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Aims: Myocardial fibrosis of the left ventricle (LV) is a prognostic factor in dilated cardiomyopathy (DCM). This study aims to evaluate whether fibrosis of right ventricular (RV) endomyocardial biopsy (EMB) can predict the degree of LV fibrosis beforehand in DCM. Methods and results: Fibrosis extent in 70 RV‐EMB specimens of DCM diagnosis was compared with that in the whole cross‐sectional LV of excised hearts in the same patients (52 explanted hearts for transplant and 18 autopsied hearts). The median interval between biopsy and excision was 4.1 (0.13–19.3) years. The fibrosis area ratio of the EMBs and excised hearts were evaluated via image analysis. The distribution of cardiovascular magnetic resonance–late gadolinium enhancement (LGE) in the intraventricular septum was classified into four quartile categories. The fibrosis area ratio in RV‐EMB correlated significantly with that in the short‐axis cut of the LV of excised hearts (r = 0.82, P < 0.0001) and with a diffuse pattern of LGE (r = 0.71, P = 0.003). In a multivariate model, after adjusting for the interval between biopsy performance and heart excision, the fibrosis area ratio in RV‐EMB was associated with that in LV‐excised heart (regression coefficient, 0.82; 95% confidence interval, 0.68–0.95; P < 0.0001). Conclusions: The fibrosis observed in RV‐EMB positively correlated with the extent of fibrosis in the LV of excised hearts in patients with DCM. The study findings may help predict LV fibrosis, considered a prognostic factor of DCM through relatively accessible biopsy techniques. [ABSTRACT FROM AUTHOR]

Driveline infection (DLI) is treated by local irrigation via driveline exit site (DLES) and surgical debridement is considered in patients with deep DLI. We describe three cases of deeply progressed superficial DLI that were considered to require surgical debridement but could be treated with a unique catheter cleaning method using intravenous indwelling catheter, a cotton swab with 10% silver nitrate solution and a monofilament nylon thread. Case 1 was a 60-y-old man with ischemic cardiomyopathy with left ventricular assist device implantation 2 y before. Daily bedside debridement with 10% silver nitrate solution was performed via the DLES. Case 2 was a 43-y-old man with ischemic cardiomyopathy who had recurrent DLI with methicillin-resistant Staphylococcus aureus , and case 3 was a 49-y-old woman with hypertrophic cardiomyopathy, who also showed improvement in their DLI with Pseudomonas aeruginosa. These cleaning methods may be useful for the deeply progressed superficial DLI. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to describe physiological changes in endometrial blood flow (minute arterioles running through the endometrium) from ovulation to the mid‐luteal phase using superb microvascular imaging. Material and methods: The study involved 17 women (median age, 32.5 years; first to third interquartile range, 29.8–40.0 years) with regular menstrual cycles who were managed in our institute from 2020 to 2021. The uterus was delineated at the sagittal section using transvaginal ultrasonography incorporated with superb microvascular imaging. For each participant, a total of 28 cycles were observed; 17 cycles observed within one day of ovulation and the implantation period, 5–7 days (D5–7) after ovulation in the same cycle, and nine cycles in which only ovulation was observed, and two cycles in which only D5–7 was observed. Therefore, 26 and 19 images at ovulation and D5–7, respectively, were acquired. Endometrial blood flow was evaluated by depth of the vascular signal in the endometrium and categorized as follows: signals only in the basal layer of the endometrium (grade 1), reaching up to half the endometrium (grade 2), and covering the whole endometrium (grade 3). Changes in the grade of endometrial blood flow from ovulation to D5–7 after ovulation, and the relationship between the grade of endometrial blood flow and the endometrial thickness on ovulation and D5–7 after ovulation, were analyzed. Statistical significance was set at p < 0.05. Results: The endometrial blood flow from ovulation to D5–7 after ovulation during the same menstrual period showed a downgrade in 14 of 17 cycles (82.3%) and no change in the remaining three cycles (17.6%), indicating a decrease in the endometrial blood flow from ovulation to D5–7 after ovulation (p = 0.001). There were differences between the grade of endometrial blood flow and median endometrial thickness on ovulation (grade 1: 5.9 mm, grade 2: 9.1 mm, and grade 3: 11.2 mm); however, no differences in the endometrial thickness were found between the grades on D5–7 after ovulation. Conclusions: In the normal menstrual cycle, endometrial blood flow decreased from ovulation to the mid‐luteal phase, and the endometrial thickness in the ovulatory phase was related to the endometrial perfusion. [ABSTRACT FROM AUTHOR]

Background: Recent studies have reported atrial involvement and coexistence of aortic stenosis in transthyretin (ATTR) cardiac amyloidosis (CA). However, pathological reports of extraventricular ATTR amyloid deposits in atrial structures or heart valves are limited, and the clinical implications of ATTR amyloid deposits outside the ventricles are not fully elucidated. Case presentation: We report 3 cases of extraventricular ATTR amyloid deposits confirmed in surgically resected aortic valves and left atrial structures, all of which were unlikely to have significant ATTR amyloidosis infiltrating the ventricles as determined by multimodality evaluation including 99mtechnetium-pyrophosphate scintigraphy, cardiac magnetic resonance, endomyocardial biopsy and their mid-term clinical course up to 5 years. These findings suggested that these were extraventricular ATTR amyloid deposits localized in the aortic valve and the left atrium. Conclusions: While long-term observation is required to fully clarify whether these extraventricular ATTR amyloid deposits are truly localized outside the ventricles or are early stages of ATTR-CA infiltrating the ventricles, our 3 cases with multimodality evaluations and mid-term follow up suggest the existence of extraventricular ATTR amyloid deposits localized in the aortic valve and left atrial structures. [ABSTRACT FROM AUTHOR]

Background Propionic acidaemia (PA) is an autosomal recessive disorder resulting from deficiency of propionyl-CoA carboxylase, a mitochondrial enzyme that metabolizes propionyl-CoA. Generally, patients with PA develop symptoms in the neonatal period due to protein intake through breastfeeding; however, late-onset PA with atypical symptoms, including cardiomyopathy, has been recently reported. Case summary We present the case of a 25-year-old male with late-onset PA complicated by advanced heart failure (HF) due to isolated secondary dilated cardiomyopathy, who required left ventricular assist device (LVAD) implantation and finally underwent heart transplantation (HTx). Initially, the patient developed HF at the age of 16 and was diagnosed with mitochondrial cardiomyopathy. Due to refractory HF, he underwent an LVAD implantation and was scheduled for HTx. During the preoperative period for HTx, the patient suffered from sepsis due to the worsening of LVAD driveline exit-site infection complicated by overt metabolic acidosis, finally leading to the diagnosis of late-onset PA. After this diagnosis, adequate nutritional interventions were introduced, and the cardiac function was partially restored enough for him to be weaned-off LVAD; however, the patient became inotrope dependent and underwent HTx. The post-HTx course was uneventful with special nutritional management, and he has experienced no adverse metabolic events in the past 3 years. Discussion Late-onset PA can cause isolated adult-onset cardiomyopathy, and LVAD or HTx should be considered when PA is complicated by advanced HF and is unresponsive to conventional medical therapies. [ABSTRACT FROM AUTHOR]

We present the case of an 82-year-old man whose left coronary ostium became obstructed 15 months after transcatheter aortic valve replacement (TAVR) with a balloon-expandable valve. The patient underwent TAVR for symptomatic severe aortic stenosis with no complications. Fifteen months after the initial TAVR, the patient complained of chest pain while exercising, and the exercise stress myocardial perfusion scintigraphy demonstrated the development of regional myocardial ischemia in the region of the left coronary artery. Coronary angiography implied severe stenosis in the ostium of the left coronary artery. Computed tomography angiography and intravascular ultrasonography indicated a soft tissue component along with stent struts, which was considered to cause delayed coronary obstruction. Our report emphasizes the importance of having a low threshold for clinically suspecting delayed coronary obstruction in patients who have undergone TAVR, even after several years of the procedure. < Learning objective: Delayed coronary obstruction (DCO) should be suspected in patients presenting with new ischemic symptoms after transcatheter aortic valve replacement (TAVR). DCO may occur even in the case of TAVR with a balloon-expandable prosthetic valve, on antithrombotic regimens, and several years after the initial procedure.> [ABSTRACT FROM AUTHOR]

l Minimally invasive stand-alone Maze procedure is promising but not standard treatment for atrial fibrillation worldwide. l We successfully performed minimally invasive stand-alone Maze procedure for 20 cases as an institutional first case series. l Sinus rhythm was well restored for one year postoperatively. l Catheter ablations post-Maze procedure successfully restored sinus rhythm in three cases. Background: Minimally invasive Maze procedure via right mini-thoracotomy approach is reportedly a promising option for paroxysmal and non-paroxysmal atrial fibrillation (AF), although it is not widely performed. This study aimed to validate feasibility and safety of minimally invasive stand-alone Maze procedure in an institutional first case series. Methods: This study enrolled an institutional consecutive series of 20 cases who underwent minimally invasive Maze procedure between November 2018 and January 2021. Concomitant tricuspid annuloplasty was performed in five cases who showed moderate tricuspid regurgitation preoperatively. Results: Minimally invasive Maze procedure using cryo-energy source was successfully accomplished with sinus rhythm being restored at the intensive care unit entry in all cases without conversion to the sternotomy approach. All cases were discharged home, while one case was complicated with stroke postoperatively. Nineteen cases (95%) showed sinus rhythm at the last follow-up, whereas one case, who had large left atrium, showed recurrent persistent AF despite optimum medical therapy. Catheter ablations were performed for residual conductions at box lesions and/or mitral/tricuspid isthmus in three cases, who showed medically refractory atrial tachycardia post-Maze procedure. Consequently, these three cases showed sinus rhythm restoration at the last follow-up Conclusions: Minimally invasive stand-alone Maze procedure with or without tricuspid annuloplasty was feasible and safe for AF in the institutional first case series. Catheter ablations for recurrent AF post-Maze procedure would be warranted. Graphical Abstract [Display omitted] [ABSTRACT FROM AUTHOR]

Carbon monoxide (CO) can arrest cellular respiration, but paradoxically, it is synthesized endogenously by heme oxygenase type 1 (Ho-1) in response to ischemic stress. Ho-1-deficient (Hmox1[sup.-/-]) mice exhibited lethal ischemic lung injury, but were rescued from death by inhaled CO. CO drove ischemic protection by activating soluble guanylate cyclase and thereby suppressed hypoxic induction of the gene encoding plasminogen activator inhibitor-1 (PAI-1) in mononuclear phagocytes, which reduced accrual of microvascular fibrin. CO-mediated ischemic protection observed in wild-type mice was lost in mice null for the gene encoding PAI-1 (Serpine1). These data establish a fundamental link between CO and prevention of ischemic injury based on the ability of CO to derepress the fibrinolytic axis. These data also point to a potential therapeutic use for inhaled CO., Author(s): Tomoyuki Fujita [1]; Koichi Toda [1]; Ann Karimova [1]; Shi-Fang Yan [1]; Yoshifumi Naka [1]; Shaw-Fang Yet [2]; David J. Pinsky (corresponding author) [1] Carbon monoxide (CO), once thought [...]

Activation of the zinc-finger transcription factor early growth response (Egr)-1, initially linked to developmental processes, is shown here to function as a master switch activated by ischemia to trigger expression of pivotal regulators of inflammation, coagulation and vascular hyperpermeability. Chemokine, adhesion receptor, procoagulant and permeability-related genes are coordinately upregulated by rapid ischemia-mediated activation of Egr-1. Deletion of the gene encoding Egr-1 strikingly diminished expression of these mediators of vascular injury in a murine model of lung ischemia/reperfusion, and enhanced animal survival and organ function. Rapid activation of Egr-1 in response to oxygen deprivation primes the vasculature for dysfunction manifest during reperfusion. These studies define a central and unifying role for Egr-1 activation in the pathogenesis of ischemic tissue damage., Author(s): Shi-Fang Yan (corresponding author) [1]; Tomoyuki Fujita [1]; Jiesheng Lu [1]; Kenji Okada [1]; Yu Shan Zou [1]; Nigel Mackman [4]; David J. Pinsky [3]; David M. Stern [1, [...]

Aims: The outcomes of patients with hypertrophic cardiomyopathy with left ventricular systolic dysfunction (HCM‐LVSD) undergoing left ventricular assist device (LVAD) implantation remain unclear. We retrospectively evaluated the clinical impact of LVAD implantation on clinical outcomes, including haemodynamics and brain natriuretic peptide (BNP) levels, in patients with HCM‐LVSD, in comparison with those with dilated cardiomyopathy (DCM). Methods and results: In this retrospective, single‐centre, observational study conducted in Japan, the medical records of patients who underwent LVAD implantation in the National Cerebral and Cardiovascular Center between 2011 and 2020 were reviewed. We enrolled 96 patients with DCM (average age: 43.5 years; 73 men) and 24 patients with HCM‐LVSD (average age: 48.3 years; 16 men). The HCM‐LVSD group had smaller left ventricles with thicker ventricular walls than the DCM group, which became more prominent after LVAD implantation. Preoperatively, BNP values were comparable between both groups; however, 3 months post‐implantation, they were significantly higher in the HCM‐LVSD group. Pulmonary artery pulsatility index, right ventricular stroke work index, and cardiac index were lower, and right atrial pressure was higher, in the HCM‐LVSD group, suggesting subclinical impairment of right ventricular function. The HCM‐LVSD group demonstrated equivalent outcomes, including overall survival, cerebrovascular accidents, right ventricular failure, LVAD‐related infections, arrhythmia, and aortic insufficiency, post‐implantation. Conclusions: Despite a decreased right ventricular function with higher BNP values, patients with HCM‐LVSD and DCM showed comparable outcomes post‐LVAD implantation. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide Open in new tab Download slide OBJECTIVES Fulminant myocarditis with cardiogenic shock requires extracorporeal life support (ECLS) and has poor outcomes. To improve outcomes, we have converted patients with severely impaired cardiac and multiorgan function from peripheral to central ECLS. In this study, we reviewed these patients' clinical outcomes and investigated associated factors. METHODS We retrospectively studied 70 consecutive patients with fulminant myocarditis under peripheral support from 2006 to 2020. Forty-eight patients underwent surgical conversion to central support, and the remaining patients continued peripheral support. The end point was survival and ventricular assist device-free survival. RESULTS More severe pulmonary congestion and multiorgan failure were present in patients with central than peripheral support. Weaning from ECLS was achieved in 95% and 62% of patients with peripheral and central support, respectively. Five-year survival was not significantly different between patients with central and peripheral support (71.2% vs 87.5%, respectively; P  = 0.15). However, the ventricular assist device-free survival rate was significantly higher in patients with central than peripheral support (82.2% vs 52.0%, respectively; P  = 0.017). A peak creatine kinase-MB level of >180 IU/l, rhythm disturbance and aortic valve closure were detrimental to functional recovery in patients with central support. CONCLUSIONS Conversion to central ECLS is feasible and safe in patients with fulminant myocarditis. Patients with severe myocardial injury as shown by a high creatine kinase-MB level, rhythm disturbance and aortic valve closure should be converted to a durable left ventricular assist device. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide A predictive model for atrial fibrillation recurrence and the rate of freedom from atrial fibrillation recurrence by each score Open in new tab Download slide A predictive model for atrial fibrillation recurrence and the rate of freedom from atrial fibrillation recurrence by each score OBJECTIVES This study aimed to develop a novel risk score model for quantitative prediction of the rate of atrial fibrillation (AF) recurrence after the Cryo-Maze procedure in patients with persistent AF. METHODS We enrolled 450 consecutive patients who underwent the Cryo-Maze procedure for persistent AF concomitant with other cardiac procedures in our institute between 2001 and 2019. We randomly divided the cohort into two groups. We derived a model in a 'development cohort' (270 patients; 60%) and validated it in a 'test cohort' (180 patients; 40%) by receiver operating characteristic curve analysis. RESULTS The median follow-up was 5.2 (interquartile range: 2.0–9.9) years. The 1-, 5-, 10- and 15-year rates of freedom from AF recurrence in the entire cohort were 91.4%, 83.5%, 76.2% and 57.1%, respectively. Risk factors for AF recurrence examined by logistic regression analysis included F-wave voltage in V1 < 0.2 mV, preoperative AF duration >5 years and left atrial volume index >100 ml/m2. Points were assigned to each risk factor according to its odds ratio. A novel risk score model was developed using these three variables and age, with a range up to 10 points. High score (>7) predicted high rates of AF recurrence after the Cryo-Maze procedure. The area under the receiver operating characteristic curve of the novel risk model score was 0.78 (95% confidence interval: 0.65–0.91) in the test cohort. CONCLUSIONS Use of the Cryo-Maze procedure should be carefully considered in patients with a higher model score because of a higher risk of AF recurrence. [ABSTRACT FROM AUTHOR]

Background The surgical treatment for postinfarction ventricular septal defect (VSD) remains challenging, especially in emergency cases. Several authors have reported the efficacy of a sandwich patch VSD repair via a right ventricular (RV) incision. However, this procedure remains uncommon, and its efficacy is still unknown, especially when performed under an emergency. Case summary We were able to perform sandwich patch VSD repair via an RV incision on seven consecutive patients with VSD following an ST-segment elevation myocardial infarction (STEMI) from March 2017 to December 2019. Bovine pericardial patches were used for sandwich patches. Two patients developed inferior STEMI, and the other patients developed anterior STEMI. Six patients received intra-aortic balloon pump prior to surgery, and the other received extracorporeal membrane oxygenation with Impella. The interval between the diagnosis of VSD and surgery was within 1 day in all patients except one (5 days). All seven patients underwent VSD repair in the emergency status. Four patients underwent concomitant coronary artery bypass grafting. The hospital mortality rate was 14.3% (1/7). Early postoperative transthoracic echocardiography revealed that only one patient developed more than trace residual shunt. The postoperative right atrial pressure was not significantly elevated at ≤12 mmHg in all patients. No patient developed early postoperative prolonged low cardiac output syndrome. Discussion In patients with postinfarction VSD, a sandwich patch VSD repair via an RV incision is a promising procedure with a low incidence of residual shunt development and hospital mortality, even in emergency cases. [ABSTRACT FROM AUTHOR]

• We reviewed outcomes in patients with left ventricular assist devices (LVAD). • Patients underwent bridge to bridge (BTB) strategy or primary implantable LVAD (iLVAD). • Overall survival was not different between the BTB and iLVAD groups. • BTB group had lower 1-year survival and freedom from the composite events rates. • BTB strategy and preoperative bilirubin were independent predictors of 1-year outcome. In Japan, patients with heart failure who have a paracorporeal left ventricular assist device (pLVAD) and cannot be weaned from the VAD may undergo conversion to implantable continuous-flow LVAD (iLVAD) via a bridge-to-bridge (BTB) strategy for bridge-to-transplantation (BTT). This study aimed to evaluate the real-world clinical status of BTB strategies. Among 134 patients who underwent iLVAD implantation for BTT, 34 patients underwent conversion from pLVAD to iLVAD (BTB group) and 100 patients underwent iLVAD implantation primarily (primary iLVAD group). The clinical characteristics and outcomes were compared between the two groups. No significant difference was found in the overall survival between the two groups (p = 0.26; log-rank test). However, the 1-year survival rate and the 1-year freedom from the composite events of death, stroke, systemic infection, and bleeding rate were lower in the BTB group than in the primary iLVAD group (survival rate, 88.2% vs. 99.0%, p = 0.0040; composite event-free survival rate, 26.1% vs. 49.8%, p = 0.030; log-rank test). Multivariate analysis indicated that the BTB strategy [hazard ratio (HR) 1.70, 95% confidence intervals (CI) 1.03–2.72; p =0.036] and serum total bilirubin levels at iLVAD implantation [HR 1.31, 95% CI 1.00–1.65; p =0.043] were independent predictors of 1-year composite events. The BTB strategy is useful in providing long-term survival in patients with acute critical diseases. However, the early mortality rate after conversion is higher in patients who underwent the BTB strategy. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide Open in new tab Download slide OBJECTIVES We aimed to analyse the pathology of paravalvular leak (PVL), and determine the long-term outcomes of redo mitral valve replacement and risk factors of all-cause mortality. METHODS Seventy-nine patients (mean age 70 ± 9 years; 54 female, 68%) who underwent redo mitral valve replacement for mitral PVL between January 2000 and May 2019 were retrospectively reviewed. Indications for PVL intervention were haemolytic anaemia (57/79, 72%), New York Heart Association class III/IV congestive heart failure (56/79, 71%) and prosthetic valve endocarditis with PVL (2/79, 3%). RESULTS PVL most commonly occurred at lateral sectors (42/79, 55%). Early mortality occurred in 2 patients (3%) due to low cardiac output syndrome. Two patients (3%) had residual PVL at discharge. Sixteen patients (23%) developed late PVL (mean follow-up, 3.4 ± 2.9 years), among whom 11 (69%) developed PVL at same area as that preoperatively. Additionally, 9 patients (56%) developed PVL at lateral sectors in late follow-up. At 1, 5 and 10 years, the survival rate was 93%, 72% and 45%; rate of freedom from cardiac death was 96%, 92% and 78%; and rate of freedom from PVL recurrence was 94%, 82% and 54%, respectively. Chronic kidney disease was the only risk factor in the multivariate analysis for mortality [ P  = 0.013; hazard ratio 4.0 (1.4–11.0)]. CONCLUSIONS Surgery for mitral PVL confers reasonable early and long-term outcomes. Greater attention to the anterolateral annulus may help prevent PVL. [ABSTRACT FROM AUTHOR]

Aims: Percutaneous veno‐arterial extracorporeal membrane oxygenation (VA‐ECMO) is utilized for patients with cardiogenic shock or cardiac arrest. However, the procedure protocol for weaning from VA‐ECMO has not been well established. The present study aimed to determine the usefulness of echocardiographic and pulmonary artery catheter parameters for predicting successful weaning from VA‐ECMO in patients with refractory cardiogenic shock. Methods and results: We retrospectively studied 50 patients who were hospitalized and supported by VA‐ECMO for >48 h between January 2013 and March 2017. Patients successfully weaned from VA‐ECMO without reintroduction of VA‐ECMO or left ventricular assist device implantation were defined as 30 day survivors. Echocardiographic and pulmonary artery catheter parameters were evaluated when ECMO flow was limited to a maximum of 1.5–2.0 L/min. Twenty‐four patients were successfully weaned from VA‐ECMO, whereas 26 were not. Fractional shortening, corrected left ventricular ejection time (LVETc, defined as LVET divided by the square root of heart rate), left ventricular outflow tract velocity time integral, and LVETc divided by pulmonary artery wedge pressure (PAWP) were significantly larger in the 30 day survivor groups. Multivariable analysis revealed LVETc∕PAWP as a significant independent predictor of successful weaning (LVETc∕PAWP, odds ratio 0.82, 95% confidence interval 0.71–0.94, P = 0.005). Receiver operating characteristic curve analysis revealed 15.9 as the optimal LVETc∕PAWP for predicting successful weaning (area under the curve 0.82). Conclusions: The present findings indicate that LVETc∕PAWP is a potential predictor of successful weaning from VA‐ECMO. [ABSTRACT FROM AUTHOR]

Since activation of the sympathetic nervous system is associated with both impaired insulin secretion and insulin resistance, or namely with diabetes, evaluation of such activation in ordinary clinical settings may be important. Therefore, we evaluated the relationships between urinary concentrations of the catecholamine metabolites, urinary normetanephrine (U-NM) and urinary metanephrine (U-M), and glucose metabolism in a general population. From 1,148 participants in the 2016 population-based Iwaki study of Japanese, enrolled were 733 individuals (gender (M/F): 320/413; age: 52.1±15.1), who were not on medication affecting serum catecholamines, not diabetic, and had complete data-set and blood glucose levels appropriate for the evaluation of insulin secretion and resistance, using homeostasis model assessment (HOMA-β and HOMA-R, respectively). Univariate linear regression analyses revealed significant correlations between both U-NM and U-M, and HOMA-β, but adjustment for multiple factors correlated with HOMA indices abolished these (β = -0.031, p = 0.499, and β = -0.055, p = 0.135, respectively). However, the correlation between U-NM and HOMA-R observed using univariate linear regression analysis (β = 0.132, p<0.001) remained significant even after these adjustments (β = 0.107, p = 0.007), whereas U-M did not correlate with HOMA-R. Furthermore, use of the optimal cut-off value of U-NM for the prediction of insulin resistance (HOMA-R >1.6) determined by ROC analysis (0.2577 mg/gCr) showed that individuals at risk had an odds ratio of 2.65 (confidence interval: 1.42–4.97) after adjustment for the same factors used above. Higher U-NM concentrations within the physiologic range are a significant risk factor for increased insulin resistance in a general Japanese population. [ABSTRACT FROM AUTHOR]