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Background: Although many observational studies have demonstrated significant relationships between obesity and cardiometabolic traits, the causality of these relationships in East Asians remains to be elucidated., Methods: We conducted individual-level Mendelian randomization (MR) analyses targeting 14,083 participants in the Japan Multi-Institutional Collaborative Cohort Study and two-sample MR analyses using summary statistics based on genome-wide association study data from 173,430 Japanese. Using 83 body mass index (BMI)-related loci, genetic risk scores (GRS) for BMI were calculated, and the effects of BMI on cardiometabolic traits were examined for individual-level MR analyses using the two-stage least squares estimator method. The β-coefficients and standard errors for the per-allele association of each single-nucleotide polymorphism as well as all outcomes, or odds ratios with 95% confidence intervals were calculated in the two-sample MR analyses., Results: In individual-level MR analyses, the GRS of BMI was not significantly associated with any cardiometabolic traits. In two-sample MR analyses, higher BMI was associated with increased risks of higher blood pressure, triglycerides, and uric acid, as well as lower high-density-lipoprotein cholesterol and eGFR. The associations of BMI with type 2 diabetes in two-sample MR analyses were inconsistent using different methods, including the directions., Conclusion: The results of this study suggest that, even among the Japanese, an East Asian population with low levels of obesity, higher BMI could be causally associated with the development of a variety of cardiometabolic traits. Causality in those associations should be clarified in future studies with larger populations, especially those of BMI with type 2 diabetes.

Background: Although many polygenic risk scores (PRS) for cardiovascular traits have been developed in European populations, it is an urgent task to construct a PRS and to evaluate its ability in non-European populations. We developed a genome-wide PRS for blood pressure in a Japanese population and examined the associations between this PRS and hypertension prevalence., Methods: We performed a cross-sectional study in 11 252 Japanese individuals who participated in the J-MICC (Japan Multi-Institutional Collaborative Cohort) study. Using publicly available GWAS summary statistics from Biobank Japan, we developed the PRS in the target data (n=7876). With >30 000 single nucleotide polymorphisms, we evaluated PRS performance in the test data (n=3376). Hypertension was defined as systolic blood pressure of 130 mm Hg or more, or diastolic blood pressure of 85 mm Hg or more, or taking an antihypertensive drug., Results: Compared with the middle PRS quintile, the prevalence of hypertension at the top PRS quintile was higher independently from traditional risk factors (odds ratio, 1.73 [95% CI, 1.32-2.27]). The difference of mean systolic blood pressure and diastolic blood pressure between the middle and the top PRS quintile was 4.55 (95% CI, 2.26-6.85) and 2.32 (95% CI, 0.86-3.78) mm Hg, respectively. Subgroups reflecting combinations of Japanese PRS and modifiable lifestyles and factors (smoking, alcohol intake, sedentary time, and obesity) were associated with the prevalence of hypertension. A European-derived PRS was not associated with hypertension in our participants., Conclusions: A PRS for blood pressure was significantly associated with hypertension and BP traits in a general Japanese population. Our findings also highlighted the importance of a combination of PRS and risk factors for identifying high-risk subgroups.

There are few studies examining the association between homocysteine (Hcy) level and the risk of hypertension with consideration for folate and vitamin B 12 as related to Hcy level. We simultaneously examined the associations of plasma levels of Hcy, folate, and vitamin B 12 , and dietary folate intake with the prevalence of hypertension. Participants included 1046 men and 1033 women (mean age ± standard deviation: 56.0 ± 8.9 years) in the Japan Multi-Institutional Collaborative Cohort Study. Dietary folate intake was estimated using a validated food frequency questionnaire. Hypertension was defined based on measured blood pressure and use of antihypertensive medication. A total of 734 participants (35.3%) had hypertension. Multivariate-adjusted odds ratios of hypertension for the highest quartile group of Hcy were 2.36 (95% CI 1.41-3.96) in men and 1.86 (95% CI 1.11-3.11) in women, as compared with the lowest group (P for trend = 0.014 and 0.005, respectively). Dietary folate intake was not correlated with hypertension in both men and women (P for trend = 0.099 and 0.703, respectively). Plasma vitamin B 12 was positively associated with hypertension only in women (P for trend = 0.027). Plasma Hcy level was positively linked with hypertension after controlling for covariates, including folate and vitamin B 12 .

The aim of this study is to show the combined effect of weight gain within normal weight range in adulthood and parental HT on the prevalence of HT. The study subjects were 44,998 individuals (19,039 men and 25,959 women) with normal weight (body mass index [BMI] 18.5-24.9) aged 35-69 years who participated in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. They were categorized into six groups by weight gain from age 20 years (<10 kg, and ≥10 kg) and by the number of parents having HT (no parent, one parent, and both parents). Odds ratios for HT were estimated after adjustment for age, sex, current BMI, estimated daily sodium intake, and other confounding factors. The prevalence of HT (31.5% in total subjects) gradually increased with greater weight gain from age 20 years and with greater number of parents with HT. Subjects who gained weight ≥10 kg and having both parents with HT showed the highest risk of having HT compared with those who gained weight <10 kg without parental HT (59.8% vs. 24.9%, odds ratio 4.25, 95% CI 3.53-5.13 after adjustment). This association was similarly observed in any category of age, sex, and BMI. Subjects who gained weight within normal range of BMI and having one or both parent(s) with HT showed the higher risk of having HT independent of their attained BMI in their middle ages. Thus, subjects having parent(s) with HT should avoid gaining their weight during adulthood, even within normal range of BMI, to reduce the risk of having HT.

The prevention of hypertension starts with the awareness of risk. Our aim was to construct a simple and well-validated risk model for nonhypertensive people in Japan consisting of basic clinical variables, using a dataset for two areas derived from the Japan Multi-Institutional Collaborative Cohort Study. We constructed a continuous-value model using data on 5105 subjects participating in both the baseline survey and a second survey conducted after 5 years. The area under the receiver operating characteristic curve (AUC) and the Hosmer-Lemeshow χ 2 statistic for the entire cohort were 0.826 and 7.06, respectively. For validation, the entire cohort was randomly divided 100 times into derivation and validation sets at a ratio of 6:4. The summarized median AUC and the Hosmer-Lemeshow χ 2 statistic were 0.83 and 12.2, respectively. The AUC of a point-based model consisting of integer scores assigned to each variable was 0.826 and showed no difference, compared with the continuous-value model. This simple risk model may help the general population to assess their risks of new-onset hypertension.

Forest walking or Shinrin-yoku is a health promotion activity in Japan. Although some studies have reported the acute effects of walking a few hours in forested areas in reducing blood pressure level compared to other environments, studies investigating whether successive walking has long-term effects in lowering blood pressure levels or lowering prevalence of hypertension are rare. This study aimed to reconfirm the presence or absence of an association between the frequency of forest walking and prevalence of hypertension in a Japanese population. This J-MICC Daiko Study was conducted targeting residents in Nagoya City. A total of 5,109 participants (1,452 men and 3,657 women; age, mean ± standard deviation: 52.5 ± 10.3 years) were included in the analysis. Age-adjusted blood pressure level by frequency of forest walking was not significant. After adjusting for age and lifestyle, the adjusted odds ratios (aORs) of the most frequent group (n=88, 1.7%; once a week or more group) relative to the less than once a month group (n=4,558, 89.2%) for prevalence of hypertension were not also significant [0.80 (95% CI: 0.40-1.62) for men and 1.48 (95% CI: 0.73-3.00) for women]. This study reconfirmed that either lowering blood pressure level or lowering the prevalence of hypertension is not associated with frequency of forest walking, similar to the results of our previous J-MICC Shizuoka Study. Given that these two studies were cross-sectional studies, cohort studies investigating the causal relationship are required to evaluate the effect of frequent forest walking on the prevention of hypertension., Competing Interests: The authors declare that they have no conflicts of interest.

Background: The purpose of this study is to determine the association of dipstick-determined trace proteinuria with metabolic syndrome (MetS) and its components in each age, gender, and eGFR category among a large general population., Methods: A total of 270,190 people (102,223 men and 167,967 women) aged 40-74 years were included. Subjects were categorized as having negative, trace, and positive proteinuria by the dipstick method., Results: The prevalence of MetS increased with increasing levels of proteinuria in any estimated glomerular filtration rate (eGFR) category (odds ratios for MetS relative to negative proteinuria: 1.22, 1.23, and 1.25 for trace proteinuria, and 2.19, 1.81, and 1.80 for positive proteinuria among subjects with eGFR of ≥ 90, 60-89, and 45-59 ml/min/1.73 m 2 , respectively). These associations were statistically significant in each age and sex category. Among MetS components, the prevalence of hypertension and diabetes increased with increasing levels of proteinuria (odds ratios for hypertension: 1.23 and 1.87, and odds ratios for diabetes: 1.28 and 2.18 for trace and positive proteinuria, respectively), which were similarly observed in any eGFR category. There were little or no differences in the prevalence of abdominal obesity and dyslipidemia (reduced HDL-cholesterol and/or elevated triglycerides) between the levels of proteinuria., Conclusion: Subjects with dipstick-determined trace proteinuria showed intermediate risk of having MetS, hypertension, and diabetes between negative and positive proteinuria in any eGFR category in a large general population. Thus, MetS components should be checked for subjects with trace proteinuria even in those with normal eGFR for the early prevention of cardiovascular diseases.

Brief exposure to passive smoking immediately elevates blood pressure. However, little is known about the association between exposure to passive smoking and chronic hypertension. We aimed to examine this association in a cross-sectional study, after controlling multiple potential confounders.Participants included 32,098 lifetime nonsmokers (7,216 men and 24,882 women) enrolled in the Japan Multi-Institutional Collaborative Cohort Study. Passive smoking was assessed using a self-administered questionnaire. The single question about exposure to passive smoking had five response options: "sometimes or almost never," "almost every day, 2 hours/day or less," "almost every day, 2 to 4 hours/day," "almost every day, 4 to 6 hours/day," and "almost every day, 6 hours/day or longer." Hypertension was defined as any of the following: systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, or use of antihypertensive medication. Multivariate-adjusted odds ratio (OR) and 95% confidence interval (CI) for hypertension were estimated by exposure level to passive smoking using unconditional logistic regression models.The multivariate-adjusted OR for hypertension in those exposed almost every day was 1.11 (95% CI: 1.03-1.20) compared with those exposed sometimes or almost never. The OR for a 1-hour per day increase in exposure was 1.03 (95% CI: 1.01-1.06, Pfor trend = .006). This association was stronger in men than in women; the ORs were 1.08 (95% CI: 1.01-1.15, Pfor trend = .036) and 1.03 (95% CI: 1.00-1.05, Pfor trend = .055), respectively.Our findings suggest importance of tobacco smoke control for preventing hypertension.

Objective: To study the non-temporary effects of successive walks in forested areas (shinrin-yoku) on hypertension prevalence and blood pressure levels., Methods: Data for the analysis were derived from the baseline survey of the Japan Multi-Institutional Collaborative Cohort (J-MICC) study in the Shizuoka area. Eligible participants were individuals aged 35-69 years who attended a health check-up center during 2006 and 2007. Of the 5,040 individuals who participated in the J-MICC study, Shizuoka, 4,666 were included in this analysis [3,174 men and 1,492 women; age (mean ± standard deviation) 52.1 ± 8.7 years]. The frequency of forest walking was estimated by a self-administrated questionnaire. Hypertension was defined as a systolic blood pressure ≥ 140 mmHg, a diastolic blood pressure ≥ 90 mmHg or, based on information provided in the questionnaire, the use of medication for hypertension., Results: After adjusting for age, body mass index (BMI), smoking status, alcohol consumption, and habitual exercise, the odds ratios of hypertension associated with forest walking once a week or more frequently, relative to less than once a month were 0.98 in men [95% confidence interval (CI) 0.68-1.42] and 1.48 (95% CI 0.80-2.71) in women. There was no significant trend between adjusted blood pressure levels and the frequency of forest walking., Conclusion: The results of our cross-sectional study in a Japanese population show no association between either blood pressure levels or the prevalence of hypertension and the frequency of forest walking.

Background. This study aimed to investigate the associations of hyperfiltration and hypofiltration with prediabetes and prehypertension. Methods. The study subjects included 99 140 people aged 20–89 years who underwent health checkups in Aichi Prefecture, Japan. The prevalence of hyperfiltration [estimated glomerular filtration rate (eGFR) above the age-/sex-specific 95th percentile] and hypofiltration (eGFR below the age-/sex-specific 5th percentile) was compared among stages of prediabetes (fasting plasma glucose <100, 100–109, 110–125 and ≥126 mg/dL for no prediabetes, Stage 1 prediabetes, Stage 2 prediabetes and diabetes, respectively) and prehypertension [blood pressure (BP) <120/80, 120–129/80–84, 130–139/85–89 and ≥140/90 mmHg for no prehypertension, Stage 1 prehypertension, Stage 2 prehypertension and hypertension, respectively). Results. The prevalence of hyperfiltration increased with increasing stage of prediabetes [odds ratios (ORs): 1.29, 1.58 and 2.47 for Stage 1 prediabetes, Stage 2 prediabetes and diabetes, respectively] and prehypertension (ORs: 1.10, 1.33 and 1.52 for Stage 1 prehypertension, Stage 2 prehypertension and hypertension, respectively). Hypofiltration was not associated with prediabetes or prehypertension. Conclusions. The prevalence of glomerular hyperfiltration increased with increasing stages of prediabetes and prehypertension. Therefore, kidney function should be monitored in subjects with prediabetes or prehypertension. In subjects with hyperfiltration, earlier treatment of hyperglycemia and high BP may be necessary to prevent the development of kidney damage. [ABSTRACT FROM AUTHOR]

To investigate the association between alcohol intake pattern in amount and frequency and metabolic syndrome (Mets) components, we simulated the change in the prevalence of Mets components by intake reduction. In order to manage Mets, alcohol intake reduction with moderation of intake pattern is required. However, evidence investigating the comparative impact of alcohol intake reduction in amount and frequency for Mets components is limited. We conducted a large-scale cross-sectional study in the general Japanese population. The study subjects included 37,371 non-drinkers and current drinkers recruited in the Japan Multi-Institutional Collaborative Cohort Study. Odds ratios (ORs) for Mets components according to alcohol intake amount and frequency were estimated using a multiple logistic regression model. The prevalence of Mets components was estimated after assumed alcohol intake reduction of a) none, b) 10 g/day (men) or 5 g/day (women), c) 20 g/day (men) or 10 g/day (women), d) less than 20 g/day (men) or 10 g/day (women) for moderate-to-heavy drinkers, e) 1-2 times/week, and f) 3-4 times/week. The ORs with alcohol intake amount and frequency increased with high blood pressure while decreasing with dyslipidemia. A J-shaped association was observed between intake amount and Mets. The estimated prevalence (%) of high blood pressure and dyslipidemia in men were a) 45.2, b) 43.0, c) 41.4, d) 40.4, e) 42.9, and f) 42.0; and a) 50.3, b) 51.8, c) 52.9, d) 50.2, e) 52.7, and f) 53.4 in women. The estimated prevalence of high blood pressure in women did not evidently decrease. Simulated alcohol intake reduction showed decreased prevalence for high blood pressure and increased prevalence for dyslipidemia in men after reduced intake amount and frequency. The largest decreased prevalence for high blood pressure was observed in men when all moderate-to-heavy drinkers reduced their alcohol intake amount to less than 20 g/day. [ABSTRACT FROM AUTHOR]