Chiho Iseki

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.

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 (≥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 (≥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 ≥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.

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.

Seasonal Blood Pressure and Body Weight Variation in Patients on Chronic Hemodialysis

Aim: The relation of ambient temperature (AMT) and relative humidity to systolic blood pressure (SBP), diastolic blood pressure (DBP), body weight (BW), and body weight gain between dialysis sessions (ΔBW) was examined in hemodialysis patients by Fourier analysis. Methods and Results: The authors recruited 144 dialysis patients from a hemodialysis center in Okinawa, Japan where there is distinct seasonal variation in monthly AMT but a constant intradiurnal temperature change throughout the year. All patients had been undergoing chronic and regular hemodialysis three times per week. SBP, DBP, and BW before dialysis sessions and ΔBW were recorded in 1994. Mean monthly Okinawa AMT in 1994 was highest in Augsut and lowest in February and March, and the mean monthly relative humidity in 1994 was highest in June and lowest in January. Mean SBP and DBP were lowest in August and June respectively, and greatest in December. BW was lowest in July and September, and greatest in February and March; ΔBW was lowest in July and greatest in January. These seasonal patterns were well reproduced by the first Fourier component. The cross-correlation coefficient showed that monthly mean AMT and SBP, DBP, BW, and ΔBW were correlated with a lag time of 5 or 6 months. The cross correlation coefficient showed that relative humidity and SBP, DBP and ΔBW were also correlated with a 6-month lag time. In analyzing subgroups of patients according to the presence or absence of antihypertensive medications, a seasonal change was observed in the SBP and DBP of patients not being treated with antihypertensives, and in the DBP of patients taking antihypertensive medications, but not in the SBP of patients taking antihypertensive medications. Conclusion: Seasonal variations in SBP, DBP, BW and ΔBW were evident. AMT and the relative humidity correlated strongly with SBP, DBP, BW and ΔBW. The clinical implications of these findings in hemodialysis patients warrant further investigation.

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.

Long-Term Blood Pressure Variability, New-Onset Diabetes Mellitus, and New-Onset Chronic Kidney Disease in the Japanese General Population

Whether long-term blood pressure (BP) variability among individuals without diabetes mellitus is associated with new-onset chronic kidney disease (CKD) risk, independently of other BP parameters (eg, mean BP, cumulative exposure to BP) and metabolic profile changes during follow-up, remains uncertain. We used data from a nationwide study of 48 587 Japanese adults aged 40 to 74 years (mean age, 61.7 years; 39% men) without diabetes mellitus or CKD (estimated glomerular filtration rate <60 mL/min per 1.73 m2 or proteinuria by dipstick). BP was measured at baseline and during 3 annual follow-up visits (4 visits). BP variability was defined as standard deviation (SD) and average real variability during the 4 visits. At the year 3 follow-up visit, 6.3% of the population had developed CKD. In multivariable-adjusted logistic regression models, 1 SD increases in SDSBP (per 5 mmHg), SDDBP (per 3 mmHg), average real variabilitySBP (per 6 mmHg), and average real variabilityDBP (per 4 mmHg) were associated with new-onset CKD (odds ratios [ORs] and 95% confidence intervals, 1.15 [1.11–1.20], 1.08 [1.04–1.12], 1.13 [1.09–1.17], 1.06 [1.02–1.10], respectively; all P<0.01) after adjustment for clinical characteristics, and with mean BP from year 0 to year 3. The associations of SDBP and average real variabilityBP with CKD remained significant after additional adjustments for metabolic parameter changes during follow-up (ORs, 1.06–1.15; all P<0.01). Sensitivity analyses by sex, antihypertensive medication use, and the presence of hypertension showed similar conclusions. Among those in the middle-aged and elderly general population without diabetes mellitus, long-term BP variability during 3 years was associated with new-onset CKD risk, independently of mean or cumulative exposure to BP and metabolic profile changes during follow-up.

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 m2) 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 m2 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.

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.

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.