High Parity Is an Independent Risk Factor for Tooth Loss in Women: A Community-Based Takahata Study in Japan.

Risk factors for tooth loss have been widely examined previously. However, no previous study has comprehensively investigated the risk factors, including lifestyle-related specific factors (parity, oral health habits, and socioeconomic status), for fewer than 20 teeth among women in the general population in Japan. This cross-sectional study explored the association of these risk factors, especially parity, with having fewer than 20 teeth among Japanese women. A self-reported questionnaire including items on lifestyle-related risk factors (parity, oral health, diet [e.g., alcohol and sucrose consumption]) and socioeconomic status was sent by post to female residents (age ≥ 40 years) of Takahata town, Yamagata Prefecture, in 2005. Multivariate logistic regression analysis including 3,854 eligible participants was performed to investigate the association between various factors (including parity) and having fewer than 20 teeth. The results indicated that, compared with nulliparous women, women with two, three, and four completed pregnancies had 2.485-, 2.844-, and 4.305-fold increased risk of having fewer than 20 teeth, respectively. Our study is the largest-scale study of the general female population in Japan and the first study to comprehensively investigate risk factors (parity, oral health status, and socioeconomic status) for fewer than 20 teeth. We thus found that higher parity, especially, two or more, was independent risk factors for having less than 20 teeth among Japanese women. In conclusion, the present study emphasizes the importance of good oral health habits in women, especially, during pregnancy and in the postpartum period, to maintain 20 or more teeth.

Increased plasma xanthine oxidoreductase activity deteriorates coronary artery spasm.

Increased reactive oxygen species (ROS) contributes to the development of endothelial dysfunction, which is involved in coronary artery spasm (CAS). Xanthine oxidoreductase (XOR) plays a pivotal role in producing both uric acid and ROS. However, the association between plasma XOR activity and CAS has not been elucidated. The aim of this study was to investigate whether plasma XOR activity is associated with CAS. We measured XOR activity in 104 patients suspected for CAS, who presented without significant coronary artery stenosis and underwent intracoronary acetylcholine provocation tests. CAS was provoked in 44 patients and they had significantly higher XOR activity as compared with those without CAS. The patients were divided into three groups based on the XOR activity. The prevalence rate of CAS was increased with increasing XOR activity. A multivariate logistic regression analysis showed that the 3rd tertile group exhibited a higher incidence of CAS as compared with the 1st tertile group [odds ratio (OR) 6.9, P = 0.001) and the 2nd tertile group (OR 3.2, P = 0.033) after adjustment for conventional CAS risk factors, respectively. The C index was significantly improved by the addition of XOR activity to the baseline model based on CAS risk factors. Furthermore, the 3rd tertile group had the highest incidence of severe spasm defined as total obstruction, flow-limiting stenosis, diffuse spasm, multivessel spasm, and/or lethal arrhythmia. This is a first report to elucidate the association of plasma XOR activity with CAS. Increased plasma XOR activity is significantly associated with CAS.

The association between urinary sodium excretion and blood pressure in a community-based population: the Yamagata (Takahata) study.

BACKGROUND: The association between salt intake and blood pressure levels is still inconclusive, and may be influenced by patient characteristics. We thus conducted a community-based cross-sectional study. METHODS: This study included 2297 subjects aged ≥ 40 years not on antihypertensive medication at the time of a health check-up. We examined the association between blood pressure levels and the estimated amount of 24-h urinary sodium excretion (e24hUNa) stratified by background characteristics. The 24-h urinary excretion levels of sodium and potassium were estimated from Kawasaki's equation using a spot urine sample. RESULTS: The association of systolic blood pressure (SBP) and diastolic blood pressure (DBP) with e24hUNa was significantly positive in a multiple linear regression model adjusted for confounders including age, sex, smoking, alcohol consumption, body mass index, diabetes, hypercholesterolemia, renal function, and potassium excretion. The regression coefficients of changes in SBP and DBP per 1 SD increase in e24hUNa (53 mEq/day) were + 1.91 mmHg and + 0.94 mmHg, respectively. In the subgroup analyses, the increase in SBP was especially greater in the elderly, in subjects with diabetes, and in subjects with reduced renal function compared to those in the counterparts. The association between SBP and e24hUNa was insignificant in subjects with eGFR ≥ 90 ml/min/1.73m2, while the association with progression of renal dysfunction was stronger and significant. CONCLUSIONS: These results demonstrated that the association between blood pressure and urinary sodium excretion was strengthened by characteristics of subjects such as aging, presence of diabetes, and renal impairment in the community-based population.

Risk factors for tooth loss in community-dwelling Japanese aged 40 years and older: the Yamagata (Takahata) study.

OBJECTIVES: The aim of the present study was to investigate comprehensively the risk factors, including some lifestyle-associated factors, oral health habits, and socioeconomic status, for having less than 20 teeth in cross-sectional study in the general population of Japan. MATERIALS AND METHODS: The survey population was the general population of individuals aged greater than or equal to 40 years in Takahata town, Japan in 2005. A postal survey with a self-administered questionnaire was distributed, and 7542 participants were entered into the final statistical analysis. The self-administered questionnaire contained items regarding some lifestyle-associated factors, oral health, and dietary intake, including alcohol and sucrose consumption. To confirm the independent association between the number of teeth and several parameters, a multivariate logistic regression analysis was used to estimate the adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: A low educational status, no dental check-ups, low frequency of brushing, older age, and smoking habit were independent risk factors for less than 20 teeth. A low educational status was a particularly significant risk factor for less than 20 teeth (OR = 1.352, 95% CI = 1.125-1.624). CONCLUSION: These results emphasize the importance of good oral health habits, such as frequent tooth brushing, routine dental check-ups, and no smoking, and indicate that more appropriate and compulsory education regarding oral health is needed to lessen the education level-derived differences in oral health. CLINICAL RELEVANCE: Poor oral health habits and low educational status are the independent risk factors for having less than 20 teeth.

Fewer teeth are a risk factor for being underweight in community-dwelling Japanese aged 40 years and older: The Yamagata (Takahata) Study.

OBJECTIVE: The aim of the present study was to investigate comprehensively, the risk factors for underweight in cross-sectional study in the general population of Japan. METHODS: The survey population was the general population of individuals aged >40 years in Takahata town, Japan in 2005. A postal survey in the form of a self-administered questionnaire was distributed, and 6084 individuals were entered into the final statistical analysis. The self-administered questionnaire contained items regarding lifestyle, oral health status, socio-economic status and dietary intake. To examine the independent relationships between an underweight status and several parameters, a multivariate logistic regression analysis was used to estimate adjusted odds ratios (ORs). RESULTS: The number of teeth, age, alcohol consumption, hypertension, spousal status, smoking habit, appetite, body weight at 20 years of age, habit of going out and physical activity were independently associated with an underweight status compared with the normal weight group. Individuals with fewer than 10 teeth were especially more likely to be underweight than individuals with more than 20 teeth (OR = 1.956, 95% CI = 1.261-3.035). CONCLUSION: This study showed an independent association between the number of teeth and an underweight status, indicating that fewer teeth can increase the risk of being underweight.

Circulating Surfactant Protein-D Is Associated With Clinical Outcomes in Peripheral Artery Disease Patients Following Endovascular Therapy.

BACKGROUND: Peripheral artery disease (PAD) is a risk factor for the development of cardiovascular disease and death. Surfactant protein-D (SP-D) is a 43-kDa protein secreted from type II pneumocytes in the lungs. Recent studies have demonstrated that circulating SP-D plays a key role in the development of atherosclerosis and is related to clinical outcomes in patients with ischemic heart disease. However, it remains unclear whether circulating SP-D is associated with clinical outcomes in patients with PAD.Methods and Results:We enrolled 364 patients with PAD who underwent endovascular therapy. We measured serum levels of SP-D and Krebs von den Lungen-6 (KL-6). During a median follow-up period of 974 days, there were 69 major adverse cardiovascular and leg events (MACLE), including 48 major adverse cardiovascular events (MACE). Kaplan-Meier analysis demonstrated that patients with high SP-D (≥110 ng/mL) had higher rates of MACE and MACLE than those with low SP-D. Multivariate Cox proportional hazard regression analysis demonstrated that SP-D, but not KL-6, was an independent predictor of MACE and MACLE. The addition of SP-D to known risk factors significantly improved the C index and net reclassification index. The circulating SP-D level was affected by sex, diabetes mellitus, and cilostazol prescription. CONCLUSIONS: Circulating SP-D was associated with clinical outcomes in patients with PAD, suggesting that it may be a new therapeutic target in these patients.

Impact of Objective Malnutrition Status on the Clinical Outcomes in Patients With Peripheral Artery Disease Following Endovascular Therapy.

BACKGROUND: Peripheral artery disease (PAD) is an athero-occlusive disease and a known risk factor for cardiovascular events. The controlling nutritional status (CONUT) score and geriatric nutritional risk index (GNRI) are objective tools for evaluating malnutrition and are reportedly associated with poor clinical outcomes in patients with fatal diseases. However, the effect of malnutrition on the clinical outcomes in patients with PAD remains unclear.Methods and Results:We enrolled 357 patients with PAD who underwent endovascular therapy. Malnutrition was diagnosed by CONUT score and GNRI as in previous reports. During a median follow-up period of 1,071 days, there were 67 major adverse cardiovascular and leg events (MACLEs). The CONUT score- and GNRI-based malnutrition statuses were identified in 56% and 46% of the patients, respectively. Proportion of malnutrition increased with advancing Fontaine class. The multivariate Cox proportional hazard regression analysis demonstrated that both the CONUT score- and GNRI-based malnutrition status was an independent predictor of MACLEs. The Kaplan-Meier analysis demonstrated that the MACLE ratio increased with deteriorating malnutrition. Finally, the addition of the CONUT score or GNRI to the known risk factors significantly improved the net reclassification index and integrated discrimination index. CONCLUSIONS: Malnutrition was common and closely associated with the clinical outcomes in patients with PAD, indicating that it is a novel therapeutic target in the management of these patients.

Biatrial volume, estimated using magnetic resonance imaging, predicts atrial fibrillation recurrence after ablation.

INTRODUCTION: The predictive value of left atrial volume (LAV) in atrial fibrillation (AF) is known, but the relationship of right atrial volume (RAV) and biatrial volume (BAV) with AF recurrence after pulmonary vein isolation (PVI) is not clear. Cardiac magnetic resonance (CMR) imaging allows us to more precisely quantify atrial volume. We investigated LAV, RAV, and BAV as predictors of AF recurrence following PVI in AF patients. METHODS AND RESULTS: We assessed 100 AF patients (age = 59.8 ± 9.5 years, 74 males, 26 females) who underwent nonenhanced CMR before their first PVI. LAV and RAV were measured using CMR. All patients were in sinus rhythm during CMR. BAV was calculated as the sum of LAV and RAV. During the 8-month follow-up, AF recurrence occurred in 23 patients. LAV, RAV, and BAV were significantly greater in patients with AF recurrence than in those without (LAV, 103.7 ± 25.8 vs 81.8 ± 24.2 mL, P < 0.001; RAV, 109.4 ± 27.0 vs 82.2 ± 19.6 mL, P < 0.001; BAV, 213.1 ± 46.7 vs 164.1 ± 38.7 mL, P < 0.001). Multivariate logistic regression analysis revealed that increased LAV, RAV, and BAV were significantly correlated with AF recurrence. The area under the receiver operation characteristic curve for BAV showed the largest value compared to that of LAV or RAV alone. CONCLUSIONS: LAV, RAV, and BAV were independent predictors of AF recurrence after PVI. Quantifying BAV may additionally improve prognostic stratification compared with LAV or RAV.

Impact of reduced forced expiratory volume on cardiac prognosis in patients with chronic heart failure.

In patients with chronic heart failure (CHF), comorbidity of airflow limitation is associated with poor outcomes. The forced expiratory volume in 1 s (FEV1) is used to evaluate the severity of airflow limitation. However, the impact of FEV1 severity on prognosis has only been partially elucidated in patients with CHF. In total, 248 consecutive patients with CHF who successfully fulfilled spirometric measurement criteria were enrolled and prospectively followed. Percent predicted FEV1 (FEV1%predicted) was associated with the New York Heart Association Functional Classification. FEV1%predicted was significantly associated with diastolic dysfunction, evaluated using echocardiography; elevated inflammation markers; and increased pulmonary arterial pressure. There were 60 cardiac events, including 9 cardiac-related deaths and 51 re-hospitalizations due to the exacerbation of CHF during a follow-up period. Kaplan-Meier analysis revealed that the lowest FEV1%predicted group had the highest event rate, irrespective of the presence of smoking history. Multivariate Cox proportional hazard analysis showed that FEV1%predicted was an independent predictor of cardiac events after adjusting for confounders. The net reclassification improvement and integrated discrimination improvement were improved by the addition of FEV1%predicted to other cardiac risk factors. Decreased FEV1%predicted was independently associated with the poor cardiac outcomes in patients with CHF.

The impact of non-alcoholic fatty liver disease fibrosis score on cardiac prognosis in patients with chronic heart failure.

Liver abnormalities have a strong impact on clinical outcomes in patients with heart failure (HF), and are known as cardio-hepatic syndrome. The non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS) has been developed to identify liver fibrosis in patients with NAFLD. It remains to be determined whether NFS is associated with cardiovascular prognosis in patients with chronic heart failure (CHF). We calculated NFS in 516 patients with CHF admitted to our hospital. The clinical endpoints were deaths due to progressive HF, myocardial infarction, stroke, and sudden cardiac death, and rehospitalization for worsening HF. There were 173 cardiovascular events noted during a median follow-up of 464 days. Patients with cardiovascular events showed a higher NFS as compared with those without. We divided the patients into four groups according to quartiles of NFS. The proportion of New York Heart Association functional class III/IV and serum brain natriuretic peptide levels were increased with increasing NFS. Kaplan-Meier analysis revealed that cardiovascular event rate was increased with increasing NFS in patients with CHF. In multivariate Cox proportional hazards analysis, NFS was independently associated with cardiovascular events after adjustment for confounding factors. Elevated NFS was associated with unfavorable outcomes in patients with CHF. Liver fibrosis assessed by NFS may provide valuable prognostic information in patients with CHF.

MafB enhances the phagocytic activity of RAW264.7 macrophages by promoting Fcgr3 expression.

This study was designed to investigate whether MafB influences the phagocytic activity of macrophages by modulating the expression of the Fc receptors for IgG (FcγRs), Fcgr2b and Fcgr3. In macrophages, FcγRs are critical for the phagocytosis of opsonized pathogens. Of these receptors, Fcgr3 has been shown to play an important role in host defense. As a model to evaluate the mechanism by which MafB influences phagocytosis, we utilized a macrophage cell-line that constitutively expresses a MafB-specific short hairpin (sh)RNA (RAW264.7-MafB-shRNA). Specifically, the levels of Fc receptor mediated-phagocytosis and the levels of FcγRs surface expression were evaluated by flow cytometry analysis, while quantitative real-time PCR analysis was utilized to examine the mRNA expression levels of FcγRs. Compared to the control cell population, RAW264.7-MafB-shRNA cells exhibited significant reductions in Fcgr3 expression and Fc receptor-mediated phagocytosis, but no difference in Fcgr2b expression. Likewise, there was markedly decreased surface expression of Fcgr3 antigen, but not Fcgr2b antigen, in RAW264.7-MafB-shRNA, compared to the control cells. Meanwhile, the observed reduction in the phagocytic activity of the MafB-shRNA-expressing cells was attenuated by ectopic expression of Fcgr3. Together, the results presented here indicate that MafB influences the phagocytic activity of macrophages by promoting Fcgr3, but not Fcgr2b, expression.

The Neutrophil-to-Lymphocyte Ratio Predicts All-Cause Mortality in Patients with Implantable Cardioverter Defibrillators.

BACKGROUND: The relationship between the neutrophil-to-lymphocyte ratio (NLR) and outcome in patients with implantable cardioverter-defibrillators (ICDs) is unclear. METHODS AND RESULTS: Consecutive patients with cardiomyopathy who had received an ICD (n = 120, mean age 64 ± 11 years) were prospectively enrolled. Blood samples were obtained on the morning of the day of implantation. Patients were followed for a median period of 61.2 months, to an endpoint of all-cause mortality or appropriate ICD shock, which occurred in 35 (29%) and 28 (23%) patients, respectively. Multivariate Cox analysis revealed that secondary prevention was only associated with appropriate ICD shocks. The NLR, brain natriuretic peptide level, and estimated glomerular filtration rate were independent predictors of all-cause mortality but not of appropriate ICD shocks. Subgroup analysis revealed that a high NLR (≥2.1) was valuable for anticipating all-cause mortality among patients who had received ICDs for primary or secondary prevention. A high NLR was also associated with death prior to appropriate ICD shock. CONCLUSION: Evaluating the NLR may be useful for predicting outcomes in patients with cardiomyopathy who have received ICDs.

Serum carboxy-terminal telopeptide of type I collagen (I-CTP) is predictive of clinical outcome in peripheral artery disease patients following endovascular therapy.

Peripheral artery disease (PAD) is a risk factor for the development of heart failure and mortality. The serum levels of carboxy-terminal telopeptide of type I collagen (I-CTP), a marker for collagen degradation derived from the extracellular matrix of vascular and myocardial tissue, is reportedly a useful marker for cardiac events in patients with heart disease. However, it remains unclear whether I-CTP can predict poor clinical outcome in patients with PAD. Serum I-CTP was measured in 246 consecutive PAD patients who underwent endovascular therapy. Patients were prospectively followed during a median follow-up period of 887 days with the end points of major adverse cardiovascular events (MACE). I-CTP was significantly higher in patients with critical limb ischemia than those without. A multivariate Cox proportional hazard analysis revealed that I-CTP was an independent predictor of MACE after adjusting for confounding factors. Patients were stratified into three groups based on I-CTP level tertile, and those with third tertile had higher levels of brain natriuretic peptide levels and high-sensitivity C-reactive protein compared to the other two groups. Kaplan-Meier analysis demonstrated that patients in the highest tertile of I-CTP also had the greatest risk of MACE. The net reclassification index significantly improved with the addition of I-CTP to basic predictors. I-CTP is a reliable marker and indicator for MACE in patients with PAD.

Associations between serum uric acid levels and the incidence of nonfatal stroke: a nationwide community-based cohort study.

BACKGROUND: Hyperuricemia is an established risk factor for cardiovascular events and mortality. This study investigated the association between serum uric acid and the incidence of nonfatal stroke in a Japanese community-based population. METHODS: We used a nationwide database of 155,322 subjects (aged 40-73, male 39 %) who participated in the annual "Specific Health Check and Guidance in Japan" checkup from 2008 to 2010. We examined the relationship between the quintiles of serum uric acid levels at baseline and the incidence of nonfatal stroke during a 2-year study period using self-reported data. RESULTS: The crude incidence of nonfatal stroke was significantly associated with serum uric acid levels at baseline, showing the lowest values in subjects with the 3rd quintile (Q3: men, 5.0-5.6; women, 3.8-4.3) of uric acid levels (mg/dL) and the highest values in subjects with the highest quintile (Q5: men ≥7.1, women ≥5.5) both in men and women (P < 0.05). In multivariate-adjusted logistic regression analysis, the odds ratio (OR) of the Q5 group was significantly higher than for the Q3 group in both men and women [men: OR 1.26, 95 % confidence interval (CI) 1.04-1.54, women: OR 1.24, 95 % CI 1.00-1.48]. In the subgroup analysis, the OR of the Q5 group of uric acid levels for incident stroke was high, irrespective of characteristics such as age, sex, and renal function. CONCLUSIONS: This study has shown that serum uric acid is independently associated with the incidence of nonfatal stroke in the general Japanese population.

DPP4 Inhibition Ameliorates Cardiac Function by Blocking the Cleavage of HMGB1 in Diabetic Mice After Myocardial Infarction.

High mobility group box 1 (HMGB1), a ubiquitous DNA-binding protein, promotes angiogenesis and tissue repair, resulting in restored cardiac function after myocardial infarction (MI). Although dipeptidyl peptidase 4 (DPP4) degrades certain peptides, it remains unclear as to whether HMGB1 is a substrate of DPP4 and whether DPP4 inhibition prevents the cleavage of HMGB1.In transgenic mice with cardiac-specific overexpression of HMGB1 (TG) and wild-type mice (WT), a diabetic state was induced by streptozotocin, and MI was created by ligation of the left anterior descending coronary artery. To inhibit DPP4 activity, a DPP4 inhibitor anagliptin was used. The plasma levels of HMGB1, infarct size, echocardiographic data, angiogenesis, and vascular endothelial growth factor (VEGF) expression in the peri-infarct area were compared among non-diabetic MI WT/TG, diabetic MI WT/TG, and anagliptin-treated diabetic MI WT/TG mice.DPP4 activity was increased in the diabetic state and blocked by anagliptin administration. The HMGB1 plasma levels were reduced in the diabetic TG compared with the non-diabetic TG mice, but DPP4 inhibition with anagliptin increased HMGB1 plasma levels in the diabetic TG mice. The infarct area was significantly larger in the diabetic TG than in the non-diabetic TG mice, and it was reduced by DPP4 inhibition. Cardiac function, angiogenesis, and VEGF expression were impaired in the diabetic TG mice, but they were ameliorated by the DPP4 inhibition to levels similar to those found in the non-diabetic TG mice.The DPP4 inhibitor ameliorated cardiac function by inhibiting the inactivation of HMGB1 in diabetic mice after MI.

Gene-environment interactions in obesity: implication for future applications in preventive medicine.

Obesity is associated with environmental factors; however, information about gene-environment interactions is lacking. We aimed to elucidate the effects of gene-environment interactions on obesity, specifically between genetic predisposition and various obesity-related lifestyle factors, using data from a population-based prospective cohort study. The genetic risk score (GRS) calculated from East Asian ancestry single-nucleotide polymorphisms was significantly associated with the body mass index (BMI) at baseline (P<0.001). Significant gene-environment interactions were observed for six nutritional factors, alcohol intake, metabolic equivalents-hour per day and the homeostasis model assessment ratio. The GRS altered the effects of lifestyle factors on BMI. Increases in the BMI at baseline per unit intake for each nutritional factor differed depending on the GRS. However, we did not observe significant correlations between the GRS and annual changes in BMI during the follow-up period. This study suggests that the effects of lifestyle factors on obesity differ depending on the genetic risk factors. The approach used to evaluate gene-environment interaction in this study may be applicable to the practice of preventive medicine.

The Clinical Value of Nongated Dual-Source Computed Tomography in Atrial Fibrillation Catheter Ablation.

INTRODUCTION: Using a high-pitch dual-source CT (DSCT), we aimed to quantify the amounts of contrast media, radiation doses, and image qualities in patients undergoing pulmonary vein (PV) isolation. METHODS AND RESULTS: The study enrolled 60 patients who were randomly assigned in a 1: 1: 1 ratio to undergo ECG-gated 64-slice multidetector computed tomography (MDCT; group I, n = 20), ECG-gated 128-DSCT (group II, n = 20), and nongated 128-DSCT (group III, n = 20). The total amount of contrast media was lower in groups II and III compared with group I (I: 54.7 ± 5.6, II: 26.6 ± 2.7, and III: 28.7 ± 6.9 mL, P < 0.001). The CT dose index was lower in groups II and III compared with group I (I: 73.1 ± 5.2, II: 3.5 ± 0.1, and III: 3.7 ± 0.1 mGy, P < 0.001). The dose length product was lower in groups II and III compared with group I (I: 1154.8 ± 82.8, II: 75.4 ± 2.3, and III: 77.2 ± 1.9 mGy × cm, P < 0.001). The total CT effective radiation dose was lower in groups II and III compared with group I (I: 16.2 ± 1.2, II: 1.1 ± 0.1, and III: 1.1 ± 0.1 mSv, P < 0.001). The total CT scan duration was shorter in group III compared with groups I and II (I: 30.8 ± 2.2, II: 23.4 ± 3.6, and III: 16.0 ± 2.4 minutes, P < 0.001). There were no significant differences in quality for integrated electroanatomical mapping (EAM) and parameters associated with PV isolation among the 3 groups. CONCLUSION: Nongated 128-DSCT provides sufficient image quality to allow integrated EAM while exposing the patient to less contrast media, lower radiation doses, and shorter CT scan durations.

Regional Differences in Frequency of Warfarin Therapy and Thromboembolism in Japanese Patients With Non-Valvular Atrial Fibrillation　- Analysis of the J-RHYTHM Registry.

BACKGROUND: The proportion of patients with atrial fibrillation (AF) treated with anticoagulation varies from country to country. In Japan, little is known about regional differences in frequency of warfarin use or prognosis among patients with non-valvular AF (NVAF). METHODS AND RESULTS: In J-RHYTHM Registry, the number of patients recruited from each of 10 geographic regions of Japan was based on region population density. A total of 7,406 NVAF patients were followed up prospectively for 2 years. At baseline, significant differences in various clinical characteristics including age, sex, type of AF, comorbidity, and CHADS2score, were detected among the regions. The highest mean CHADS2score was recorded in Shikoku. Frequency of warfarin use differed between the regions (P<0.001), with lower frequencies observed in Hokkaido and Shikoku. Baseline prothrombin time international normalized ratio differed slightly but significantly between the regions (P<0.05). On univariate analysis, frequency of thromboembolic events differed among the regions (P<0.001), with the highest rate seen in Shikoku. An inverse correlation was detected between frequency of thromboembolic and of major hemorrhagic events (P=0.062). On multivariate analysis, region emerged as an independent risk for thromboembolism. CONCLUSIONS: Thromboembolic risk, frequency of warfarin use, and intensity and quality of warfarin treatment differed significantly between geographic regions of Japan. Region was found to be an independent predictor of thromboembolic events. (Circ J 2016; 80: 1548-1555).

Contact Force-Guided Deep Engagement with a Steerable Sheath in the Distal Great Cardiac Vein: A Case Report.

Ablation of ventricular tachycardia originating from the great cardiac vein involves the difficult step of deep engagement with an ablation catheter. The catheter and a steerable sheath (MobiCath, Biosense Webster, Diamond Bar, CA, USA) were advanced alternately only when the contact force vector was parallel to the coronary venous system. Deep engagement with a steerable sheath ensured a powerful backup force during ablation.

Additive clinical value of serum brain-derived neurotrophic factor for prediction of chronic heart failure outcome.

The importance of the central nervous system in cardiovascular events has been recognized. Recently, brain-derived neurotrophic factor (BDNF), a member of the neurotrophic factor family, is involved in depression mechanisms and also in stress and anxiety. Because BDNF is reported about cardioprotective role, we elucidated whether BDNF is associated with cardiovascular events in patients with chronic heart failure (CHF). We examined serum BDNF levels in 134 patients with CHF and 23 control subjects. The patients were followed to register cardiac events for a median of 426 days. BDNF was significantly lower in CHF patients than in control subjects (25.8 ± 8.4 vs 14.7 ± 8.4, P < 0.0001). Serum BDNF was also lower in patients with cardiac events than in event-free patients (16.1 ± 8.0 vs 12.5 ± 8.5, P < 0.0001). The cutoff value of BDNF was determined by performing receiver operating characteristic curve analysis. Kaplan-Meier analysis demonstrated that patients with low levels of BDNF experienced higher rates of cardiac events than those with high levels of BDNF. Multivariate Cox hazard analysis demonstrated that low BDNF levels (≤12.4 ng/mL) were an independent prognostic factor for cardiac events (hazard ratio 2.932, 95 % confidence interval 1.622-5.301; P = 0.0004). Adding levels of BDNF to the model with BNP levels, age, and eGFR for the prediction of cardiac events yielded significant net reclassification improvement of 0.429 (P < 0.001) and an integrated discrimination improvement of 0.101 (P < 0.001). Low serum BDNF levels were found in patients with CHF, and these levels were found to be independently associated with an increased risk of cardiac events.