Kozo Tanno

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.

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.

Influence of the Great East Japan Earthquake and Tsunami 2011 on Occurrence of Cerebrovascular Diseases in Iwate, Japan

Background and Purpose— Little information is available regarding the occurrence of cerebrovascular diseases after tsunamis. This study was performed to determine the influence of the tsunami damage caused by the Great East Japan earthquake on occurrence of cerebrovascular diseases. Methods— Subjects from the coastline and inland areas of Iwate Prefecture who developed cerebrovascular diseases before and after the disaster were included in the analysis. Standardized incidence ratios of 2011 against the previous 3 years were calculated in two 4-week periods before and four 4-week periods after the disaster, according to stroke subtype, sex, age group, and flood damage. Results— The standard incidence ratio for cerebrovascular diseases was 1.20 (1.00–1.40) in the first 4-week period after the disaster and was not significant in other periods. The standard incidence ratios in the first 4-week period for cerebral infarction, intracerebral hemorrhage, and subarachnoid hemorrhage were 1.22 (0.98–1.46), 1.15 (0.76–1.55), and 1.20 (0.52–1.88), respectively. These values were 1.51 (1.19–1.88) for men, 1.35 (1.06–1.64) for subjects aged ≥75 years, and 1.35 (1.06–1.64) for the high flooding areas. The standard incidence ratio of cerebral infarction in the first 4-week period for men aged ≥75 years in the high flooding areas was 2.34 (1.34–3.34). Conclusions— In the areas highly flooded by the tsunami caused by the Great East Japan earthquake, the occurrence of cerebral infarction among elderly men more than doubled in the first 4 weeks after the disaster.

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 selenium levels are inversely associated with death risk among hemodialysis patients

BACKGROUND Previous studies have indicated that serum selenium levels are decreased in hemodialysis patients. Selenium deficiency may contribute to an increased risk for death among hemodialysis patients. METHODS A population-based prospective cohort study in adult hemodialysis patients was conducted. A total of 1041 patients were enrolled. Patients were divided into quartile groups according to serum selenium levels. Mortality rates between the groups were compared by the log-rank test. Associations between serum selenium levels and cause-specific mortality risks in hemodialysis patients were examined by Coxs regression model. RESULTS A total of 382 patients died during the 5-year follow-up period (median follow-up period, 4.9 years). Crude mortality rates in quartile groups according to serum selenium levels were 134.5, 99.9, 85.9 and 55.2 (per 1000 patient-years), respectively. The lowest quartile group had significantly higher mortality rates from all-cause and infectious disease-related death than the rates in the other three groups (P < 0.001, by log-rank test). Mortality rates from cardiovascular and malignant disease-related death were similar between the groups. A strong inverse relationship between selenium levels and infectious disease-related death was observed even after multivariate adjustment (trend P = 0.024). CONCLUSIONS Serum selenium levels were inversely associated with death risk, especially death risk due to infectious disease, among hemodialysis patients. Decreased serum selenium level may contribute to immunity dysfunction and may increase the risk of death from infectious disease in hemodialysis patients.

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, Pearsons 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.

Associations of ikigai as a positive psychological factor with all-cause mortality and cause-specific mortality among middle-aged and elderly Japanese people: findings from the Japan Collaborative Cohort Study.

OBJECTIVE To determine whether presence of ikigai as a positive psychological factor is associated with decreased risks for all-cause and cause-specific mortality among middle-aged and elderly Japanese men and women. METHODS From 1988 to 1990, a total of 30,155 men and 43,117 women aged 40 to 79 years completed a lifestyle questionnaire including a question about ikigai. Mortality follow-up was available for a mean of 12.5 years and was classified as having occurred in the first 5 years or the subsequent follow-up period. Associations between ikigai and all-cause and cause-specific mortality were assessed using a Coxs regression model. Multivariate hazard ratios (HRs) were adjusted for age, body mass index, drinking and smoking status, physical activity, sleep duration, education, occupation, marital status, perceived mental stress, and medical history. RESULTS During the follow-up period, 10,021 deaths were recorded. Men and women with ikigai had decreased risks of mortality from all causes in the long-term follow-up period; multivariate HRs (95% confidence intervals, CIs) were 0.85 (0.80-0.90) for men and 0.93 (0.86-1.00) for women. The risk of cardiovascular mortality was reduced in men with ikigai; the multivariate HR (95% CI) was 0.86 (0.76-0.97). Furthermore, men and women with ikigai had a decreased risk for mortality from external causes; multivariate HRs (95% CIs) were 0.74 (0.59-0.93) for men and 0.67 (0.51-0.88) for women. CONCLUSION The findings suggest that a positive psychological factor such as ikigai is associated with longevity among Japanese people.

The Tohoku Medical Megabank Project: Design and Mission

The Great East Japan Earthquake (GEJE) and resulting tsunami of March 11, 2011 gave rise to devastating damage on the Pacific coast of the Tohoku region. The Tohoku Medical Megabank Project (TMM), which is being conducted by Tohoku University Tohoku Medical Megabank Organization (ToMMo) and Iwate Medical University Iwate Tohoku Medical Megabank Organization (IMM), has been launched to realize creative reconstruction and to solve medical problems in the aftermath of this disaster. We started two prospective cohort studies in Miyagi and Iwate Prefectures: a population-based adult cohort study, the TMM Community-Based Cohort Study (TMM CommCohort Study), which will recruit 80 000 participants, and a birth and three-generation cohort study, the TMM Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study), which will recruit 70 000 participants, including fetuses and their parents, siblings, grandparents, and extended family members. The TMM CommCohort Study will recruit participants from 2013 to 2016 and follow them for at least 5 years. The TMM BirThree Cohort Study will recruit participants from 2013 to 2017 and follow them for at least 4 years. For children, the ToMMo Child Health Study, which adopted a cross-sectional design, was also started in November 2012 in Miyagi Prefecture. An integrated biobank will be constructed based on the two prospective cohort studies, and ToMMo and IMM will investigate the chronic medical impacts of the GEJE. The integrated biobank of TMM consists of health and clinical information, biospecimens, and genome and omics data. The biobank aims to establish a firm basis for personalized healthcare and medicine, mainly for diseases aggravated by the GEJE in the two prefectures. Biospecimens and related information in the biobank will be distributed to the research community. TMM itself will also undertake genomic and omics research. The aims of the genomic studies are: 1) to construct an integrated biobank; 2) to return genomic research results to the participants of the cohort studies, which will lead to the implementation of personalized healthcare and medicine in the affected areas in the near future; and 3) to contribute the development of personalized healthcare and medicine worldwide. Through the activities of TMM, we will clarify how to approach prolonged healthcare problems in areas damaged by large-scale disasters and how useful genomic information is for disease prevention.

Genome-wide association study identifies 112 new loci for body mass index in the Japanese population

Obesity is a risk factor for a wide variety of health problems. In a genome-wide association study (GWAS) of body mass index (BMI) in Japanese people (n = 173,430), we found 85 loci significantly associated with obesity (P < 5.0 × 10−8), of which 51 were previously unknown. We conducted trans-ancestral meta-analyses by integrating these results with the results from a GWAS of Europeans and identified 61 additional new loci. In total, this study identifies 112 novel loci, doubling the number of previously known BMI-associated loci. By annotating associated variants with cell-type-specific regulatory marks, we found enrichment of variants in CD19+ cells. We also found significant genetic correlations between BMI and lymphocyte count (P = 6.46 × 10−5, rg = 0.18) and between BMI and multiple complex diseases. These findings provide genetic evidence that lymphocytes are relevant to body weight regulation and offer insights into the pathogenesis of obesity.

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.