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

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.

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.

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.

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.

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.

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.

Risk of developing low glomerular filtration rate or elevated serum creatinine in a screened cohort in Okinawa, Japan.

There are no known predictors of renal dysfunction, particularly for a community-based screening. We evaluated the changes in serum creatinine (SCr) and glomerular filtration rate (GFR) among screenees who participated in the screening program of the Okinawa General Health Maintenance Association both in 1983 and 1993. A total of 4,662 screenees at least 30 years of age at the 1983 screening were analyzed to examine whether they developed high SCr (>or=1.4 mg/dl for men, >or=1.2 mg/dl for women) or low GFR (<60 ml/min/1.73 m2). Overall, mean GFR (mean+/-SD) decreased slightly from 72.7+/-11.7 ml/min/1.73 m2 to 70.8+/-15.0 ml/min/1.73 m2. In 1983, the prevalences of high SCr and low GFR were 3.6% and 13.2%, respectively, and in 1993, they were 8.1% and 24.2%, respectively. Among the variables studied, dipstick proteinuria was the strongest predictor: the adjusted odds ratio (95% CI) was 1.282 (1.076-1.527, p<0.01) for high SCr and 1.215 (1.116-1.322, p<0.01) for low GFR. Dipstick proteinuria was best for detecting subjects who might develop low GFR in a screening setting. In subjects without proteinuria, systolic blood pressure was a significant predictor for low GFR (the adjusted odds ratio [95% CI] was 1.015 [1.009-1.020, p<0.01]) and for high SCr (the adjusted odds ratio [95% CI] was 1.028 [1.016-1.040, p<0.01]). In conclusion, the present study suggests that a dipstick urine test for proteinuria and both systolic and diastolic blood pressure are useful to identify those who are at risk of developing high SCr and low GFR and consequently end-stage renal disease.

Changes in the demographics and prevalence of chronic kidney disease in Okinawa, Japan (1993 to 2003).

To compare the risk factor demographics and the prevalence of chronic kidney disease (CKD), we analyzed two databases from the 1993 (N=143,948) and 2003 (N=154,019) mass screenings in Okinawa, Japan (Okinawa General Health Maintenance Association registry). We estimated the glomerular filtration rate (GFR) using serum creatinine (SCr) levels. SCr was measured by the modified Jaffe method in 1993 and by enzyme assay in 2003; the relation between the two methods was: SCr (Jaffe) = 0.194 + 1.079 x SCr (enzyme). CKD prevalence was compared using the estimated GFR calculated by the abbreviated Modification of Diet in Renal Disease (MDRD) equation. SCr was measured in 66.2% (1993) and 69.8% (2003) of the total screenees. Proteinuria was present in 3.4% (1993) and 4.3% (2003) of the total screened population, respectively. The prevalence of CKD (GFR<60 ml/min/1.73 m(2)) was similar between the two databases, being 15.7% in 1993 and 15.1% in 2003. However, the demographics of the CKD risk factors changed during the study period. The mean level of systolic blood pressure decreased, whereas the prevalence of obesity and the mean levels of serum cholesterol and fasting plasma glucose increased. In 2003, the estimated prevalence of metabolic syndrome in the general population of Japan calculated using the modified National Cholesterol Education Program (NCEP) criteria was 19.1%. The prevalence of CKD was significantly associated with that of metabolic syndrome: the age- and sex-adjusted odds ratio was 1.332 (95% confidence interval [CI], 1.277-1.389; p<0.0001). In conclusion, the demographics of the participants of the general screenings in Okinawa, Japan differed between the 1993 and 2003 screenings, but the prevalence of CKD seemed to be similar, or at least did not increase substantially, between the two databases.

Metabolic syndrome and risk of developing chronic kidney disease in Japanese adults.

Metabolic syndrome is a risk factor for the development of cardiovascular disease. Few prospective studies, however, have examined metabolic syndrome as a risk factor for chronic kidney disease (CKD) in an Asian population. We studied the occurrence of CKD in 6,371 subjects without CKD or diabetes mellitus at baseline 1997 through 2002 in Okinawa, Japan. CKD was defined as dipstick-positive proteinuria (>or=1+) or a low estimated glomerular filtration rate (<60 mL/min/1.73 m2). Metabolic syndrome was defined according to the modified criteria of the Adult Treatment Panel III in which body mass index (>or=25 kg/m2) was substituted for the waist circumference measurement. Logistic analysis was used to analyze the effect of metabolic syndrome on the development of CKD. During the 5-year follow-up, 369 (5.7%) participants developed CKD. After adjusting for age, sex, current cigarette smoking and alcohol drinking habits at baseline, the relative risk of developing CKD was 1.86 (95% confidence interval: 1.43-2.41, p<0.0001) in subjects with metabolic syndrome. Compared with those without metabolic syndrome risk components, the adjusted relative risk (95% confidence interval) was 1.49 (1.10-2.01), 1.89 (1.38-2.59), and 2.65 (1.19-3.68) in those with 1, 2, or >or=3 metabolic syndrome risk components, respectively. Metabolic syndrome is a significant risk factor for the development of CKD in the Japanese population. Detection and treatment of metabolic syndrome should be stressed as a strategy to prevent CKD.

Increased pulse wave velocity is associated with low creatinine clearance and proteinuria in a screened cohort.

BACKGROUND: Chronic kidney disease (CKD) is a risk factor for future cardiovascular disease. Although pulse wave velocity (PWV), which reflects arterial stiffness, was increased in subjects with CKD, little is known regarding whether renal function is associated with PWV in a low-risk population and whether proteinuria and decreased renal function synergistically affect PWV. METHODS: Subjects are 3,387 persons (mean age, 52 years) who attended a health checkup program in Okinawa, Japan. We measured brachial-ankle PWV (baPWV) by using an automatic oscillometric method. Proteinuria was semiquantified by using the dipstick method. Creatinine clearance (CCr) was estimated by using the Cockcroft-Gault formula. RESULTS: baPWV was accelerated with increases in age, systolic blood pressure, fasting glucose level, and total cholesterol level; male sex; presence of proteinuria; and decrease in CCr. All these factors independently predicted baPWV in multiple regression analysis. When subjects were divided into 6 groups according to CCr of 90 or greater, 60 to 89, or 30 to 59 mL/min (> or =1.50, 1.00 to 1.48, or 0.50 to 0.98 mL/s) and the absence or presence of proteinuria, baPWV, after adjustment for age, sex, and systolic blood pressure, increased in a stepwise fashion corresponding to decreases in CCr regardless of proteinuria, with the relationship exaggerated in the presence of proteinuria. CONCLUSION: Arterial stiffness increases with a decrease in renal function or with proteinuria independently of other risk factors.

Proteinuria as a significant determinant of hypertension in a normotensive screened cohort in Okinawa, Japan.

To evaluate the influence of proteinuria on the development of hypertension in normotensive screened subjects. We studied 4,428 normotensive subjects without heart disease (2888 men, 1540 women, age 19-89 years) who were participants in a 1-day health evaluation in both 1997 and 2000. The 3-year frequency of developing hypertension was 6.0% in subjects without proteinuria, and 13.5% in subjects with proteinuria. The odds ratio for developing hypertension by age (year) increased approximately 1.6%. Obesity was associated with an approximately 40% increased risk of hypertension; proteinuria increased the risk of hypertension 2-fold. Proteinuria was a significant predictor of developing hypertension. Age, obesity, and initial blood pressure level also contributed to the development of hypertension. In conclusion, proteinuria is a powerful predictor of developing hypertension. Age and obesity are also associated with increased risk of hypertension. Lifestyle modification might thus be necessary, particularly in subjects with proteinuria.

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.

Relationship between predicted creatinine clearance and proteinuria and the risk of developing ESRD in Okinawa, Japan.

BACKGROUND: Chronic kidney disease and a low creatinine clearance (CrCl) are relatively common, particularly in the aged population. However, the renal outcome of a low CrCl is not known. METHODS: Participants in a 1993 mass screening conducted by the Okinawa General Health Maintenance Association in Okinawa, Japan, were investigated. A total of 95,255 subjects (40,157 men, 55,098 women) older than 20 years for whom serum creatinine (SCr) data were available were studied. CrCl was calculated as a surrogate marker of glomerular filtration rate by using the Cockcroft-Gault method. All dialysis patients who were treated in Okinawa were independently registered in the Okinawa Dialysis Study registry. Participants in the 1993 screening who later entered a dialysis program were identified by using the 2 computer registries. The cumulative incidence of end-stage renal disease (ESRD) was calculated according to baseline CrCl level in quartiles. The significance of CrCl for the risk for developing ESRD was evaluated by means of Cox analysis after adjusting for age, sex, blood pressure, and proteinuria. RESULTS: CrCl values were distributed into quartiles: CrCl I, less than 50.2 mL/min (<0.84 mL/s; n = 23,076); CrCl II, 50.2 to 63.9 mL/min (0.84 to 1.07 mL/s; n = 23,039); CrCl III, 64.0 to 79.3 mL/min (1.07 to 1.32 mL/s; n = 23,147); and CrCl IV, 79.4 mL/min or greater (> or =1.32 mL/s; n = 23,036). One hundred eighty-one subjects with data for SCr level were identified in the dialysis registry. Seven-year cumulative incidences of ESRD per 1,000 subjects were 86.8 in CrCl I, 13.6 in CrCl II, 8.3 in CrCl III, and 7.9 in CrCl IV in patients who had proteinuria, whereas they were 1.2, 0.7, 0.04, and 0.13 in those who did not have proteinuria, respectively. As CrCl category decreased, the adjusted hazard ratio for the risk of developing ESRD was 4.353 (95% confidence interval, 3.412 to 5.553; P < 0.0001). CONCLUSION: The prevalence of a low CrCl (CrCl I, <50.2 mL/min [<0.84 mL/s]) was relatively high in the elderly population. Subjects with a low CrCl who had proteinuria were at high risk of developing ESRD. However, the cumulative incidence of ESRD was not as high in patients with a low CrCl not associated with proteinuria. Screening by means of dipstick for proteinuria is useful, particularly among the elderly, to identify subjects in a high-risk population.

Significance of hyperuricemia as a risk factor for developing ESRD in a screened cohort.

BACKGROUND: Uric acid may be a true mediator of renal disease and progression. However, epidemiological evidence for the significance of serum uric acid levels on the risk for developing end-stage renal disease (ESRD) is scarce in a setting of community-based screening. METHODS: Participants in a 1993 mass screening conducted by the Okinawa General Health Maintenance Association in Okinawa, Japan, were investigated: 48,177 screenees (22,949 men, 25,228 women) older than 20 years for whom serum uric acid data were available were studied. All dialysis patients treated in Okinawa were independently registered in the Okinawa Dialysis Study registry. Participants in the 1993 screening who later entered a dialysis program were identified by using 2 computer registries. The cumulative incidence of ESRD was calculated according to quartiles of baseline serum uric acid levels for each sex. The significance of hyperuricemia (serum uric acid level > or = 7.0 mg/dL [> or =416 micromol/L] in men and > or = 6.0 mg/dL [> or =357 micromol/L] in women) for the risk for developing ESRD was evaluated by means of the Cox model after adjusting for age, blood pressure, body mass index, proteinuria, hematocrit, and total cholesterol, triglyceride, fasting blood glucose, and serum creatinine levels. RESULTS: Mean serum uric acid level was 6.4 +/- 1.4 (SD) mg/dL (381 micromol/L) in men and 4.8 +/- 1.1 mg/dL (286 micromol/L) in women. Prevalences of hyperuricemia were 31.9% in men and 13.6% in women. By the end of 2000, a total of 103 screenees (53 men, 50 women) entered dialysis programs. Calculated incidences of ESRD per 1,000 screenees were 1.22 for men without hyperuricemia and 4.64 for men with hyperuricemia and 0.87 for women without hyperuricemia and 9.03 for women with hyperuricemia. Adjusted hazard ratios for hyperuricemia were 2.004 (95% confidence interval, 0.904 to 4.444; P = not significant) in men and 5.770 (95% confidence interval, 2.309 to 14.421; P = 0.0002) in women. CONCLUSION: Screenees with hyperuricemia were associated with a greater incidence of ESRD. Hyperuricemia (serum uric acid > or = 6.0 mg/dL [> or =357 micromol/L]) was an independent predictor of ESRD in women. Strategies to control serum uric acid levels in the normal range may reduce the population burden of ESRD.