Shigeaki Hinohara

Polymorphism of the C-Reactive Protein (CRP) Gene Is Related to Serum CRP Level and Arterial Pulse Wave Velocity in Healthy Elderly Japanese

The objective of this study was to clarify relationships between the C-reactive protein (CRP) gene and both the serum level of CRP and arterial pulse wave velocity (PWV), using haplotype analysis of healthy elderly Japanese. Five single-nucleotide polymorphisms (SNPs) of the human CRP gene (rs1341665, rs3091244, rs1800947, rs1130864 and rs1205) were used to genotype 315 healthy elderly Japanese subjects (mean age, 77.9±4.1 years; male/female ratio, 0.96). Linkage disequilibrium was analyzed for the five SNPs. The frequency of each haplotype and diplotype was estimated using the expectation/maximization (EM) algorithm. There were statistically significant associations between the CRP level and two CRP genotypes; the p value for the T allele of rs3091244 (CT+AT+TT vs. CC+CA+AA) was 0.002 (95% confidential interval [CI], 2.1–24), and the p value for the T allele of rs1130864 (TT+TC vs. CC) was 0.002 (95% CI, 2.1–24). The only genotype that was significantly associated with arterial PWV was the C allele of rs1800947, with a p value of 0.039. The haplotype was constructed using rs1341665, rs3091244 and rs1800947, in that order. There was a significant association between the CRP level and the T-T-G haplotype, with a p value of 0.002 (95% CI, 2.1–24). There was a significant association between arterial PWV and the C-C-C haplotype, with a p value of 0.039. We concluded that rs3091244, rs1130864 and the T-T-G haplotype are genetic markers for elevated basal CRP levels. rs1800947 and the C-C-C haplotype appear to be susceptibility markers for atherosclerosis, but this requires confirmation.

Assessing Items on the SF-8 Japanese Version for Health-Related Quality of Life: A Psychometric Analysis Based on the Nominal Categories Model of Item Response Theory

OBJECTIVES The Short Form-8 (SF-8) questionnaire is a commonly used 8-item instrument of health-related quality of life (QOL) and provides a health profile of eight subdimensions. Our aim was to examine the psychometric properties of the Japanese version of the SF-8 instrument using methodology based on nominal categories model. METHODS Using data from an adjusted random sample from a nationally representative panel, the nominal categories modeling was applied to SF-8 items to characterize coverage of the latent trait (theta). Probabilities for response choices were described as functions on the latent trait. Information functions were generated based on the estimated item parameters. RESULTS A total of 3344 participants (53%, women; median age, 35 years) provided responses. One factor was retained (eigenvalue, 4.65; variance proportion of 0.58) and used as theta. All item response category characteristic curves satisfied the monotonicity assumption in accurate order with corresponding ordinal responses. Four items (general health, bodily pain, vitality, and mental health) cover most of the spectrum of theta, while the other four items (physical function, role physical [role limitations because of physical health], social functioning, and role emotional [role limitations because of emotional problems] ) cover most of the negative range of theta. Information function for all items combined peaked at -0.7 of theta (information = 18.5) and decreased with increasing theta. CONCLUSION The SF-8 instrument performs well among those with poor QOL across the continuum of the latent trait and thus can recognize more effectively persons with relatively poorer QOL than those with relatively better QOL.

A pilot trial to predict frailty syndrome: The Japanese Health Research Volunteer Study

Most definitions of frailty utilize US populations in their development. The concept of frailty has not been well studied in Japan, which has the largest percentage of older patients (per capita) in the world. We created a 5-year prospective cohort study of community-dwelling older Japanese adults. Participants were not frail at baseline, based on our definition adapted from the Canadian Study for Health and Aging Clinical Frailty Scale. Participants underwent a comprehensive geriatric assessment (CGA) at baseline, and final assessments were either in person or via mailed survey. We enrolled 407 individuals (184 men, mean age 78 ± 4 years; 223 women, mean age 77 ± 4 years). Sixty-five participants met criteria for frailty by the end of the study. In univariate analyses, eighteen separate parameters were associated with frailty, some of which included: age, gender, handgrip, timed walk, systolic blood pressure, pulse pressure, cognitive status, living alone, and hearing deficits. In multivariate analyses, the following elements remained associated with frailty: timed walk, pulse pressure, cognition deficits and hearing deficits. We established cut-off points for timed walk (5m/3s) and pulse pressure (60 mmHg). We then created a simple additive score for these four factors (present = 1; absent = 0). A score of 0 had a 93% negative predictive value for frailty while a score of 4 had a 70% positive predictive value. While further study is needed, this work creates an easy-to-administer tool that may be generalizable to other populations.

Left ventricular geometric patterns and QT dispersion in borderline and mild hypertension: their evolution and regression.

To investigate whether QT dispersion increases in borderline and mild hypertension during a longitudinal observation of > 3 years and whether it is improved with medications, left ventricular geometric patterns and QT dispersion were studied with special regard to their longitudinal changes in 85 male borderline and mild hypertensive subjects with left ventricular mass index < 125 g/m2. These subjects were followed for > 3 years without medication. Thirty-two patients with a left ventricular mass index > 125 g/m2 at the end of follow-up period were further observed using antihypertensive drugs for an additional 3 years. Echocardiograms and electrocardiograms were obtained at the beginning and end of the follow-up period. At the end of the follow-up period, subjects were classified into four groups based on ventricular geometric patterns determined by left ventricular mass index and relative wall thickness in diastole. The QT dispersion was greater in patients with concentric hypertrophy (56+/-18 msec) than in patients with normal geometry (41+/-17 msec) (P < .05) and increased significantly in the former group during the follow-up period. After medication, the left ventricular mass index regressed and the QT dispersion decreased (from 55+/-21 to 50+/-26 msec, P < .01) in these patients. Thus, these findings suggest that changes in the QT dispersion reflect both concentric evolution and regression of left ventricular hypertrophy.

Prospective studies on left ventricular geometric patterns and exercise tolerance in unmedicated men with borderline and mild hypertension

Objective This study was designed and conducted to assess the clinical significance of left ventricular geometric patterns and physical fitness in subjects with untreated borderline and mild hypertension. Methods Symptom-limited maximal treadmill stress testings and echocardiographic examinations were administered to 192 previously unmedicated men. Left ventricular geometric patterns were determined by the combined criteria of left ventricular mass index and relative wall thickness.subject whose left ventricular mass index was <125 g/m2 were followed up for more than 3 years. Results Normalized treadmill time was lower and pressure rate products at peak exercise were higher in patients with concentric hypertrophy than in those with normal geometry. Of the 77 patients who revealed left ventricular mass index at baseline <125 g/m2 and who were successfully followed without medication for more than 3 years, 18 demonstrated concentric hypertrophy at the final follow-up examination. During the follow-up period, these 18 patients had significant further augmentation of concentric geometric features, significant decreases in both cardiac output and normalized treadmill time, and significant increases in casual blood pressure and total peripheral resistance compared with those at baseline. Conclusion Patients with concentric hypertrophy exhibited slightly but significantly impaired levels of physical fitness and cardiac work efficiency, and the progression of concentric hypertrophy demonstrated further impairments of these conditions. Therefore, not only lowering blood pressure, but also improving left ventricular hypertrophy, cardiovascular hemodynamics, and physical fitness might be required in patients with concentric hypertrophy.

A haplotype of the CYP4F2 gene associated with myocardial infarction in Japanese men

This study assessed associations between the CYP4F2 gene and myocardial infarction (MI), using a haplotype-based case-control study of 234 MI patients and 248 controls genotyped for 5 single-nucleotide polymorphisms (rs3093105, rs3093135, rs1558139, rs2108622, rs3093200). For men, G allele frequency of rs2108622 and frequency of the T-C-G haplotype were significantly higher, and frequency of the T-C-A haplotype was significantly lower for MI patients than for controls (P=0.006, P=0.001 and P=0.002, respectively).

Association Between Frequency of Pruritic Symptoms and Perceived Psychological Stress: A Japanese Population-Based Study

OBJECTIVE To evaluate the relationship between frequency of pruritic symptoms experienced over a 1-month period and psychological stress. DESIGN Cohort study. SETTING Population-based study in Japan. PARTICIPANTS A total of 2224 participants at least 18 years old and without psychiatric disorders participated in the Japan Health Diary Study (October 2003), a cohort study comprising a representative sample in Japan. MAIN OUTCOME MEASURES Frequency of pruritic symptoms assessed by self-reported health diaries over the 1-month period and subsequent psychological stress measured using the Japanese version of the Perceived Stress Scale. RESULTS The 2224 participants had a mean age of 44.6 years, 1212 (54.5%) were women, and 70 (3.1%) presented with pruritic symptoms. Multivariable analysis showed that patients with pruritic symptoms had significantly higher psychological stress than those without pruritic symptoms (beta coefficient, 2.33; 95% confidence interval [CI], 0.53-4.14; P = .01). Furthermore, a linear trend was observed between increased psychological stress and increased severity of pruritic symptoms, with beta coefficients for the first, second, and third tertiles for symptoms of 0.81 (95% CI, -1.97 to 3.59), 1.77 (95% CI, -0.82 to 4.37), and 4.86 (95% CI, 1.29 to 8.43), respectively (P value for trend, .004). CONCLUSION Our results suggest that frequency of pruritic symptoms is associated with psychological stress in the general population.

Relationships between working status and health or health-care utilization among Japanese elderly.

Background:  As we have previously proposed redefining elderly from “65 years and over” to “75 and over” in Japan, many elderly Japanese now keep working beyond the traditional retirement age, around 60–65 years of age, in this rapidly aging society. It is important to assess the influence of working status on health and health‐care utilization among elderly Japanese.

Higher Internality of Health Locus of Control Is Associated With the Use of Complementary and Alternative Medicine Providers Among Patients Seeking Care for Acute Low-back Pain

ObjectivesGiven that persons with a stronger belief in internal health locus of control (HLC) have been shown to comply well with medical advice, HLC internality may play an important role in low-back pain (LBP) prevention and management because it requires the patients own commitment. Previous studies in conditions other than LBP have shown that the use of complementary and alternative medicine (CAM) is associated with high HLC internality. Here, we examined the relationship between CAM facility visits and internality of HLC in persons with LBP. MethodsWe analyzed the data from the Health Diary Study, which surveyed the health-related behavior of 3477 persons sampled from the general population of Japan. Among 2377 participants aged 18 to 75 years, 673 reported LBP during the study period. We examined CAM facility visits and HLC among 81 previously untreated LBP patients who sought care from western medical doctors or CAM providers during the 1-month study period. ResultsOf the 81 patients, 40 reported at least 1 CAM visit, whereas 41 visited western medical doctors only. Participants who visited CAM facilities had a higher internality score than those who visited western medical doctors after controlling for age, sex, size of residential city, and bodily pain score of the Short Form-8 Health Survey scale. DiscussionVisitors to CAM facilities had a stronger belief in internal HLC. This finding suggests that visitors to CAM facilities are more sensitive to educational intervention for the self-management of LBP than those who visit western medicine. In order not to miss the opportunity of reaching these patients, the education should be more emphasized on CAM facilities.

A 2-week prognostic prediction model for terminal cancer patients in a palliative care unit at a Japanese general hospital.

Objective: We aimed to develop a prognostic prediction model for 2-week survival among patients with terminal cancer in a palliative care unit (PCU). Methods: A prospective cohort study was conducted on terminal cancer patients in the PCU for 11 months at a general hospital in Tokyo, Japan. We collected data regarding demographics, treatment history, performance status, symptoms, and laboratory results. Patients who survived more than 2 weeks were labeled ‘long survivors’ and those who died within 2 weeks were grouped as ‘short survivors’. Stepwise logistic regression model was constructed for the model development and bootstrapping was used for the internal model validation. Results: In 158 subjects whose data were available for the analysis, 109 (69%) subjects were categorized as long survivors and 49 (31%) subjects as short survivors. A prognostic prediction model with a total score of 8 points was constructed as follows: 2 points each for anorexia, dyspnea, and edema; 1 point each for blood urea nitrogen >25 mg/dl and platelets <260,000/mm3. Area under the receiver operating characteristic (ROC) curve of this model was 83.2% (95% CI: 75.3–91.0%). Bootstrapped validation beta coefficients of the predictors were similar to the original cohort beta coefficients. Conclusion: Our prognostic prediction model for estimating 14-day survival for patients with terminal cancer on the PCU ward included five clinical predictors that are readily available in the clinical setting and showed a relatively high accuracy. External validation is needed to confirm the model’s generalizability.