Abstract: Although various environmental factors, such as a high-salt diet, a smoking habit, excessive alcohol intake, and physical inactivity, influence the development of hypertension, genetic variation also contributes to an individual's susceptibility to this condition. The purpose of the present study was to identify gene polymorphisms that confer susceptibility or resistance to hypertension, and thereby contribute to the prediction of the genetic risk for this condition. The study population comprised 2752 unrelated Japanese individuals (1370 men, 1382 women), including 1276 subjects with hypertension (774 men, 502 women) and 1476 controls (596 men, 880 women). The genotypes for 50 polymorphisms of 35 candidate genes were determined by a method that combines polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Evaluation of genotype distributions by the Chi-square test and subsequent multivariable logistic regression analysis with adjustment for age, sex, body mass index, smoking status, and the prevalence of diabetes mellitus and hypercholesterolemia revealed that the -14C-->T polymorphism of ABCA1, the C-->G (Ser2229Cys) polymorphism of ROS1, the C-->T (Asn591Asn) polymorphism of LDLR, the 13989A-->G (Ile118Val) polymorphism of CYP3A4, the C-->G and A-->C polymorphisms of ADIPOR1, and the -519A-->G polymorphism of MMP1 were significantly (P<0.05) associated with the prevalence of hypertension. Systolic and diastolic blood pressure differed significantly among genotypes for the -14C-->T polymorphism of ABCA1 and the C-->G (Ser2229Cys) polymorphism of ROS1, with the variant T and G alleles, respectively, being related to increased blood pressure. These results suggest that polymorphisms of ABCA1 and ROS1 are determinants of blood pressure and the development of hypertension in Japanese individuals. Determination of genotypes for ABCA1 and ROS1 may thus prove informative for the prediction of the genetic risk for hypertension.

Abstract: BACKGROUND: Although several environmental factors influence the development of myocardial infarction (MI), genetic factors have been shown to contribute to individual susceptibility to this condition. OBJECTIVE: To identify gene polymorphisms that confer susceptibility to MI in order to allow assessment of genetic risk for this condition. METHODS: 3433 unrelated Japanese people (1931 men, 1502 women) were entered into the study. These comprised 1328 subjects with MI (1036 men, 292 women) and 2105 controls (895 men, 1210 women). The genotypes for 40 polymorphisms of 31 candidate genes were determined with a method that combines PCR and sequence-specific oligonucleotide probes with suspension array technology. RESULTS: The chi(2) test revealed that six polymorphisms were significantly (false discovery rate <0.05) related to the prevalence of MI. Further examination by multivariable logistic regression analysis with adjustment for age, sex, body mass index and the prevalence of hypertension, diabetes mellitus and hypercholesterolaemia, in addition to a stepwise forward selection procedure found that the A-->C (Gln1334His) polymorphism (rs3742207) of the collagen type IV alpha-1 gene (COL4A1) and the A-->G polymorphism (rs4804611) of the zinc finger protein 627 gene (ZNF627) were significantly (p<0.05) associated with the prevalence of MI. The variant C allele of COL4A1 was protective against MI, whereas the variant G allele of ZNF627 represented a risk factor for this condition. CONCLUSIONS: Determination of genotypes for COL4A1 and ZNF627 may prove informative for assessment of the genetic risk for MI.

Abstract: BACKGROUND: We determined associations between habitual physical activity and metabolic syndrome in elderly persons. METHODS: Pedometer/accelerometers measured step count and activity intensity on a 24-hour basis in 220 free-living Japanese persons 65-84 years old throughout an entire year. At year end, participants were screened for metabolic syndrome (modified criteria of National Cholesterol Education Program Adult Treatment Panel III [NCEP-ATP III]). RESULTS: Most individuals 65-74 years old who took > 10,000 steps/d and/or spent > 30 min/d of activity > 3 metabolic equivalents (METs) had < or = 2 metabolic syndrome diagnostic markers, as did those 75-84 years old with > 8000 steps/d and/or > 20 min/d at > 3 METs. Multivariate-adjusted logistic regression analyses showed that the risk of metabolic syndrome was 4.3 (1.6-11.7) and 3.3 (1.3-8.8) times greater in the least active quartiles of participants (taking < 4700 steps/d and spending < 9 min/d at > 3 METs, respectively) relative to the most active quartiles (taking > 8500 steps/d and spending > 24 min/d at > 3 METs, respectively). CONCLUSIONS: The metabolic syndrome is less likely in elderly people taking > 8000-10,000 steps/d, and reaching an intensity > 3 METs for > 20-30 min/d, relative to their sedentary peers.

Abstract: The interactions of sex, age, season, and habitual physical activity were examined in 41 male and 54 female Japanese age 65-83 yr, using a pedometer/accelerometer that determined step counts and amounts of physical activity (<3 and >3 metabolic equivalents [METs]) throughout each 24-hr period for an entire year. All 3 measures were greater in men than in women. In women, age was negatively correlated with step count and activity <3 METs, but in men, it was correlated with step count and activity >3 METs. Irrespective of sex or age, all 3 activity variables were low in the winter, peaking in spring or autumn. In the summer, step counts matched the annual average, but durations of activity <3 and >3 METs were, respectively, longer and shorter than in other seasons. These findings have practical implications for those promoting physical activity for older adults.

Abstract: The purpose of this study was to investigate whether a 48-week multicomponent exercise program could improve the risk factors for fall and hip fracture. Fifty elderly women 65-70 years of age participated. These participants were divided into an exercise group (25 subjects) that attended an exercise program and a control group (25 subjects) that did not. The exercise program included stretching for 9 min, strength training for 10 min followed by 23 min of weight-bearing exercise at an intensity above 65%-75% of the maximal heart rate, and 18 min of balance and posture correction training. The program was conducted three times per week for 48 weeks. The 10-m maximal walk time, maximal step length, and eyes-open-one-legged-stand time in the exercise group improved significantly (P < 0.05). Concerning deoxypyridinoline, the exercise group achieved a significant improvement (P < 0.05) after the 48 weeks. Bone mineral density (BMD) of the femoral neck and trochanter in the exercise group was significantly increased after the exercise program; also body sway was significantly improved (P < 0.05). In conclusion, a multi-component exercise program with weight-bearing exercise at a moderate intensity and gait training may be effective in offsetting a decline in BMD and improving aggravation of bone resorption in this population. In addition, this program has a positive effect on postural stability and gait ability.

Abstract: The aim of the present study was to identify gene polymorphisms that confer susceptibility to obesity. A total of 5448 unrelated Japanese individuals from two independent populations were examined: subject panel A comprised 4252 individuals who visited participating hospitals; subject panel B comprised 1196 community-dwelling elderly individuals. The genotypes for 95 polymorphisms of 67 candidate genes were determined. The chi(2) test revealed that six polymorphisms were related (p<0.05) to the prevalence of obesity in subject panel A; after application of Bonferroni's correction, however, only the 2677G --> A/T polymorphism (rs2032582) of the ATP-binding cassette, subfamily B, member 1 gene (ABCB1) was significantly associated (p=0.0003) with obesity. Subsequent multivariable logistic regression analysis also revealed that the 2677G --> A/T polymorphism of ABCB1 was significantly associated with obesity. For validation of this association, the 2677G --> A/T polymorphism of ABCB1 was examined in subject panel B and again found to be significantly associated with obesity. Body mass index was significantly (p=0.01) greater for individuals with the variant T allele of this polymorphism than for those with the GG genotype in the combined subject panels A and B. Our results suggest that the ABCB1 genotype may prove informative for assessment of genetic risk for obesity in Japanese individuals.

Abstract: BACKGROUND AND PURPOSE: Although genetic epidemiologic studies have implicated several genetic variants as risk factors for ischemic or hemorrhagic stroke, the genetic determinants of these conditions remain largely unknown. We performed an association study to identify gene polymorphisms that confer susceptibility to atherothrombotic cerebral infarction, intracerebral hemorrhage, or subarachnoid hemorrhage. METHODS: The study population comprised 3432 unrelated Japanese individuals: 1362 stroke patients (822 with atherothrombotic cerebral infarction, 333 with intracerebral hemorrhage, and 207 with subarachnoid hemorrhage) and 2070 controls. The genotypes for 50 polymorphisms of 38 candidate genes were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. RESULTS: An initial chi(2) test (false discovery rate <0.05) and subsequent multivariable logistic-regression analysis with adjustment for conventional risk factors (P<0.05) revealed that the -14C-->T polymorphism (rs1800977) of ABCA1, the A-->C (rs3027898) and C-->T (Ser532Leu, rs1059703) polymorphisms of IRAK1, and the G-->C (Cys2229Ser) polymorphism (rs619203) of ROS1 were significantly associated with atherothrombotic cerebral infarction; that the -428G-->A polymorphism (rs710968) of LIMK1 was significantly associated with intracerebral hemorrhage; and that the 13989A-->G (Ile118Val) polymorphism (NC_000007.12) of CYP3A4 was significantly associated with subarachnoid hemorrhage. CONCLUSIONS: Genotypes for ABCA1, IRAK1, and ROS1 may prove useful for assessment of the genetic risk for atherothrombotic cerebral infarction, whereas those for LIMK1 and CYP3A4 may be similarly beneficial in assessment of the genetic risk for intracerebral hemorrhage and subarachnoid hemorrhage, respectively. Validation of these findings will require additional studies with independent subject panels.

Abstract: Metabolic syndrome is a risk factor for cardiovascular disease. The aim of the present study was to identify genetic variants that confer susceptibility to atherothrombotic cerebral infarction among individuals with metabolic syndrome in order to allow prediction of genetic risk for this condition. The study population comprised 1284 unrelated Japanese individuals with metabolic syndrome, including 313 subjects with atherothrombotic cerebral infarction and 971 controls. The genotypes for 296 polymorphisms of 202 candidate genes were determined with a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. The Chi-square test, multivariable logistic regression analysis with adjustment for age, sex, body mass index, and the prevalence of hypertension, hypercholesterolemia, and diabetes mellitus, as well as a stepwise forward selection procedure revealed that the 2445G-->A (Ala54Thr) polymorphism (rs1799883) of FABP2, the -108/3G-->4G polymorphism of IPF1 (S82168), the A-->G (Thr94Ala) polymorphism (rs2241883) of FABP1, the G-->A (Asp2213Asn) polymorphism (rs529038) of ROS1, the -11377C-->G polymorphism (rs266729) of ADIPOQ, the 162A-->C polymorphism (rs4769055) of ALOX5AP, the -786T-->C polymorphism (rs2070744) of NOS3, and the 3279C-->T polymorphism (rs7291467) of LGALS2 were associated (P<0.05) with the prevalence of atherothrombotic cerebral infarction. Among these polymorphisms, the 2445G-->A (Ala54Thr) polymorphism of FABP2 was most significantly associated with this condition. Our results suggest that FABP2, IPF1, FABP1, ROS1, ADIPOQ, ALOX5AP, NOS3, and LGALS2 are susceptibility loci for atherothrombotic cerebral infarction among Japanese individuals with metabolic syndrome. Genotypes for these polymorphisms, especially for the 2445G-->A (Ala54Thr) polymorphism of FABP2, may prove informative for the prediction of genetic risk for atherothrombotic cerebral infarction among such individuals.

Abstract: PURPOSE: Daily variations of physical activity in the elderly remain unclear. We thus used a uniaxial accelerometer/pedometer to examine the variability of step counts for 1 yr, determining the minimum number of days observation needed to obtain reliable estimates of annual physical activity. METHODS: Subjects were 37 males and 44 females, healthy Japanese, aged 65-83 yr. The pedometer was worn on the waistband throughout 1 yr, accumulating information on the individual's daily step count. RESULTS: The step count spectrum showed peaks with periods of 2.3, 3.5, and 7.0 d and an aperiodic component that had a greater power at low frequencies (i.e., non-white noise). These characteristics were absent in randomly resequenced data. To ensure that 80% of total variance was attributable to between-subjects variance, 25 and 8 consecutive days of observation were needed in male and female subjects, respectively. To achieve 90% on this same measure of reliability, 105 and 37 consecutive days of observation were required. In contrast, 4 d of randomly timed observations yielded 80% reliability for both men and women, and 11 and 9 d gave 90% reliability in men and women, respectively. If sampling also took account of season and day of the week, the respective observation periods for men and women were reduced to 8 and 4 d (i.e., 2 and 1 consecutive days of sampling every 89 d) for 80% and to 16 and 12 d (i.e., 4 and 3 consecutive days every 89 d) for 90% reliability. CONCLUSION: When estimating annual step counts, seasonal and/or random sampling of data allows collection of reliable data during substantially fewer days than needed for consecutive observations.

Abstract: The Physical Activity Questionnaire for Elderly Japanese (PAQ-EJ) is a self-administered physical activity questionnaire for elderly Japanese; the authors report here on its repeatability and direct and indirect validity. Reliability was assessed by repeat administration after 1 month. Direct validation was based on accelerometer data collected every 4 s for 1 month in 147 individuals age 65-85 years. Indirect validation against a 10-item Barthel index (activities of daily living [ADL]) was completed in 3,084 individuals age 65-99 years. The test-retest coefficient was high (r = .64-.71). Total and subtotal scores for lower (transportation, housework, and labor) and higher intensity activities (exercise/sports) were significantly correlated with step counts and durations of physical activity <3 and >or=3 METs (r = .41, .28, .53), respectively. Controlling for age and ADL, scores for transportation, exercise/sports, and labor were greater in men, but women performed more housework. Sex- and ADL- or age-adjusted PAQ-EJ scores were significantly lower in older and dependent people. PAQ-EJ repeatability and validity seem comparable to those of instruments used in Western epidemiological studies.

Abstract: INTRODUCTION: We determined associations between bone health and the quantity and quality of habitual physical activity in a cohort of 172 free-living Japanese aged 65-83 years (76 men, 96 women). METHODS: The number of steps taken and the intensity of physical activity were measured every 4 s throughout each 24-h period for 1 year, using a specially adapted accelerometer that distinguished up to 11 levels of physical activity (expressed in metabolic equivalents, METs). At the end of the year, a quantitative ultrasonic technique assessed each participant's osteosonic index (OSI, reflecting bone stiffness in the calcaneus). RESULTS: The data were significantly described by linear and exponential regression models which showed that in both sexes the OSI score increased with increasing daily physical activity, up to the observed maximum values of approximately 14,000 steps/day and 50 min/day at an intensity >3 METs. However, when data were categorized into quartiles of physical activity, OSI scores were not significantly greater in persons exceeding recommended minimum standards of habitual physical activity (corresponding to counts of around 6,900 and 6,800 steps/day and durations >3 METs of around 18 and 16 min/day in men and women, respectively). All who met such criteria (with the exception of a few women) had OSI scores above the threshold for a clinical diagnosis of osteoporosis. Multivariate-adjusted logistic regression analyses predicted that men and especially women who engaged in <6,800 steps/day and <16 min/day of moderate-intensity physical activity were, respectively, 4.9-8.4 and 2.2-3.5 times more likely to sustain fractures than those participating in >8,200 steps/day and >25 min/day of activity >3 METs. CONCLUSION: Causation cannot be inferred from a cross-sectional study. Nevertheless, we suggest that from the viewpoint of bone health, elderly people should be encouraged to engage in low- and moderate-intensity habitual physical activity, taking >7,000 steps/day with a duration >15 min/day at >3 METs.

Abstract: The purpose of the present study was to identify genetic variants that confer susceptibility to dyslipidemia. A total of 5213 individuals from two independent populations were examined: Subject panel A comprised 3794 individuals who visited participating hospitals; subject panel B comprised 1419 community-dwelling elderly individuals. The genotypes for 100 polymorphisms of 65 candidate genes were determined. The chi(2) test and multivariable logistic regression analysis revealed that seven polymorphisms of APOA5, APOC3, APOA1, ACAT2, and LPL were significantly associated with hypertriglyceridemia, six polymorphisms of APOA5, LIPC, and CYP3A4 with low HDL-cholesterol, and three polymorphisms of APOE and CCR2 with high LDL-cholesterol in subject panel A. For validation of these associations, the same polymorphisms were examined in subject panel B. Six polymorphisms of APOA5, APOC3, APOA1, and LPL were again significantly associated with hypertriglyceridemia, three polymorphisms of APOA5 with low HDL-cholesterol, and two polymorphisms of APOE with high LDL-cholesterol. Serum triglyceride, HDL-cholesterol, and LDL-cholesterol concentrations differed significantly among genotypes of these corresponding polymorphisms in both subject panels. These results indicate that polymorphisms of APOA5, APOC3, APOA1, and LPL are determinants of hypertriglyceridemia and that those of APOA5 and APOE are determinants of low HDL-cholesterol and high LDL-cholesterol, respectively, in Japanese individuals.

Abstract: OBJECTIVE: The objective of this study was to investigate associations between accelerometer measurements of physical activity and psychosocial variables in older people. METHODS: Subjects were 184 Japanese aged 65-85 years. An accelerometer provided step count and physical activity intensity data throughout each 24-hour period for 1 year. At the end of the year, anxiety, depression, and cognitive function were assessed. RESULTS: Controlling for age, the daily number of steps, and the daily duration of moderate-intensity physical activity showed significant negative correlations with depressive mood. CONCLUSION: A depressive mood is associated with the quantity and quality of habitual physical activity.

Abstract: We hypothesized that the health-related quality of life (HRQOL) would be poorer in physically inactive older adults. This was tested in a sample of 73 male and 108 female free-living healthy Japanese participants, age 65-85 years. We measured accelerometer step counts and their metabolic equivalents (METs) throughout each 24-hr period for 1 year. At the end of the year, HRQOL was assessed. Physical activity was grouped into quartiles. HRQOL was poorer in the lowest quartiles of participants with respect to both step count and duration of activity >3 METs; however, our sample showed no better HRQOL in those participants exceeding minimum standards of daily physical activity, corresponding to counts of around 5,500 and 4,500 steps/day and durations of around 13 and 14 min/day in men and women, respectively. Causation cannot be demonstrated from this cross-sectional study, but nevertheless we suggest that elderly individuals should be encouraged to meet such standards of habitual physical activity.

Abstract: In Japan, the "bedridden state" is one of the most serious problems the aged face, and it is becoming a social problem. The main causes of the bedridden state are cerebrovascular disorders and bone fractures following falls. The purpose of this study was to predict risk factors for falls and resultant bone fracture due to osteoporosis. We explored mobility parameters for possible fall prevention. In order to examine the correlation between the risk of falling and resultant bone fracture due to osteoporosis, logistic regression analysis was performed between bone mass (independent variable) and various factors dependent variables: body mass index [BMI], body fat percentage, atherogenic index, presence of transformation-related osteoarthritis of knee, presence of transformation-related osteoarthritis of spine, maximum step length, single-leg stance with open eyes, and hip-joint flexion motion angle); predictive factors were then examined. Predictive factors were determined by the stepwise method. Subjects who could not perform the "single-leg stance with open eyes" test had a risk of falling and bone fracture 2.49 times as large as that of subjects who could. The "single-leg stance with open eyes" test may be considered a useful method for the early detection of the risk of falling and bone fracture associated with osteoporosis. As a first step to identify factors predicting the occurrence of falls and bone fractures due to osteoporosis, we intended to discover an indicator that would help to detect incipient osteoporosis.

Abstract: Seasonal changes in ambient temperature and day length are thought to modify habitual physical activity. However, relationships between such environmental factors and the daily physical activity of older populations remain unclear. The present study thus examined associations between meteorological variables and the number of steps taken per day by elderly Japanese. Continuous pedometer counts over a 450-day period were collected from 41 healthy subjects (age 71+/-4 years), none of whom engaged in any specific occupational activity or exercise programs. An electronic physical activity monitor was attached to a belt worn on the left side of the body throughout the day. Daily values for mean ambient temperature, duration of bright sunshine, mean wind speed, mean relative humidity, and precipitation were obtained from local meteorological stations. The day length was calculated from times of sunrise and sunset. Based on the entire group of 41 subjects (ensemble average), a subject's step count per day decreased exponentially with increasing precipitation (r2=0.19, P<0.05). On days when precipitation was <1 mm, the step count increased with the mean ambient temperature over the range of -2 to 17 degrees C, but decreased over the range 17-29 degrees C. The daily step count also tended to increase with day length, but the regression coefficient of determination attributable to step count and mean ambient temperature (r2=0.32, P<0.05) exceeded that linking the step count and day length (r2=0.13, P<0.05). The influence of other meteorological factors was small (r2<or=0.03) and of little practical significance. On days when precipitation is <1 mm, physical activity is associated more strongly with ambient temperature than with day length, duration of bright sunshine, wind speed, or relative humidity. Our findings have practical implications for health promotion efforts designed to increase the physical activity of elderly people consistently in the face of seasonal variations in environmental conditions.

Abstract: The purpose of this study was to investigate the effect of combined aerobic and resistance training on abdominal fat. Our participants in the study consisted of thirty obese women. They were separated into three groups: a control group (n=10), an aerobic training group (n=10) and a combined training group (n=10). The aerobic training group was composed of 60-70% HRmax (intensity), 60 minutes a day (duration) for 6 days a week (frequency). The combined training group was separated into resistance training (3 days a week, Mon, Wed, Fri) and the aerobic training (3 days a week, Tue, Thu, Sat). The levels for abdominal fat volume were measured by determining the subcutaneous fat volume (SFV), visceral fat volume (VFV), and VFV/SFV by CT (computed tomography). The VO(2max) was significantly (p<0.05) increased in both groups. The subcutaneous fat and visceral fat levels were decreased in the combined training group more than in the aerobics training group. Also, the lean body mass (LBM) was significantly increased only in the combined training group. In addition, the total cholesterol, triglyceride and LDL-C were significantly (p<.05) decreased and the HDL-C was significantly (p<.05) increased in both groups. In conclusion, our results observed that combined training decreased abdominal subcutaneous fat and visceral fat more than aerobic training only.

Abstract: The purpose of this study was to investigate whether a 36-week complex exercise program helps to improve the risk factors for fall and hip fracture. Participant group for this study was 47 women in the range of age 65-68. The exercise program was conducted three times per week for 36 weeks. This study proved that the complex exercise program with weight bearing exercise at a moderate intensity and the gait training were highly effective in offsetting the decline in BMD, hormone metabolic substrate in elderly women. In addition, this exercise program had a positive effect on their postural stability.