Kei Tsumura

Serum uric acid and the risk for hypertension and Type 2 diabetes in Japanese men: The Osaka Health Survey

Objective To investigate the association of serum uric acid level with the risk for hypertension and Type 2 diabetes. Design Prospective cohort study. Setting Work site in Osaka, Japan. Participants A total of 6356 Japanese men, aged 35–60 years with systolic blood pressure < 140 mmHg and diastolic blood pressure < 90 mmHg, normal glucose intolerance, and no history of hypertension or diabetes at baseline. Main outcome measures Blood pressure was measured by standard techniques, using 160/95 mmHg for diagnosis of hypertension. Type 2 diabetes was defined as a fasting plasma glucose level ⩾ 126 mg/dl or a 2 h post–loaded plasma glucose level ⩾ 200 mg/dl. Results During the 61 716 person–years follow-up period, we confirmed 639 cases of hypertension and 454 cases of Type 2 diabetes. Serum uric acid level was associated with an increased risk for hypertension but not for Type 2 diabetes. After adjustment for known risk factors, including daily alcohol consumption, the serum uric acid level was associated with an increased risk for hypertension; the relative risks for hypertension were 1.00 for quintile 1 of the serum uric acid level, 1.24 [95% confidence interval (CI), 0.94–1.65] for quintile 2, 1.34 (CI, 1.03–1.76) for quintile 3, 1.76 (CI, 1.35–2.29) for quintile 4, and 2.01 (CI, 1.56–2.60) for quintile 5 (P for trend < 0.001). Even among both non-drinkers and lean subjects, serum uric acid level was associated with an increased risk for hypertension. Conclusions Serum uric acid level was associated with an increased risk for hypertension but not for Type 2 diabetes.

Walking to work and the risk for hypertension in men : The Osaka Health Survey

There is good evidence that physical activity reduces the risk for cardiovascular disease (1-6), possibly in part by lowering blood pressure (7). Although mild or moderate physical activity, such as brisk walking, is a recommended part of the treatment protocol for persons with hypertension (8, 9), it is not known whether mild physical activity, especially walking, reduces the risk for hypertension. With few exceptions, epidemiologic studies of physical activity and hypertension have been cross-sectional rather than prospective. Physical activity was inversely related to blood pressure in cross-sectional and controlled studies (7), and in two prospective studies (10, 11), vigorous exercise was inversely related to the subsequent risk for hypertension. Physicians in Japan usually advise their patients to walk to work as often as they can, and indeed, for middle-aged working Japanese men, the journey to and from work seems to be the main source of exercise. We prospectively examined the relation of mild physical activity, especially walking to work, and leisure-time physical activity to the risk for hypertension during 6 to 16 years of observation. Methods The Osaka Health Survey The Osaka Health Survey is an ongoing cohort study of risk factors for chronic diseases, including hypertension and diabetes. Study participants are male employees of a gas company in Osaka, Japan. Japanese law requires all employers to conduct annual health screenings for all employees. For the purposes of the Osaka Health Survey, in addition to these annual screenings, all employees 35 years of age or older undergo more detailed biennial clinical examinations and complete questionnaires on health-related behaviors, including exercise. Study Sample Between 1981 and 1990, 7979 Japanese men 35 to 63 years of age at entry who had sedentary occupations were enrolled in the study. We excluded 1875 men because they had physician-diagnosed hypertension, borderline hypertension (systolic blood pressure 140 and<160 mm Hg, diastolic blood pressure 90 and<95 mm Hg, or both in men without a history of hypertension), diabetes, or impaired glucose tolerance (fasting plasma glucose level 6.1 mmol/L [ 110 mg/dL] and<7.8 mmol/L [<140 mg/dL] in men with no history of diabetes) at entry. The study sample ultimately consisted of 6104 men. Data Collection and Measurements The biennial clinical examination consisted of a medical history; a physical examination; blood pressure measurement; anthropometric measurements; measurement of the fasting plasma glucose level; and surveys of health-related behaviors, such as physical activity, smoking, and daily alcohol consumption. Trained nurses took all measurements. Participants were asked to fast for 12 hours and to avoid smoking and heavy physical activity for more than 2 hours before the examination. After a 5-minute rest in a quiet room, a standard mercury sphygmomanometer was used to measure systolic and diastolic blood pressures in the right arm while the participant was seated. Pressure was measured twice, at an interval of a few minutes. Anthropometric measurements included height and body weight, which were measured while the participant was wearing light clothing without shoes. Body mass index was calculated as the weight in kilograms divided by the height in meters squared. The questionnaire completed by each participant elicited information on leisure-time physical activity, the duration of the walk to work, the nature of the participants occupation, and the level of activity involved. Leisure-time physical activity was defined as physical activity unrelated to the participants work. Questions about leisure-time physical activity were as follows: Do you engage in any regular physical exercise, such as jogging, bicycling, swimming, and tennis, long enough to work up a sweat (lasting 30 minutes or more)? If yes, how many times per week? What exercise is this? The questions about regular physical exercise have been validated as a measure of physical exercise (12-15). In the analysis, participants were classified as engaging in regular physical exercise at least once per week or less than once per week. They were also classified into one of three categories of exercise frequency: 0 (less than once per week), once per week, or two or more times per week. The question about the duration of the walk to work was How long does it take you to walk to this office? Occupational activity was scored as 1 if the participants work was mostly sedentary and 2 if he worked outside or if the job required a lot of lifting and walking. In the present study, we excluded all participants who reported a score of 2 for their occupational activities. Questions about alcohol intake included items about the type of alcoholic beverage, the weekly frequency of alcohol consumption, and the usual amount consumed daily. Alcohol intake was converted to total alcohol consumption (in milliliters of ethanol per day) by using standard Japanese tables. Current and past smoking habits were classified according to the type and quantity of cigarettes smoked daily. Participants were classified as current smokers, past smokers, or nonsmokers. Hypertension was also diagnosed during the biennial study clinical examinations. All participants underwent medical screening by a physician at least once annually, and hypertension was also diagnosed by the physicians. Hypertension was defined by using World Health Organization criteria as physician-diagnosed hypertension (systolic blood pressure 160 mm Hg, diastolic blood pressure 95 mm Hg, or both) or use of antihypertensive medication (16). Statistical Analysis Age-adjusted mean values and relevant population characteristics were computed for the duration of the walk to work by using analysis of covariance for continuous variables and the direct method for categorical variables. For each participant, person-years of follow-up were counted from the date at study entry to the date of diagnosis of hypertension or 1 April 1997, whichever came first. The rate of follow-up was 94% of the total potential person-years of follow-up. Multivariate Cox proportional-hazards regression models were used to evaluate the simultaneous effects of the duration of the walk to work, the frequency of leisure-time physical activity, age, body mass index, daily alcohol consumption, smoking status, and fasting plasma glucose level. Baseline systolic and diastolic blood pressure were not included in our primary analyses because they could presumably be in the causal pathway between the exposures (such as physical activity, age, body mass index, and alcohol consumption) and risk for hypertension. However, we included systolic and diastolic blood pressure in further models to assess the effect of physical activity on the risk for hypertension independent of their effects on systolic and diastolic blood pressure. The linear trends in risks were evaluated by entering indicators for each categorical level of exposure or by using the median value for each category. As a reference category, we used men with the lowest level of physical activity. To address the potential misclassification of leisure-time physical activity over time, additional analyses were performed on the basis of the data at both study entry (1981 to 1990) and the examination done 4 years after (1985 to 1994) each participant was enrolled. We also performed analyses that excluded participants who developed hypertension between study entry (1981 to 1990) and the third examination done 4 years later (1985 to 1994). We calculated the 95% CI for each relative risk (17), and all P values are two-tailed. Statistical analyses were performed by using the SPSS 7.5J software package (SPSS, Inc., Chicago, Illinois). We estimated the number needed to walk, a value analogous to the number needed to treat. The number needed to treat for a given therapy is the reciprocal of the absolute risk reduction for that treatment (18). A 95% CI for the number needed to treat is obtained simply by taking reciprocals of the values defining the 95% CI of the absolute risk reduction (19). In our study, the number needed to walk was defined as the number of men who would have to adopt walking to avoid a single case of hypertension. The number needed to treat must always be based on an outcome for a specific period of time (20); thus, in estimating the number needed to walk, we chose an observation period of 10 years between study entry (1981 to 1986) and the examination done 10 years after (1991 to 1996) each participant was enrolled. Role of the Funding Source The funding agencies did not participate in the collection, analysis, or interpretation of data presented in this report or in the decision to submit the manuscript for publication. Results Of the 6104 men eligible for this study between 1981 and 1990, we excluded 87 men who did not undergo medical check-ups during the follow-up period. The study sample for analysis consisted of 6017 men. During the 59 784 person-years of follow-up between 1981 and 1997, 626 men developed hypertension. As the duration of the walk to work increased, body weight and the body mass index decreased (P for trend=0.037 and 0.035, respectively) (Table 1). We identified no significant relation between the duration of the walk to work and the levels of leisure-time physical activity (P for trend=0.062). Table 1. Baseline Characteristics according to Duration of the Walk to Work Duration of the Walk to Work The duration of the walk to work was associated with a decreased risk for incident hypertension (Table 2). After adjustment for age, body mass index, daily alcohol consumption, smoking status, frequency of leisure-time physical activity, systolic blood pressure, diastolic blood pressure, and fasting plasma glucose level, the relative risk for hypertension was 0.71 (95% CI, 0.52 to 0.97) in men whose walk to work lasted 21 minutes or more compared with those whose

Pulsatility of Ascending Aortic Pressure Waveform Is a Powerful Predictor of Restenosis After Percutaneous Transluminal Coronary Angioplasty

BACKGROUND Because ascending aortic pressure has a greater effect on coronary perfusion during diastole than systole, we hypothesized that a high coronary diastolic-to-systolic pressure ratio prevents coronary lesions from restenosing after percutaneous transluminal coronary angioplasty (PTCA) and that ascending aortic pulsatility relative to mean pressure is higher in patients with restenosis than in those without restenosis. The purpose of this study was to evaluate prospectively whether the morphology of the ascending aortic pressure wave can be used to predict restenosis after PTCA. METHODS AND RESULTS We measured the coronary artery diameter and the aortic pressure before PTCA. To quantify the relative magnitude of the pulsatile-to-mean aortic pressure, we normalized the pulse pressure to mean pressure and referred to this value as the fractional pulse pressure (PPf). We prospectively investigated the effect of PPf in relation to subsequent risk of restenosis after PTCA in patients with coronary artery disease. PPf was a powerful predictor of restenosis. Crude cumulative incidence rates of restenosis were 17.6% for the lowest, 33.3% for the middle, and 77. 8% for the highest tertile of PPf levels. After adjustments for age, smoking habits, systolic blood pressure, type 2 diabetes, hypercholesterolemia, old myocardial infarction, vessel location, vessel size, and sex, the odds ratio of restenosis was 33.5 (95% confidence interval, 2.04 to 550.6) for the highest tertile of the PPf level compared with the lowest tertile level. CONCLUSIONS Pulsatility of the ascending aortic pressure is a predictive factor for restenosis after PTCA.

Reflection in the arterial system and the risk of coronary heart disease.

BACKGROUND Although it was reported that the augmentation index and inflection time are closely related to reflection in the arterial system and large artery function, it is not known whether these indices of the ascending aortic pressure waveform increase the risk of coronary heart disease (CHD). The purpose of this study was to evaluate whether the aortic reflection of the ascending aortic pressure waveform is related to an increased risk of CHD. METHODS We enrolled 190 men and women who had chest pain, normal contractions, no local asynergy, and no history of myocardial infarction. We measured the ascending aortic pressure using a fluid-filled system. The inflection time was defined as the time interval from initiation of a systolic pressure waveform to the inflection point. We investigated the association between the inflection time and augmentation index of the ascending aorta and the risk of CHD. RESULTS Both the inflection time and augmentation index were associated with an increased risk of CHD. The crude prevalence rates of CHD were 66.0% for the shortest quartile and 10.6% for the longest quartile of the inflection time, and 17.0% for the lowest quartile and 40.4% for the highest quartile of the augmentation index. The multiple-adjusted odds ratio of CHD was 30.8 (95% confidence interval [CI] 7.43-128.05) for the shortest quartile of the inflection time compared with the longest quartile and was 3.82 (95% CI 1.26-11.59) for the highest quartile of the augmentation index compared with the lowest quartile. CONCLUSIONS The augmentation index and inflection time were associated with an increased risk of CHD.

Impact of cigarette smoking on the incidence of Type 2 diabetes mellitus in middle-aged Japanese men: the Osaka Health Survey

Aims To assess the impact of cigarette smoking on the incidence of Type 2 diabetes mellitus (DM) in middle‐aged Japanese men.

Leisure‐time physical activity at weekends and the risk of Type 2 diabetes mellitus in Japanese men: the Osaka Health Survey

Aims To investigate association between leisure‐time physical activity at weekends and the risk of developing Type 2 diabetes mellitus (DM).

Pulsatility of ascending aortic blood pressure waveform is associated with an increased risk of coronary heart disease

BACKGROUND Although it was reported that pulse pressure of the peripheral artery could differentiate patients with coronary heart disease (CHD) from those without CHD, it is not known whether pulsatility of the ascending aortic pressure waveform differentiates patients with CHD from those without CHD. The purpose of this study was to evaluate whether the pulsatility of ascending aortic pressure is associated with an increased risk of CHD. METHODS For this study, we enrolled 293 subjects who had chest pain, normal contractions, no local asynergy, and no history of myocardial infarction. We measured the ascending aortic pressure using a fluid-filled system. To quantify the relative magnitude of the pulsatile to mean artery pressure, we normalized the pulse pressure to the mean pressure and referred to this value as the fractional pulse pressure (PPf). We investigated the association between the PPf and the risk of CHD. RESULTS The PPf of the ascending aorta was associated with an increased risk of CHD. The multiple-adjusted odds ratio of CHD was 2.93 (95% CI, 1.44 to 5.94) for the middle tertile of the PPf level and was 3.93 (95% CI, 1.74 to 8.85) for the highest tertile compared with the lowest tertile. CONCLUSION Ascending aortic pulsatility is related to an increased risk of CHD.

Blood pressure response after two-step exercise as a powerful predictor of hypertension: the Osaka Health Survey.

Objective To investigate the relationship between blood pressure at 4 min after exercise using a Masters two-step and the risk for hypertension. Design Prospective cohort study. Setting Work site in Osaka, Japan. Participants A total of 6557 Japanese men, aged 35–63 years with systolic blood pressure (SBP) < 140 mmHg and diastolic blood pressure (DBP) < 90 mmHg, and no history of hypertension or diabetes at baseline. Main outcome measures Blood pressure was measured by standard techniques, using 160/95 mmHg for diagnosis of hypertension. Normotension was defined as no history of hypertension, and SBP < 130 mmHg and DBP < 85 mmHg. High normal blood pressure was defined as no history of hypertension and SBP ⩾ 130 and < 140 mmHg or DBP ⩾ 85 and < 90 mmHg. Results During the 63 696 person-years follow-up period, we confirmed 660 cases of hypertension. SBP and DBP after exercise were associated with an increased risk for developing hypertension. The multiple-adjusted relative risk for SBP and DBP after exercise were 1.55 per 10 mmHg (confidence interval, 1.42–1.69) and 1.55 per 10 mmHg (confidence interval, 1.42–1.69), respectively. These associations were independent of resting SBP and DBP. Even after stratifying subjects according to blood pressure at rest, SBP or DBP at 4 min after exercise was associated with an increased risk for hypertension in subjects with normotension or high normal blood pressure at rest. Conclusions The blood pressure response after exercise with a two-step was associated with an increased risk for hypertension, independently of resting blood pressures.

QT dispersion as a predictor of acute heart failure after high-dose cyclophosphamide.

No useful predictor of risk of acute heart failure in peripheral-blood stem-cell transplantation (PBSCT) regimens, Including high-dose cyclophosphamide, has previously been available. Corrected QT dispersion can predict acute heart failure after high-dose cyclophosphamide chemotherapy used in PBSCT.

An Adult Case of Fanconi Syndrome Due to a Mixture of Chinese Crude Drugs

We examined a 35-year-old male case of acquired Fanconi syndrome induced by a mixture of Chinese crude drugs. Renal glycosuria, hypokalemia, hypophosphatemia, metabolic acidosis, a low threshold of tubular bicarbonate excretion, and generalized aminoaciduria were observed after the patient had taken the drugs for 6 months. When he stopped taking them, all laboratory data improved. He took the drugs again on his own judgment, leading to a second bout of Fanconi syndrome. This is the first case in which Chinese crude drugs have been known to cause acquired Fanconi syndrome.