Association between visceral fat accumulation and decline in the estimated glomerular filtration rate based on cystatin C in the Japanese urban population: the KOBE study.

Although metabolic syndrome, including visceral fat accumulation, causes kidney and cardiovascular diseases, the impact of visceral fat accumulation on mild decreased renal function remains unclear. This study examines the association between visceral fat area (VFA) measured by bioimpedance methods and the estimated glomerular filtration rate based on serum cystatin C (eGFRcys) in the Japanese urban population. This community-based cross-sectional study enrolled 952 individuals (287 men, 665 women) who participated in the second follow-up survey of the Kobe Orthopedic and Biomedical Epidemiological (KOBE) study. We compared the multivariate-adjusted means of eGFRcys among VFA quartile groups by gender using the analysis of covariance. Models were adjusted for age, high blood pressure, hypercholesterolemia, glucose intolerance, smoking, and alcohol use, and further adjusted for body mass index (BMI). The highest VFA quartile group had lower eGFRcys than the lowest VFA quartile group after adjusted for cardiometabolic risk factors, except for BMI (93.1 [95% confidence interval (CI), 90.1-96.2] vs. 82.1 [95% CI, 79.1-85.0] in men and 95.8 [95% CI, 94.1-97.5] vs. 89.4 [95% CI, 87.8-90.9] in women). Moreover, further adjustment for BMI revealed a similar result in men (93.5 [95% CI, 89.8-97.2] vs. 81.6 [95% CI, 77.9-85.3]), while no significant association was found in women. This study suggests a significant association between increased VFA levels and lower eGFRcys levels independent of cardiometabolic risk factors, such as glucose intolerance and hypercholesterolemia in men and women, as well as independent of BMI in men.

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.

Total protein intake and subsequent risk of chronic kidney disease: the Circulatory Risk in Communities Study.

BACKGROUND: Whether dietary protein intake worsens renal function in the general population has been discussed but not yet determined. We aimed to examine the longitudinal association between dietary protein intake and risk of incident chronic kidney disease (CKD). METHODS: We conducted a 12-year follow-up study with 3,277 Japanese adults (1,150 men and 2,127 women) aged 40-74 years, initially free from CKD, who participated in cardiovascular risk surveys from two Japanese communities under the Circulatory Risk in Communities Study. The development of CKD was defined by the estimated glomerular filtration rate (eGFR) during the follow-up period. Protein intake was measured at baseline by using the brief-type self-administered diet history questionnaire. We estimated sex-, age-, community- and multivariate-adjusted hazard ratios (HR) for incident CKD were calculated using the Cox proportional hazards regression models according to quartiles of percentage of energy (%energy) from protein intake. RESULTS: During 26,422 person-years of follow-up, 300 participants developed CKD (137 men and 163 women). The sex-, age-, and community-adjusted HR (95% confidence interval, CI) for the highest (≥16.9%energy) versus lowest (≤13.4%energy) quartiles of total protein intake was 0.66 (0.48-0.90), p for trend = 0.007. The multivariable HR (95%CI) was 0.72 (0.52-0.99), p for trend = 0.016 after further adjustment for body mass index, smoking status, alcohol drinking status, diastolic blood pressure, antihypertensive medication use, diabetes mellitus, serum total cholesterol levels, cholesterol-lowering medication use, total energy intake, and baseline eGFR. The association did not vary by sex, age, and baseline eGFR. When examining animal and vegetable protein intake separately, the respective multivariable HRs (95%CIs) were 0.77 (0.56-1.08), p for trend = 0.036, and 1.24 (0.89-1.75), p for trend = 0.270. CONCLUSIONS: Higher protein intake, more specifically animal protein intake was associated with a lower risk of CKD.

[Determinants of salt taste threshold among urban residents: the KOBE study].

Objectives　Though having a high salt taste threshold has been associated with hypertension, its exact determinants remains unclear. This study aimed to identify the determinants of salt taste threshold in a community-based population and to determine the relationship between salt taste thresholds and the simultaneous presence of multiple determinants.Methods　Of the 1,117 participants of the baseline survey of the Kobe study, a cohort study of healthy urban residents, aged 40-74 years, with no history of cancer or cardiovascular diseases, nor undergoing treatment for hypertension, diabetes, or dyslipidemia, was conducted. Among them, 1,116 underwent the salt taste threshold test, and urine samples were collected to determine their estimated salt intake. The salt taste threshold test was carried out using SALSAVE®, with a salt taste threshold of 0.6% defined as normal, and that of 0.8% or more defined as high. A binomial logistic regression model was used, with high salt taste threshold as the objective variable, and life and family status, education, smoking and alcohol drinking status, intake status of salt dried fish, stress indicators, and daily salt intake (estimated from the urine sample) as the explanatory variables. A binomial logistic regression analysis was conducted, through multivariate analysis using the forced entry method, with factors influencing salt taste threshold as explanatory variables, and salt taste threshold (normal/high) as the objective variable. This analysis was performed excluding the urinary sodium-to-potassium ratio to account for multicollinearity with the estimated daily salt intake.Results　The mean age was 60.9±9.0 years for men, and 58.0±8.7 years for women. The salt taste threshold was normal in 80.9% (n=903) of the participants (73.6% [n=251] men and 84.1% [n=652] women), and high in 19.1% (n=213) of the participants (26.3% [n=90] men and 15.9% [n=123] women). Multivariate analysis revealed that smoking habits were significantly associated with a higher salt taste threshold, with an odds ratio (95% confidence interval) of 2.51 (1.33-4.74) for all participants. The odds ratio for a high salt taste threshold was 1.45 (1.03-2.03) for the top 25% estimated daily salt intake group, showing a significant association with a high salt taste threshold. In the analysis by sex, smoking habits were associated with higher salt taste thresholds, while an association with estimated daily salt intake was observed only in men.Conclusion　Smoking status and estimated daily salt intake were associated with higher salt taste thresholds in healthy urban residents.

Longitudinal Trends in Blood Pressure Associated With the Frequency of Laughter: The Circulatory Risk in Communities Study (CIRCS), a Longitudinal Study of the Japanese General Population.

BACKGROUND: The frequency of laughter has been associated with cardiovascular disease and related biomarkers, but no previous studies have examined association between laughter and changes in blood pressure levels. We sought to identify temporal relationships between frequency of laughter in daily life and systolic and diastolic blood pressure changes in participants from 2010 through 2014. METHODS: Participants were 554 men and 887 women aged 40-74 years who answered self-administered questionnaire quantifying frequency of laughter at baseline. We measured participant blood pressure levels twice using automated sphygmomanometers for each year from 2010 to 2014. The associations between laughter and changes in blood pressure over time were analyzed using linear mixed-effect models. RESULTS: There was no significant difference in blood pressure according to frequency of laughter at baseline in either sex. Men with frequency of laughter 1 to 3 per month or almost never had significantly increased systolic and diastolic blood pressure levels over the 4-year period (time-dependent difference: 0.96 mm Hg (95% confidence interval [CI], -0.2 to 1.8; P = 0.05). Changes in blood pressure associated with infrequent laughter (ie, 1 to 3 per month or almost never) were evident in men without antihypertensive medication use over 4 years (0.94 mm Hg; 95% CI, -0.2 to 2.0; P = 0.09) and men who were current drinkers at baseline (1.29 mm Hg; 95% CI, -0.1 to 2.3; P = 0.04). No significant difference was found between frequency of laughter and systolic (0.23 mm Hg; 95% CI, -1.0 to 1.5; P = 0.72) and diastolic (-0.07 mm Hg; 95% CI, -0.8 to 0.7; P = 0.86) blood pressure changes in women. CONCLUSIONS: Infrequent laughter was associated with long-term blood pressure increment among middle-aged men.

[The search for a predictor of deterioration of the nonspecific stress index K6 among urban residents: The KOBE study].

Objective　To explore health-related and socioeconomic factors that can predict future deterioration in Psychological Distress Scale (K6) scores.Method　We conducted a baseline (2010, 2011) self-administered questionnaire survey of the Kobe Orthopedic and Biomedical Epidemiological study (KOBE study) involving 1,117 participants who had no previous history of cancer or cardiovascular diseases and were not under treatment for hypertension, diabetes, or dyslipidemia. We used the Japanese K6 as an indicator of stress and defined K6≧5 points as a high-stress group and K6<5 points as a low-stress group. A four-year follow-up survey (2014, 2015) was conducted on 1,004 people (follow-up rate of 90%). We excluded 39 participants with missing values, and 185 people whose K6 score was higher than 5 points at baseline. A final total of 780 participants' scores were examined for: gender, age, living situation, physical activity level, average sleep time, as well as the K6 score, the Japanese Hearing Handicap Inventory for Elderly (HHIE-S), and the Japanese Oswestry Disability Index (ODI). We conducted a logistic regression analysis using K6≧5 points at the four-year follow-up survey as the dependent variable and each factor at the baseline survey as the independent variable.Results　Of the 780 subjects analyzed, 132 (16.9%) were highly stressed (K6≧5 points) at the four-year follow-up point. A logistic regression analysis found age (40s/70s) (odds ratio 3.38, 95% confidence interval 1.45-7.86), living situation (single/living together) (odds ratio 1.98, 95% confidence interval 1.07-3.68), and ODI scores (every 1%) (odds ratio 1.05, 95% confidence interval 1.01-1.09), to all be significantly associated with high stress.Conclusion　This study suggests that age, living situation, and ODI scores are related to future stress.

[Association of the combined estimated 24-h urinary Na/K ratio and body mass index with blood pressure: Cross-sectional data from the KOBE study].

Objective　Several studies have suggested that high dietary Na/K ratio and body mass index (BMI) increase the prevalence of hypertension. However, there have been a few reports on the combination of these two factors and their relationship with hypertension. This study aimed to examine the association of the combined estimated 24-h urinary Na/K ratio (24h-u-Na/K) (high or low) and BMI (high or low) with the risk of high blood pressure.Method　We performed a cross-sectional study involving 1,112 participants (340 men and 772 women) of the Kobe Orthopedic and Biomedical Epidemiological study (KOBE study) who had no cardiovascular diseases or current anti-hypertensive medications. Sex-specific analyses were performed. The 24h-u-Na/K ratio was calculated from an estimation formula using collected spot urine. Participants were divided into four groups based on their 24h-u-Na/K ratio (low or high) and BMI (low or high), with the cutoff points being the median and 25 kg/m2, respectively.　Participants with systolic blood pressure (SBP) ≥130 mmHg or diastolic blood pressure (DBP) ≥80 mmHg were diagnosed with high blood pressure. Odds ratios (ORs) for high blood pressure according to the combined risks of high 24h-u-Na/K and BMI were examined with a logistic regression analysis.Results　The average SBP/DBP for men and women was 122.7/77.9 and 113.3/69.1 mmHg, respectively, and prevalence of high blood pressure among men and women was 47.4% and 21.3%, respectively. The mean BMI was 22.8 kg/m2 for men and 20.9 kg/m2 for women. The median 24h-u-Na/K was 3.2 for men and 3.1 for women. The prevalence of high blood pressure (men, women) was the highest in the group in which both 24h-u-Na/K and BMI were high (60.0%, 62.9%; men: P=0.273; women: P<0.001). In the same group, the multivariate-adjusted ORs for high blood pressure were significantly higher for both men (2.59; 95% confidence interval [CI]: 1.15-5.86) and women (10.78; 95% CI: 4.87-23.88) compared to the reference group with both factors classified as low. Women with low BMI but high 24h-u-Na/K also demonstrated a higher risk for high blood pressure (OR: 1.62; 95% CI: 1.10-2.40).Conclusion　The risk of high blood pressure was the highest when both BMI and 24h-u-Na/K were high. The current specific healthcare guidance in Japan is focused on obese individuals. However, in order to prevent hypertension more effectively, additional focus should be placed on the Na/K diet. Increased intake of vegetables and fruits and reduced intake of salt should be strongly recommended.

Daily Habit of Water Intake in Patients with Cerebral Infarction before its Onset; Comparison with a Healthy Population: A Cross-Sectional Study.

BACKGROUND: While water intake is frequently recommended to prevent cerebral infarction (CI), only few studies have been published on this topic. OBJECTIVES: This study retrospectively estimated the daily non-alcohol drink (NAD) intake in CI patients before CI onset and compared it with NAD in healthy subjects. METHODS: We performed a cross-sectional study on CI patients in 3 hospitals and healthy subjects in the Kobe Orthopedic and Biomedical Epidemiologic (KOBE) study. Data from 1,287 subjects (274 CI patients and 1,013 healthy subjects) were used for the analyses. By dividing the CI patients into "increased", "unchanged", and "decreased" groups according to their current NAD intake, we compared the NAD intake between these 3 groups and healthy subjects by analyses of covariance and the post hoc test, adjusting for sex, age, surveyed month, body mass index, alcohol drinking history, and smoking history. Under the assumption that the NAD intake in the "unchanged" group was equal to the NAD intake before CI onset, the OR of less NAD intake for CI adjusting for the relevant variables in the "unchanged" group and the healthy subjects was calculated; the cut-off point was chosen using Youden's index. RESULTS: The mean age (mean ± SD) of the participants was 62.8 ± 9.3 years. One hundred and fifty-one patients (36 women) were included in the "increased" group; 105 (30 women), in the "unchanged" group; 18 (2 women), in the "decreased" group; and 1,013 (706 women), in the "healthy" group. The mean NAD intake was 1,702.5 ± 670.2 mL in the "increased" group, 1,494.2 ± 611.2 mL in the "unchanged" group, 1,268.0 ± 596.1 mL in the "decreased" group, and 1,720.6 ± 686.0 mL in the "healthy" group. After adjusting for the relevant variables, a significant difference in NAD intake between the groups was observed (F = 6.1, p < 0.001), and a post hoc test demonstrated significant differences (p < 0.05) in NAD intake between the "healthy" and "unchanged" groups, and between the "increased" and "unchanged" groups. The OR of less NAD intake (<1,570 mL/day, chosen using Youden's index) for CI was 2.48 (95% CI 1.52-4.07). CONCLUSION: This study showed that daily NAD intake before CI onset in CI patients was less than that in healthy persons, indicating that sufficient intake of NAD may be protective for CI.

Higher serum uric acid level is inversely associated with renal function assessed by cystatin C in a Japanese general population without chronic kidney disease: the KOBE study.

BACKGROUND: Although several epidemiological studies have suggested that high serum uric acid (SUA) levels are related to a decline in kidney function, only a few studies have investigated using cystatin C to calculate estimated glomerular filtration rate (eGFR). We aimed to clarify the relationship between SUA levels and kidney function assessed by cystatin C in a Japanese general community population without chronic kidney disease (CKD). METHODS: We conducted a community-based cross-sectional study that included 1086 healthy participants, aged 40-74 years, without CKD and not undergoing treatment of hyperuricemia, who had participated in the baseline survey of the Kobe Orthopedic and Biomedical Epidemiological (KOBE) study. The preconditions for participation in this study were no past histories of cardiovascular disease or cancer, and not undergoing treatment for diabetes, hypertension, or dyslipidemia. We classified the participants into quartiles stratified by sex according to their SUA level and then examined the relationship with eGFR. The odds ratios for having a low eGFR, defined as the lowest quartile of eGFR (i.e., ≤78.4 mL/min/1. 73m2) was estimated according to SUA quartiles (men, Q1 ≤ 5.0, Q2 5.1-5.9, Q3 6.0-6.6, and Q4 ≥ 6.7; women, Q1 ≤ 3.8, Q2 3.9-4.3, Q3 4.4-4.9, and Q4 ≥ 5.0 mg/dL) after adjustment for age, body mass index, systolic blood pressure, HbA1c, high and low density lipoprotein cholesterol, and smoking and drinking habits. The adjusted mean of each quartile was also calculated. RESULTS: Multivariable-adjusted means of eGFR showed a graded decrease in higher SUA quartiles (men, Q1 90.5, Q2 88.0, Q3 83.5, and Q4 82.0; women, Q1 95.7, Q2 91.3, Q3 89.2, and Q4 86.7). In addition, the multivariable-adjusted odds ratios for having a lower eGFR (95% confidence interval) for each SUA quartile compared with Q1 was Q2 2.29 (0.98, 5.35), Q3 4.94 (2.04, 11.97), and Q4 8.01 (3.20, 20.04) for men, and was Q2 2.20 (1.12, 4.32), Q3 2.68 (1.39, 5.20), and Q4 4.96 (2.62, 9.41) for women. CONCLUSIONS: There was a graded inverse relationship between mild elevations in SUA levels and eGFR assessed by cystatin C in an apparently healthy Japanese population without CKD. This association was similar in both men and women.

Physique at Birth and Cardiovascular Disease Risk Factors in Japanese Urban Residents: the KOBE Study.

AIM: This study investigated the relationship between birth physique and cardiovascular risk factors in Japanese urban residents aged 40 years and more. METHODS: A self-administered questionnaire on birth physique was performed among 624 individuals (165 men and 459 women) who participated in the KOBE study. We examined whether self-reported birth physique and available recorded birth weights matched for 72 participants. Then the association between birth physique and risk factors for all participants was examined by gender. Body size at birth in the questionnaire (large, medium, small) was set as an exposure and laboratory values from the baseline survey (2010-2011) were used as outcomes. RESULTS: Mean (standard deviation) recorded birth weight of 72 participants was 3665 (318), 3051 (300), and 2653 (199) g, in the large, medium, and small group, respectively. In the analysis for all participants, odds ratio for having both hypertension and impaired glucose tolerance were significantly higher in the small versus large birth weight group, which was 7.42 (95% CI 1.75-31.50) for men and 4.44 (95% CI 1.14-17.30) for women after adjusting for age, body mass index, smoking/alcohol/exercise habits, and menstrual status in women. Similar results were observed in participants with recorded birth weight. CONCLUSIONS: The present study indicates that individuals with small physique at birth might be at higher risk for hypertension and impaired glucose tolerance in middle age compared to those with large birth weight.

Estimated 24 h Urinary Sodium-to-Potassium Ratio Is Related to Renal Function Decline: A 6-Year Cohort Study of Japanese Urban Residents.

The effect of the sodium-to-potassium ratio (Na/K) on renal function within the clinically normal range of renal function are limited. We investigated the effects of an estimated 24 h urinary Na/K (e24hUNa/K) on a 6-year renal function decline among 927 urban Japanese community dwellers with no history of cardiovascular diseases and medication for hypertension, diabetes, or dyslipidemia. We partitioned the subjects into quartiles according to the e24hUNa/K. The estimated glomerular filtration rate (eGFR) was calculated using the chronic kidney disease epidemiology collaboration (CKD/EPI) formula and renal function decline was defined as an absolute value at or above the third quartile of the eGFR decline rate. A multivariable logistic regression model was used for estimation. Compared with the first quartile of the e24hUNa/K, multivariable-adjusted odds ratios (ORs) for eGFR decline in the second, third, and fourth quartiles were 0.96 (95% confidence interval: 0.61-1.51), 1.06 (0.67-1.66), and 1.65 (1.06-2.57), respectively. These results were similar when the simple spot urine Na/K ratio was used in place of the e24hUNa/K. Apparently healthy urban residents with an almost within normal range mean baseline eGFR and high e24hUNa/K ratios had an increased risk for a future decline in renal function. Reducing the Na/K ratio may be important in the prevention of chronic kidney disease in its early stage.

Being Conscious of Water Intake Positively Associated with Sufficient Non-Alcohol Drink Intake Regardless of Seasons and Reasons in Healthy Japanese; the KOBE Study: A Cross Sectional Study.

The present study sought to clarify if being conscious of water intake (CWI) is associated with sufficient non-alcohol drink (NAD) intake. We used data of healthy participants without diabetes, aged 40-74 years, in the Kobe Orthopedic and Biomedical Epidemiologic (KOBE) study. The association between being CWI and NAD intake was evaluated by multivariate linear regression analyses after adjusting for age, sex, surveyed months (seasons), alcohol drinking, health-awareness life habits, socioeconomic factors, serum osmolarity, estimated daily salt intake, and reasons for NAD intake. Among 988 (698 women and 290 men) participants eligible for the present analyses, 644 participants (65.2%) were CWI and 344 participants (34.8%) were not CWI (non-CWI). The most popular reason for being CWI was to avoid heat stroke in summer and to prevent ischemic cerebral stroke in winter. The CWI group took more NAD, especially decaffeinated beverages, than the non-CWI group (1846.7 ± 675.1 mL/day vs. 1478.0 ± 636.3 ml/day, p < 0.001). There was a significant association between being CWI and NAD intake in multivariate linear regression analyses ever after adjusting for the relevant variables (ß = 318.1, p < 0.001). These findings demonstrated CWI, regardless of the reasons and the seasons, was associated with high NAD intake in Japanese healthy population.

Association between impairment of salty taste recognition and masked hypertension based on home blood pressure in Japanese residents: the KOBE study.

Excessive salt intake is an established risk factor for hypertension. We conducted a cross-sectional study to examine the association between salty taste recognition and estimated salt intake and masked hypertension in a healthy Japanese normotensive population. The participants were 892 apparently healthy community residents (246 men and 646 women) aged between 40 and 74 years with blood pressure below 140/90 mm Hg. Salty taste recognition was assessed using a salt-impregnated taste strip. Daily salt intake was calculated as estimated 24 h urinary sodium excretion using spot urine tests. Each participant performed home blood pressure measurements for a minimum of 5 days per week. The participants were classified into three groups according to their salty taste recognition threshold evaluated by the salt concentrations of the taste strips (0.6%, 0.8%, and ≥ 1.0%). In women, the multivariate odds ratio (95% confidence interval) for masked hypertension ( ≥ 135/85 mm Hg) was 2.98 (1.16-7.64) in the ≥ 1.0% group compared with that in the 0.6% group. In men, the proportion of masked hypertension in the ≥ 1.0% group did not differ from that in the 0.6% group, and no correlation was identified between estimated daily salt intake and the salty taste recognition threshold. In conclusion, impairment of salty taste recognition was associated with masked hypertension in women even with normal blood pressure in the clinical setting.

Serum Albumin and High-Sensitivity C-reactive Protein are Independent Risk Factors of Chronic Kidney Disease in Middle-Aged Japanese Individuals: the Circulatory Risk in Communities Study.

AIM: It is important to explore predictive markers other than conventional cardiovascular risk factors for early detection and treatment of chronic kidney disease (CKD), a major risk factor for end-stage renal failure. We hypothesized that serum albumin and high-sensitivity C-reactive protein (hs-CRP) to be independent markers, and examined their associations with the risk of CKD. METHODS: We examined the associations of serum albumin and hs-CRP levels with the risk of incident CKD, in 2535 Japanese adults aged 40-69 years without CKD at baseline during a median 9.0-year follow-up after adjustment for known cardiovascular risk factors. RESULTS: During the follow-up period, 367 cases of CKD developed. In multivariable analyses adjusted for known risk factors, the CKD hazard ratios (95% confidence intervals) for the highest versus lowest quartiles of serum albumin levels were 0.69 (0.40-1.17) for men and 0.42 (0.28-0.64) for women. Corresponding values for hs-CRP were 0.95 (0.54-1.67) for men and 1.85 (1.25-2.75) for women. The association of combined serum albumin and hs-CRP with the risk of CKD was examined for women. The hazard ratio was 1.72 (1.17-2.54) for low versus higher albumin levels at lower hs-CRP levels, but such an association was not observed at high hs-CRP level. The hazard ratio was 1.96 (1.44-2.66) for high versus lower hs-CRP levels at higher serum albumin levels, but such association was not observed at low serum albumin level. CONCLUSION: Both low serum albumin and high hs-CRP levels were predictive of CKD for women.