Cost-effectiveness of mass screening for dipstick hematuria in Japan.

BACKGROUND: Dipstick urine tests are a simple and inexpensive method for detecting kidney and urological diseases, such as IgA nephropathy and bladder cancer. The nationwide mass screening program, Specific Health Checkup (SHC), started in Japan in 2008 and targeted all adults between 40 and 74 years of age. Dipstick urine tests for proteinuria and glucosuria are mandatory as part of the SHC, but dipstick urine tests for hematuria are not. However, the dipstick hematuria test is often administered simultaneously with these mandatory tests by some health insurers. Hematuria is common in Japanese general screening participants, particularly elderly women, and the necessity of mass screening using the dipstick hematuria test has been discussed. This study aimed to evaluate the cost-effectiveness of mass screening for dipstick hematuria tests in addition to the SHC. METHODS: Using a decision tree and Markov modeling, we conducted a cost-effectiveness analysis from a Japanese societal perspective. RESULTS: Compared with the current SHC, mass screening for dipstick hematuria tests, in addition to the SHC, costs less and gains more, which means cost-saving. Similar findings were observed in the sex-specific analysis. CONCLUSION: Our results suggest that mandating the dipstick hematuria test could be justifiable as an efficient use of finite healthcare resources. The results have implications for mass screening programs not only in Japan but worldwide.

Survival benefit of continuous positive airway pressure in Japanese patients with obstructive sleep apnea: a propensity-score matching analysis.

STUDY OBJECTIVES: Continuous positive airway pressure (CPAP) improves quality of life in patients with obstructive sleep apneas. However, the long-term benefit in all-cause mortality and cardiovascular death are limited among Japanese. METHODS: We conducted a retrospective study of patients treated in our sleep clinic in Okinawa, Japan. All patients with full-scale polysomnography from September 1990 to December 2010 were investigated in terms of outcomes such as death (dates and causes of death) between 2012 and 2013 by chart review, telephone calls, and letters of inquiry. Propensity-score matching was performed to balance baseline characteristic differences between a CPAP user group and a nonuser group. The primary outcomes were all-cause mortality and a composite of cardiovascular disease mortality, such as heart disease and stroke, between the two groups. RESULTS: The CPAP user group, almost double in number, had more severe obstructive sleep apnea, more comorbidities, smoking, and alcohol consumption compared to the nonuser group but no significant difference in Epworth Sleepiness Scale. Propensity-score matching selected 1,274 of 4,519 patients as the CPAP user group and 1,274 of 2,128 as the CPAP nonuser group. Mean age of the patients was 52.3 (±13.5) years and 79% were men. After a median follow-up of 79 (interquartile interval, 24 to 128) months in the CPAP user group and 73.5 (interquartile interval, 26 to 111) in the non-CPAP group, death from all causes occurred in 53 (4.2%) patients in CPAP user group and in 94 (7.4%) patients in CPAP nonuser group. The leading cause of death was malignancy in each group. The hazard ratios for all-cause mortality and cardiovascular disease deaths were 0.56 (95% confidence interval (CI), 0.41-0.78) and 0.54 (95% CI, 0.28-1.03) between CPAP user group and CPAP nonuser group, respectively. CONCLUSIONS: In obstructive sleep apnea patients, CPAP use was associated with lower all-cause mortality.

Impact of Metabolic Syndrome on the Mortality Rate among Participants in a Specific Health Check and Guidance Program in Japan.

Objective In Japan, the Specific Health Check and Guidance (Tokutei-Kenshin) program was started in 2008 to decrease the social burden related to metabolic syndrome (MetS). However, so far this program has not been found to have any impact on the mortality rate. Methods The subjects consisted of individuals who participated in the Tokutei-Kenshin in seven districts between 2008 and 2015. Using a National database of death certificates, we identified those who might have died and then further confirmed such deaths with the collaboration of the regional National Health Insurance agency and public health nurses. The diagnosis of MetS was made according to the Japanese criteria. The causes of death were classified by ICD-10. Mortality risk was evaluated after adjusting for age, sex, smoking, alcohol intake and past medical history such as stroke, heart disease and kidney disease. Results Among the total of 664,926 subjects, we identified 8,051 fatal cases by the end of 2015. The crude death rate was 1.6% for those with MetS, 1.3% for those with preliminary metabolic syndrome, and 1.1% those without MetS. In MetS, the adjusted hazard ratio (95% confidence interval) was 1.08 (1.02-1.15) for all-cause and 1.39 (1.22-1.58) for cardiovascular disease mortality when the reference was for those without MetS. Conclusion The death rate was found to be significantly higher among the participants with MetS.

Dipstick proteinuria and all-cause mortality among the general population.

BACKGROUND: Dipstick proteinuria, but not albuminuria, is used for general health screening in Japan. How the results of dipstick proteinuria tests correlate with mortality and, however, is not known. METHODS: Subjects were participants of the 2008 Tokutei-Kenshin (Specific Health Check and Guidance program) in six districts in Japan. On the basis of the national database of death certificates from 2008 to 2012, we used a personal identifier in two computer registries to identify participants who might have died. The hazard ratio (95% confidence interval, CI) was calculated by Cox-proportional hazard analysis. RESULTS: Among a total of 140,761 subjects, we identified 1641 mortalities that occurred by the end of 2012. The crude mortality rates were 1.1% for subjects who were proteinuria (-), 1.5% for those with proteinuria (+/-), 2.0% for those with proteinuria (1+), 3.5% for those with proteinuria (2+), and 3.7% for those with proteinuria (≥ 3+). After adjusting for sex, age, body mass index, estimated glomerular filtration rate, comorbid condition, past history, and lifestyle, the hazard ratio (95% CI) for dipstick proteinuria was 1.262 (1.079-1.467) for those with proteinuria (+/-), 1.437 (1.168-1.748) for those with proteinuria (1+), 2.201 (1.688-2.867) for those with proteinuria (2+), and 2.222 (1.418-3.301) for those with proteinuria (≥ 3+) compared with the reference of proteinuria (-). CONCLUSION: Dipstick proteinuria is an independent predictor of death among Japanese community-based screening participants.

Glucosuria and all-cause mortality among general screening participants.

BACKGROUND: Dipstick urine tests are used for general health screening in Japan, but how the test results (e.g., glucosuria) relate to mortality is unknown. METHODS: Subjects participated in a nationwide screening in 2008 in six districts in Japan. We identified those who might have died using the national database of death certificates from 2008 to 2012 (total registered ~ 6 million) and verified candidates with the regional National Health Insurance Agency and public health nurses. Diabetes mellitus (DM) was defined as HbA1c ≥ 6.5%, fasting blood glucose ≥ 126 mg/dl, or medicated for DM. Hazard ratio (HR) and 95% confidence interval (CI) were calculated by Cox proportional hazard analysis. Glucosuria was defined as dipstick ≥ 1 +. RESULTS: Among 209,060 subjects, we identified 2714 fatalities (median follow-up 3.57 years). Crude mortality rates were 1.2% for those without glucosuria and 3.4% for those with glucosuria. After adjusting for sex, age, body mass index, comorbidity (DM, hypertension, and dyslipidemia), history (stroke, heart disease, and kidney disease), and lifestyle (smoking, drinking, walking, and exercise), the HR (95% CI) for dipstick glucosuria was 1.475 (1.166-1.849, P < 0.001). DM subjects with glucosuria (N = 4655) had a higher HR [1.302 (1.044-1.613, P = 0.020)] than DM subjects without glucosuria (N = 20,245), and non-DM subjects with glucosuria (N = 470) had a higher HR [2.511 (1.539-3.833, P < 0.001)] than non-DM subjects without glucosuria (N = 183,690). CONCLUSION: Dipstick glucosuria significantly affected mortality in Japanese community-based screening participants.

Importance of glomerular filtration rate change as surrogate endpoint for the future incidence of end-stage renal disease in general Japanese population: community-based cohort study.

BACKGROUND: Because of the necessity for extended period and large costs until the event occurs, surrogate endpoints are indispensable for implementation of clinical studies to improve chronic kidney disease (CKD) patients' prognosis. METHODS: Subjects with serum creatinine level for a baseline period over 1-3 years were enrolled (n = 69,238) in this community-based prospective cohort study in Okinawa, Japan, and followed up for 15 years. The endpoint was end-stage renal disease (ESRD). The percent of estimated glomerular filtration rate (%eGFR) change was calculated on the basis of the baseline period. RESULTS: Subjects had a mean ± SD age, 55.59 ± 14.69 years; eGFR, 80.15 ± 21.15 ml/min/1.73 m2. Among the subjects recruited, 15.81% had a low eGFR (<60 ml/min/1.73 m2) and 36.1/100,000 person years developed ESRD. Cox proportional hazards models adjusted for baseline characteristics showed that the risk of ESRD tended to be high with high rates of decrease in %eGFR changes over 2 or 3 years in the high- and low-eGFR groups. The specificities and positive predictive values for ESRD based on a cutoff value of %eGFR change of less than -30% over 2 or 3 years were high in the high- and low-eGFR groups. CONCLUSIONS: %eGFR change tends to be associated with the risk of ESRD. %eGFR change of less than -30% over 2 or 3 years can be a candidate surrogate endpoint for ESRD in the general Japanese population.

A nationwide prospective cohort study of patients with advanced chronic kidney disease in Japan: The Reach-J CKD cohort study.

BACKGROUND: Epidemiology and outcomes of Japanese patients with advanced chronic kidney disease (CKD)-an estimated glomerular filtration rate (eGFR) < 45 ml/min/1.73 m2-has remained largely unexamined. METHODS: We conducted a nationwide survey to determine the distribution of Japanese CKD patients, and are conducting a cohort study of these patients. A questionnaire eliciting details about facilities and their CKD practices was sent to all clinics/hospitals with nephrologists. Based on the survey results, we recruited 2400 advanced CKD patients receiving nephrologist care from at least 30 representative facilities throughout Japan, selected randomly with stratification by region and facility size. Through patient questionnaires and nephrologist-practice surveys aligned with the international CKD Outcomes and Practice Patterns Study (CKDopps), we shall annually or semi-annually collect patient, physician and clinic data prospectively, detailing CKD practices for 5 years, with a primary outcome of death or renal replacement therapy initiation, and secondary outcomes being decline of eGFR by 30% or 50%, CKD progression to CKD G5, or a cardiovascular event. RESULTS: Of 790 eligible, responding facilities, 330 (41.8%) treat ≥80 advanced CKD patients in the average 3-month period. Regional distribution of these facilities is similar to that of persons in the general population. Hence, the 30 facilities selected for data collection appear to be geographically representative in Japan. CONCLUSIONS: Our study will enhance understanding of various CKD practices and biological data associated with CKD progression, and allow international comparisons using the CKDopps platform. This will provide evidences to improve the health and quality of life for patients with advanced CKD.

Association of dipstick hematuria with all-cause mortality in the general population: results from the specific health check and guidance program in Japan.

Background: Dipstick urine tests are used for general health screening in Japan. The effects of this screening on mortality have not been examined, especially with regard to hematuria. Methods: Subjects were those who participated in the 2008 Tokutei-Kenshin (nationwide specific health check and guidance program) in six districts in Japan. Using the national database of death certificates from 2008 to 2012, we identified subjects who might have died. We verified the candidates in collaboration with the regional National Health Insurance agency and public health nurses. Data were released to the research team supported by the Ministry of Health, Labor, and Welfare of Japan. Dipstick results of 1+ and higher were defined as hematuria (+). Hazard ratio (HR) [95% confidence interval (CI)] was calculated using the Cox proportional hazard analysis. Results: Among 112 115 subjects, we identified that 1290 had died by the end of 2012. In hematuria (-) subjects, the crude mortality rates were 1.2% (1.8% in men, 0.7% in women), whereas in hematuria (+) subjects, they were 1.1% (2.9% in men, 0.7% in women). After adjusting for age, body mass index, estimated glomerular filtration rate, proteinuria, comorbid condition (diabetes mellitus, hypertension and dyslipidemia), past history (stroke, heart disease and kidney disease) and lifestyle (smoking, drinking, walking and exercise), the HR (95% CI) for dipstick hematuria (+) in men was 1.464 (1.147-1.846; P = 0.003), whereas that for hematuria (-) was 0.820 (0.617-1.073; P = 0.151). Conclusions: Dipstick hematuria is significantly associated with mortality in men among Japanese community-based screening participants.

Mortality risk among screened subjects of the specific health check and guidance program in Japan 2008-2012.

BACKGROUND: In Japan, the Specific Health Check and Guidance (Tokutei-Kenshin) has started in 2008. However, the relationship between the baseline characteristics and mortality has not been examined. METHODS: Subjects were those who participated at the 2008 Tokutei-Kenshin in six districts with baseline data of serum creatinine. Using National database of death certificate from 2008 to 2012, we identified those who might have died and confirmed further with the collaborations of the regional National Health Insurance agency and public health nurses. The data was released to the research team supported by the Ministry of Health, Labor, and Welfare of Japan, and is governed by strict regulation and is completely encrypted with the individual's name and residence. Causes of death were classified by ICD-10. RESULTS: Among the total of 295,297 subjects, we identified 3764 fatal cases by end of 2012. The median BMI was 23.8 kg/m2 in men and 22.5 kg/m2 in women, respectively. Proteinuria, dipstick 1+ and over, was positive in 5.3%. The median eGFR was 73.8 ml/min/1.73 m2 among those with data available in 81% of the total cohort (N = 239,274). The leading cause of death was neoplasm in both genders. It was 51.6% of the total, 50.4% in men and 53.7% in women. The second cause of death was circulatory; 20.4% of the total, 21.1% in men and 19.2% in women. CONCLUSION: Half of the causes of death was related to neoplasm among the cohort of the Tokutei-Kenshin. Effects of baseline demographics such as lifestyle and CKD remained to be studied.

Effect of glomerular filtration rate and proteinuria on medical cost among screened subjects.

BACKGROUND: Chronic kidney disease is a predictor of end-stage renal disease (ESRD) and cardiovascular disease (CVD). Therefore, the medical expenses are higher with the decrease in glomerular filtration rate (GFR). However, few studies have examined the medical expenses according to the baseline GFR. METHODS: We investigated the relationship between GFR at health checks and medical expenses, combining the registries of both the health checks and report of medical expenses (receipts). The health checks were done from April 2008 to March 2009, and the eligible subjects were covered by the Okinawa Branch of the Japan Health Insurance Association. All reports of medical expenses were reviewed from April 2008 to March 2010 (24 months). RESULTS: A total of 74,354 subjects, 38.2 % females with the mean age of 48.1 years, were examined according to whether they had visited medical facilities during the study period. The total number of receipts was 773,276. The average receipt point, 1 point = 10 Yen, was 686,410 (eGFR < 15), 56,408 (eGFR 15-29), 47,263 (eGFR 30-44), 24,372 (45-59), 16,018 (eGFR 60-74), 13,893 (eGFR 75-89), 13,990 (eGFR 90-104), 14,717 (eGFR 105-119), and 19,139 (eGFR 120 and over), respectively. The relationship between eGFR and medical expense was U-shaped, and the expense was lowest at eGFR 75-89. CONCLUSION: We demonstrate that the medical expenses increase as eGFR decreases. Subjects with higher eGFR, 120 and over, seemed to have higher medical expenses.

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.

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.

Proteinuria and decreased body mass index as a significant risk factor in developing end-stage renal disease.

BACKGROUND: Body mass index (BMI) is a significant predictor of developing end-stage renal disease (ESRD). The relation between a change in BMI (DeltaBMI) and the incidence of ESRD has not been examined in any large epidemiologic studies. METHODS: We determined the DeltaBMI in subjects who participated in the Okinawa General Health Maintenance Association (OGHMA) screenings in 1983 and again in 1993. Screenees were free of ESRD at the 1993 screening and were then monitored until the end of 2000 to determine whether they developed ESRD. Participants were identified using ID numbers, birthdates, and other identifiers. Details of every ESRD patient treated in Okinawa are maintained in an independent community-based dialysis registry. Multivariate logistic analyses were performed to determine the significance of a DeltaBMI on the incidence of ESRD using SAS. The ethics committee of the OGHMA approved the study protocol. Only coded data were used for this study. RESULTS: Among the 92,364 subjects aged 30-89 years screened in 1983, 29,011 (31.4%) returned for the 1993 screening. The median DeltaBMI was 2.1%, and the subjects were divided into two groups: DeltaBMI < 2.1% (G1) and DeltaBMI > or = 2.1% (G2). The cumulative incidence of ESRD was 0.31% in G1 (ESRD in 44) and 0.14% in G2 (ESRD in 21). The odds ratio (95% confidence interval) of developing ESRD based on a DeltaBMI was 2.268 (1.284-4.000, P < 0.01) after adjusting for age, sex, systolic blood pressure, BMI in 1983, and proteinuria. CONCLUSION: The findings of the present study suggest that a DeltaBMI is an independent risk factor for the incidence of ESRD, especially for those with proteinuria. The reasons for the BMI change were not recorded in this study. Unintentional weight loss, however, might warrant evaluation for the presence or progression of chronic kidney disease.

Association between heart rate and multiple risk factor syndrome: cross-sectional analysis of a screened cohort in Okinawa, Japan.

BACKGROUND: Increased heart rate (HR) and metabolic syndrome are risk factors for cardiovascular morbidity and mortality, but their relationship has not been studied in a large, screened cohort. METHODS AND RESULTS: The association between HR and multiple risk factor syndrome, resembling metabolic syndrome, was examined in participants of a health evaluation program in 1997. Of the 8,432 subjects (5,223 males, 3,209 females, 18-89 years of age), 1,502 (1,185 males, 317 females) were diagnosed with multiple risk factor syndrome and these subjects had higher HR than those without the syndrome (p<0.0001); subjects with a higher number of risk factors had higher HR than those with fewer risk factors (males, p<0.0001; females, p<0.0001). After adjusting for age, sex, and lifestyle factors, subjects within the highest HR quartile had a 2.5-fold higher risk for multiple risk factor syndrome than those in the lowest quartile (p<0.0001). An increase of 10 beats/min was associated with an approximately 30% increase in the risk for multiple risk factor syndrome. CONCLUSIONS: A higher HR is closely associated with multiple risk factor syndrome.

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.

Higher heart rate predicts the risk of developing hypertension in a normotensive screened cohort.

BACKGROUND: A higher heart rate (HR) is associated with cardiovascular morbidity and mortality. Hypertension is an important cardiovascular risk factor. The present study evaluated whether a higher HR was associated with the development of hypertension in normotensive, screened subjects. METHODS AND RESULTS: Among normotensive participants of a 1-day health evaluation in 1997, we studied those who also participated in the program in 2000 (n=4,331; 2,823 men (65%), 1,508 women; mean age 47+/-9 years). Subjects were divided into 4 groups based on their HR in 1997: quartile 1 (HR or=71, n=1,124). The 3-year frequency of developing hypertension in 2000 was 4.5% for quartile 1, 6.8% for quartile 2, 6.0% for quartile 3, and 7.2% for quartile 4 (p=0.0424). Subjects with a higher HR were likely to have a greater number of metabolic syndrome components and a higher incidence of proteinuria. In a logistic regression analysis adjusted for gender, age, alcohol consumption, exercise, atherosclerotic risk factors, and lifestyle, the odds ratios (95% confidence intervals) for the development of hypertension were 1.53 (1.04-2.24) for quartile 2, 1.35 (0.90-2.02) for quartile 3, and 1.61 (1.10-2.37) for quartile 4, compared with quartile 1 as a reference. CONCLUSION: A higher HR was associated with the development of hypertension. Subjects with a higher HR should be followed carefully, even if they are normotensive.

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.

Relationship between dyslipidemia and the risk of developing end-stage renal disease in a screened cohort.

BACKGROUND: Disturbances in lipid metabolism are often observed in patients with renal failure and could be a risk factor for end-stage renal disease (ESRD). However, few studies have examined abnormal lipid metabolism as a risk factor for the development of ESRD in the general population. METHODS: We examined the cumulative incidence of ESRD based on the results of a community-based mass screening in Okinawa, Japan, which was conducted in 1993 by the Okinawa General Health Maintenance Association. Screenees who developed ESRD by the end of 2000 were identified through the Okinawa Dialysis Study registry. RESULTS: Total cholesterol (TC) data were available for 133,338 (92.6%) of the total 143,948 screenees) and triglyceride (TG) data were available for 132,094 (91.8%). Dyslipidemia was defined as TC > or = 220 mg/dl or TG > or = 150 mg/dl. The cumulative incidences of ESRD, per 1000 screenees, were 1.12 for those without dyslipidemia and 2.53 for those with dyslipidemia. The adjusted hazard ratio (95% confidence interval) for dyslipidemia was 0.856 (0.484-1.516) for men and 1.260 (0.661-2.400) for women; neither was significant when adjustment was made for age, systolic blood pressure, diastolic blood pressure, body mass index, creatinine clearance, diabetes mellitus, and proteinuria. CONCLUSIONS: The present study showed dyslipidemia to be an insignificant predictor of development of ESRD in the general Okinawa population.