ambulatory blood pressure (BP) and the risk of home hypertension in a normotensive population and whether considering ambulatory BP improves the 10-year prediction model for home hypertension risk, which was developed in the previous Ohasama Study. METHODS: In this prospective study, we followed up with 410 participants (83.2% women; age, 53.6 years) without a home and ambulatory hypertension in the general population of Ohasama, Japan. The Cox model was used to assess the hazard ratios (HRs) for home hypertension (home BP ≥ 135/≥85 mmHg or the initiation of antihypertensive treatment) and model improvement. RESULTS: During a mean 14.2-year follow-up, 225 home hypertension incidences occurred. The HR (95% confidence interval) for home hypertension incidence per 1-SD higher (=6.76 mmHg) 24-hour systolic BP (SBP) was 1.59 (1.33 to 1.90), after adjustments for possible confounding factors, including baseline home SBP. Harrell's C-statistics increased from 0.72 to 0.73 (P = 0.11) when 24-hour SBP was added to the basic 10-year home hypertension prediction model, which includes sex, age, body mass index, smoking status, office SBP, and baseline home SBP. Continuous net reclassification improvement (0.53, P < 0.0001) and integrated discrimination improvement (0.028, P = 0.0014) revealed improvement in the model. CONCLUSIONS: A total of 24-hour SBP could be an independent predictor of future home hypertension. Home BP and 24-hour BP can longitudinally influence each other in the long term.

Female Reproductive Events and Subclinical Atherosclerosis of the Brain and Carotid Arteriopathy: the Ohasama Study.

AIMS: Few studies have investigated the subclinical atherosclerotic changes in the brain and carotid artery, and in East Asian populations. We sought to investigate whether gravidity, delivery, the age at menarche and menopause and estrogen exposure period are associated with subclinical atherosclerosis of the brain and carotid arteriopathy. METHODS: This cross-sectional study formed part of a cohort study of Ohasama residents initiated in 1986. Brain atherosclerosis and carotid arteriopathy were diagnosed as white matter hyperintensity (WMH) and lacunae evident on brain magnetic resonance imaging (MRI) and carotid intimal media thickness (IMT) or plaque revealed by ultrasound, respectively. The effect of the reproductive events on brain atherosclerosis and carotid arteriopathy was investigated using logistic regression and general linear regression models after adjusting for covariates. RESULTS: Among 966 women aged ≥ 55 years in 1998, we identified 622 and 711 women (mean age: 69.2 and 69.7 years, respectively) who underwent either MRI or carotid ultrasound between 1992-2008 or 1993-2018, respectively. The highest quartile of gravidity (≥ 5 vs. 3) and delivery (≥ 4 vs. 2), and the highest and second highest (3 vs. 2) quartiles of delivery were associated with an increased risk of WMH and carotid artery plaque, respectively. Neither of age at menarche, menopause, and estrogen exposure period estimated by subtracting age at menarche from age at menopause was associated with atherosclerotic changes of brain and carotid arteries. CONCLUSIONS: Higher gravidity and delivery are associated with subclinical atherosclerosis of the brain and carotid plaque.

Association of home and office systolic and diastolic hypertension with glucose metabolism in a general population: the Ohasama study.

OBJECTIVE: This study was performed to investigate the association of hypertension subtypes with glucose metabolism among the Japanese general population. METHODS: The study involved 646 residents (mean age: 62.4 years) without treatment for hypertension or a history of diabetes from Ohasama, a rural Japanese community, who underwent an oral glucose tolerance test. Hypertension subtypes [normotension, isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), and systolic and diastolic hypertension (SDH)] were defined on the basis of home and office SBP and DBP (HBP and OBP, respectively). The estimated means of blood glucose related indices among the groups were compared by analysis of covariance adjusted for possible confounding factors. RESULTS: Blood glucose related indices were not different among the morning HBP-defined hypertension subtypes. Participants with evening HBP-defined ISH had a significantly higher estimated mean BG at 120 min, higher homeostasis model assessment-insulin resistance (HOMA-IR) and lower Matsuda-DeFronzo index than participants with NT (all P < 0.021). Participants with OBP-defined SDH had a significantly higher estimated mean fasting blood glucose; blood glucose at 30, 60 and 120 min; and HOMA-IR and a lower Matsuda-DeFronzo index than participants with NT (all P < 0.0025). CONCLUSION: The blood glucose related indices were different among hypertension subtypes. Participants with evening HBP-defined ISH and OBP-defined SDH had higher blood glucose levels and insulin resistance than participants with correspondingly defined normotension, while those with morning HBP did not. These findings suggest the importance of measuring evening HBP and office blood pressure for early detection of coexisting hypertension and diabetes.

Regular dental visits, periodontitis, tooth loss, and atherosclerosis: The Ohasama study.

OBJECTIVE: We aimed to explore the association between regular dental visits and atherosclerosis and between periodontitis, number of remaining teeth, and atherosclerosis among community dwellers in Japan. BACKGROUND: Few studies have examined the association between regular dental visits, periodontitis, tooth loss, and atherosclerosis in community dwellers in Japan. METHODS: The participants of this cross-sectional study included community dwellers aged ≥55 years and residing in Ohasama. Exposure variables were regular dental visits; periodontitis, defined as radiographic alveolar bone loss (BL); the Centers for Disease Control/American Academy of Periodontology (CDC/AAP) classification; and number of remaining teeth. The primary outcome was atherosclerosis, defined as maximum carotid intima-media thickness ≥1.1 mm or confirmation of atheromatous plaque. RESULTS: Of 602 participants, 117 had atherosclerosis. In the multivariate model, compared to those with regular dental visits, the odds ratio (OR) (95% confidence intervals [CIs]) of atherosclerosis among those with the absence of regular dental visits was 2.16 (1.03-4.49). Regarding BL-max, compared with those in the first quartile, ORs (95% CIs) of those in the second, third, and fourth quartiles were 1.15 (0.65-2.30), 0.65 (0.32-1.35), and 1.57 (0.81-3.01), respectively. Regarding CDC/AAP classification, compared to those with no or mild periodontitis, ORs (95% CIs) for those with moderate and severe periodontitis were 2.48 (0.61-10.1) and 4.26 (1.01-17.5), respectively. Regarding the number of remaining teeth, compared to those with ≥20 teeth, ORs (95%CIs) for those with 10-19 and 1-9 teeth were 1.77 (1.004-3.12) and 0.96 (0.52-1.80), respectively. CONCLUSION: The absence of regular dental visits and presence of periodontitis are associated with atherosclerosis among community dwellers in Japan.

Association between urinary sodium-to-potassium ratio and home blood pressure and ambulatory blood pressure: the Ohasama study.

OBJECTIVE: No studies have demonstrated the association between urinary sodium-to-potassium (Na/K) ratio and all out-of-office blood pressure (BP) [home morning and evening BP (self-measured at home), and 24-h, daytime, and night-time ambulatory BP] in the same cohort. We aimed to assess, which type of out-of-office BP is more strongly associated with urinary Na/K ratio in the general population. METHODS: This cross-sectional study was conducted in the general population of Ohasama, Japan. Home and ambulatory BP levels were measured, and 24-h urine samples were obtained from 875 participants (men, 25.5%; mean age, 60.1 years). The urinary Na/K ratio in the 24-h urine samples was calculated. RESULTS: The median (interquartile range) urinary Na/K ratio was 4.19 (3.36-5.26). Significant positive trends of home morning, home evening, 24-h, and daytime SBP were observed across quartiles of urinary Na/K ratio (trend P  < 0.041; adjusted mean values between Q1 and Q4 of urinary Na/K ratio: 121.0-125.5 mmHg for home morning, 120.1-123.8mmhg for home evening, 121.6-123.4mmHg for 24-h, 127.5-129.5 mmHg for daytime). Urinary Na/K ratio was not significantly associated with office or night-time SBP and nocturnal BP fall (trend P > 0.13). In the model with both home morning or evening SBP and daytime SBP, only home SBP was significantly associated with urinary Na/K ratio (P < 0.048 for home SBP). CONCLUSION: These findings suggest that urinary Na/K ratio might be more strongly associated with home BP than with 24-h and daytime BP but was not associated with night-time BP.

Predictive power of home blood pressure in the evening compared with home blood pressure in the morning and office blood pressure before treatment and in the on-treatment follow-up period: a post hoc analysis of the HOMED-BP study.

The predictive power of home blood pressure (BP) in the evening compared with home BP in the morning and office BP has been controversial. The predictive power of evening BP was compared to that of morning BP and office BP. The likelihood ratio test between one model containing a single BP index with traditional risk factors and a similar model further containing another BP index was used to assess whether the additional BP index significantly improved the adequacy of the model. Of 3266 patients with mild-to-moderate hypertension who were on antihypertensive medications (men 50.6%, age 59.5 ± 10.0 years), 58 experienced a major adverse cardiovascular event during a median follow-up of 7.1 years. The hazard ratios for a one standard deviation increment of evening home systolic/diastolic BP were 1.26 (0.98-1.62)/1.43 (1.09-1.88) in the baseline untreated period and 1.46 (1.17-1.81)/1.63 (1.26-2.11) during the on-treatment follow-up period. When evening BP at baseline and that during follow-up were included in the same model, only the latter significantly improved the prediction models (P = 0.006/0.005 for systolic/diastolic BP). Then, evening home BP vs. morning BP during follow-up was tested. The former did not improve the prediction models (P > 0.2), but the latter significantly improved the models (P ≤ 0.048). Similarly, when evening home BP and office BP during follow-up were analyzed, only the former significantly improved the prediction models (P ≤ 0.015). In conclusion, evening BP could be a more potent predictor than office BP, but it was inferior compared to morning BP in the treatment of mild-to-moderate hypertensive patients.

Prediction Models for the 5- and 10-Year Incidence of Home Morning Hypertension: The Ohasama Study.

BACKGROUND: We aimed to develop risk prediction models for new-onset home morning hypertension. METHODS: We followed up 978 participants without home hypertension in the general population of Ohasama, Japan (men: 30.1%, age: 53.3 years). The participants were divided into derivation (n = 489) and validation (n = 489) cohorts by their residential area. The C-statistics and calibration plots were assessed after the 5- or 10-year follow-up. RESULTS: In the derivation cohort, sex, age, body mass index, smoking, office systolic blood pressure (SBP), and home SBP at baseline were selected as significant risk factors for new-onset home hypertension (≥135/85 mm Hg or the initiation of antihypertensive treatment) using the Cox model. In the validation cohort, Harrell's C-statistic for the 5-/10-year home hypertension was 0.7637 (0.7195-0.8100)/0.7308 (0.6932-0.7677), when we used the full model, which included the significant risk factors in the derivation cohort. The calibration test revealed good concordance between the observed and predicted 5-/10-year home hypertension probabilities (P ≥ 0.19); the regression slope of the observed probability on the predicted probability was 1.10/1.02, and the intercept was -0.04/0.06, respectively. A model without home SBP was also developed; for the 10-year home hypertension risk, the calibration test revealed a good concordance (P = 0.19) but Harrell's C-statistic was 0.6689 (0.6266-0.7067). CONCLUSIONS: The full model revealed good ability to predict the 5- and 10-year home morning hypertension risk. Although the model without home SBP is acceptable, the low C-statistic implies that home BP should be measured to predict home morning hypertension precisely.