The trends of antihypertensive drug prescription based on the Japanese national data throughout the COVID-19 pandemic period.

In 2020, concerns arose about the potential adverse effects of angiotensin II type 1 receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) on patients with the Coronavirus Disease 2019 (COVID-19). However, there is no national data on antihypertensive prescriptions during the COVID-19 pandemic in Japan. This study aimed to explore the trends in antihypertensive drug prescriptions in Japan throughout COVID-19 pandemic period. This study used data from the National Database (NDB) Open Data in Japan, an annual publication by the Ministry of Health, Labour and Welfare. To capture changes before and after social activity restrictions, the present study focused on extracting the number of prescribed oral medicine tablets for outpatients from the NDB Open Data from 2018 to 2021. The fiscal year 2020 exhibited the lowest for both outpatient claims and prescribed drugs. In contrast, all categories of antihypertensive drug prescription showed annual increases, and no specific changes in the prescription patterns of ARBs and ACEIs around fiscal year 2020 were observed. This study implies that antihypertensive drug prescriptions were adequately maintained throughout the COVID-19 pandemic in Japan.

Combined effects of blood pressure and glucose status on the risk of chronic kidney disease.

This study aimed to assess the combined effects of blood pressure (BP) and glucose status on chronic kidney disease (CKD) incidence in young and middle-aged adults. We examined data from 1,297,341 Japanese individuals aged <60 years (60.1% men; mean age 41.4 ± 9.3 years) with no history of CKD at baseline. The interval-censored Cox proportional hazards model with covariates was used. During a median follow-up period of 2.1 years, new onset CKD (estimated glomerular filtration rate <60 ml/min/1.73 m2 and/or proteinuria) occurred in 80,187 participants. In participants without antihypertensive treatment (AHT), the adjusted hazard ratios (95% confidence interval) per 1-standard deviation, that is, 15 mmHg increase in systolic BP for CKD incidence, were 1.08 (1.07-1.09), 1.12 (1.10-1.13), and 1.15 (1.12-1.18) in normoglycemia, borderline glycemia, and diabetes groups, respectively. These ratios were significantly higher in the borderline glycemia and diabetes groups compared with those in the normoglycemia group (interaction p < 0.0001). The interaction between BP and borderline glycemia was evident when the outcome definition was restricted to proteinuria. In participants under AHT, systolic BP was most strongly associated with CKD risk in the diabetes group, although no significant interaction was observed. High BP and high glucose status may synergistically increase the incidence of CKD. Strict BP management may play an important role in the early prevention of CKD in individuals with worse glucose status within the young and middle-aged population. This large-scale longitudinal cohort study showed high BP and diabetes synergistically increased the risk of CKD in individuals without AHT. Strict BP management may play an important role in the early prevention of CKD in individuals with worse glucose status within the young and middle-aged population.

The association between depressive symptoms and masked hypertension in participants with normotension measured at research center.

Masked hypertension is a risk factor for cardiovascular diseases. However, masked hypertension is sometimes overlooked owing to the requirement for home blood pressure measurements for diagnosing. Mental status influences blood pressure. To reduce undiagnosed masked hypertension, this study assessed the association between depressive symptoms and masked hypertension. This cross-sectional study used data from the Tohoku Medical Megabank Project Community-Based Cohort Study (conducted in Miyagi Prefecture, Japan, from 2013) and included participants with normotension measured at the research center (systolic blood pressure<140 mmHg and diastolic blood pressure <90 mmHg). Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (Japanese version). Masked hypertension was defined as normotension measured at the research center and home hypertension (home systolic blood pressure ≥135 mmHg or home diastolic blood pressure ≥85 mmHg). The study comprised 6705 participants (mean age: 55.7 ± 13.7 years). Of these participants, 1106 (22.1%) without depressive symptoms and 393 (23.2%) with depressive symptoms were categorized to have masked hypertension. Sex-specific and age-adjusted least mean squares for home blood pressure, not for research blood pressure were significantly higher in the group with depressive symptoms in both sex categories. The multivariate odds ratio for masked hypertension in the patients with depressive symptoms was 1.72 (95% confidence interval: 1.26-2.34) in male participants and 1.30 (95% confidence interval: 1.06-1.59) in female ones. Depressive symptoms were associated with masked hypertension in individuals with normotension measured at the research center. Depressive symptoms may be one of the risk factors for masked hypertension. Depressive symptoms were associated with masked hypertension in individuals with normotension measured at research center.

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.

The impact of clinical inertia on uncontrolled blood pressure in treated hypertension: real-world, longitudinal data from Japan.

We aimed to quantify the impact of inadequate pharmacological therapy on uncontrolled blood pressure (BP) using Japanese real-world data. This retrospective cohort study used databases provided by DeSC Healthcare, Inc (Tokyo, Japan). We identified 27,652 patients with hypertension (age, 60.7 ± 9.1 years; men, 56.4%) who were not receiving antihypertensive treatment at the initial visit (pre-treatment) and were under treatment at the next visit (post-treatment). Patients were classified into the following groups by the number of antihypertensive drug classes and defined daily dose (DDD): one antihypertensive drug class with a low dose (DDD < 1.0), one antihypertensive drug class with a moderate-to-high dose (DDD ≥ 1.0), two antihypertensive drug classes with a low dose (DDD < 2.0), two antihypertensive drug classes with a moderate-to-high dose (DDD ≥ 2.0), and ≥three antihypertensive drug classes. The pre-treatment systolic/diastolic BP was 157.7 ± 15.4/94.2 ± 11.5 mmHg. Overall, 43.0% of patients had uncontrolled BP (post-treatment BP ≥ 140/ ≥ 90 mmHg). High pre-treatment BP was a strong factor for uncontrolled BP. After adjustments for covariates, including the pre-treatment mean BP, the proportion of patients with uncontrolled BP was 2.08 times higher in the one antihypertensive drug class with a low dose group than in the ≥three antihypertensive drug classes group. The preventable fraction due to

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.

Association of Central Blood Pressure and Carotid Intima Media Thickness with New-Onset Hypertension in People with High Normal Blood Pressure.

AIM: People with high normal blood pressure (BP) have a higher risk of cardiovascular events than those with normal BP; therefore, progression to hypertension (HT) should be prevented. We aimed to assess the HT risk using central BP and carotid intima media thickness (CIMT) in people with high normal BP. METHODS: This prospective cohort study used the Tohoku Medical Megabank Community-Based Project Cohort Study (conducted from 2013 in Miyagi Prefecture in Japan). The participants had a high normal BP, defined as a systolic BP of 120-139 mmHg and diastolic BP ＜90 mmHg using brachial BP measurement during the baseline survey. The outcome was new-onset HT during the secondary survey, conducted four years after the baseline survey. RESULTS: Overall, 4,021 participants with high normal BP during the baseline survey, with an average age of 58.7 years, were included; 1,030 (26%) were diagnosed with new-onset HT during the secondary survey, 3.5±0.7 years after the baseline survey. The multivariable odds ratio (95% confidence interval) for HT in the highest versus lowest quartile of central BP was 1.7 (1.2-2.4, p=0.0030), and that of CIMT was 1.8 (1.4-2.4, p＜0.001). Subgroup analysis according to age (＜60 and ≥ 60 years) and sex revealed that the central BP was influential in groups with younger age and female individuals; CIMT was influential in all groups. CONCLUSIONS: Higher central BP and thicker CIMT at the baseline were correlated with new-onset HT in individuals with high normal BP, independent of brachial systolic BP and other cardiovascular risk factors.

Prognostic Significance of Home and Ambulatory Blood Pressure: Summary of Longitudinal Evidence from the Ohasama Study.

The Ohasama Study is a long-term prospective cohort study of the general population in the town of Ohasama (currently, Hanamaki city) in Iwate Prefecture, Japan, that was started in 1986. Ohasama is a typical farming village in the Tohoku region that consists of part-time farming households that cultivate mainly fruit trees. At the start of the study, the prevention of hypertension, a main cause of strokes, was taken to be an important issue in public health activities because of the many people who died or needed care as a result of strokes in Ohasama. A home blood pressure measurement program was then begun with the aim of preventing hypertension while increasing a sense of solidarity among community residents and the awareness that "one must protect one's own health." As a result, this project became the world's first community-based epidemiological study using home blood pressure, as well as 24-hour ambulatory blood pressure, for which measurements were also initiated. In the 1990s, the Ohasama Study reported a linear "the lower, the better" relationship between out-of-office blood pressure and cardiovascular risk. To date, we have accumulated advanced evidence regarding the clinical significance of out-of-office blood pressure. Those have contributed to hypertension management guidelines around the world. This article summarizes the results of representative long-term follow-up studies of the Ohasama Study.

Cross-classification by systolic and diastolic blood pressure levels and chronic kidney disease, proteinuria, or kidney function decline.

Predicting and preventing new-onset chronic kidney disease (CKD) through blood pressure (BP) measurements is worthwhile. This study assessed the risk of CKD, which was defined as proteinuria and/or an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, according to cross-classification by systolic and diastolic BP (SBP and DBP). This retrospective population-based cohort study analyzed data from 1,492,291 participants without CKD and without antihypertensive treatment in the JMDC database, which contains the annual health check-up data of Japanese aged <75 years. During a mean follow-up of 3.2 years, CKD incidence, proteinuria, and eGFR <60 mL/min/1.73 m2 occurred in 92,587, 67,021, and 28,858 participants, respectively. When the SBP/DBP <120/<80 mmHg group was set as a reference, both high SBP and DBP were significantly associated with an elevated CKD risk. DBP tended to be more strongly associated with CKD risk than SBP; the hazard ratio of CKD was 1.44-1.80 in the group with SBP/DBP of 130-139/≥90 mmHg and 1.23-1.47 in the group with SBP/DBP of ≥140/80-89 mmHg. A similar result was observed for developing proteinuria and eGFR <60 mL/min/1.73 m2. SBP/DBP ≥150/<80 mmHg was strongly associated with an elevated CKD risk due to the increased risk of eGFR decline. High BP, especially isolated high DBP levels, is a significant risk factor for CKD among individuals around middle age without kidney disease. Moreover, attention should be paid to kidney function, particularly eGFR decline, in the case of low DBP with extremely high SBP levels.

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.

Secondhand smoke exposure is associated with the risk of hypertensive disorders of pregnancy: the Japan Environment and Children's Study.

Hypertensive disorders of pregnancy (HDP) are associated with poor maternal and neonatal prognoses. Although several studies have indicated an effect of secondhand smoke (SHS) exposure on HDP, such evidence is lacking in Japan. Therefore, we analyzed data from the Japan Environment and Children's Study, a large-scale epidemiological investigation, to elucidate a possible link between SHS exposure and HDP risk. Data were obtained from the all-birth fixed datasets and included information on 104,062 fetuses and their parents. SHS exposure was assessed in terms of the frequency (rarely, 1-3, or 4-7 days/week) and the daily duration of exposure (<1, 1-2, or ≥2 h(s)/day). Modified Poisson regression model analyses were performed with adjustment for known risk factors for HDP. Additionally, the population attributable fractions (PAFs) of SHS exposure and maternal smoking to HDP prevalence were estimated. The relative risks of developing HDP among individuals with SHS exposures of 4-7 days/week and ≥2 h/day were 1.18 and 1.27 (95% confidence interval: 1.02-1.36 and 0.96-1.67), respectively, compared to the reference groups (rare exposure and <1 h/day). The PAFs for the risk of HDP due to SHS exposure and perinatal smoking were 3.8% and 1.8%, respectively. Japanese women with greater exposure to SHS have a higher risk of HDP after adjustment for possible confounding factors; thus, relevant measures are required to reduce SHS exposure to alleviate HDP risk. The association between second-hand smoking exposure and hypertensive disorders of pregnancy risk was analyzed using the JECS data. The relative risks in 4-7 days/week and ≥2 h/day of SHS exposures were 1.18 and 1.27, respectively. The PAFs due to SHS exposure and maternal smoking were 3.80% and 1.81%, respectively.

Evaluation of the feasibility of human papillomavirus sponge-type self-sampling device at Japanese colposcopy clinics.

AIM: Self-sampling human papillomavirus (HPV) testing has been introduced for cervical cancer screening worldwide. In Japan, there are two types (brush and sponge) of HPV self-sampling devices. However, the recommended type for cervical cancer screening remains unclear. This study aimed to evaluate the feasibility of the HPV self-sampling device-sponge type (HSD-ST). Additionally, we aimed to examine the positive rate (sensitivity) for cervical intraepithelial neoplasia (CIN) 2 or worse using the HSD-ST. Finally, we aimed to perform a questionnaire survey regarding the usability of the HSD-ST. METHODS: We included 165 women who underwent HPV testing at one of three gynecologic clinics. First, the women used the HSD-ST and completed a questionnaire regarding its usability. Subsequently, they underwent physician-sampling HPV testing and cytology. We examined the agreement rate of HPV positivity between self- and physician-sampling HPV testing. RESULTS: The HPV-positive rates of self- and physician-collected samples were 59.4% and 62.4%, respectively, with an overall concordance rate of 88.5% and a calculated kappa coefficient of 0.76, indicating high concordance. Moreover, the positive (sensitivity) rates for CIN2 or worse were 81.4% and 89.8% in the self- and physician-collected samples, respectively. CONCLUSIONS: Our findings demonstrated the feasibility and usability of the HSD-ST.

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.

Insulin-like growth factor-1 levels are associated with high comorbidity of metabolic disorders in obese subjects; a Japanese single-center, retrospective-study.

Insulin like growth factor-1 (IGF-1) plays important roles in metabolic functions, especially in adulthood. Additionally, obese subjects are reportedly predisposed to having low absolute IGF-1 levels. However, the prevalence and clinical characteristics of obese subjects with low IGF-1 levels are unknown. We examined 64 obese subjects with a body mass index (BMI) ≥ 35 kg/m2, with no history of endocrinological disorders, receiving inpatient care. IGF-1 levels were interpreted based on the IGF-1 standard deviation score (SDS) clinically used and standardized by age and sex (low IGF-1 group; ≤ - 2.0 SDS and standard IGF-1 group; - 2.0 < and < + 2.0 SDS). Notably, 26.6% of the subjects had low IGF-1. Body fat mass and percentage, but not BMI, were significantly higher in the low than in the standard IGF-1 group. Furthermore, natural log-transformed high-sensitivity C-reactive protein, and the frequencies of dyslipidemia and hyperuricemia were higher in the low IGF-1 group. Moreover, among the subjects without diabetes, fasting glucose levels were significantly higher in the low IGF-1 group. Stepwise variable selection procedure revealed body fat percentage to be a parameter most strongly associated with low IGF-1. Thus, low IGF-1 levels may be an important marker of adiposity-associated metabolic disorders in obese patients.