Angiotensin-converting enzyme (ACE) insertion/deletion polymorphism and survival in a cohort of chronic hemodialysis patients.

BACKGROUND: There are conflicting reports regarding the relationship between the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and the initiation and progression of cardiovascular disease. Moreover, there is no report regarding the relationship between the ACE I/D polymorphism and the prognosis of chronic dialysis patients. METHODS: We examined the frequency of the ACE I/D polymorphism in 727 chronic hemodialysis patients in Okinawa, Japan, and observed the prognosis over 2 years in 407 men and 320 women with mean age (SD) of 55.5 (13.9) years with a mean duration of dialysis of 84.3 (66.6) months. RESULTS: Genotype frequencies were 42.1% for II, 43.2% for ID, and 14.7% for DD. The relative risks of death were examined by Cox-proportional hazards analysis after adjusting for age, sex, age at the start of dialysis, presence of diabetes mellitus and hypertension and total cholesterol and serum albumin levels. The adjusted hazard ratio (95% confidence interval) was 1.03 (0.38 - 2.85) for DD genotype and 1.50 (0.83 - 2.70) for DD+ID genotype when compared to II genotype. CONCLUSION: ACE I/D polymorphism appears to have no relation to the short-term prognosis in chronic hemodialysis patients.

Family history of hypertension and blood pressure in a screened cohort.

We sought to determine whether a family history of hypertension is quantitatively associated with the prevalence of hypertension and blood pressure in a screened cohort. Clinical data and family (parents and siblings) histories regarding hypertension were collected from 9,914 individuals (probands) who were interviewed and examined during a one-day clinic by the Okinawa General Health Maintenance Association in 1997. We used logistic analysis to calculate odds ratios with adjustments for age, sex, body mass index, total cholesterol, presence of diabetes mellitus, alcohol use, cigarette smoking, and status of physical exercise. The age- and sex-adjusted hypertension prevalences in probands were 29.0% for those with 1 family member with a history of hypertension (n=2,112), 37.6% for those with 2 hypertensive family members (n=374), and 47.3% for those with 3 or more hypertensive family members (n=68). In contrast, only 16.4% of probands who reported no family history of hypertension (n=7,360) were hypertensive themselves. The trend of the prevalence according to the number of family members with a history of hypertension was significantly positive (p=0.003). The adjusted odds ratios (95% confidence interval) of hypertension were 2.74 (2.43-3.10) for 1 member, 4.62 (3.62-5.90) for 2 members, and 6.04 (3.51-10.4) for 3 or more members with a history of hypertension. In patients without antihypertensive medication (n=9,009), systolic/diastolic blood pressure (mean +/- SD) was 121 +/- 17/75 +/- 11 for 1 member, 124 +/- 18/77 +/- 12 for 2 members, and 127 +/- 17/78 +/- 11 for 3 or more members with a history of hypertension. In contrast, the mean systolic/diastolic blood pressure of probands who reported no family history of hypertension (n=7,360) was 119 +/- 15/74 +/- 10 mmHg, which was significantly (p<0.05) lower than that of any of the groups with hypertensive family members. In conclusion, an increase in the number of family members with hypertension was associated with an increasing prevalence of hypertension and blood pressure in the probands, independent of conventional risk factors for hypertension. Family members of hypertensive subjects may need to be treated in primary prevention efforts related to hypertension.

Significance of hyperuricemia on the early detection of renal failure in a cohort of screened subjects.

A high level of serum creatinine (S-Cr) is a predictor of end-stage renal disease (ESRD), but only a few studies have investigated the prevalence of high S-Cr and its correlates in a large population. We analyzed the data collected from 6,403 subjects (4,222 men and 2,181 women) who participated in the Okinawa General Health Maintenance Association (OGHMA) screening both at 1997 and 1999. The computer-saved data included sex, age, blood chemistries, blood pressure, medical histories, and lifestyles. Multivariate Cox proportional hazard analyses were performed to identify the correlates of developing high S-Cr levels: > or = 1.4 mg/dl in men and > or = 1.2 mg/dl in women. The prevalence of high S-Cr was 3.0% (N=193), which was 4.1% in men (N=175) and 0.8% in women (N=18), and increased with age in both sexes at the 1997 screening. Among those who showed normal levels of S-Cr in 1997 (N=6,210), 241 subjects (223 men and 18 women) developed high S-Cr. The 2-year cumulative incidence of high S-Cr was 5.5% in men and 0.8% in women. Other than sex, serum uric acid was the most significant correlate for developing high S-Cr. The adjusted relative risk (95% confidence interval) of those with serum uric acid 8.0 mg/dl and over was 2.91 (1.79-4.75) in men and 10.39 (1.91-56.62) in women when compared to those with serum uric acid less than 5.0 mg/dl. Prevalence of high levels of S-Cr was relatively high in men. Other than gender, serum uric acid was a significant positive correlate of developing high S-Cr in this sample of the Japanese population.

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 (DeltaBW) 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 DeltaBW were recorded in 1994. Mean monthly Okinawa AMT in 1994 was highest in August 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; DeltaBW 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 DeltaBW were correlated with a lag time of 5 or 6 months. The cross correlation coefficient showed that relative humidity and SBP, DBP and DeltaBW 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 DeltaBW were evident. AMT and the relative humidity correlated strongly with SBP, DBP, BW and DeltaBW. The clinical implications of these findings in hemodialysis patients warrant further investigation.

Risk of developing end-stage renal disease in a cohort of mass screening.

The prognostic significance of abnormal findings has not been demonstrated in a setting of mass screening. To evaluate the relative risk of end-stage renal disease (ESRD) indicated by various results of community-based mass screening, we utilized the registries of both community mass screening and chronic dialysis programs. In 1983, a total of 107,192 subjects over 18 years of age (51,122 men and 56,070 women) participated in dipstick urinalysis and blood pressure measurement in Okinawa, Japan. During ten years of follow-up, we identified 193 dialysis patients (105 men and 88 women) among them. Logistic regression analysis of clinical predictors of ESRD over 10 years was done and the adjusted odds ratio and 95% confidence interval were calculated in each of the predictors with adjustment to others. In the clinical predictors such as sex, age at screening, proteinuria, hematuria, systolic and diastolic blood pressure, proteinuria was the most potent predictor of ESRD (adjusted odds ratio 14.9, 95% confidence interval 10.9 to 20.2), and the next most potent predictor was hematuria (adjusted odds ratio 2.30, 95% confidence interval 1.62 to 3.28). Being of male gender was a significant risk factor for ESRD (adjusted odds ratio 1.41, 95% confidence interval 1.04 to 1.92). Diastolic blood pressure was also a significant predictor of ESRD (adjusted odds ratio 1.39, 95% confidence interval 1.17 to 1.64), but systolic blood pressure was not. In a mass screening setting, positive urine test, high diastolic blood pressure, and male sex were identified as the significant predictors of ESRD. Effect of glycosuria and other possible predictors of ESRD remained to be determined.