Fermented brown rice beverage distinctively modulates the gut microbiota in Okinawans with metabolic syndrome: A randomized controlled trial.

Accumulating evidence to date suggests that brown rice is superior to white rice in regard to its beneficial impact on a number of risk factors of the metabolic syndrome (MetS). However, little is known about the influence of fermented brown rice beverage on the gut microbiota in humans. We therefore hypothesized that its impact would beneficially alter the gut microbiota composition of patients with MetS. Using a 4-week randomized, single-arm study design, subjects (n = 40) were advised to consume a daily fermented brown rice beverage (BA) or fermented white rice beverage (WA) as a replacement of their main meal. Clinical and anthropometric measurements as well as fecal samples were collected at baseline and immediately after completion of the intervention. Gut microbiota was analyzed using 16S ribosomal RNA sequencing and capillary electrophoresis-time-of-flight mass spectrometry was used to measure plasma short-chain fatty acids. Interestingly, ingestion of BA in contrast to WA resulted in a unique elevation in the abundance of number of beneficial species belonging to the Clostridia class, associated with reduced inflammation, and increased short-chain fatty acid production: Lactobacillales bacterium DJF B280 (P = .005), Butyrate producing bacterium A2 207 (P = .012), and Firmicutes bacterium DJF VP44 (P = .038). This study demonstrates that consumption of BA is effective to beneficially modulate the gut microbiota compared with WA in patients with MetS.

A high normal ankle--brachial index is associated with electrocardiography-determined left ventricular hypertrophy: the Okinawa Peripheral Arterial Disease Study (OPADS).

OBJECTIVES: We aimed to determine if the ankle--brachial index (ABI) increased with age as a result of increased arterial stiffness and wave reflection, and whether this was associated with left ventricular hypertrophy (LVH). METHODS: An observational cross-sectional study was conducted in 13 396 participants aged 19-89 years who attended a health check-up. Brachial and ankle blood pressures were measured by an automatic oscillometric method. Electrocardiography-determined LVH (ECG-LVH) was defined by computer-interpreted Minnesota codes using resting 12-leads ECG. RESULTS: The mean age of the participants was 53 years (54% women). The prevalence of ECG-LVH was 13%; this was the lowest in participants with normal blood pressure and increased with an increase in the hypertension grade. The ABI was higher in participants with ECG-LVH than in those without (1.13±â€Š0.07 vs. 1.15 ±â€Š0.07, P < 0.001). The prevalence of ECG-LVH was the highest in participants with the highest quartile of ABI (16%), followed by those with the third quartile (14%), second quartile (12%), and the lowest quartile of ABI (9%). The odds ratio for ECG-LVH was significantly higher for participants with a higher quartile of ABI than those with the lowest, before and after adjustment for several covariates. Similar results were observed in sensitivity analysis of individuals with normal kidney function, younger than 65 years, and without diabetes mellitus, performed in order to reduce the influence of a medial arterial calcification-mediated increase in ABI. CONCLUSION: High ABI is a possible marker of arterial stiffness and/or wave reflection that, even in the normal range, is associated with ECG-LVH.

Development of Electrocardiographic Left Ventricular Hypertrophy and Resting Heart Rate Over Time: Findings From the OGHMA Study.

Both elevated resting heart rate (HR) and electrocardiographic left ventricular hypertrophy (ECG-LVH) are signs of a poor prognosis. Although elevated resting HR is a known risk factor for cardiovascular disease and target organ damage, the association between resting HR and the development of ECG-LVH is unclear. In the present study, 6860 subjects (4203 men, 2657 women, 19-89 years of age) without ECG-LVH at baseline were evaluated and followed for a mean duration of 3.7±1.4 years. During the follow-up period, 484 (7.1%) subjects developed ECG-LVH. Cox regression analysis revealed that each 10 beats/min increase in resting HR was associated with a 22% reduction in the development of ECG-LVH (95% confidence interval: 12%-30%, P < .0001) in men. While an increase in HR tended to be associated with the development of ECG-LVH in women, the relationship was not significant. In contrast to the concept that an elevated resting HR is a cardiovascular risk factor, these findings revealed that resting HR was negatively associated with the development of ECG-LVH in men.

Association between high-normal ankle-brachial index and hypertension incidence: the Okinawa Peripheral Arterial Disease Study.

OBJECTIVES: Arterial stiffness is associated with longitudinal increases in blood pressure and hypertension development. A screened cohort was used to test whether increases in the ankle-brachial index (ABI) with age occur as a result of increasing arterial stiffness and wave reflection and is associated with hypertension incidence. METHODS: We analysed the data of 1344 participants without hypertension at baseline who underwent ABI measurements at least twice with an interval of at least 36 months. Participants with abnormal ABI values were excluded. RESULTS: The median age of participants was 51 years (55% women). The ABI was lowest for participants younger than 40 years and increased with age. At the time of the follow-up visit (median follow-up period, 47 months), 224 (17%) participants had developed hypertension. Multiple linear regression analysis revealed that baseline ABI was positively and independently associated with the yearly change in brachial SBP and hypertension incidence. Compared with participants with a normal ABI (1.00-1.19), the adjusted odds ratio for hypertension incidence was significantly higher for participants with a high-normal ABI (1.20-1.39) before and after multivariate adjustment for conventional risk factors (odds ratio, 2.17, 95% confidence interval 1.20-3.95). Addition of ABI to a model containing conventional risk factors did not improve the c-statistics but the net reclassification index of ABI was 0.17 (95% confidence index 0.01-0.37) for hypertension incidence. CONCLUSION: Baseline ABI was positively and independently associated with the yearly change in SBP and hypertension incidence.

Change in Ankle-Brachial Index Over Time in a Screened Japanese Cohort　- The Okinawa Peripheral Arterial Disease Study.

BACKGROUND: The temporal change in ankle-brachial index (ABI) in the general population, especially in those aged <40 years, remains unclear. METHODS AND RESULTS: ABIs of 23,673 individuals were measured in 1-day health checkups between 2003 and 2010. Among them, 1,117 participants aged 28-76 years (mean 53±9 years) whose ABI was measured at least twice within an interval of ≥4 years (mean: 4.9 years) were selected for this study. Baseline ABI was the lowest at age <40 years and increased with age. ABI significantly increased in participants aged <40 and 40-49 years, but not in participants aged 50-59 and ≥60 years. ABI increased in participants with borderline-low baseline ABI (0.9

A high normal ankle-brachial index combined with a high pulse wave velocity is associated with cerebral microbleeds.

OBJECTIVES: Arterial stiffness is associated with the pathogenesis of cerebral microbleeds (CMBs). The ankle-brachial index (ABI) is used to predict arterial stiffness. We hypothesized that the increase in ABI with age occurs as a result of increasing arterial stiffness and wave reflection, and is thus associated with target organ damage. The aim of this study was to investigate the relationship between ABI, brachial-ankle pulse wave velocity (baPWV), and CMBs. METHODS: We recruited 990 cardiovascular disease-free and stroke-free participants [median age 53 (24-86) years, 531 were woman] who underwent brain MRI, ABI, and baPWV at a health checkup. RESULTS: The prevalence of CMBs was 4%. Both ABI (1.14 vs. 1.10) and baPWV (17.29 vs. 14.68 m/s) were higher in participants with CMBs than those without. Cutoff values of ABI and baPWV for the presence of CMBs were 1.12 and 16.07 m/s, respectively. Multivariate logistic regression analysis showed that ABI at least 1.12 [odds ratio (OR) 2.57, 95% confidence interval (CI) 1.30-5.37, P < 0.05] and baPWV at least 16.07 m/s (OR 2.08, 95% CI 1.02-4.38, P < 0.05) were independently associated with CMBs. Moreover, the combination of ABI at least 1.12 and baPWV at least 16.07 m/s was strongly associated with CMBs (OR 5.26, 95% CI 1.93-16.92, P < 0.05). CONCLUSION: A high normal ABI, combined with a high baPWV, was strongly associated with CMBs in a screened Japanese cohort, suggesting a novel use for ABI as a predictor for target organ damage.

Factors associated with visceral fat accumulation in the general population in Okinawa, Japan.

AIM: To investigate the clinical and biochemical factors associated with visceral fat accumulation in the general population. METHODS: We enrolled 1004 subjects who underwent a medical health checkup between April 2008 and March 2009. The medical health checkup included the following tests: Height, body weight, waist circumference (WC), systolic blood pressure, diastolic blood pressure, urinalysis, blood-cell counts, blood chemistry, electrocardiography, chest radiography, and abdominal computed tomography (CT) for visceral fat accumulation. The patients' medical history and lifestyle factors were collected privately by nurses using a self-administered questionnaire, and they included questions regarding physical activity, sleep duration, dietary habits, smoking, and alcohol consumption. Visceral fat area (VFA) was defined as the sum of the intraperitoneal fat area at the level of the umbilicus with CT density in the range of -150 to -50 Hounsfield units. RESULTS: The mean age and body mass index (BMI) of the study subjects were 57.0 years and 24.4 kg/m(2). In both male and females, VFA was significantly and positively correlated with WC (r = 0.532, P < 0.01; r = 0.612, P < 0.01). Subjects with high levels of VFA were primarily male with significantly higher age, height, body weight, BMI, systolic blood pressure (BP), diastolic BP, and hemoglobin in all subjects (P < 0.05). A multivariate logistic regression analysis revealed that VFA had a positive relationship with age ≥ 56, BMI ≥ 25 kg/m(2), and triglyceride level ≥ 149 in males (P < 0.05), whereas it had a positive relationship with age ≥ 58, BMI ≥ 24.4 kg/m(2), high-density lipoprotein cholesterol level < 40 mg/dL, and current drinking in females (P < 0.05). CONCLUSION: These results suggest that gender differences exist in the clinical and biochemical parameters associated with visceral fat accumulation.

Associations between serum uric acid levels and the incidence of hypertension and metabolic syndrome: a 4-year follow-up study of a large screened cohort in Okinawa, Japan.

The purpose of this study was to examine the associations between serum uric acid (SUA) levels and the incidences of hypertension and metabolic syndrome (MetS) in a large screened cohort of Japanese men and women. We evaluated 4812 subjects (males, 2528; females, 2284; mean age, 47.5 years) who underwent health checkups between 2006 and 2010 and were free of hypertension and MetS in 2006. After 4 years, 618 (13%), 764 (16%) and 158 (3%) subjects developed hypertension, MetS and hypertension with MetS, respectively. Increased SUA levels were significantly and positively associated with the incidences of hypertension, MetS and hypertension with MetS. Compared with the first quartile of SUA levels, the odds ratios (95% confidence intervals) for the third and fourth quartiles, respectively, were as follows: 1.5 (1.1-2.1; P = 0.0128) and 1.8 (1.2-2.5; P = 0.0022) for hypertension, 1.3 (0.9-1.9; P = 0.1910) and 1.8 (1.2-2.7; P = 0.0039) for MetS and 2.7 (1.1-6.6; P = 0.0276) and 3.2 (1.3-8.0; P = 0.0115) for hypertension with MetS. In conclusion, increased SUA levels were significantly and independently associated with the incidences of hypertension and MetS in subjects without hypertension or MetS at baseline. Increased SUA levels might also be correlated with the incidence of hypertension with MetS.

A high normal ankle-brachial index is associated with proteinuria in a screened cohort of Japanese: the Okinawa Peripheral Arterial Disease Study.

OBJECTIVES: We hypothesized that ankle-brachial index (ABI) increased with age as a result of arterial stiffness, and decreased when flow-limiting atherosclerotic stenosis occurred in the lower limbs. As arterial stiffness is associated with proteinuria, we investigated the relationship between ABI and prevalence of proteinuria. METHODS: A cross-sectional study of ABI and proteinuria with 13,193 participants aged 21-89 years (53% women) from health checkups between July 2003 and March 2010 was conducted. ABI was measured using the automatic oscillometric method, and stratified into four groups: ABI ≤ 0.9 (low); 0.9 < ABI <1.0 (borderline low); 1.0 ≤ ABI <1.2 (normal); and 1.2 ≤ ABI <1.4 (high normal). RESULTS: In participants with ABI at least 1.0, ABI was positively correlated with SBP, pulse pressure, and brachial-ankle pulse wave velocity. In participants with ABI less than 1.0, all indices were negatively correlated with ABI. The prevalence of proteinuria, defined as ≥ 1+ by dipstick, was significantly higher in low (23%) and high normal ABI (10%) compared with borderline low (6%) and normal ABI (7%). In participants at least 60 years, proteinuria was significantly associated with only low ABI [odds ratio (OR) 3.22, 95% confidence interval 1.34-7.41] compared with normal ABI before and after multivariable adjustment. In participants less than 60 years, adjusted OR for proteinuria was only significantly associated with high normal ABI (OR 1.32, 95% confidence interval 1.01-1.74). CONCLUSION: High normal ABI in younger participants may be a result of arterial stiffness and associated with proteinuria.

Age- and sex-related effects on ankle-brachial index in a screened cohort of Japanese: the Okinawa Peripheral Arterial Disease Study (OPADS).

AIMS: Age-related change of ankle-brachial index (ABI) within the general population, especially <40 years, has not been determined in large population studies. We evaluated the value of the ABI by age- and sex-related differences in a screened cohort. METHODS AND RESULTS: The ABI was examined in 13,211 participants (aged 21-89 years) in a health evaluation programme. The mean ABI was lower in women than in men at all ages. The ABI was lowest at <40 years, and increased with age; the maximum was at 60-69 years in both sexes. In participants <40 years, 186 (22%) of women and 108 (9.8%) of men had a borderline ABI (0.9-1.0). The prevalence of an ABI ≤0.9 in men increased with age, and sharply rose to 3.3% at ≥70 years. Conversely, women demonstrated a J-curve relationship, where the prevalence of an ABI ≤0.9 was lowest at 60-69 years (0.2%), and increased at <40 (0.9%) and ≥70 years (1.6%). The prevalence of atherosclerotic risk factors was higher in participants with an ABI ≤0.9 than those with an ABI >0.9 in men, both ≤60 and >60 years, and in women >60 years. In women ≤60 years, however, the prevalence of atherosclerotic risk factors in participants with an ABI >0.9 was as small as those with an ABI ≤0.9. CONCLUSION: The ABI increased with age until 60-69 years, and was lower in women than in men. It is unlikely that a low ABI in younger healthy women always indicate that existence of arterial stenosis.

Hyperuricemia predicts future metabolic syndrome: a 4-year follow-up study of a large screened cohort in Okinawa, Japan.

The aim of this study was to determine whether hyperuricemia could predict future metabolic syndrome (MetS) in a large screened cohort of Japanese male and female subjects. We evaluated 5936 subjects (3144 male subjects, 2792 female subjects; mean age 48.7 years) who underwent health checkup programs in 2006 and 2010, who were MetS free in 2006. At baseline, hyperuricemia was detected in 927 male subjects (29.5%) and 276 female subjects (9.9%). Subjects with baseline hyperuricemia had significantly higher MetS prevalence in 2010 than those without (male subjects: 34.8 vs. 20.6%, P<0.0001; female subjects: 15.6 vs. 4.8%, P<0.0001). Compared with subjects in the first quintile of uric acid levels at baseline, the age-adjusted odds ratios (ORs) for MetS cumulative incidence among subjects in the third, fourth and fifth quintiles were, 1.8 (95% confidence interval (CI): 1.4-2.4: P<0.0001), 2.1 (95% CI: 1.6-2.8: P<0.0001) and 3.2 (95% CI: 2.4-4.1: P<0.0001), respectively, for male subjects and 2.4 (95% CI: 1.3-4.7: P=0.0075), 3.0 (95% CI: 1.6-5.7: P=0.0010) and 4.8 (95% CI: 2.6-8.8: P<0.0001), respectively for female subjects. Multivariable logistic analysis revealed that hyperuricemia was significantly associated with MetS cumulative incidence in male subjects (OR 1.5: 95% CI: 1.3-1.8, P<0.0001) and female (OR 2.0, 95% CI: 1.3-3.0, P<0.0001). In conclusion, hyperuricemia is a significant and independent predictor of MetS in Japanese male and female subjects. For both genders, MetS risk increases with increased serum uric acid levels.

Changes in serum uric acid have a reciprocal effect on eGFR change: a 10-year follow-up study of community-based screening in Okinawa, Japan.

Hyperuricemia is common among patients with hypertension and metabolic syndrome and therefore may be a cause of or result from these comorbid conditions. Few studies, however, have examined the relationship between the presence-absence of hyperuricemia and changes in the estimated glomerular filtration rate (eGFR) using the large cohort of the general population. We examined subjects who participated in two screenings, in 1993 and 2003, in Okinawa, Japan, yielding data on serum creatinine and uric acid levels (N=16,630). eGFR (ml min(-1) per 1.73 m(2)) was calculated using the formula used by the Japanese Society of Nephrology. In both sexes, a uric acid (UA) level >7.0 mg dl(-1) was defined as hyperuricemia (H), and a UA level below that threshold was classified as normouricemia (N). Based on the absence or presence of hyperuricemia in both the 1993 screening and the 2003 screening, we categorized patients into four groups: group 1, N/N; group 2, H/N; group 3, N/H; and group 4, H/H. Multiple regression analysis was performed to estimate the independent effects of several variables on the decline in eGFR. In all groups, an increase in UA from 1993 to 2003 (ΔUA) was a strong independent risk factor for a decline in eGFR than that of the baseline levels of UA, the presence of hypertension, or diabetes. The estimated decline in eGFR per 1 mg dl(-1) increase in UA was 4.19, 1.91, 2.36 and 2.01 ml min(-1) per 1.73 m(2) in groups 1, 2, 3 and 4, respectively. The results suggest that UA has a role in chronic kidney disease (CKD) progression. We have no information on medications used, such as xanthine oxidase, uricosuric drugs and hypotensives; therefore, the impact of hyperuricemia might be underestimated in our analysis. The results suggest that maintaining a normal range of UA is important to maintain eGFR decline in a normal range.

Trends in the incidence of stroke and cardiovascular risk factors on the isolated island of Okinawa: the Miyakojima study.

BACKGROUND: Rapid deterioration of cardiovascular risk control, especially obesity, has occurred in Okinawa; this may affect cardiovascular disease incidence, including stroke. METHODS: Cross-sectional field studies were conducted in 2 periods, 1988-1991 as the first period, and 2002-2005 as the second period, in the isolated island of Okinawa, Miyakojima. To evaluate population backgrounds related to cardiovascular risk factors, data from the health checkup programs conducted in 1987 and 2001 were surveyed. RESULTS: Total of 257 patients in the first period and 370 in the second were diagnosed with first-time stroke. The age-adjusted annual incidence rate of first-time stroke of the first and second periods was 124 and 144 per 100,000 standard population of Japan. The age-adjusted annual incidence rate showed an upward trend for brain infarction (50 to 73) and downward trend for brain hemorrhage (61 to 54); however, those trends were not significant. The health checkup surveys illustrated that blood pressure decreased in all age groups during the second survey period. However, the body mass index increased in patients aged 50 years or more. Fasting blood glucose levels of patients aged 30-79 years and non-HDL cholesterol levels of patients aged 50-79 years significantly increased. CONCLUSIONS: In Miyakojima, the incidence of first-time stroke and all of its subtypes did not change significantly between two periods, even though blood pressure decreased significantly in the second period. Metabolic deterioration may be associated with the upward trend in incidence of brain infarction.

Elevated resting heart rate is associated with white blood cell count in middle-aged and elderly individuals without apparent cardiovascular disease.

We investigated the association between resting heart rate (HR) and inflammation markers in a healthy population. White blood cell (WBC) count was used as a surrogate marker of subclinical inflammation. Smoking status, body mass index, resting HR, high-density lipoprotein cholesterol, triglycerides, uric acid, and glycated hemoglobin were significantly associated with WBC in both men and women. Blood pressure and fasting plasma glucose levels, however, were associated with WBC only in women. Logistic regression analysis indicated that for every 10 beats per minute increase in HR, the odds ratio of an increase in the WBC was approximately 1.3 in both men and women. These findings indicate the clinical significance of resting HR for identifying individuals at risk of subclinical inflammation and a future cardiovascular event.

C-reactive protein is a predictor for developing proteinuria in a screened cohort.

BACKGROUND: The relationship between C-reactive protein (CRP) and proteinuria is not known. METHODS: We examined 20,077 screenees (men: 52.4%) of the Okinawa General Health Maintenance Association (OGHMA) registry who were examined between 2004 and 2006. Cross-sectional and longitudinal relationships between CRP and dipstick proteinuria were examined. The OGHMA central laboratory measured creatinine and CRP levels using an autoanalyzer (normal: <0.30 mg/dl). The glomerular filtration rate was estimated using the Japanese formula. RESULTS: The prevalence of dipstick-positive proteinuria increased from 5.2% in screenees with a low CRP level of <0.10 mg/dl to 12.3% in those with high CRP levels (0.30-0.90 mg/dl). The CRP values did not affect the mean (SD) estimated glomerular filtration rate: 76.9 (13.7) with low CRP and 76.4 (15.1) with high CRP levels. We examined the relationship between baseline CRP and the development of proteinuria among subjects screened in 2004. Of 8,315 subjects without proteinuria examined again by 2006, 370 (4.4%) had developed proteinuria. The odds ratio (95% CI) for high CRP levels (0.30-0.90 mg/dl; reference CRP: <0.10 mg/dl) was 1.433 (1.013-2.028; p = 0.0422) after adjusting for multivariate variables, suggesting that CRP is closely associated with the prevalence and incidence of proteinuria. CONCLUSION: A prospective study on the development of proteinuria among those with high CRP levels is warranted. Screenees with high CRP levels may need to be followed up carefully despite the absence of traditional risk factors for proteinuria.

Effect of heart rate on the risk of developing metabolic syndrome.

High heart rate and metabolic syndrome are risk factors for cardiovascular morbidity and mortality. The relationship between heart rate and risk of developing metabolic syndrome has not been studied in a large cohort. We examined the relationship between heart rate and the risk of developing metabolic syndrome in individuals who participated in a health evaluation program from 1997 to 2002. Among the 7958 individuals who participated in the program, 1677 were excluded from our study because they were being treated for heart disease or had been diagnosed with metabolic syndrome at baseline examination. A total of 6281 individuals (3789 men and 2492 women, 20-89 years of age) were evaluated. They were categorized according to their baseline heart rate and were followed up for a mean of 47+/-16 months (range: 7-71 months). Over the 5-year period, 619 individuals (9.9%) developed metabolic syndrome. Men with elevated baseline heart rates were more likely to experience metabolic syndrome than were those with normal heart rates. This was not true for female patients. The odds ratio (95% confidence interval) of developing metabolic syndrome among men in the highest quartile for heart rate was 1.725 (1.282-2.320) compared with those in the lowest quartile. Each increase in the heart rate category led to an approximately 1.2-fold increase in the risk of developing metabolic syndrome for men only, even after adjusting for age and lifestyle. Elevated heart rate is a risk factor for developing metabolic syndrome in men.

Prevalence of anemia according to stage of chronic kidney disease in a large screening cohort of Japanese.

BACKGROUND: The prevalence of chronic kidney disease (CKD) is high in developed countries, including Japan. However, little is known about the prevalence of anemia according to the estimated glomerular filtration rate (eGFR) among Japanese. METHODS: We studied screenees on the Okinawa General Health Maintenance Association (OGHMA) registry in 1993 (N = 94,602; 54,848 women and 39,754 men) who had both serum creatinine and hematocrit data. Anemia was defined as follows: hematocrit level <40% in men, <32% in women aged <50 years, and <35% in women aged >or=50 years. GFR was estimated using a new Japanese equation: eGFR (ml/min per 1.73 m(2)) = 194 x serum creatinine(1.094) x age(0.287) x 0.739 (if female). RESULTS: The prevalence of anemia clearly increased as CKD progressed below an eGFR of 60 ml/min per 1.73 m(2) in both genders. Logistic analysis adjusted with body mass index and older age (>or=70 years) revealed that the odds ratio for complications of anemia was significantly increased below an eGFR of 45 ml/min per 1.73 m(2) in women and 90 ml/min per 1.73 m(2) in men. The association of lower kidney function with anemia was found to be more prevalent: adjusted odds ratio >or=2.0, from approximately 50 ml/min per 1.73 m(2). CONCLUSION: The present study suggested that there might be as many as 1,000,000 people with CKD stage 3-5 complicated with anemia in Japan.

Heart rate as a risk factor for developing chronic kidney disease: longitudinal analysis of a screened cohort.

BACKGROUND: High heart rate and chronic kidney disease (CKD) are both risk factors for cardiovascular morbidity and mortality. The relationship between heart rate and the risk of developing CKD, however, has not been studied in a large screened cohort. METHODS AND RESULTS: We examined the relationship between heart rate and the risk of developing CKD in participants in a health evaluation program. CKD was diagnosed as glomerular filtration rate of less than 60 mL/min/1.73 m(2), calculated using the Modification of Diet in Renal Disease (MDRD) study equation or dipstick proteinuria. Among 7,958 subjects, 1,199 subjects diagnosed with CKD or with arrhythmia at baseline examination were excluded. A total of 6,759 subjects (4,268 men, 2,491 women, 20-84 years of age) were evaluated. The subjects were quadrisected according to baseline heart rate. The subjects were followed up for a mean of 47 +/- 16 months (range 7-71 months). Seven hundred and thirty-four subjects developed CKD over the 5-year follow-up period. Subjects with a high heart rate had greater magnitude of decreasing glomerular filtration rate (eGFR) and higher odds ratio of developing proteinuria. Cox analysis indicated that each heart rate category increment led to approximately 1.1 times increase in the risk of developing CKD, eGFR less than 60 mL/min/1.73 m(2), and 1.2 times increase of the risk of developing proteinuria in middle-aged or older subjects. CONCLUSIONS: High heart rate is a risk factor for developing CKD in middle-aged or older subjects.

Decreased body mass index as an independent risk factor for developing chronic kidney disease.

BACKGROUND: Obesity and metabolic syndrome are risk factors for the development of chronic kidney disease (CKD). Few studies have examined the effect of change in body mass index (DeltaBMI) on CKD incidence in a general screening setting. METHODS: Subjects of this study were screenees that participated in the screening program of the Okinawa General Health Maintenance Association in 1993 and 2003 in Okinawa, Japan. Using identification number, birth date, sex, and other recorded identifiers, we identified 33,389 subjects among the 1993 screening participants (N = 143,948) who also participated in the 2003 screening. CKD was defined as estimated glomerular filtration rate <60 ml/min/1.73 m(2), according to the modification of diet in renal disease study equation. Obesity was defined as BMI > or = 25 kg/m(2). RESULTS: CKD prevalence was 13.8% in 1993 and 22.4% in 2003. The incidence of developing CKD in 10 years was 15.5%. The effect of DeltaBMI on CKD incidence was evaluated after considering other confounding factors such as age, sex, blood pressure, BMI, fasting plasma glucose, and proteinuria. Median DeltaBMI was 1.0%. The adjusted odds ratio (95% CI) for the effect of DeltaBMI on CKD incidence was 1.111 (1.026-1.204, P < 0.01; entire study population), 1.271 (1.116-1.448, P = 0.0030; men), and 1.030 (0.931-1.139, NS; women), when DeltaBMI > or = 1% was taken as a reference. DeltaBMI was an independent predictor of CKD incidence. CONCLUSIONS: The present results suggest that there was an inverse relationship between DeltaBMI and CKD incidence among screened subjects. The reasons for this observation are not clear, but careful follow-up for DeltaBMI is necessary, particularly in obese men with proteinuria.