Increased body mass index above the upper normal limit is significantly associated with renal dysfunction among community-dwelling persons.

PURPOSE: Body mass index (BMI) is a simple index of weight-to-height that is commonly used to classify people as underweight, overweight or obesity, and high BMI has been clearly linked to increased risk of illness in adults. However, few studies have examined the significance of upper normal weight as a risk factor for the development of chronic kidney disease (CKD) in the general Japanese population. METHODS: We conducted a prospective cohort study designed as part of the Nomura study. We recruited a random sample of 421 men aged 67 ± 10 (mean ± standard deviation; range 24-95) years and 565 women aged 68 ± 9 (22-84) years during their annual health examination in a single community. We examined the relationship between quartiles of baseline BMI and renal dysfunction after a 3-year evaluation based on estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations modified by the Japanese coefficient. CKD was defined as having dipstick-positive proteinuria (≥ 1 +) or a low eGFR (< 60 mL/min/1.73 m2). RESULTS: Of the 986 participants, a total of 134 (13.6%) participants, including 72 (17.1%) men and 62 (11.0%) women, received a new diagnosis of CKD during the study period, and 25 (9.7%), 19 (8.0%), 47 (19.0%), and 43 (17.8%) diagnoses were received in the BMI-1 (BMI, < 20.7 kg/m2), BMI-2 (BMI, 20.7 to 22.5 kg/m2), BMI-3 (BMI, 22.6 to 24.4 kg/m2), and BMI-4 (BMI ≥ 24.5 kg/m2) groups, respectively. Using BMI-2 as the reference group, the non-adjusted odds ratio (OR) (95% confidence interval) for CKD was 2.70 (1.53-4.75) for BMI-3 and 2.49 (1.40-4.42) for BMI-4, and the multivariable-adjusted OR was 2.52 (1.40-4.56) for BMI-3 and 2.30 (1.26-4.22) for BMI-4. CONCLUSIONS: Increased BMI from upper normal weight is strongly associated with the development of CKD in community-dwelling persons.

Total bilirubin independently predicts incident metabolic syndrome among community-dwelling women.

BACKGROUND: Metabolic syndrome (MetS) is related to the increased risk of major cardiovascular diseases (CVD). The link between high serum total bilirubin (TBL) is cross-sectionally related to MetS and its components. However, whether serum TBL predicts incidence of MetS and its components remains inconclusive. METHODS: The present study included 893 women aged 70 ±â€¯9 years from a rural village. We examined the relationship between serum TBL and MetS based on the modified criteria of the National Cholesterol Education Program's Adult Treatment Panel (NCEP-ATP) III report in a cross-sectional (N = 893) and cohort (N = 288) data. RESULTS: In the cross-sectional study, serum TBL (ß = 0.536, p < 0.001) as well as age, alcohol consumption, exercise habits, history of CVD, SUA, GGT, and ALT was significantly and dependently associated with number of MetS components, but in the cohort study serum TBL was not associated with number of MetS components. Compared with the 1st tertile of serum TBL (0.20-0.55 mg/dL), multivariate-adjusted odds ratio (95% confidence interval) for the 2nd -3rd tertiles of serum TBL (0.54-2.00 mg/dL) was 0.70 (0.51-0.95) in the cross-sectional study and 0.41 (0.21-0.81) in the cohort study. CONCLUSIONS: Our data demonstrated an independently negative association between serum TBL and MetS in Japanese community-dwelling women.

Serum uric acid to creatinine ratio is a useful predictor of renal dysfunction among diabetic persons.

BACKGROUND: Serum uric acid (SUA) has been shown to be a predictor of renal disease progression in most but not all studies. This study aims to test whether renal function-normalized SUA {i.e, SUA/creatinine (Cr) ratio} is a predictor of decreased renal function among diabetic patients. METHODS: The subjects comprised 185 men aged 72 ±â€¯11 (mean ±â€¯standard deviation) years and 175 women aged 77 ±â€¯10 years from a rural hospital. We examined the relationship between SUA/creatinine (Cr) ratio and renal function evaluated by estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease Study Group equation. RESULTS: Annual eGFR decline rate was significantly increased with increased tertile of baseline SUA/Cr ratio (p = 0.011), and prevalence of the rapid progression types (≥3.0 ml/min/1.73 m2/year) was significantly higher in the second and third tertile (≥7,21) of baseline SUA/Cr ratio than the first tertile (<5.86) (p = 0.032). Pearson's correlation coefficient showed that baseline SUA/Cr ratio (r = 0.136, p = 0.012) as well as systolic blood pressure (SBP) and SUA were significantly correlated with annual eGFR decline rate. Multiple regression analysis using annual eGFR decline rate as an objective variable, adjusted for confounding factors as explanatory variables, showed that baseline SUA/Cr ratio (ß = 0.334, p < 0.001) as well as gender and SBP were significantly and independently associated with annual eGFR decline rate. The multivariate-adjusted odds ratios (ORs) (95% confidence interval) of the baseline tertile of the SUA/Cr ratio for rapid progression of annual eGFR decline rate were 1.0, 3.15 (1.66-5.95) and 3.19 (1.57-6.51), respectively. CONCLUSION: Our data demonstrated that baseline SUA/Cr ratio was independently and significantly associated with future renal function decline among diabetic patients.

Association of neutrophil-to-lymphocyte ratio with early renal dysfunction and albuminuria among diabetic patients.

PURPOSE: Neutrophil-to-lymphocyte ratio (NLR) was widely studied as a prognostic marker in various medical and surgical specialties, but its significance in diabetic kidney disease is not yet established. METHODS: The subjects comprised 199 men aged 73 ± 11 (mean ± standard deviation) years and 187 women aged 77 ± 10 years from a rural hospital. We examined the relationship between NLR calculated by analyzing differential leukocyte count in complete blood picture and renal function evaluated by estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease Study Group equation and urinary albumin excretion (UAE). RESULTS: NLR was negatively related to eGFR and positively related to UAE. Multiple linear regression analysis using eGFR and UAE as an objective variables, adjusted for confounding factors as explanatory variables showed that NLR (ß = - 0.101, p = 0.009) as well as age, body mass index, serum uric acid, and presence of uric acid lowing medication were significantly and independently associated with eGFR, and NLR (ß = 0.113, p = 0.031) as well as prevalence of cardiovascular disease, systolic blood pressure, presence of antihypertensive medication, presence of antilipidemic medication, and eGFR were significantly and independently associated with UAE. The multivariate-adjusted odds ratios (95% confidence interval) of NLR for stage 3a (eGFR < 60 mL/min/1.73 m2), stage 3b (eGFR < 45 mL/min/1.73 m2), and microalbuminuria (UAE ≥ 30 mg/g Cr) were 1.90 (1.02-3.56) and 2.99 (1.28-6.98), and 1.77 (1.04-3.01), respectively. Next, to examine the consistency of the observed association between NLR and eGFR, we performed subgroup analyses. There was a significant interaction (p = 0.006) only between the two groups regarding antihypertensive medication (absence: ß = - 0.272, p < 0.001 and presence: ß = - 0.029, p = 0.564). CONCLUSIONS: Our data suggested that NLR might be important as a potential factor for evaluating patients with a higher degree of albuminuria among diabetic outpatients.

Serum Uric Acid to Creatinine Ratio Independently Predicts Incident Metabolic Syndrome Among Community-Dwelling Persons.

BACKGROUND: Metabolic syndrome (MetS) is related to the increased risk of major cardiovascular disease. The link between high serum uric acid (SUA) and creatinine (Cr) levels is causally related to MetS and its components. However, whether renal function-normalized SUA [i.e., SUA to Cr ratio (SUA/Cr)] predicts incident MetS and its components remains inconclusive. MATERIALS AND METHODS: We conducted a prospective cohort study designed as part of the Nomura study. The subjects comprised 447 men ages 68 ± 10 years and 625 women ages 68 ± 9 years from a rural village, and 155 (34.7%) men and 310 women (49.6%) had MetS at baseline. We found participants who underwent a similar examination 3 years later and analyzed the relationship between baseline SUA/Cr and incident MetS defined according to the modified criteria of the National Cholesterol Education Program-Adult Treatment Panel III (NCEP ATP III). RESULTS: One hundred forty-nine (33.3%) men and 286 (45.8%) women had MetS after a 3-year follow-up. Multiple linear regression analysis was performed to evaluate the contribution of possible confounding factors for MetS. In women only, baseline SUA/Cr, as well as baseline number of MetS and age, was significantly and independently associated with the number of MetS components at follow-up. The multivariable-adjusted odds ratios (95% confidence interval) for incident MetS across three quartiles of baseline SUA/Cr (1st-2nd, 3rd, and 4th) were 1.00, 1.62 (0.97-2.69), and 2.07 (1.20-3.56), respectively. Furthermore, when subjects were stratified by age, estimated glomerular filtration rate (eGFR), and presence of baseline MetS, baseline SUA/Cr was also a significant and independent determinant for incident MetS in women with age ≥60 years, eGFR ≥70 mL/min/1.73 m2, and presence of baseline MetS. CONCLUSIONS: Baseline SUA/Cr was significantly associated with incident MetS among community-dwelling women.

Interactive association of serum uric acid and total bilirubin with renal dysfunction among community-dwelling subjects.

PURPOSE: Chronic kidney disease is a major public health concern. Serum uric acid (SUA) at high levels was oxidative stress agents, and total bilirubin (T-BiL) at mildly increased levels was potent antioxidants, but whether SUA and T-BiL produce an additive interaction for the risk of renal dysfunction remains unclear. METHODS: The subjects comprised 567 men aged 71 ± 8 (mean ± standard deviation) years and 853 women aged 70 ± 8 years from a rural village. We examined the relationship between SUA and T-BiL, and renal function was evaluated by estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease Study Group equation. RESULTS: Stepwise multiple regression analysis using eGFR as an objective variable, adjusted for risk factors as explanatory variables, showed that SUA (ß = -0.358, p < 0.001) as well as age (ß = -0.534, p < 0.001), drinking status (ß = 0.119, p < 0.001), and the presence of antihypertensive medication (ß = -0.058, p = 0.005) were significantly and independently associated with eGFR, but T-BiL was not associated with eGFR. While in the group with the highest tertile of SUA, T-BiL (ß = 0.081, p = 0.032) was significantly and independently associated with eGFR, and in the group with the lowest to middle tertile of SUA, T-BiL was not associated with eGFR. In addition, interaction between SUA and T-BiL (F = 8.512, p = 0.004) as well as age, drinking status, the presence of antihypertensive medication, SUA, and T-BiL was a significant and independent determinant for eGFR. CONCLUSIONS: Our data demonstrated that low T-BiL could be important as a potential risk factor for renal dysfunction in those with high SUA.

Gender difference in preference of specialty as a career choice among Japanese medical students.

BACKGROUND: In Japan, the absolute deficiency of doctors and maldistribution of doctors by specialty is a significant problem in the Japanese health care system. The purpose of this study was to investigate the factors contributing to specialty preference in career choice among Japanese medical students. METHODS: A total of 368 medical students completed the survey giving an 88.2 % response rate. The subjects comprised 141 women aged 21 ± 3 (range, 18-34) years and 227 men aged 22 ± 4 (range, 18-44) years. Binary Logistic regression analysis was performed using specialty preferences as the criterion variable and the factors in brackets as six motivational variables (e.g., Factor 1: educational experience; Factor 2: job security; Factor 3: advice from others; Factor 4: work-life balance; Factor 5: technical and research specialty; and Factor 6: personal reasons). RESULTS: Women significantly preferred pediatrics, obstetrics & gynecology, and psychology than the men. Men significantly preferred surgery and orthopedics than the women. For both genders, a high odds ratio (OR) of "technical & research specialty" and a low OR for "personal reasons" were associated with preference for surgery. "Technical & research specialty" was positively associated with preference for special internal medicine and negatively for pediatrics. "Work-life balance" was positively associated with preference for psychology and negatively for emergency medicine. Among the women only, "technical & research specialty" was negatively associated with preference for general medicine/family medicine and obstetrics & gynecology, and "job security" was positively associated for general medicine/family medicine and negatively for psychology. Among men only, "educational experience" and "personal reasons" were positively, and "job security" was negatively associated with preference for pediatrics. For both genders, "work-life balance" was positively associated with preference for controllable lifestyle specialties. CONCLUSION: We must acknowledge that Japanese medical students have dichotomized some motivations for their specialty preference based on gender. Systematic improvements in the working environment are necessary to solve these issues.

Factors associated with the choice of general medicine as a career among Japanese medical students.

BACKGROUND: In Japan, there is a shortage of young physicians in various specialties; the present situation of general medicine or family medicine (GM/FM) in particular is risky. The factors influencing the career choice of Japanese medical students are poorly understood. This study aims to identify factors related to choosing GM/FM as a career. METHODS: The study was designed as a cross-sectional survey. Students at one medical school in Japan filled out a questionnaire. Students were asked to state their intended medical specialty, and they rated the importance of specific individual and occupational aspects using a 4-point likert scale. Factor analysis was performed on the variables. Reliability of the factor scores was estimated using Cronbach's alpha coefficients; biserial correlations between the factors and career choices were calculated. Furthermore, multiple linear regression analysis was performed using career choice (GM/FM vs. others) as the criterion variable and the factors plus demographic characteristics as confounding variables. RESULTS: Factor analysis produced six factors that explained future career plans. Medical students in this study had a positive and realistic idea about GM/FM, but only 18.8% of them chose GM/FM first as a career. The significant variables associated with choosing GM/FM first as a career were: 'Admission from hometown' (ß=0.189, P=0.001), 'Student preparing for the entrance exam' (ß=0.172; P=0.001), 'Intent for rural practice' (ß=0.123, P=0.016), and 'Work-life balance' (ß=0.126, P=0.013). While significant variables that were negatively associated with choosing GM/FM were 'Presence of medical relatives' (ß=-0.107, P=0.037) and 'Scientific orientation' (ß=-0.125, P=0.013). CONCLUSIONS: Strategies have been suggested, such as recruiting medical students with significant variables that were associated with choosing GM/FM first as a career. By engaging students early in their choice of career, we may be able to increase enthusiasm for this specialty.

Serum Uric Acid Is Positively Associated with Handgrip Strength among Japanese Community-Dwelling Elderly Women.

Serum uric acid (UA) has strong anti-oxidant properties. Muscle strength and mass decrease with age, and recently, this decrease has been defined as sarcopenia. Sarcopenia may be triggered by oxidative stress. We investigated whether serum UA is associated with handgrip strength (HGS), which is a useful indicator of sarcopenia, among Japanese community-dwelling elderly persons. The present study included 602 men aged 72 ± 7 years and 847 women aged 71 ± 6 years from a rural village. We examined the cross-sectional relationship between serum UA and HGS. In both genders, HGS increased significantly with increased serum UA levels. A multiple linear regression analysis using HGS as an objective variable and various confounding factors as explanatory variables showed that in men age, drinking status, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and estimated glomerular filtration ratio (eGFRCKDEPI) were independently and significantly associated with HGS, and in women, serum UA as well as age, body mass index, drinking status, diastolic blood pressure, and eGFRCKDEPI were independently and significantly associated with HGS. In women, age and multivariate-adjusted HGS were significantly higher in the Quartile-3 (4.8-5.4 mg/dL) and Quartile-4 groups (5.5-9.3 mg/dL) of serum UA than in the lower groups (0.7-4.7 mg/dL). These results suggest that serum UA may have a protective role in aging-associated decline in muscle strength in community-dwelling elderly women.

Handgrip strength is associated with metabolic syndrome among middle-aged and elderly community-dwelling persons.

The association of low muscle strength with cardio-metabolic risks remains controversial. The present study included 742 men aged 70 ± 9 years and 937 women aged 70 ± 8 years from a rural village. We examined the cross-sectional relationship between relative muscle strength defined by handgrip strength (HGS)/body weight (BW) ratio, and metabolic syndrome (MetS) based on the modified criteria of the National Cholesterol Education Program's Adult Treatment Panel (NCEP-ATP) III report and its components. Of these, 203 men (27.4%) and 448 women (47.8%) had MetS. In men, increasing quartile of HGS/BW ratio was significantly and independently associated with high waist circumference {odds ratio, 0.31; 95% confidence interval (CI), 0.24-0.41} and elevated triglyceridemia (0.71, 0.59-0.86). In women, it was also significantly and independently associated with high waist circumference (0.41; 0.36-0.48), high blood pressure (0.78; 0.66-0.92), Low HDL-cholesterolemia (0.84; 0.73-0.98) and elevated triglyceridemia (0.65; 0.53-0.79). In both genders, the prevalence of MetS significantly decreased in relation to increasing HGS/BW ratio. After adjustment for age, smoking status, drinking status, LDL-C, estimated glomerular filtration ratio (eGFR), and medication, the respective odds ratio (95% CI) for the quartile of HGS/BW ratio for MetS was 1.00, 0.54 (0.34-0.85), 0.32 (0.19-0.53), and 0.16 (0.09-0.29) in men, and 1.00, 0.76 (0.50-1.16), 0.33 (0.22-0.51), and 0.16 (0.10-0.25) in women. These results suggest that HGS/BW ratio was significantly and negatively associated with an increased risk of cardio-metabolic disorders in Japanese-community dwelling persons.

Mildly elevated serum total bilirubin levels are negatively associated with carotid atherosclerosis among elderly persons with type 2 diabetes.

Diabetes is strongly associated with several mechanisms of tissue damage such as oxidative stress. Serum bilirubin may have a beneficial role in preventing oxidative changes in cardiovascular disease (CVD). Limited information is available on whether serum bilirubin is an independent confounding factor for carotid atherosclerosis among elderly persons with type 2 diabetes. The study subjects were 169 men aged 79 ± 8 (mean ± SD) years and 205 women aged 81 ± 8 years that were enrolled consecutively from patients in the medical department. Carotid intima-media thickness (IMT) and plaque were derived via B-mode ultrasonography. Multiple linear regression analysis showed that serum total bilirubin (ß = -0.160) was significantly associated with carotid IMT. Compared to subjects with a serum total bilirubin of tertile-1 (0.13-0.58 mg/dL), the multivariate-adjusted odds ratio (95% confidence interval) of carotid IMT ≥1.0 mm including plaque and carotid plaque was 0.46 (0.23-0.93) and 0.32 (0.17-0.60) in the Tertile-3 group (0.87-1.93 mg/dL), respectively. Next, data were further stratified by gender, age, smoking status, medication and prevalence of CVD. There were no significant differences in serum total bilirubin levels between selected subgroups. Our data demonstrated a negative association between serum total bilirubin and carotid atherosclerosis among elderly persons with type 2 diabetes.

Characteristics of Japanese medical students associated with their intention for rural practice.

INTRODUCTION: In Japan, the maldistribution of physicians between urban and rural areas is increasing. It is important to know the practice location expectations of future physicians. METHODS: The study was designed as a cross-sectional survey. In 2009-2013, students at a medical school in Japan completed a questionnaire containing 50 items with four-point Likert scales. The students rated the importance of specified individual and occupational aspects. Furthermore, students were asked to state their intention to practice in a rural area. RESULTS: The study sample consisted of 368 students (88.2% response rate). Significant variables that were associated with a positively motivated intent for rural practice were 'presence of a role model' (odds ratio (OR), 5.42; 95% confidence interval (CI), 1.58-18.5), 'admission by school recommendation' (OR, 7.68; 95%CI, 2.14-27.6), 'growing up in a rural area' (OR, 6.16; 95%CI, 1.01-37.6), 'general medicine/family medicine as the first career choice' (OR, 5.88; 95%CI, 2.43-14.2), 'interest in the targeted population' (OR, 16.7; 95%CI, 3.97-69.9), 'memorable experience at a class or clinical rotation' (OR, 3.94; 95%CI, 3.73-416), and 'location of their medical school' (OR, 11.4; 95%CI, 2.79-46.2). CONCLUSIONS: The present study suggests that medical schools might recruit students with characteristics associated with intention for rural practice.

Changes in oxidized low-density lipoprotein cholesterol are associated with changes in handgrip strength in Japanese community-dwelling persons.

Nordic walking (NW), characterized by the use of two walking poles, has positive effects on several muscle groups. Muscle strength and mass decrease with age, and recently, this decrease is defined as sarcopenia. Sarcopenia may be triggered by oxidative stress. We investigated whether changes in the oxidative stress marker, malondialdehyde-modified low-density lipoprotein (MDA-LDL)/LDL-cholesterol (LDL-C) ratio are associated with change in handgrip strength (HGS), which is a useful indicator of sarcopenia, by a 12-week NW exercise among Japanese community-dwelling persons. The present study included 65 women aged 67±7 years and 9 men aged 71±8 years from a rural village. NW exercise of 120 min per week was performed for 12 weeks. Before and at the end of the 12-week intervention, various confounding factors and HGS were measured. 12-week changes in various factors were calculated by subtracting the baseline values from the 12-week values. Changes in HGS and follow-up HGS increased progressively with decreased changes in the MDA-LDL/LDL-C ratio after the 12-week walking exercise (r=-0.32, P=0.006 and r=-0.35, P=0.002, respectively). Multiple linear regression analysis showed that changes in HDL-C (ß=0.26, P=0.019) and MDA-LDL/LDL-C ratio (ß=-0.32, P=0.004) were significantly and independently associated with changes in HGS. When the data were further stratified by gender, change in the MDA-LDL/LDL-C ratio was significantly and similarly associated with change in HGS in women only. These results suggest that change in MDA-LDL/LDL-C ratio may be a predictor for HGS after a 12-week NW exercise in community-dwelling persons.

Brachial-ankle pulse wave velocity is a predictor of walking distance in community-dwelling adults.

Arterial stiffness represents the cumulative effects of cardiovascular risk factors, including aging, on the arterial wall, and has been found to be a surrogate marker of cardiovascular disease. However, it remains unknown whether baseline arterial stiffness is independently associated with improvement in functional abilities after exercise training. The subjects were 72 adults (9 men and 63 women) aged 67 ± 7 years from a rural village. Before and at the end of a 12-week Nordic walking program, 6-min walk distance (6MWD) as functional abilities, metabolic characteristics, and the mean of the right and left brachial-ankle pulse wave velocity (baPWV) as a marker of arterial stiffness were measured. Higher baseline mean baPWV levels correlated significantly with shorter baseline 6MWD (P < 0.001), and also with the follow-up 6MWD (P < 0.001) and change rate (P = 0.019) in 6MWD after the 12-week training program. Multivariate linear regression analysis was employed to evaluate the contribution of baseline mean baPWV for 6MWD parameters showing that baseline mean baPWV values were significantly and independently associated with follow-up 6MWD (ß = -0.523, P < 0.001) and change rate in 6MWD (ß = -0.399, P < 0.001) as well as baseline 6MWD (ß = -0.522, P < 0.001), but was not associated with change after the 12-week training program. Higher baPWV, a measurement of arterial stiffness, might be a predictor of functional abilities after exercise training, independent of confounding factors, in the general population.

Association between serum bilirubin and estimated glomerular filtration rate among elderly persons.

Chronic kidney disease (CKD) is a major public health problem. However, few studies have examined the significance of serum bilirubin as a risk factor for the development of CKD in the general Japanese population. The subjects comprised 413 men (mean age: 79±9 years; (range, 60-100 years) and 637 women (mean age: 81±8 years; range, 60-106 years) who visited the medical department of Seiyo Municipal Nomura Hospital. We examined the relationship between increased serum bilirubin and renal function that was evaluated by estimated glomerular filtration rate (eGFR) using CKD-EPI equations modified by a Japanese coefficient. Stepwise multiple regression analysis with eGFR as the objective variable, and adjusted risk factors as the explanatory variables, showed that serum bilirubin (ß = 0.11, P<0.001) was significantly and independently associated with eGFR, in addition to gender, age, prevalence of antihypertensive medication, triglycerides, prevalence of antidiabetic medication, and serum uric acid. Compared with stages 1+2 (eGFR ≥60.0 ml/min/1.73 m2), mean multivariate-adjusted odds ratio {95% (confidence interval (CI)} for hypobilirubinemia (first quartile, <0.52 mg/dL) was 3.52 (range: 1.88-6.59). Next, to control potential confounding factors, data were further stratified by gender, age, medication (antihypertensive, antidyslipidemic, and antidiabetic agents), and prevalence of cardiovascular disease. The standardized coefficient for eGFR was significant in both groups, and there was no interaction between the groups. Our data demonstrated an independent positive association between serum bilirubin and eGFR in both genders. Low serum bilirubin level would be useful as a potential risk factor for renal function.

Mildly elevated serum bilirubin levels are negatively associated with carotid atherosclerosis among elderly persons.

Serum bilirubin may have a beneficial role in preventing oxidative changes in atherosclerosis. Limited information is available on whether serum total bilirubin is an independent confounding factor for carotid atherosclerosis {for example, intima-media thickness (IMT), plaque} measured noninvasively by B-mode ultrasonography only among elderly persons. The study subjects were 325 men aged 79 ± 8 (mean ± standard deviation) years and 509 women aged 81 ± 8 years that were enrolled consecutively from patients aged ≥ 60 years in the medical department. Carotid IMT and plaque were derived via B-mode ultrasonography. Multiple linear regression analysis showed that in men age (ß = 0.199, p = 0.002), smoking status (ß = 0.154, p = 0.006), GGT (ß = -0.139, p = 0.039), and GGT (ß = -0.133, p = 0.022) were significantly and independently associated with carotid IMT, and in women age (ß = 0.186, p < 0.001), systolic blood pressure (ß = 0.104, p = 0.046), diastolic blood pressure (ß = -0.148, p = 0.004), prevalence of antihypertensive medication (ß = 0.126, p = 0.004), fasting plasma glucose (ß = 0.135, p = 0.003), GGT (ß = -0.104, p = 0.032), estimated glomerular filtration rate, serum bilirubin (ß = -0.119, p = 0.006), and prevalence of cardiovascular disease (CVD) (ß = 0.103, p = 0.017) were also independently associated with carotid IMT. The odds ratios (ORs) {95% confidence interval (CI)} of increasing serum bilirubin category were negatively associated with carotid IMT ≥ 1.0 mm and plaque in both genders. Compared to subjects with a serum bilirubin of Quartile-1, the multivariate-OR (95% CI) of carotid plaque was 0.25 (0.11-0.57) in the Quartile-4 male group, and 0.41 (0.21-0.78) in the Quartile-2 female group, 0.51 (0.26-0.98) in the Quartile-3 female group, and 0.46 (0.24-0.89) in the Quartile-4 female group. Our data demonstrated an independently negative association between serum bilirubin and carotid atherosclerosis in both genders.

Effect of weight loss on central systolic blood pressure in elderly community-dwelling persons.

Central blood pressure (BP) has been shown to strongly associate with cardiovascular disease and outcome. Recent studies have demonstrated a relationship between changes in body size by exercise training and peripheral BP; however, the effect on changes in central BP is unknown. The aim of this study was to assess whether changes in body size are independently related to changes in central BP in the elderly. The subjects were 11 men (mean age, 68±6 years) and 84 women (68±7 years) from a rural village. Before and at the end of the 12-week training program, metabolic variables, and first peak radial systolic BP (SBP1) and second peak radial SBP (SBP2) as estimates of central SBP, were obtained. Radial augmentation index (AI) was calculated as follows: ((SBP2-diastolic BP (DBP))/(SBP1-DBP)) × 100 (%) and we used AI corrected at heart rate 75 per min (AI@75). After the 12-week training program, weight loss correlated strongly with reduction in brachial mean arterial pressure (MAP), radial SBP1, SBP2 and AI@75. After adjusting for confounding factors, weight loss was significantly and independently associated with each reduction in brachial MAP (ß=0.34, P=0.001), radial SBP1 (ß=0.31, P=0.002), SBP2 (ß=0.37, P<0.001) and AI@75 (ß=0.36, P=0.001). These findings suggest that weight loss by a 12-week training program may be an effective strategy to improve central BP parameters among Japanese elderly persons.

Carotid atherosclerosis as a surrogate maker of cardiovascular disease in diabetic patients.

Many studies have shown that carotid intima-media thickness (IMT) is associated with cardiovascular disease (CVD). Although it remains inconclusive whether assessment of carotid IMT is useful as a screening test for CVD in Japanese diabetic patients, a total of 271 patients (151 men aged 66 ± 10 (standard deviation) years and 220 women aged 71 ± 8 years) were divided into two groups based on the presence of CVD. We cross-sectionally assessed the ability of carotid IMT to identify CVD corresponding to treatment that was examined by receiver-operating characteristic (ROC) curve analyses. Among the 271 diabetic patients, 199 non-CVD and 72 CVD patients were examined. Multiple linear regression analysis using the presence of CVD as an objective variable showed that carotid IMT (ß = 0.259, P < 0.001) as well as other confounding factors was a significant independent contributing factor. The ROC curve analysis showed that the best marker of CVD was carotid IMT, with an area under the ROC curve of 0.718 (95% confidence interval (CI), 0.650-0.785). The greatest sensitivity and specificity were obtained when the cut-off value of mean carotid IMT was set at 0.95 mm (sensitivity = 0.71, specificity = 0.60, and accuracy = 0.627). Our study suggests that carotid IMT may be useful for screening diabetic patients with CVD.

Usefulness of combining serum uric acid and high-sensitivity C-reactive protein for risk stratification of patients with metabolic syndrome in community-dwelling women.

Metabolic syndrome (MetS) is associated with an increased risk of major cardiovascular events. In women, increased uric acid (UA) levels are associated with MetS and its components. High-sensitivity C-reactive protein (hsCRP) levels are also associated with MetS, and hsCRP levels could be modulated by UA. We investigated whether combining UA and hsCRP levels are independently associated with MetS and insulin resistance in Japanese community-dwelling women. From a single community, we recruited 1,097 women (63 ± 12 years) during their annual health examination, and examined the cross-sectional relationship between UA, hsCRP, and MetS and insulin resistance, which was evaluated by homeostasis of minimal assessment of insulin resistance. Of these subjects, 218 women (19.9 %) had MetS. Multiple linear regression analysis was performed to evaluate the contribution of each confounding factor for MetS and insulin resistance, both UA and hsCRP as well as age and alcohol consumption, were independently and significantly associated with MetS and insulin resistance. The adjusted-odds ratios (95 % confidence interval) for MetS across tertiles of UA and hsCRP were 1.00, 1.45 (0.95-2.22), and 2.61 (1.74-3.93), and 1.00, 1.80 (1.18-2.74), and 3.23 (2.15-4.85), respectively. In addition, the combination increased UA, and hsCRP was also a significant and independent determinant for MetS and insulin resistance. In direction associations, we also observed a synergistic effect between these two molecules (F = 2.76, P = 0.027). These results suggested that combined assessment of UA and hsCRP levels provides incremental information for risk stratification of patients with MetS, independent of other confounding factors in community-dwelling women.

A slightly low hemoglobin level is beneficially associated with arterial stiffness in Japanese community-dwelling women.

Pulse wave velocity (PWV) is a simple and noninvasive method of measuring arterial stiffness for the assessment of cardiovascular disease in high-risk populations. This association may be further confounded by hemoglobin status, which is involved in the development of atherosclerosis. We randomly recruited 120 men and 223 women aged 69 ± 9 and 68 ± 7 years, respectively, during their annual health examination in a single community. Arterial stiffness was evaluated by brachial-ankle PWV (baPWV). The value of baPWV was different from men and women. In men, baPWV was not related to hemoglobin levels (r = 0.013, P = .886), but in women baPWV increased significantly and progressively with increased hemoglobin levels (r = 0.276, P < .001). Stepwise multiple regression analysis using the baPWV as objective variables, adjusted for confounding factors as explanatory variables, showed that only in women, hemoglobin levels (ß = 0.165, P = .001) as well as age (ß = 0.268, P < .001), body mass index (BMI; ß = -0.165, P < .001), systolic blood pressure (SBP; ß = 0.429, P < .001), prevalence of antihypertensive (ß = 0.154, P = .002), heart rate (HR; ß = 0.108, P = .017), and antilipidemic medication (ß = 0.094, P = .036), and estimated glomerular filtration rate (eGFR; ß = -0.147, P = .003) were significantly and independently associated with baPWV. Multivariate-adjusted baPWV was significantly higher in hemoglobin groups of ≥12.7 g/dL (Group-2, Group-4) than in the lowest hemoglobin group (10.0-12.6 g/dL; P = .032). A slightly low hemoglobin level was beneficially associated with arterial stiffness in community-dwelling women but not men.