Yoshiharu Ikemiya

Blood Pressure Predicts Risk of Developing End-Stage Renal Disease in Men and Women

Abstract— Blood pressure as a risk factor for development of end‐stage renal disease has not been fully studied, particularly in women. We studied the development of end‐stage renal disease from 1983 through 2000 in 98 759 subjects, 46 881 men and 51 878 women, 20 to 98 years of age, who were screened in 1983 in Okinawa, Japan. Data for all dialysis patients registered from 1983 to 2000 in Okinawa were used to identify the screened subjects in whom end‐stage renal disease developed. In follow‐up, 400 subjects, 231 men and 169 women, had end‐stage renal disease. Age, body mass index, and adjusted relative risk for systolic and diastolic blood pressure for both men and women were measured. When these results were compared with an optimal blood pressure, the relative risk of development of end‐stage renal disease for those with high‐normal blood pressure and hypertension were significant in both men and women. Hypertension is a significant risk factor for development of end‐stage renal disease not only in men but also in women. Control of blood pressure within normal levels should be stressed as a strategy to prevent end‐stage renal disease in both men and women.

Low Serum Cholesterol as a Risk Factor for Hemorrhagic Stroke in Men

The relation between the level of total serum cholesterol and stroke is controversial. The relation between serum total cholesterol and subtypes of stroke was examined in the participants of a community-based mass screening program in Okinawa, Japan. A total of 38,053 subjects, whose serum level of cholesterol had been determined during a mass screening carried out in 1983, were examined to see whether they had experienced stroke during a 3-year period from 1988 to 1991. Of them, 315 subjects aged 33-93 years (174 men, 141 women) had had a stroke during that period. The types of stroke were cerebral infarction in 164, cerebral hemorrhage in 111, subarachnoid hemorrhage in 19, and others in 21. In men, the odds ratio of cerebral hemorrhage was 0.71 (95% confidence interval, 0.55-0.95), and the odds ratio of cerebral hemorrhage associated with serum level of cholesterol < or =167 mg/dl, 168-191 mg/dl, 192-217mg/dl, and > or =218mg/dl were 1.00 (reference), 0.70 (0.38-1.30), 0.77 (0.55-1.08), 0.73 (0.56-0.96), respectively. Lower serum cholesterol was an independent predictor of cerebral hemorrhage in men.

Multiple risk factor clustering of hypertension in a screened cohort.

Objective A family history of hypertension, obesity, diabetes mellitus, hypercholesterolaemia and hypertriglyceridaemia have all been associated with the risk for hypertension. We evaluated whether the clustering of these risk factors increases the risk for hypertension or whether the accumulation of risk factors is associated with the blood pressure level in non-hypertensive subjects. Methods and subjects We assessed the clinical data and family history of hypertension (in parents and siblings) for 9914 individuals (6163 men and 3751 women, 18–89 years old) who were screened in Okinawa, Japan, in 1997. Results In 9914 subjects (2465 hypertensive and 7449 non-hypertensive subjects), all the five factors were positively associated with hypertension. The odds ratios (95% confidence interval) for the number of risk factors were 1.88 (1.62–2.18) for one risk factor, 3.06 (2.62–3.57) for two, 5.25 (4.37–6.30) for three, 8.71 (6.48–11.72) for four and 24.48 (8.49–70.56) for five, after adjusting for age, sex, alcohol consumption, cigarette smoking and physical exercise habits. In non-hypertensive subjects, multivariate regression analyses showed that the number of risks was positively correlated with blood pressure; the regression coefficient was 1.96 (P < 0.0001) for systolic blood pressure, and 1.47 (P < 0.0001) for diastolic blood pressure after adjusting for age and sex. Conclusions Clustering of risk factors was significantly associated with hypertension. The number of risk factors positively correlated with the blood pressure levels in nonhypertensive subjects. The accumulation of risk factors may play an important role in the pathogenesis of hypertension, and thus the aggregation of risk factors may need to be addressed in primary prevention efforts related to hypertension.

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 × 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 m2) 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.

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 (≥1.4 mg/dl for men, ≥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

BackgroundDisturbances 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.MethodsWe 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.ResultsTotal 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 ≥ 220 mg/dl or TG ≥ 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.ConclusionsThe present study showed dyslipidemia to be an insignificant predictor of development of ESRD in the general Okinawa population.

Prevalence of high fasting plasma glucose and risk of developing end-stage renal disease in screened subjects in Okinawa, Japan.

BackgroundThe number of diabetic dialysis patients is increasing worldwide. Only a few studies, however, have examined the effect of diabetes mellitus (DM) as a risk factor for the development of end-stage renal disease (ESRD) in the general population.MethodsWe examined the cumulative incidence of ESRD based on the results of community-based mass screening in Okinawa, Japan, performed in 1993 by the Okinawa General Health Maintenance Association. Fasting plasma glucose (FPG) data were available for 78 529 screenees (37 197 men and 41 332 women). DM was diagnosed when the FPG was 126 mg/dl or more. Screenees who developed ESRD by the end of 2000 were identified through the Dialysis Registry, Okinawa Dialysis Study.ResultsThe mean (SD) FPG was 96.5 (22.8) mg/dl, ranging from 45 to 577 mg/dl. The prevalence of DM among the screenees was 4089 (5.2%). A total of 133 screenees (82 men and 51 women) developed ESRD during the 7.75-year study period. The adjusted odds ratio (95% confidence interval [CI]) in the high-FPG group for the risk of developing ESRD was 3.098 (95% CI, 1.738–5.525; P = 0.0001), when adjusted for age, sex, systolic blood pressure, diastolic blood pressure, body mass index, total cholesterol, triglyceride, hematocrit, serum creatinine, hematuria, and proteinuria.ConclusionsThe results of the present study indicated that FPG is a significant, independent predictor of ESRD. FPG and proteinuria measurements are euqally important in detecting individuals at high risk for developing ESRD.

Serum cholesterol and risk of end-stage renal disease in a cohort of mass screening

BackgroundTo evaluate the relative risk of end-stage renal disease (ESRD), indicated by basal serum cholesterol levels, we examined data from the 1983 community-based, mass screening registry and chronic dialysis program in Okinawa, Japan.MethodsData on serum cholesterol were available for a total of 38,053 subjects (17,859 men and 20,194 women), in addition to dipstick urinalysis and blood pressure data. Between 1983 and the end of 1995, we identified 99 ESRD dialysis patients (62 men and 37 women) among the screening participants.ResultsThe cumulative incidence and risk of ESRD were calculated for the following quartile definitions of serum cholesterol level: ≤167 mg/dL, 168 to 191 mg/dL, 192 to 217 mg/dL, and ≥218 mg/dL. The cumulative incidence of ESRD was 179, 216, 315, and 334 per 100,000 screened subjects in the respective serum cholesterol level quartiles. Logistic regression analysis on the prediction of ESRD by serum cholesterol level quartile was done, and the odds ratio (95% confidence interval) was 1.25 (1.04–1.49). However, the significance was lost when adjusted for the results of urinalysis or blood pressure measurements. Serum cholesterol levels were dependent on the degree of proteinuria by dipstick and blood pressure findings.ConclusionThe present study suggests that serum cholesterol may not be an independent predictor of ESRD. Whether the result was due to racial difference or was organ specific remains to be determined.

Outcome of subjects with elevated serum creatinine in a community-based mass screening

BackgroundThe outcome and prognosis of screened subjects with elevated levels of serum creatinine (>-176.8 μmol/L [≥2.0 mg/dL]) in a community-based mass health screening were examined in Okinawa, Japan.MethodsFrom 1983 to 1992, a total of more than 1.24 million people had received at least 1 screening by the Okinawa General Health Maintenance Association. The status of 250,091 individuals for whom data on serum creatine levels was available, as of January 1, 1996, was examined by using information from the Okinawa Dialysis Study registry, which included data on the end-stage renal disease (ESRD) program, and by reviewing the medical charts.ResultsA total of 289 screened subjects (187 men and 102 women) were investigated in this study. The total duration of observation was 1081.8 person-years. Clinical demographics and the incidence of ESRD, and the death of patients with ESRD before starting dialysis therapy (ESRD+death) were compared in 2 consecutive periods: A (1983 to 1987) and B (1988 to 1992). The incidence of ESRD and ESRD+death was 122.4 (161.5) per 1000 person-years in period A, whereas that of period B was 143.8 (170.2) per 1000 person-years. In the period 1988 to 1992, the hazards ratio for ESRD and ESRD+death was 1.50 and 1.38, respectively. The 95% confidence interval was 1.05 to 2.15 and 0.99 to 1.91, respectively, when compared to the period of 1983 to 1987.ConclusionThis study shows that the risk of ESRD and ESRD+death is not decreasing, therefore the current strategy for the prevention of ESRD is not satistactory. Further study is needed to determine the underlying causes and mechanisms of the progression of renal disease.