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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.

The COLM study is an investigator-initiated trial comparing the combination therapy using an angiotensin II receptor blocker (ARB), olmesartan, and a calcium channel blocker (CCB) with that using an ARB and a diuretic in high-risk elderly hypertensive patients. Here we describe the rationale and study design. Olmesartan was administered concomitantly with a long-acting dihydropyridine CCB (ARB/CCB group) or with a low-dose diuretic (ARB/diuretic group) to elderly hypertensive patients with a history of or risk factors for cardiovascular disease. Cardiovascular morbidity and mortality as a primary end point were compared between the two groups, with the target blood pressure (BP) being

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 (

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 x 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 (GFR60 ml/min/1.73 m(2)) 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; p0.0001). 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.

A high plasma aldosterone concentration (PAC) is known to be associated with poor outcome in patients with cardiac disease. However, the prognostic value of PAC in chronic hemodialysis (HD) patients is unknown. In 1996 we examined 128 hypertensive patients treated with antihypertensive drugs, excluding angiotensin-converting enzyme inhibitors, who were undergoing chronic HD (ages 61.8+/-13.8 years, 62% male), and for whom PAC (ng/dl) data were obtained. We followed up these patients until November 2003. During the follow-up period, 30 patients died. About half of all patients (48%) had PAC values above the normal range. We assigned the 128 patients to a lower (22.9) or higher (or = 22.9) PAC group according to the median baseline PAC. The survival rate as calculated by the Kaplan-Meier method was 90.6% in the higher PAC group and 62.5% in the lower PAC group (p=0.003). In multivariate analysis, serum potassium and plasma renin activity were independent determinants of PAC. Cox proportional hazards analysis, with adjustment for other variables including diabetes, showed that lower PAC was independently predictive of death. The adjusted hazard ratio (95% confidence interval) of the lower PAC group was 2.905 (1.187-7.112, p=0.020). The significance of PAC became marginal by adjustment with albumin or potassium. These results indicate that higher PAC is common, but not associated with an increase in total and cardiovascular deaths among hypertensive patients undergoing chronic HD. The association between lower PAC and poor survival may be driven by volume retention and/or lower potassium.

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

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.

A family history of hypertension, obesity, diabetes mellitus, hypercholesterolemia, and hypertriglyceridemia have all been associated with risk of hypertension. We retrospectively conducted a longitudinal study in a large screened cohort to explore the effect of the clustering of these five risk factors on the elevation of blood pressure (BP) in normotensive subjects at baseline. The study group comprised 4,857 normotensive subjects not treated with antihypertensive drugs (systolic BP140 mmHg, diastolic BP90 mmHg, 3,111 men and 1,746 women) who were followed up from 1997 to 1999. By 1999, 360 subjects had BP at the hypertensive level (systolic BPor = 140 mmHg or diastolic BPor = 90 mmHg). The incidence of subjects whose BP became hypertensive was 37 per 1,000 person-years. After adjusting for age, sex, systolic BP and other clinical factors, multiple logistic analysis showed that the relative risk of BP elevation was 1.49 (95% Cl: 1.09 to 2.05) in subjects with one risk factor; 1.65 (95% Cl: 1.15 to 2.27) in those with two risk factors; 1.42 (95% Cl: 0.91 to 2.32) in those with three; and 4.86 (95% Cl: 2.58 to 9.16) in those with four or more when compared with subjects with no risk factors. Multiple regression analysis showed that the number of risk factors was positively correlated with an increase in BP from 1997 to 1999; the regression coefficient was 0.51 (p = 0.001) for increase in systolic BP, and 0.31 (p = 0.008) for increase in diastolic BP after adjusting for age and sex. In conclusion, clustering of risk factors significantly predicted the development of hypertension.

Cross-sectional studies have shown that home blood pressure (BP) correlates with hypertensive target organ damage better than clinic BP. However, there have been few longitudinal studies regarding the predictive value of home BP on the changes in organ damage in treated hypertensive patients. Clinic and home BP over a 12-month period, antihypertensive medication use, echocardiographic and electrocardiographic results, and serum creatinine and urinary protein levels were examined in 209 treated hypertensive patients in 1993. These patients were prospectively followed for 5 years. The patients were divided into 4 subgroups according to hypertension control as follows: good control (

A questionnaire survey was administered to Japanese clinical specialists in hypertension in order to gauge their opinions on the 1999 revised version of the Guidelines for Hypertension in the Elderly prepared by the Comprehensive Research Project on Aging and Health of the Ministry of Health and Welfare. Out of 162 council members of the Japanese Society of Hypertension, 122 (75%) replied. The majority (93%) of respondents approved of the guidelines in general, and 72% of them approved of the age-related setting of a therapeutic goal for blood pressure. Sixty-five percent of respondents selected long-acting Ca antagonists, ACE inhibitors and low-dose diuretics as first-line agents for hypertension without complications in the elderly. The results of the questionnaire survey should be reflected in the next version of the guidelines. (Hypertens Res 2002; 25: 69-75)

To clarify whether significant interrelations between hyperinsulinemia and cardiovascular diseases exist in Japanese, we analyzed serum insulin levels, fasting and after oral glucose load, in relation to blood pressure (BP), serum lipids, and incidence of acute myocardial infarction (MI) and stroke in 584 male employees of a railroad company with borderline to mild hypertension (age: 49 +/- 7 years, BP: 139 +/-13/90 +/- 8 mmHg, body mass index: BMI 24.0 +/- 2.8, mean +/- SD). Those who were taking antihypertensive drugs and/or hypoglycemic agents were excluded. The subjects were classified into five groups of comparable size according to sigma IRI (area composed by insulin levels at 0, 1, 2 hours post glucose load). Although averaged age, levels of fasting glucose and HbA1c were not significantly different among quintiles, the hyperinsulinemic groups had higher levels of fasting IRI and sigma glucose. Multiple regression analysis revealed that sigma IRI was associated positively with BMI, sigma glucose, systolic BP, total cholesterol, and negatively with HDL-cholesterol. During 7-year follow-up 7 cases with MI and 15 cases with stroke were registered. The subjects with MI, but not with stroke were involved in higher deciles of insulin levels. These results indicate that the insulin resistance syndrome exists in Japanese middle-aged men with borderline to mild hypertension. The association with cardiovascular morbid events appeared to be evident in coronary heart disease but not in cerebrovascular disease.

Over the past two decades there has been a precipitous fall in the age-adjusted rate of deaths due to cerebrovascular disease in Japan, while the rate of deaths due to heart disease has fallen only slightly. Mortality from heart disease since 1984 has been greater than that from cerebrovascular disease. However, an epidemiologic survey in Okinawa indicates that the incidence of stroke is 4.4times higher than that of acute myocardial infarction: the average age-adjusted annual incidences of stroke and acute myocardial infarction per 100, 000 people aged 40years and older were 315 and 72, respectively. The National Nutrition Survey and National Survey on Circulatory Disorders revealed that during the last 10 years the averages of systolic and diastolic blood pressures of Japanese decreased, especially in those aged 50 and older, and the prevalence of hypertension as well as of left ventricular hypertrophy diagnosed by electrocardiography decreased significantly in both men and women. This may be attributable to widespread education concerning hypertension and antihypertensive treatment. However, the average serum total cholesterol concentration increased by 12mg/dl in men and 16mg/dl in women and the prevalence of hypercholesterolemia increased in both men and women during the last 10years. Furthermore, 61% of men still smoke. Research results show that the mortality and morbidity rates for cardiovascular diseases are changing in Japan. This seems to be related to the fact that Japanese people are adopting a more westernized pattern of food intake. There is a concern that the incidence of acute myocardial infarction might greatly increase in the near future. (Hypertens Res 1994; 17: 215-219)

The purpose of the present study is to determine accurate incidence rates of stroke and acute myocardial infarction among the residents in Okinawa, where the census population was 1, 222, 398 in 1990 and mortality due to cerebrovascular and heart diseases is lowest in Japan. A co-operative study group including almost all hospitals and clinics in Okinawa was established for the survey. Between April 1, 1988 and March 31, 1991, 4, 756 cases of stroke and 1, 059cases of acute myocardial infarction were identified. The average age-adjusted annual incidence per 100, 000 population was 137 for stroke and 31 for acute myocardial infarction. In the population aged 40 years and older, the respective values were 315 and 72, indicating the stroke incidence to be 4.4 times higher than that of acute myocardial infarction. The incidence ratio for men to women was 1.7:1 for stroke and 2.9:1 for acute myocardial infarction. Among stroke cases, 51.3% were diagnosed as cerebral infarction, 35.7% as cerebral hemorrhage, 7.7% as subarachnoid hemorrhage and 5.3% as others. Computed tomography of the head was performed in 98.4% of all stroke cases. The case ascertainment, evaluated by comparing the registered cases and death certificates in a certain city, was almost complete. The incidence of acute myocardial infarction is still much lower than that of stroke in Japan. (Hypertens Res 1992; 15:111-119)

The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2009)

Correction to: Hypertension Research (2009) 32, 11–23; doi:10.1038/hr.2008.2 A machine number specified in the JSH Guidelines (Chapter 2, page 15) was incorrect. On page 15, in the paragraph referring to the measurement of central blood pressure and augmentation index (AI) from radial artery pulse waves, the device ‘Omron Healthcare HEM7000AI’ was stated as being used.

A number of major clinical trials have demonstrated the clinical benefits of lowering blood pressure and have indicated that a majority of patients with hypertension will require more than one drug to achieve optimal blood pressure control. However, there is little data showing which antihypertensive combination best protects patients from cardiovascular events and which best achieves the target blood pressure with the fewest adverse events. The Combination Therapy of Hypertension to Prevent Cardiovascular Events (COPE) trial is the first large-scale investigator-initiated multicenter study with a prospective, randomized, open, blinded endpoint evaluation (PROBE) design to directly compare cardiovascular mortality and morbidity, incidence of adverse drug reaction, and degree of blood pressure reduction in Japanese hypertensive patients for a combination of angiotensin receptor blockers, β-blockers or thiazide diuretics in addition to a calcium antagonist, benidipine hydrochloride, with a response-dependent dose titration scheme.

Response to : The Contribution of Nutrition to the Protective Value of High Plasma Aldosterone Concentrations in Hemodialysis Patients