Hyperuricemia as a predictor of hypertension in a screened cohort in Okinawa, Japan.

Several epidemiological studies have shown a positive association between serum uric acid levels and the risk of hypertension. However, subjects in these studies were mostly men, or were incompletely examined for lifestyle-related variables. We prospectively examined the relation between hyperuricemia and the risk of developing hypertension with consideration for alcohol consumption and smoking habits in a large screened cohort of men and women. A total of 4,489 individuals (2,927 men and 1,562 women) who did not have hypertension and were not currently using antihypertensive medication were examined at the Okinawa General Health Maintenance Association in 1977. Subjects were re-examined in 2000. Hyperuricemia was defined as a serum uric acid level >or=7.0 mg/dl in men and >or=6.0 mg/dl in women. Hypertension was defined as systolic blood pressure (SBP) >or=140 mmHg, and/or diastolic blood pressure (DBP) >or=90 mmHg. A total of 289 subjects (201 men and 88 women) were hypertensive (SBP >or=140 mmHg, and/or DBP >or=90 mmHg) in 2000. Multivariate analysis was performed for development of hypertension in hyperuricemic subjects, adjusted for age, family history of hypertension, alcohol consumption, cigarette smoking, obesity, hypercholesterolemia, hypertriglyceridemia, low high-density lipoprotein cholesterol, and diabetes mellitus. The adjusted odds ratio (95% confidence interval) in men was 1.48 (1.08-2.02) and in women was 1.90 (1.03-3.51) (p <0.05, respectively). The results showed hyperuricemia to be a new predictor of hypertension development in both men and women.     

Prevalence and correlates of diabetes mellitus in a screened cohort in Okinawa, Japan.

The incidence of end-stage renal disease due to diabetes mellitus (DM) is increasing. There have been too few epidemiological studies of the predictors of DM nephropathy, particularly type 2 DM, among a statistically significant population. We studied the prevalence and correlates of DM in a screened cohort in Okinawa, Japan. A total of 9,914 screenees (6,163 men and 3,751 women) over 18 years of age underwent a 1-day health check at the Okinawa General Health Maintenance Association between April 1997 and March 1998. Subjects were considered to have DM if they showed a fasting plasma glucose > or = 126 mg/dl and hemoglobin A1c > or = 7.0%, or if they were receiving treatment for DM. Non-DM subjects were followed-up until March 2000 to see whether or not they developed DM. Relative risk for developing DM was evaluated by Cox proportional hazard analysis after adjusting for confounding variables. A total of 673 screenees (520 men and 153 women) were diagnosed with DM. The prevalence of DM was 67.9 per 1,000 screenees (84.4 for men and 40.8 for women). A total of 7,125 non-DM screenees were examined a second time. Among them, 164 screenees (130 men and 34 women) had developed DM during the follow-up period. Over 2 years, the cumulative incidence of DM was 2.3% (2.9% in men and 1.3% in women). The adjusted relative risk (95% confidence interval) for developing DM was highest for proteinuria, or 1.90 (1.14-3.17). The results indicated that the prevalence and incidence of DM were high among this screened cohort in Okinawa, Japan. Subjects with proteinuria may thus be at high risk for developing DM.     

Estimated protein intake and blood pressure in a screened cohort in Okinawa, Japan.

We examined the relation between protein intake and blood pressure in a screened cohort in Okinawa, Japan. A total of 1,299 screened subjects, 885 men and 414 women, were examined at the Okinawa General Health Maintenance Association. Daily intake of sodium (Na) and potassium (K) was estimated from Na, K, and creatinine excretion by the method of Kawasaki et al., and daily protein intake was estimated by the method of Maroni et al. as the estimated daily urinary excretion of urea nitrogen. Mean (SD) daily protein intake was 71.8 (18.6) g in men and 54.0 (13.5) g in women, and the mean (SD) daily protein intake per unit kg body weight was 1.1 (0.2) g/kg in men and 1.0 (0.2) g/kg in women. In men, both systolic blood pressure (SBP) and diastolic blood pressure (DBP) were higher in those with lower protein intake (LP; < 1.0 g/kg/day) than in those with higher protein intake (HP; > or = 1.0 g/kg/day) (p < 0 .05 for DBP). In women, both SBP and DBP were higher in those with LP than in those with HP, but these differences were not statistically significant. However, urinary excretion of both Na and K was lower in those with LP than in those with HP, respectively, both in men and women (p < 0.0001). In summary, estimated daily protein intake was about 1.1 g/kg in men and 1.0 g/kg in women. Despite the higher urinary excretion of Na, both SBP and DBP tended to be lower in those with higher daily protein intake, particularly in men.     

Hyperuricemia and cardiovascular risk factor clustering in a screened cohort in Okinawa, Japan.

The relation between serum uric acid level and cardiovascular risk factors is complex and has been investigated mainly in men. We examined the correlation between serum uric acid level and obesity, hypertension, dyslipidemia, and diabetes mellitus (DM) in both men and women of a screened cohort in Okinawa, Japan. A total of 9,914 individuals (6,163 men and 3,751 women ranging in age from 18 to 89 years) who were screened at Okinawa General Health Maintenance Association were subjects in this study. Hyperuricemia was defined as a serum uric acid level > or = 7.0 mg/dl in men and > or = 6.0 mg/dl in women. The odds ratios (95% confidence intervals) for the presence of hyperuricemia in men were 1.75 (1.56-1.97) for obesity, 1.42 (1.25-1.62) for hypertension, 1.16 (1.02-1.30) for hypercholesterolemia, 1.80 (1.60-2.03) for hypertriglyceridemia, 1.19 (1.02-1.40) for hypo-high density lipoprotein (HDL) cholesterolemia, and 0.61 (0.49-0.75) for DM; in women, they were 2.02 (1.62-2.53) for obesity, 1.64 (1.29-2.10) for hypertension, 1.31 (1.04-1.65) for hypercholesterolemia, 1.95 (1.51-2.51) for hypertriglyceridemia, 1.53 (0.96-2.44) for hypo-HDL cholesterolemia, and 1.20 (0.76-1.90) for DM. Hyperuricemic subjects had higher rates of coexistence of two or more of these cardiovascular risk factors than non-hyperuricemic subjects (63.8% vs. 43.2% in men; 58.9% vs. 27.6% in women). The present study revealed that hyperuricemia is positively associated with obesity, hypertension, and dyslipidemia in both men and women, and that hyperuricemic subjects tend to have a clustering of these cardiovascular 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.     

Cardiovascular risk factors associated with pulse pressure in a screened cohort in Okinawa, Japan.

We evaluated the association between pulse pressure (PP) and cardiovascular risk factors in a screened cohort. Individuals who were receiving medications for hypertension or heart disease, who had no ECG record, or who had a record of arrhythmia were excluded. In total, 8,508 subjects (5,299 men and 3,209 women; age range, 18 to 89 years) were studied. Subjects were divided into four PP classes: PP.1 (PP < or = 40 mmHg, n=2,127), PP.2 (40 < or = PP < or = 44 mmHg, n=2,127), PP.3 (44 < or = PP < or = 50 mmHg, n=2,127) and PP.4 (50 mmHg < or = PP, n=2,127). Multiple regression analysis was used for evaluating the association between PP and cardiovascular risk factor or lifestyle. In men, the regression coefficient was 0.27 for age, 2.50 for diabetes mellitus, 0.33 for uric acid, 0.20 for body mass index, 0.07 for heart rate, -0.83 for current smoking habit and 1.23 for habitual drinking. In women, the regression coefficient was 0.37 for age, 4.09 for diabetes mellitus, 0.42 for body mass index, 0.14 for heart rate, and 0.84 for habitual exercise. In both men and women, PP was significantly increased in association with an increase in the number of risk factors (diabetes mellitus, obesity, current drinking status, heart rate, and hyperuricemia). In conclusion, higher PP was associated with cardiovascular risk factors. These associations were similar in both men and women.     

Urinary potassium excretion and sodium sensitivity in blacks

Based on racial differences in urinary potassium excretion and responses to diuretics, we present a model suggesting that a major cause of sodium sensitivity in blacks is an augmented activity of the Na-K-2Cl cotransport in the thick ascending limb of Henle's loop. This would result in an increased ability to conserve not only sodium but also water, and an upward and rightward shift in the operating point of tubuloglomerular feedback, which may cause an increase in the glomerular capillary hydraulic pressure and predilection to glomerular injury with and without hypertension. In this sense, the biological implication of sodium sensitivity in blacks and in humans in general has ramifications above and beyond salt-evoked increase in blood pressure.     

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.     

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.     

Urinary sodium and potassium excretion and risk of hypertension in Chinese: report from a community-based cohort study in Taiwan

BACKGROUND: Dietary sodium intake is associated with blood pressure and hypertension risk. However, most of the studies have been conducted in whites and it is not clear whether the effects exist in Asian populations. OBJECTIVE: The purpose of the present study was to investigate the role of 24-h urinary sodium excretion and hypertension risk among ethnic Chinese. DESIGN: A prospective cohort design on community. SETTING AND PARTICIPANTS: One thousand five hundred and twenty middle-aged and elderly participants who were free from hypertension at baseline and had available urine electrolyte data. MAIN OUTCOME MEASURES: Hypertension incidence. RESULTS: During a median 7.93 years of follow-up (interquartile range = 4.07-9.04 years), we documented 669 cases of incident hypertension. The multivariate risk was 1.26 (95% confidence interval = 1.01-1.57; P = 0.043) for individuals in the highest quartile of urinary sodium excretion as compared with those in the second quartile. A significant J-shape relationship between urinary sodium excretion and the risk of hypertension was observed, with the test for linear relation being rejected (P = 0.046). Participants who were in the highest quartile of urinary sodium excretion and higher baseline blood pressure had a 2.43-fold increased risk of hypertension (95% confidence interval = 1.72-3.22) compared with those in the lowest quartiles of urinary sodium and lower blood pressure. CONCLUSION: Urinary sodium excretion was associated with the risk of hypertension among ethnic Chinese. Urinary sodium excretion, as a marker of dietary sodium intake, can be useful for a comprehensive evaluation of hypertension risk in Asian populations.     

Urinary sodium and potassium excretion and the risk of type 2 diabetes: a prospective study in Finland

Aims/hypothesis No previous studies on the association between salt intake and the risk of type 2 diabetes have been reported. The aim of this study was to assess whether high salt intake, measured by 24-h urinary sodium excretion, is an independent risk factor for type 2 diabetes.Methods We followed prospectively 932 Finnish men and 1,003 women aged 35–64 years with complete data on 24-h urinary sodium and potassium excretion and other study parameters. Hazard ratios for the incidence of type 2 diabetes were estimated for different levels of 24-h urinary sodium and potassium excretion.Results During a mean follow-up of 18.1 years, there were 129 incident cases of type 2 diabetes. The multivariate-adjusted (age, sex, study year, body mass index, physical activity, systolic blood pressure, antihypertensive drug treatment, education, smoking and coffee, alcohol, fruit, vegetable, sausage, bread and saturated fat consumption) hazard ratio for diabetes for the highest vs combined lower quartiles of 24-h urinary sodium excretion was 2.05 (95% CI, 1.43–2.96). This positive association persisted in non-obese and obese subjects, in normotensive and hypertensive subjects, as well as in men and women. Potassium excretion was not associated with the risk of type 2 diabetes.Conclusions/interpretation High sodium intake predicted the risk of type 2 diabetes, independently of other risk factors including physical inactivity, obesity and hypertension. These results provide direct evidence of the harmful effects of high salt intake in the adult population, although the confounding effect of other dietary factors cannot be fully excluded.     

Urinary excretion of vasoactive factors are correlated to sodium excretion.

BACKGROUND: The relationship between urinary vasoactive factors and sodium excretion has not been adequately addressed in humans. PROCEDURE: Excretion rates of sodium, nitrates/nitrites (NOx), cGMP, and endothelin-1 (ET-1) were measured before and after ingestion of a mixed electrolyte solution (8 oz Gatorade) while undergoing a routine cardiovascular evaluation in a sample of 51 normotensive young adults. RESULTS: Significant correlations were detected for changes in excretion between all four variables, r ranged from 0.50 to 0.86 (P < .001). Correlations were higher in African Americans than white Americans. CONCLUSIONS: The association of renal ET-1 and NO activity with sodium excretion supports the hypothesis that these factors play a role in the physiologic response to acute changes in sodium intake, particularly in African Americans.     

Urinary sodium and potassium excretion, body mass index, alcohol intake and blood pressure in three Japanese populations

Standardised data on blood pressure, 24 hour urinary electrolyte excretion and other lifestyle factors were obtained in three Japanese populations as part of the INTERSALT study. Urinary sodium excretion and sodium/potassium ratio were significantly (P less than 0.01) higher in Toyama (a semi-rural area in central Japan) than in Tochigi (a rural area 100 km north of Tokyo) and Osaka. There were also significant (P less than 0.01) differences between the centres in diastolic blood pressure (highest in Toyama), although systolic pressure was similar in all three centres. Average potassium excretion was low (46 mmol/day), and the prevalence of both heavy alcohol drinking (greater than or equal to 300 ml/week) and smoking was high in men (33% and 61% respectively); compared with other countries, there were favourable levels of body mass index (mean 22.4 kg/m2). Despite a recent decline in sodium consumption in Japan, which has been accompanied by a fall in blood pressure levels, in the prevalence of hypertension and also in stroke mortality, average sodium excretion in the three centres was high compared to other countries (187 mmol/day). Applying overall INTERSALT regression coefficients to the Japanese data, suggested that further falls in sodium intake together with a modest increase in potassium intake and a reduction (in men) in the prevalence of heavy alcohol drinking could have an important impact on average blood pressures and the prevalence of hypertension. It can be expected that these nonpharmacological approaches to improved blood pressure levels will be accompanied by continued reductions in mortality from stroke.     

Subcutaneous dirofilariasis in Okinawa, Japan.

A nematode within a subcutaneous nodule excised from an elderly Okinawan man has been tentatively identified in sections as an immature Dirofilaria repens--the first to be reported from Japan.     

Urinary sodium excretion and blood pressure in chronic psychiatric in-patients.

Studies of populations or communities with no rise in blood pressure (BP) with advancing age and low prevalence of hypertension, may provide aetiological clues on the cause of hypertension. Within westernised societies, low blood pressures have been reported amongst chronic psychiatric in-patients and closed order secluded nuns. To investigate factors associated with BP in chronic psychiatric in-patients, we surveyed the BP and lifestyle factors in 89 such subjects in low security wards in three psychiatric hospitals. The average age of examines was 48.1 years (s.d. 15.8) and the patients had been in hospital for a mean of 8.6 years (range 1.1 to 51.7 years). The mean systolic and diastolic blood pressures of this group were 122.0 mm Hg (s.d. 14.2) and 76.9 mm Hg (s.d. 8.5) respectively. This was lower than pressures obtained when they were admitted to hospital (mean systolic BP change -17.1 mm Hg (s.d. 14), paired t-test P < 0.001; mean diastolic BP change -3.7 mm Hg (s.d. 12.2), paired t-test P < 0.001). BP at examination was significantly correlated with the urinary sodium to creatinine ratio (r = 0.302, P = 0.027), but not with the urinary sodium or potassium concentrations or potassium/creatinine ratio. The change in mean systolic BP (that is, the difference in BP between admission and examination) was significantly correlated with sodium/creatinine ratio (r = 0.62, P < 0.0001), urinary sodium concentration (r = 0.27, P = 0.045) and urinary sodium/potassium ratio (r = 0.36, P = 0.008). No relationship was found between BP and the nature of the psychiatric diagnosis or the type of psychotropic medication that was being prescribed. Stepwise multiple regression demonstrated that urinary sodium creatinine ratio and age were predictive of the change in systolic BP since admission to hospital. Our study confirms previous observations of lower mean systolic and diastolic blood pressures in chronic psychiatric subjects after a long in-patient stay. This fall is related to a low urine sodium excretion and suggests that a low dietary sodium intake may, in part, account for the low BP, or the difference between BP in the stressed and relaxed state, seen in these patients.     

Urinary aldosterone excretion and erythrocyte and plasma sodium and potassium ion concentration in persons of different ages]

Practically healthy persons (79 in all) aged from 20 to 80 years and over were examined. The work was aimed at the study of the character of aldosterone excretion and its correlation with the ionic composition of erythrocytes and the peripheral blood plasma in persons at various age periods. As revealed, the activity of glomerular zone of the adrenal cortex in persons aged from 20 to 40 years displayed sexual differences: 1.33 times more aldosterone was excreted with the urine in women than in men. With the advance of age there occurred a functional decrease in the glomerular zone of the adrenal cortex. In senile persons (aged 80 years and over) this difference was entirely eliminated. Sodium ions in erythrocytes increased, but remained unchanged in the peripheral blood plasma. Potassium ion concentration fell both in the erythrocytes and in the blood plasma. A reduction of aldosterone content failed to alter the sodium-retention effect of its action which corresponded to the concept on increase of tissue sensitivity to hormones with the advance of age.