Prevalence of Earlobe Creases and Their Association With History of Cardiovascular Disease in Patients Undergoing Hemodialysis: A Cross-Sectional Study.

Earlobe creases are surrogate markers for high risk of cardiovascular disease. There is no data concerning earlobe creases among hemodialysis patients, who have an increased risk of cardiovascular disease. A cross-sectional study was conducted to determine the prevalence of earlobe creases and their association with prevalent cardiovascular disease among hemodialysis patients. Patients undergoing hemodialysis were recruited from five outpatient hemodialysis centers. Both earlobes were photographed during a dialysis session with the patient in a supine position and the photos evaluated independently by two experienced nephrologists blinded to the participants' clinical characteristics. Prevalent cardiovascular diseases were defined as a history of myocardial infarction, cerebrovascular accident, or peripheral vascular disease. Sensitivity, specificity, and positive and negative predictive values for detection of prevalent cardiovascular disease were calculated. Logistic analysis was used to examine the association between earlobe creases and prevalent cardiovascular disease. Earlobe creases were identified in 24.5% of 330 hemodialysis patients (200 men; mean age, 67.8 years). The prevalence of earlobe creases increased with age for men (P for trend <0.0001), but not for women (P for trend = 0.07). Sensitivity, specificity, and positive and negative predictive values were 30.9% (95% confidence interval, 21.9-41.6), 77.5% (71.9-82.3), 30.9% (21.9-41.6), and 77.5% (71.9-82.3), respectively. Multivariate logistic analyses indicated the prevalence of earlobe crease was not associated with prevalent cardiovascular diseases. The prevalence is similar to that previously reported for Japanese individuals not undergoing dialysis. No association between earlobe creases and prevalent cardiovascular diseases was identified.

Continuous Reduction of Protein-Bound Uraemic Toxins with Improved Oxidative Stress by Using the Oral Charcoal Adsorbent AST-120 in Haemodialysis Patients.

Accumulation of protein-bound uraemic toxins (PBUTs) is one of the reasons for the development of uraemia-related complications including cardiovascular disease; however, conventional haemodialysis is limited in its ability to remove PBUTs. We aimed to examine whether the oral charcoal adsorbent AST-120 has an additive effect on PBUT removal in haemodialysis patients. During the 4-week study, anuric patients undergoing haemodialysis received AST-120 (6 g/day) in the last 2 weeks (n = 10) or the first 2 weeks (n = 10). Serum levels of total and free PBUTs such as indoxyl sulfate, p-cresyl sulfate, and phenyl sulfate at the pre- and postdialysis sessions were measured before and after AST-120 use and after discontinuation. Levels of the oxidative stress markers oxidized albumin and 8-isoprostane were also measured. AST-120 use induced dramatic reduction of indoxyl sulfate (total, 45.7% [33.2-50.5%]; free, 70.4% [44.8-79.8%]), p-cresyl sulfate (total, 31.1% [25.0-48.0%]; free, 63.5% [49.3-70.9%]), and phenyl sulfate (free, 50.6% [32.3-71.2%]) levels; however, this effect disappeared after the discontinuation of AST-120. AST-120 use also induced substantial reduction of the oxidized albumin and 8-isoprostane levels. In conclusion, oral administration of AST-120 had additive effects on the continuous reduction of some PBUTs in anuric patients undergoing haemodialysis.

Increased Proinflammatory Cytokine Production and Decreased Cholesterol Efflux Due to Downregulation of ABCG1 in Macrophages Exposed to Indoxyl Sulfate.

One of the possible causes of enhanced atherosclerosis in patients with chronic kidney disease (CKD) is the accumulation of uremic toxins. Since macrophage foam cell formation is a hallmark of atherosclerosis, we examined the direct effect of indoxyl sulfate (IS), a representative uremic toxin, on macrophage function. Macrophages differentiated from THP-1 cells were exposed to IS in vitro. IS decreased the cell viability of THP-1 derived macrophages but promoted the production of inflammatory cytokines (IL-1ß, IS 1.0 mM: 101.8 ± 21.8 pg/mL vs. 0 mM: 7.0 ± 0.3 pg/mL, TNF-α, IS 1.0 mM: 96.6 ± 11.0 pg/mL vs. 0 mM: 15.1 ± 3.1 pg/mL) and reactive oxygen species. IS reduced macrophage cholesterol efflux (IS 0.5 mM: 30.3% ± 7.3% vs. 0 mM: 43.5% ± 1.6%) and decreased ATP-binding cassette transporter G1 expression. However, lipid uptake into cells was not enhanced. A liver X receptor (LXR) agonist, T0901317, improved IS-induced production of inflammatory cytokines as well as reduced cholesterol efflux. In conclusion, IS induced inflammatory reactions and reduced cholesterol efflux in macrophages. Both effects of IS were improved with activation of LXR. Direct interactions of uremic toxins with macrophages may be a major cause of atherosclerosis acceleration in patients with CKD.

Intact parathyroid hormone and whole parathyroid hormone assay results disagree in hemodialysis patients under cinacalcet hydrochloride therapy.

BACKGROUND: The parathyroid gland secretes 1-84 and 7-84 parathyroid hormone (PTH) fragments, and its regulation is dependent on stimulation of the extracellular calcium-sensing receptor. While the intact PTH system detects both PTH fragments, the whole PTH system detects the 1-84PTH but not the 7-84PTH. Cinacalcet hydrochloride (CH) binds to calcium-sensing receptor as a calcimimetic. Here we investigated the role of CH treatment in the assessment of parathyroid gland function. METHODS: Stable adult dialysis patients for whom CH therapy was planned were included. Patients for whom CH therapy was not planned were simultaneously included as the control group. RESULTS: The CH group (n = 44) showed significantly higher circulating levels of Ca, intact PTH, and whole PTH, before the CH treatment than the control group (n = 112). The Ca, intact PTH, and whole PTH levels decreased along with the CH therapy, and the Ca levels became comparable in the 8th week of treatment and thereafter. The CH group in the 8th week and thereafter showed significantly lower whole/intact PTH ratios than the control group, while the whole/intact PTH ratio was not significantly different between before and during the CH therapy. A multiple regression analysis revealed that the whole/intact PTH ratio was almost constant, but both the serum Ca level and a CH therapy could potentially modify the fixed number. When the whole PTH levels were estimated by intact PTH levels using the relationship between them in the control group, the levels were clearly overestimated in the CH group. CONCLUSIONS: Although the direct effect of CH on the whole/intact PTH ratio is masked by its hypocalcemic action, we could successfully demonstrate that the ratio in CH users is lower than that in the non-users with comparable levels of serum Ca. Evaluating parathyroid function with intact PTH according to the clinical practice guidelines in patients being treated with CH may lead to significant overestimation and subsequent overtreatment.

Cause-specific excess mortality among dialysis patients: comparison with the general population in Japan.

Despite significant therapeutic advances, mortality of dialysis patients remains unacceptably high. The aim of this study is to compare mortality and its causes in dialysis patients with those in the general Japanese population. We used data for 2008 and 2009 from the Japanese Society for Dialysis Therapy registry and a national Vital Statistics survey. Cardiovascular mortality was defined as death attributed to heart failure, cerebrovascular disorders, myocardial infarction, hyperkalemia/sudden death, and pulmonary thromboembolism. Non-cardiovascular mortality was defined as death attributed to infection, malignancies, cachexia/uremia, chronic hepatitis/cirrhosis, ileus, bleeding, suicide/refusal of treatment, and miscellaneous. We calculated standardized mortality ratios and age-adjusted mortality differences between dialysis patients and the general population for all-cause, cardiovascular versus non-cardiovascular, and cause-specific mortality. During the 2-year study period, there were 2,284,272 and 51,432 deaths out of 126 million people and 273,237 dialysis patients, respectively. The standardized mortality ratio for all-cause mortality was 4.6 (95% confidence interval, 4.6-4.7) for the dialysis patients compared to the general population. Age-adjusted mortality differences for cardiovascular and non-cardiovascular disease were 33.1 and 30.0 per 1000 person-years, respectively. The standardized mortality rate ratios were significant for all cause-specific mortality rates except accidental death. Our study revealed that excess mortality in dialysis patients compared to the general population in Japan is large, and differs according to age and cause of death. Cause-specific mortality studies should be planned to improve life expectancies of dialysis patients.

A combination of healthy lifestyle factors is associated with a decreased incidence of chronic kidney disease: a population-based cohort study.

A combination of healthy lifestyle factors is associated with lower risks of coronary heart disease, diabetes and stroke, but little is known about its association with chronic kidney disease (CKD). This study analyzed the effect of a combination of healthy lifestyle factors on the incidence of proteinuria among participants without CKD. Of the 7565 persons aged 40-79 years who participated in the Specific Health Checkups and Guidance System in Sado Island, Japan in 2008, 4902 participants (2015 males) without CKD were included. The healthy lifestyle score was calculated by summing the total number of lifestyle factors for which the participants were at low risk. Low risk was defined as (1) nonsmoker, (2) body mass index (BMI) <25 kg m(-2), (3) moderate or less alcohol consumption, (4) regular exercise and (5) better eating patterns. Logistic analysis was used to examine the relationship between the baseline score in 2008 and the development of proteinuria in 2009. Proteinuria developed in 2.2% of participants (males, 3.2; females, 1.5%). Compared with participants with a healthy lifestyle score of 0 to 2, participants with a score of 5 had a lower risk (odds ratio: 0.39, 95% confidence interval: 0.16-0.94), independently of having diabetes, hypertension and hypercholesterolemia. Overall, 47% of the cases in this cohort could be attributed to lack of adherence to this low-risk pattern. These findings underscore the importance of a healthier lifestyle in preventing CKD.

High mortality rate of infectious diseases in dialysis patients: a comparison with the general population in Japan.

Infectious disease is the second leading cause of death among dialysis patients, and it is generally assumed that the mortality rate of infectious disease is considerably higher in dialysis patients than in the general population. There are no comprehensive studies on this issue and on the contribution of each category of infectious disease to excess mortality in dialysis patients in Japan. We used mortality data reported to the Japanese Society for Dialysis Therapy and national Vital Statistics data for 2008 and 2009. We calculated standardized mortality ratios and compared the mortality rates for each category of infectious disease. During the 2-year study period, 274,683 and 10,435 deaths from infectious diseases were recorded in 126 million people and 273,237 dialysis patients, respectively. The standardized mortality ratio for all infectious diseases was 7.5 (95% confidence interval, 7.3-7.6) in dialysis patients with respect to the general population in Japan. The categories of infectious disease with a significantly higher standardized mortality ratio among the dialysis patients were sepsis, peritonitis, influenza, tuberculosis, and pneumonia and in that order. In particular, the mortality rate of sepsis contributed to 69.5% of the difference in infectious disease mortality between dialysis patients and the general population. This study underlines markedly increased mortality from infectious diseases, particularly from sepsis, in dialysis patients compared with the general population.

Seropositivity for anti-HCV core antigen is independently associated with increased all-cause, cardiovascular, and liver disease-related mortality in hemodialysis patients.

BACKGROUND: It is not known whether chronic or past hepatitis C virus (HCV) infection contributes to the high mortality rate in hemodialysis patients. METHODS: This prospective study of 1077 adult hemodialysis patients without hepatitis B virus infection used Poisson regression analysis to estimate crude and sex- and age-adjusted rates (per 1000 patient-years) of all-cause, cardiovascular, infectious disease-related and liver disease-related mortality in patients negative for HCV antibody (group A), patients positive for HCV antibody and negative for anti-HCV core antigen (group B), and patients positive for anti-HCV core antigen (group C). The relative risks (RRs) for each cause of death in group B vs group C as compared with those in group A were also estimated by Poisson regression analysis after multivariate adjustment. RESULTS: A total of 407 patients died during the 5-year observation period. The sex- and age-adjusted mortality rate was 71.9 in group A, 80.4 in group B, and 156 in group C. The RRs (95% CI) for death in group B vs group C were 1.23 (0.72 to 2.12) vs 1.60 (1.13 to 2.28) for all-cause death, 0.75 (0.28 to 2.02) vs 1.64 (0.98 to 2.73) for cardiovascular death, 1.64 (0.65 to 4.15) vs 1.58 (0.81 to 3.07) for infectious disease-related death, and 15.3 (1.26 to 186) vs 28.8 (3.75 to 221) for liver disease-related death, respectively. CONCLUSIONS: Anti-HCV core antigen seropositivity independently contributes to elevated risks of all-cause and cause-specific death. Chronic HCV infection, but not past HCV infection, is a risk for death among hemodialysis patients.

Thyroid hormone receptor repression is linked to type I pneumocyte-associated respiratory distress syndrome.

Although the lung is a defining feature of air-breathing animals, the pathway controlling the formation of type I pneumocytes, the cells that mediate gas exchange, is poorly understood. In contrast, the glucocorticoid receptor and its cognate ligand have long been known to promote type II pneumocyte maturation; prenatal administration of glucocorticoids is commonly used to attenuate the severity of infant respiratory distress syndrome (RDS). Here we show that knock-in mutations of the nuclear co-repressor SMRT (silencing mediator of retinoid and thyroid hormone receptors) in C57BL/6 mice (SMRTmRID) produces a previously unidentified respiratory distress syndrome caused by prematurity of the type I pneumocyte. Though unresponsive to glucocorticoids, treatment with anti-thyroid hormone drugs (propylthiouracil or methimazole) completely rescues SMRT-induced RDS, suggesting an unrecognized and essential role for the thyroid hormone receptor (TR) in lung development. We show that TR and SMRT control type I pneumocyte differentiation through Klf2, which, in turn, seems to directly activate the type I pneumocyte gene program. Conversely, mice without lung Klf2 lack mature type I pneumocytes and die shortly after birth, closely recapitulating the SMRTmRID phenotype. These results identify TR as a second nuclear receptor involved in lung development, specifically type I pneumocyte differentiation, and suggest a possible new type of therapeutic option in the treatment of RDS that is unresponsive to glucocorticoids.

Serum low-density lipoprotein to high-density lipoprotein ratio as a predictor of future acute myocardial infarction among men in a 2.7-year cohort study of a Japanese northern rural population.

AIM: To examine and compare the predictive value of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), TC/HDL-C and LDL-C/HDL-C ratios for future cardiovascular outcomes in the general Japanese population. METHODS: A total of 24,566 eligible participants aged 18 years or older, without cardiovascular disease, were enrolled through multiphase health screening and divided into quartile groups based on lipoprotein levels or ratios. Primary endpoints of the study were definitive acute myocardial infarction (AMI) and ischemic stroke, and cases of sudden death with unknown causes were not included. We used Cox proportional hazard models to examine the relationships between the quartiles and incidences of AMI or ischemic stroke, adjusting for traditional risk factors. RESULTS: Mean age was 63.7 years for males and 60.7 years for females. Mean follow-up period was 2.7 years, and 40 cases of AMI and 182 cases of ischemic stroke were recorded. The hazard ratio (HR) for AMI was significantly higher in the top quartile of the LDL-C/HDL-C ratio and LDL-C levels, and third quartile of TC among male participants. The HR of male participants with a LDL-C/HDL-C ratio of 2.6 or higher was significantly higher than other quartiles. No association between lipoprotein levels or their ratio quartiles and ischemic stroke was seen for either sex after adjusting for risk factors. CONCLUSIONS: Our results indicated that the LDL-C/HDL-C ratio is an independent predictor for AMI, and the importance of better management of cardiovascular risks among people with high LDLC/HDLC ratios for the prevention of future cardiovascular disease.

Comparison of low-density lipoprotein cholesterol concentrations measured by a direct homogeneous assay and by the Friedewald formula in a large community population.

BACKGROUND: We compare the direct homogeneous low-density lipoprotein cholesterol (LDL-C) assay with the Friedewald formula (FF) for determination of LDL-C in a large community-dwelling population. METHODS: A total of 21,194 apparently healthy subjects aged 40 to 79 years with triglyceride (TG) concentrations <4.52 mmol/l were enrolled. LDL-C were directly measured by the enzymatic homogeneous assay (LDL-C (D)) and also estimated by the FF (LDL-C (F)). Paired t-test, Pearson's correlation coefficient and linear regression analysis were performed and the concordances of the National Cholesterol Education Program (NCEP) risk category were estimated. RESULTS: Both in fasting (n=3270) and nonfasting samples (n=17,924), LDL-C (D) highly correlated with LDL-C (F): r=0.971 and 0.955, respectively. Concordant results for NCEP categories were 84.8% for fasting samples and 80.1% for nonfasting samples. However, the bias between the 2 measurements increased in samples with TG concentrations >1.69 mmol/l, especially in nonfasting samples. CONCLUSIONS: The results showing less variability of the direct LDL-C assay than that of the FF in nonfasting samples suggest that epidemiological studies can use LDL-C measured by the direct assay both in fasting and nonfasting samples.

Plasma B-type natriuretic peptide level and cardiovascular events in chronic kidney disease in a community-based population.

BACKGROUND: Plasma B-type natriuretic peptide (BNP) levels are confounded by renal dysfunction, so this study examined whether plasma BNP might be a reliable biomarker of the onset of cardiovascular (CV) events in a population-based cohort with impaired renal function. METHODS AND RESULTS: Baseline data, including plasma BNP, serum creatinine, and urinary protein levels, were determined in participants from a community-based population. Estimated glomerular filtration rate (eGFR) was calculated, and chronic kidney disease (CKD) was defined as either: eGFR <60 mlxmin(-1)x1.73 m(-2) and/or proteinuria (CKD definition-1) or GFR <60 mlxmin(-1)x1.73 m(-2) (CKD definition-2). The CV endpoint was surveyed prospectively. The cohorts were followed for 5,275 person-years for CKD definition-1, and for 4,350 person-years for CKD definition-2. The CV event-free survival rate in the highest BNP quartile in either CKD definition was the lowest among the quartile groups (P<0.001). In multivariate Cox regression models adjusted by traditional CV risk factors and atrial fibrillation, relative risk (RR) for CV events was significantly higher in the highest BNP quartile compared with the lowest BNP quartile (CKD definition-1, RR 3.51, P<0.01: CKD definition-2, RR 4.67, both P<0.01). CONCLUSIONS: Plasma BNP level provides strong predictive information about the future onset of CV events in CKD subjects selected from the general population.

Standardized prevalence ratios for chronic hepatitis C virus infection among adult Japanese hemodialysis patients.

BACKGROUND: Many studies have estimated the prevalence of anti-hepatitis C virus (HCV) antibody among hemodialysis (HD) patients; however, the prevalence of HCV core antigen-which indicates the presence of chronic HCV infection-is not known. METHODS: Standardized prevalence ratios (SPRs) for anti-HCV antibody and HCV core antigen among HD patients (n = 1214) were calculated on the basis of data from the general population (n = 22 472) living in the same area. RESULTS: The prevalences of anti-HCV antibody and HCV core antigen were 12.5% and 7.8%, respectively, in male hemodialysis patients, and 8.5% and 4.1% in female hemodialysis patients. The SPRs (95% confidence interval) for anti-HCV antibody and HCV core antigen were 8.39 (6.72-10.1) and 12.9 (9.66-16.1), respectively, in males, and 5.42 (3.67-7.17) and 8.77 (4.72-12.8) in females. CONCLUSIONS: The prevalences of chronic HCV infection among male and female HD patients were 13-fold and 9-fold, respectively, those of the population-based controls. Further studies should therefore be conducted to determine the extent of chronic HCV infection among HD patients in other populations and to determine whether chronic HCV infection contributes to increased mortality in HD patients.

Gender-specific risk stratification with plasma B-type natriuretic peptide for future onset of congestive heart failure and mortality in the Japanese general population.

BACKGROUND: Elevated plasma B-type natriuretic peptide (BNP) levels suggest a high risk for future onset of cardiovascular events including congestive heart failure (CHF) and mortality. In the general population, although median plasma BNP levels have been reported to be higher in women than in men, the incidence of CHF and mortality are lower in women. However, no studies have examined gender-specific risk stratification of plasma BNP levels for future onset of CHF and mortality. METHODS: Subjects of this study were recruited from our general population. Baseline data including plasma BNP were determined in 13,466 subjects (men 4527, women 8939; median age = 64 yrs). A multivariate Cox regression analysis was performed to examine the predictive ability of plasma BNP for new onset of CHF and mortality. RESULTS: The mean follow-up duration was 2.9 years. After adjustment for traditional cardiovascular risk factors including atrial fibrillation, hazard ratios for CHF development for values above the 75th percentile of BNP were 13.4 (p<0.001) in men and 8.5 (p<0.001) in women. Similarly, each increment of 1SD in log BNP levels increased the hazard ratio by 8.8 (p<0.001) in men, and 6.7 (p<0.001) in women. The area under the receiver operating characteristic curve was significant for prediction of the onset of CHF (men; 0.853, women; 0.838). In addition, increased plasma BNP levels implied high risk of any-cause mortality in men (above the 75th percentile; hazard ratio = 1.8, p=0.005: increment of 1SD; hazard ratio = 1.4, p=0.024), but this relationship was suboptimal in women. CONCLUSION: Measurements of plasma BNP provides strong predictive information about future onset of CHF in both sexes, with predictive ability for death being effective especially in men.

[Association between homebound status and newly certified need of care among elderly in a rural community: the Iwate-Kenpoku cohort (Iwate-KENCO) study].

OBJECTIVE: The purpose of this study was to evaluate the association between homebound status and newly certified need of care among elderly in a rural community and to clarify the characteristics of those in homebound status. METHODS: The Iwate-KENpoku COhort (Iwate-KENCO) study (26,469 participants) spanned the period from 2002 to 2004 and was conducted in northern Iwate Prefecture, Japan. In the present study, 12,056 elderly (men, 4,751; women, 7,305) participated after being screened for eligibility (> or =65 years of age; without certification for need of care; and without a history of stroke, cardiac heart failure, or ischemic heart disease). Being homebound was operationally defined as walking outdoors for less than 5 minutes per day. Cox's proportional hazard model was used to estimate the hazard risk (HR) for newly certified need of care and the 95% confidence interval (95% CI) after controlling for confounding factors by gender. RESULTS: After a mean follow-up period of 2.65 years, 200 men (4.2%) and 412 women (5.6%) obtained certification for need of care. Homebound status was significantly associated with newly certified need of care in women (HR=1.64, 95%CI=1.29-2.09), but not in men (HR=1.07, 95%CI=0.76-1.52). Homebound status among elderly women was associated with nutritional status, missing teeth, and irregular daily rhythms. CONCLUSION: These findings suggest that being homebound is a risk factor for elderly women receiving certification for need of care.

Predictive value of plasma B-type natriuretic peptide for ischemic stroke: a community-based longitudinal study.

OBJECTIVE: Structural heart diseases including atrial fibrillation are precursors for ischemic stroke. Plasma B-type natriuretic peptide (BNP) has been reported to be increased in patients with several types of structural heart diseases. However, the predictive value of plasma BNP for ischemic stroke remains unknown. We have studied the predictive ability of plasma BNP for future development of stroke in community dwelling adults. METHODS: Subjects of this community-based study were recruited from the general population (n=13,466). Plasma BNP levels and cardiovascular risk factors were determined at baseline. The incidence of ischemic stroke in the cohort was identified from regional stroke registry data. A multivariate Cox regression analysis was performed to analyze the relationship between plasma BNP levels and the risk of stroke. RESULTS: During a mean follow-up period of 2.8 years, 102 participants (65 males, 37 females) experienced a first ischemic stroke. In men, after adjustment for classical cardiovascular risk factors and atrial fibrillation, the hazard ratio (HR) for ischemic stroke was significantly elevated in the highest plasma BNP quartile (HR=2.38; 95% CI=1.07-5.29). In women, the relationship between plasma BNP levels and risk of ischemic stroke was of marginal significance after adjusting for the presence or absence of atrial fibrillation (HR=3.03; 95% CI=0.84-10.92, P=0.09). CONCLUSION: Elevated plasma BNP levels predict the risk of ischemic stroke within men from the general population.

Cardiovascular risk factors in the Japanese northeastern rural population.

BACKGROUND: People living in the northeastern part of Japan have high prevalences of hypertension and stroke. The current status of cardiovascular risk factors in them should be elucidated. METHODS: The survey was carried out from 2002 to 2004 in the northeastern part of the main island of Japan. A total of 26,472 Japanese men and women were enrolled (acceptance rate: 84.5%). Sex- and age-specific prevalences of cardiovascular risk factors were determined. Mean values of predictive markers (high-sensitivity C reactive protein (hsCRP), brain natriuretic peptide (BNP) and microalbuminuria) were also determined in each group. Risk factor-related variables in non-hypertensive subjects and hypertensive subjects were compared. RESULTS: Proportions of subjects with hypertension, diabetes and dyslipidemia were 46.0%, 7.6%, and 30.3%, respectively, in males and 38.6%, 4.0%, and 38.5%, respectively, in females. Mean values of hsCRP and BNP were 1.41 mg/L and 26.5 pg/mL, respectively, in males and 1.01 mg/L and 23.7 pg/mL, respectively, in females. Proportions of male and female subjects with microalbuminuria were 22.0% and 23.4%, respectively. These markers become higher with advance of age. Prevalence of atrial fibrillation was 1.56%, and it increased with advance of age in both men and women. High prevalences of cardiovascular risk factors in this area were found. Hypertensive subjects who did not take anti-hypertension medication accounted for about 20% of total subjects and their blood pressure remained poorly controlled. CONCLUSION: Attention should be given to cardiovascular risk factors in the Japanese northeastern rural population.

Serum C-reactive protein levels can be used to predict future ischemic stroke and mortality in Japanese men from the general population.

BACKGROUND: High C-reactive protein (CRP) levels have been reported to be associated with an increased risk of atherosclerotic cardiovascular events. The relationship of CRP levels to the risk of cerebrovascular events in the Japanese population, which has a lower prevalence of coronary artery disease and a lower CRP level than Western populations, has not been fully clarified. The present study examined the predictive value of serum high sensitivity CRP (hs-CRP) levels for future cerebrovascular events and mortality in the general Japanese population. METHODS: The subjects for this community-based, prospective cohort study were recruited from the general population (n=7901, male only, mean age=64.0 years). Serum hs-CRP levels and cardiovascular risk factors were determined at baseline. The mean follow-up period was 2.7 years. After excluding subjects with a cardiovascular history, the relationships between hs-CRP levels and cerebrovascular events and mortality were assessed. RESULTS: During follow-up, 130 participants had a first stroke (95 ischemic strokes), and 161 participants died. The hs-CRP tertile level was a significant predictor for a first ischemic stroke (3rd tertile, HR=1.77: 95% Cl, 1.04-3.03, compared with the 1st tertile), after adjustment for age and classical cardiovascular risk factors. Similar trends were observed for the prediction of all-cause mortality (3rd tertile, HR=2.26: 95% Cl, 1.49-3.42, compared with the 1st tertile). CONCLUSION: CRP levels can be used to predict future ischemic stroke and mortality in Japanese men from the general population, independently from traditional cardiovascular risk factors.

Dietary intake of n-3 polyunsaturated fatty acids is inversely associated with CRP levels, especially among male smokers.

OBJECTIVE: To examine whether dietary intake of n-3 polyunsaturated fatty acid (n-3PUFA) is associated with serum C-reactive protein (CRP) levels with regard to smoking status in the Japanese general population in a cross-sectional study. METHODS AND RESULTS: A total of 14,191 participants aged 40-69 years were enrolled and divided into quartile groups according to their intake of n-3PUFA. Multivariate-adjusted logarithm-transformed CRP levels were compared between the quartile groups with regard to smoking status after adjusting for traditional risk factors and intake of saturated fatty acids. Adjusted CRP levels were inversely associated with dietary intake of n-3PUFA for both the male subjects and female subjects (p<0.05 for trend). A linear trend was not seen between intake of n-3PUFA and adjusted CRP levels in male nonsmokers. Adjusted CRP level in the lowest quartile group of n-3PUFA was significantly higher than the levels in other groups in male smokers. CONCLUSION: Sufficient dietary intake of n-3PUFA may attenuate inflammatory reaction and this effect is more evident among high-risk populations such as male smokers although the small numbers of female ex-smokers and nonsmokers limited statistical power to draw strong conclusions about these groups.

[Development of effective antigen delivery carrier to dendritic cells via Fc receptor in cancer immunotherapy].

In cancer immunotherapy with dendritic cells (DCs), which are the most potent antigen-presenting cells, it is important that DCs present peptides derived from tumor-associated antigens on major histocompatibility complex (MHC) class I molecules and activate tumor-specific cytotoxic T lymphocytes. However, exogenous antigens are generally presented on MHC class II but not class I molecules. To develop effective immunotherapy for cancer, an antigen delivery carrier that can induce MHC class I presentation of exogenous antigens is necessary. Several strategies to induce DCs to present exogenous antigens on MHC class I molecules have been reported. First, DCs that phagocytosed a particulate form of antigens present peptides derived from the antigens on MHC class I molecules. Second, DCs that incorporated antigens via certain endocytic receptors such as Fc receptors efficiently present peptides on MHC class I molecules. We combined these two strategies and prepared antigen-containing IgG-conjugated liposomes (IgG-liposomes). In this study, we investigated the feasibility of IgG-liposomes as antigen delivery carriers in cancer immunotherapy with DCs. Immunization of mice with DCs that endocytosed ovalbumin (OVA)-containing IgG-liposomes, but not OVA-containing bare liposomes or soluble OVA, completely prevented the growth of OVA-expressing lymphoma cells. These results suggest that IgG-liposomes represent an efficient antigen delivery carrier for DCs in cancer immunotherapy.