Long-term effects of candesartan and amlodipine on cardiovascular mortality and morbidity in Japanese high-risk hypertensive patients: rationale, design, and characteristics of candesartan antihypertensive survival evaluation in Japan extension (CASE-J Ex).

Candesartan Antihypertensive Survival Evaluation in Japan (CASE-J) trial was conducted to compare the effects of the angiotensin II receptor blocker (ARB) candesartan and the calcium channel blocker (CCB) amlodipine on the incidence of cardiovascular (CV) events in Japanese high-risk hypertensive patients. After 3.2years follow-up, CV events rate was 17.6-17.7 per 1000 person-years in each group, which was much lower than we expected. Since it has not been known whether the same efficacy of two drugs is sustained beyond the current trial, a longer follow-up period will be needed. The Steering Committee of CASE-J trial decided to extend the trial for 3years as an observational study (CASE-J Ex). In CASE-J Ex, the primary end point is a composite of CV events and the secondary endpoints are all-cause death and new-onset diabetes. After Committee's decision, 245 doctors agreed to participate in CASE-J Ex and 2236 patients (1141 with candesartan-based regimens and 1095 with amlodipine-based regimens) were re-enrolled. The baseline characteristics of CASE-J Ex participants were similar to CASE-J participants and still balanced well between candesartan and amlodipine. Recently, the interest of antihypertensive treatment has focused to differentiation of the effects of antihypertensive agents on the incidence of CV events as well as blood pressure lowering effect. CASE-J Ex will clarify the long-term effects of ARB and CCB on CV mortality and morbidity. Additionally, because the number of diabetic patients is increased, the evidences from CASE-J Ex will be valuable.

Outcome study of renal biopsy patients in Okinawa, Japan.

Here we report a community-based epidemiologic study of patients who received renal biopsy in Okinawa, Japan between 1967 and 1994. The total number of cases was 2832 (1395 men and 1437 women), and the mean (SD) age at biopsy was 30.0 (10.0) years (range 1.0 to 88.0 years). The most common clinical indications for renal biopsy were proteinuria/hematuria (46.7%), nephrotic syndrome (21.2%), acute glomerulonephritis (10.1%), and systemic lupus erythematosus (7.5%). Patients who received renal biopsy between 1985 and 1994 (N= 1480) were much less likely to have acute glomerulonephritis than patients treated between 1967 and 1984 (N= 1352); the rates of proteinuria/hematuria, renal failure, and diabetes mellitus were slightly higher in the later period. Okinawa patients who began dialysis between 1971 and 2000 (N= 5246) were also studied. Among them, a total of 468 patients (260 men and 208 women) began dialysis after renal biopsy. The cumulative incidence of end-stage renal disease (ESRD) among these patients was 17% in 17 years. Half of these patients developed ESRD in the 5.8 years after renal biopsy. Among the dialysis patients, the biopsy rate was 12.6% in chronic glomerulonephritis, 1.7% in diabetes mellitus, 2.6% in nephrosclerosis, and 52.1% in systemic lupus erythematosus. The diagnoses of primary renal diseases were primarily made clinically. The survival rate after starting dialysis therapy was slightly better in those with than in those without renal biopsy but this finding was not statistically significant (adjusted hazards ratio 0.855, 95% CI 0.711-1.028, P= 0.095). The clinical significance of renal biopsy, other than its provision of histologic evidence, remains to be shown.

Japanese society of hypertension (JSH) guidelines for self-monitoring of blood pressure at home.

UNLABELLED: Home blood pressure (BP) measurements are indispensable for the improvement of hypertension management in medical practice as well as for the recognition of hypertension in the population. The Working Group for Establishment of Guidelines for Measurement Procedures of Self-Monitoring of Blood Pressure at Home of the Japanese Society of Hypertension has established standards for all techniques and procedures of home BP measurements. The recommendations are as follows. RECOMMENDATION: 1) Arm-cuff devices based on the cuff-oscillometric method that have been validated officially, and the accuracy of which has been confirmed in each individual, should be used for home BP measurement. 2) The BP should be measured at the upper arm. Finger-cuff devices and wrist-cuff devices should not be used for home BP measurements. 3) Devices for home BP measurement should be adapted to the American Association for Medical Instrumentation (AAMI) standards and the British Hypertension Society (BHS) guidelines. In addition, the difference between the BP measured by the auscultatory method and that measured using the device should be within 5 mmHg in each individual. The home measurement device should be validated before use, and at regular intervals during use. 4) Home BP should be monitored under the following conditions. The morning measurement should be made within 1 h after waking, after micturition, sitting after 1 to 2 min of rest, before drug ingestion, and before breakfast. The evening measurement should be made just before going to bed, sitting after 1 to 2 min of rest. 5) Home BP should be measured at least once in the morning and once in the evening. 6) All home BP measurements should be documented without selection, together with the date, time, and pulse rate. Use of devices with a printer or an integrated circuit memory is useful to avoid selection bias. 7) The home BP in the morning and that in the evening should be averaged separately for a certain period. The first measurement on each occasion should be used for totaling. 8) Home BP values averaged for a certain period indicate hypertension when 135/80 mmHg and over and definite hypertension when 135/85 mmHg and over. Normotension is defined as less than 125/80 mmHg and definite normotension as less than 125/75 mmHg. Home BP measurements based on these guidelines can be considered an appropriate tool for clinical decision-making, and it is hoped that these guidelines will serve to reduce confusion and confirm the place of home BP measurement in clinical practice.

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.

Urinary excretion of sodium and potassium in a screened cohort in Okinawa, Japan.

Information regarding daily intake of sodium (Na) is useful for both normotensive and hypertensive subjects. We measured urinary excretion of sodium (U-Na) and urinary excretion of potassium (U-K) to estimate daily salt intake in a cohort of health screening subjects in Okinawa, Japan. Urine samples were obtained from 2,411 subjects (1,554 men and 857 women) who were examined on a half-day dry-doc at the Okinawa General Health Maintenance Association (OGHMA). Four hundred and one subjects were examined twice, once between September and November in 1997, and once between September and November in 1998. The mean U-Na was 182 mEq/day for men and 176 mEq/day for women. The mean U-K was 54 mEq/day for men and 50 mEq/day for women. U-Na was higher in young men, and U-K was lower in young women. In both men and women, smokers had a significantly lower Na excretion compared to nonsmokers. Subjects treated for hypertension had a significantly lower Na excretion (173 mEq/day) compared to subjects not treated for hypertension (192 mEq/day). Our findings suggest that Na excretion in screened subjects in Okinawa is lower than the national average. Sodium excretion, however, was higher in young men than in elderly subjects, and K excretion was lower in young women than in elderly subjects. Both trends are disadvantageous for controlling hypertension.

Increase in pulse pressure relates to diabetes mellitus and low HDL cholesterol, but not to hyperlipidemia in hypertensive patients aged 50 years or older.

Higher pulse pressure is associated with higher cardiovascular risk. We investigated the relationship between pulse pressure and known metabolic risk factors in hypertensive patients who had not experienced stroke or myocardial infarction. In a multicenter cross-sectional survey made in 1995, we registered 939 hypertensive patients aged > or = 50 years. Of these, 734 had never experienced stroke or myocardial infarction. We divided these 734 patients into two groups based on the value of their pulse pressures: 396 patients with a pulse pressure > or = 60 mmHg, and 338 patients with a pulse pressure<60 mmHg. The average pulse pressure value was 72 +/- 12 mmHg in the former group, and 49 +/- 8 mmHg in the latter group. The former group exhibited advanced age, a higher women-to-men ratio, lower high-density lipoprotein (HDL) cholesterol, and higher systolic and lower diastolic blood pressure. Diabetes mellitus (DM) and left ventricular hypertrophy were more frequently noticed in the former group than in the latter group. The prevalence of hyperlipidemia, however, was similar in the two groups. The association of pulse pressure with DM and low HDL cholesterol was statistically significant by multiple logistic analysis adjusted for age, sex, and other known cardiovascular risk factors. In conclusion, pulse pressure increases with advancing age. DM made a substantially larger contribution to the increase in pulse pressure than hyperlipidemia.

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.