Prevalence of Fabry Disease in Korean Men with Left Ventricular Hypertrophy.

BACKGROUND: Fabry disease is an X-linked recessive disorder caused by deficiency of the lysosomal enzyme α-galactosidase A (α-Gal A). Previous studies identified many cases of Fabry disease among men with left ventricular hypertrophy (LVH). The purpose of this study was to define the frequency of Fabry disease among Korean men with LVH. METHODS: In this national prospective multicenter study, we screened Fabry disease in men with LVH on echocardiography. The criterion for LVH diagnosis was a maximum LV wall thickness 13 mm or greater. We screened 988 men with LVH for plasma α-Gal A activity. In patients with low α-Gal A activity (< 3 nmol/hr/mL), we searched for mutations in the α-galactosidase gene. RESULTS: In seven men, α-Gal A activity was low. Three had previously identified mutations; Gly328Arg, Arg301Gln, and His46Arg. Two unrelated men had the E66Q variant associated with functional polymorphism. In two patients, we did not detect GLA mutations, although α-Gal A activity was low on repeated assessment. CONCLUSION: We identified three patients (0.3%) with Fabry disease among unselected Korean men with LVH. Although the prevalence of Fabry disease was low in our study, early treatment of Fabry disease can result in a good prognosis. Therefore, in men with unexplained LVH, differential diagnosis of Fabry disease should be considered.

Heat induces myogenic transcription factors of myoblast cells via transient receptor potential vanilloid 1 (Trpv1).

Exercise generates heat, blood flow, and metabolic changes, thereby inducing hypertrophy of skeletal muscle cells. However, the mechanism by which heat incudes hypertrophy in response to heat is not well known. Here, we hypothesized that heat would induce differentiation of myoblast cells. We investigated the underlying mechanism by which myoblast cells respond to heat. When mouse myoblast cells were exposed to 42 °C for over 30 min, the phosphorylation level of protein kinase C (PKC) and heat shock factor 1 (Hsf1) increased, and the mRNA and protein expression level of heat shock protein 70 (Hsp70) increased. Inhibitors of transient receptor potential vanilloid 1 (Trpv1), calmodulin, PKC, and Hsf1, and the small interfering RNA-mediated knockdown of Trpv1 diminished those heat responses. Heat exposure increased the phosphorylation levels of thymoma viral proto-oncogene 1 (Akt), mammalian target of rapamycin (mTOR), eukaryotic translation initiation factor 4E binding protein 1 (Eif4ebp1), and ribosomal protein S6 kinase, polypeptide 1 (S6K1). The knockdown of Trpv1 decreased these heat-induced responses. Antagonists of Hsp70 inhibited the phosphorylation level of Akt. Finally, heat increased the protein expression level of skeletal muscle markers such as myocyte enhancer factor 2D, myogenic factor 5, myogenic factor 6, and myogenic differentiation 1. Heat also increased myotube formation. Knockdown of Trpv1 diminished heat-induced increases of those proteins and myotube formation. These results indicate that heat induces myogenic transcription factors of myoblast cells through the Trpv1, calmodulin, PKC, Hsf1, Hsp70, Akt, mTOR, Eif4ebp1, and S6K1 pathway. Moreover, heat increases myotube formation through Trpv1.

Effects of sauna bath on heart failure: A systematic review and meta-analysis.

BACKGROUND: Sauna bath has potential as a lifestyle treatment modality for heart failure (HF). It is important to analyze the current evidence to help suggest paths of future study and potential for clinical application. HYPOTHESIS: Sauna bath has a positive effect on HF patients. METHODS: PubMed, Cochrane Library, and CINAHL databases were searched to identify randomized and nonrandomized controlled studies to compare effects of sauna bath with no sauna bath. Studies were searched for both infrared sauna bath and Finnish sauna bath. The strength of evidence was rated using a modified GRADE approach. Out of 1444 studies, nine met the inclusion criteria and were included in this review. Seven of these nine studies were included in the meta-analysis. Only studies with infrared sauna bath met the inclusion criteria. RESULTS: In the meta-analysis, exposure to an infrared sauna bath in 60°C for 15 minutes, followed by a 30-minute rest in warm environment, five times a week for 2 to 4 weeks, was associated with a significant reduction in B-type natriuretic peptide, cardiothoracic ratio, and an improvement in left-ventricular ejection fraction. There was no significant effect on left-ventricular end-diastolic diameter, left atrial diameter, systolic blood pressure, or diastolic blood pressure. The strength of evidence varied from moderate to insufficient. CONCLUSION: Infrared sauna bath was associated with short-term improvement in cardiac function. More evidence is needed about long-term effects of sauna bath and the effects of a Finnish sauna on cardiovascular health among patients with HF or other cardiovascular diseases.

Sex differences in impact of coronary artery calcification to predict coronary artery disease.

OBJECTIVE: To assess sex-specific differences regarding use of conventional risks and coronary artery calcification (CAC) to detect coronary artery disease (CAD) using coronary CT angiography (CCTA). METHODS: The Nationwide Gender-specific Atherosclerosis Determinants Estimation and Ischemic Cardiovascular Disease Prospective Cohort study is a prospective, multicentre, nationwide cohort study. Candidates with suspected CAD aged 50-74 years enrolled from 2008 to 2012. The outcome was obstructive CAD defined as any stenosis ≥50% by CCTA. We constructed logistic regression models for obstructive CAD adjusted for conventional risks (clinical model) and CAC score. Improvement in discrimination beyond risks was assessed by C-statistic; net reclassification index (NRI) for CAD probability of low (<30%), intermediate (30%-60%) and high (≥60%); and risk stratification capacity. RESULTS: Among 991 patients (456 women, 535 men; 65.2 vs 64.4 years old), women had lower CAC scores (median, 4 vs 60) and lower CAD prevalence (21.7% vs 37.0%) than men. CAC significantly improved model discrimination compared with clinical model in both sexes (0.66-0.79 in women vs 0.61-0.83 in men). The NRI for women was 0.33, which was much lower than that for men (0.71). Adding CAC to clinical model had a larger benefit in terms of moving an additional 43.3% of men to the most determinant categories (high or low risk) compared with -1.4% of women. CONCLUSIONS: The addition of CAC to a prediction model based on conventional variables significantly improved the classification of risk in suspected patients with CAD, with sex differences influencing the predictive ability. TRIAL REGISTRATION NUMBER: UMIN-CTR Clinical Trial: UMIN000001577.

Increase in the Regional Cerebral Blood Flow following Waon Therapy in Patients with Chronic Fatigue Syndrome: A Pilot Study.

Objective Chronic fatigue syndrome (CFS) is a complex disorder, with no consensus on therapeutic options. However, Waon therapy has been reported to be an effective treatment. The purpose of this study was to evaluate changes in the cerebral blood flow (CBF) before and after Waon therapy in CFS patients and to investigate the correlation between such changes and the therapeutic efficacy of Waon therapy. Methods Eleven patients (2 men and 9 women, mean age 27 years old) diagnosed with CFS participated in the study. The disease duration was 8-129 months, and the performance status was 5-8 (on a scale of 0-9). All patients underwent CBF scintigraphy using brain single-photon emission computed tomography (SPECT) with technetium-99m ethyl cysteinate dimer (99mTc-ECD) before and after Waon therapy. CBF changes after Waon therapy were evaluated using a statistical analysis of imaging data, which was performed with a statistical parametric mapping software program (SPM5). Results Waon therapy reduced symptoms in all 11 patients. We also observed an increase in the CBF within the prefrontal region, orbitofrontal region, and right temporal lobe. These results indicated that an improvement in clinical symptoms was linked to an increase in the CBF. Conclusion The results indicated abnormalities of the cerebral function in the prefrontal region, orbitofrontal region, and right temporal lobe in CFS patients and that Waon therapy improved the cerebral function and symptoms in CFS patients by increasing the regional CBF. To our knowledge, this is the first report to clarify the CBF changes in CFS patients before and after Waon therapy.

Comparison of echocardiographic parameters to assess right ventricular function in pulmonary hypertension.

Although measurement of right ventricular ejection fraction (RVEF) may be relevant for evaluation of therapeutic efficacy and/or prognosis in patients with pulmonary hypertension, RVEF obtained by echocardiography has limited accuracy. In contrast, radionuclide and/or magnetic resonance imaging can measure RVEF more reliably. In this study, we investigated the relationship between RVEF measured by radionuclide angiography and the echocardiographic parameters that are recommended by the American Society of Echocardiography as representative of right heart function. There were 23 study participants with pulmonary hypertension who underwent radionuclide angiography and 2-dimensional and Doppler echocardiography (n = 30 measurements). RVEF measured by radionuclide angiography correlated with right ventricular Tei index (RV Tei index) measured by Doppler echocardiography (r = -0.601, P < 0.0005). Receiver operating characteristic curve analysis showed that an RV Tei index cut-off value of 0.371 was the best of predictor of RVEF ≤35% (area under the curve = 0.768, sensitivity = 0.857, selectivity = 0.667). Multiple regression analysis showed that RVEF was correlated with the RV Tei index, and this association was independent of other echocardiographic right ventricular function parameters (r = -0.644, P < 0.005). The RV Tei index measured by Doppler echocardiography may be an acceptable surrogate marker of RVEF in patients with pulmonary hypertension.

Neurohumoral Modulation During Waon Therapy in Chronic Heart Failure　- Subanalysis of Waon-CHF Study.

BACKGROUND: Heart failure (HF) is a disease of neurohumoral dysfunction and current pharmacological therapies for HF have not improved mortality rates, thus requiring additional new strategies. Waon therapy for HF patients may be a complementary strategy with peripheral vasodilation via nitric oxide. We hypothesized that Waon therapy would improve neurohumoral factors, such as natriuretic peptides (NP) and the renin-angiotensin-aldosterone system (RAAS) in HF.Methods and Results:Plasma samples were collected from patients enrolled in the WAON-CHF Study (Waon therapy (n=77) or control (n=73)) before and after the treatment. B-type NP (BNP), C-type NP (CNP), and aldosterone (Aldo) levels were measured by respective specific radioimmunoassays. Although clinical parameters significantly improved in the Waon group compared with the control group, BNP, Aldo, and CNP levels were not statistically different between groups. On subanalysis with patient variables, BNP levels were improved in the Waon group treated with angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker or spironolactone. In addition, Aldo levels were improved in the Waon group patients with diabetes mellitus, hypertension, and inotrope use, and CNP levels were improved in Waon group patients with estimated glomerular filtration rate <60 mL/min/1.73 m2. These changes were not observed in the control group. CONCLUSIONS: Waon therapy may accelerate the favorable actions of RAAS modulators in HF. (WAON-CHF Study: UMIN000006705).

The number of microvascular complications is associated with an increased risk for severity of periodontitis in type 2 diabetes patients: Results of a multicenter hospital-based cross-sectional study.

AIMS/INTRODUCTION: To explore the relationships between periodontitis and microvascular complications as well as glycemic control in type 2 diabetes patients. MATERIALS AND METHODS: This multicenter, hospital-based, cross-sectional study included 620 patients with type 2 diabetes. We compared the prevalence and severity of periodontitis between patients with ≥1 microvascular complication and those without microvascular complications. We also compared the prevalence and severity of periodontitis among patients with different degrees of glycemic control. RESULTS: After adjusting for confounding factors, multiple logistic regression analysis showed that the severity of periodontitis was significantly associated with the number of microvascular complications (odds ratio 1.3, 95% confidence interval 1.1-1.6), glycated hemoglobin ≥8.0% (64 mmol/mol; odds ratio 1.6; 95% confidence interval 1.1-2.3), and older age (≥50 years; odds ratio 1.7; 95% confidence interval 1.1-2.6). However, the prevalence of periodontitis was not significantly associated with the number of microvascular complications, but was associated with male sex, high glycated hemoglobin (≥8.0% [64 mmol/mol]), older age (≥40 years), longer duration of diabetes (≥15 years) and fewer teeth (≤25). Furthermore, propensity score matching for age, sex, diabetes duration and glycated hemoglobin showed that the incidence of severe periodontitis was significantly higher among patients with microvascular complications than among those without microvascular complications (P < 0.05). CONCLUSIONS: The number of microvascular complications is a risk factor for more severe periodontitis in patients with type 2 diabetes, whereas poor glycemic control is a risk factor for increased prevalence and severity of periodontitis.

Heat induces interleukin-6 in skeletal muscle cells via TRPV1/PKC/CREB pathways.

Interleukin-6 (IL-6) is released from skeletal muscle cells and induced by exercise, heat, catecholamine, glucose, lipopolysaccharide, reactive oxygen species, and inflammation. However, the mechanism that induces release of IL-6 from skeletal muscle cells remains unknown. Thermosensitive transient receptor potential (TRP) proteins such as TRPV1-4 play vital roles in cellular functions. In this study we hypothesized that TRPV1 senses heat, transmits a signal into the nucleus, and produces IL-6. The purpose of the present study is to investigate the underlying mechanisms whereby skeletal muscle cells sense and respond to heat. When mouse myoblast cells were exposed to 37-42°C for 2 h, mRNA expression of IL-6 increased in a temperature-dependent manner. Heat also increased IL-6 secretion in myoblast cells. A fura 2 fluorescence dual-wavelength excitation method showed that heat increased intracellular calcium flux in a temperature-dependent manner. Intracellular calcium flux and IL-6 mRNA expression were increased by the TRPV1 agonists capsaicin and N-arachidonoyldopamine and decreased by the TRPV1 antagonists AMG9810 and SB366791 and siRNA-mediated knockdown of TRPV1. TRPV2, 3, and 4 agonists did not change intracellular calcium flux. Western blotting with inhibitors demonstrated that heat increased phosphorylation levels of TRPV1, followed by PKC and cAMP response element-binding protein (CREB). PKC inhibitors, Gö6983 and staurosporine, CREB inhibitors, curcumin and naphthol AS-E, and knockdown of CREB suppressed the heat-induced increases in IL-6. These results indicate that heat increases IL-6 in skeletal muscle cells through the TRPV1, PKC, and CREB signal transduction pathway.NEW & NOTEWORTHY Heat increases the release of interleukin-6 (IL-6) from skeletal muscle cells. IL-6 has been shown to serve immune responses and metabolic functions in muscle. It can be anti-inflammatory as well as proinflammatory. However, the mechanism that induces release of IL-6 from skeletal muscle cells remains unknown. Here we show that heat increases IL-6 in skeletal muscle cells through the transient receptor potential vannilloid 1, PKC, and cAMP response element-binding protein signal transduction pathway.

Prevalence and clinical features of Fabry disease in Japanese male patients with diagnosis of hypertrophic cardiomyopathy.

BACKGROUND: The prevalence of Fabry disease (FD) in Japanese patients presenting with unexplained left ventricular hypertrophy (LVH) has remained unclear. METHODS: We measured plasma α-galactosidase A activity in 177 men with a diagnosis of hypertrophic cardiomyopathy (HCM) (maximum LV wall thickness ≥15mm). RESULTS: Two patients (1.1%) showed very low α-galactosidase A activity [0.0 and 0.3nmol/hr/ml (normal range: 3.6-17.6nmol/hr/ml)], and a clinical diagnosis of cardiac variant of FD was finally made. One patient was a 55-year-old man who came to our hospital because of abnormal results of electrocardiography and showed concentric LVH in echocardiography. A missense mutation, R112L, was identified. The other was a 74-year-old man who had been diagnosed with HCM at the age of 60 years in another hospital and was referred for evaluation of repeated hospitalization for heart failure. Although echocardiography revealed asymmetric septal hypertrophy (ASH) with interventricular septal wall thickness of 16mm and posterior wall thickness of 11mm and reduced LV ejection fraction with hypokinetic posterior wall motion, his echocardiographic findings at the initial diagnosis of HCM were not ASH but concentric LVH with normal LV systolic function. A splicing mutation, IVS4+919G>A, was identified. CONCLUSIONS: The prevalence of FD in Japanese male patients with a clinical diagnosis of HCM was found to be 1.1%. These patients showed late onset and concentric LVH at initial presentation.

Waon Therapy for Managing Chronic Heart Failure　- Results From a Multicenter Prospective Randomized WAON-CHF Study.

BACKGROUND: Waon therapy improves heart failure (HF) symptoms, but further evidence in patients with advanced HF remains uncertain. METHODS AND RESULTS: In 19 institutes, we prospectively enrolled hospitalized patients with advanced HF, who had plasma levels of B-type natriuretic peptide (BNP) >500 pg/ml on admission and BNP >300 pg/ml regardless of more than 1 week of medical therapy. Enrolled patients were randomized into Waon therapy or control groups. Waon therapy was performed once daily for 10 days with a far infrared-ray dry sauna maintained at 60℃ for 15 min, followed by bed rest for 30 min covered with a blanket. The primary endpoint was the ratio of BNP before and after treatment. In total, 76 Waon therapy and 73 control patients (mean age 66 years, men 61%, mean plasma BNP 777 pg/ml) were studied. The groups differed only in body mass index and the frequency of diabetes. The plasma BNP, NYHA classification, 6-min walk distance (6MWD), and cardiothoracic ratio significantly improved only in the Waon therapy group. Improvements in NYHA classification, 6MWD, and cardiothoracic ratio were significant in the Waon therapy group, although the change in plasma BNP did not reach statistical significance. No serious adverse events were observed in either group. CONCLUSIONS: Waon therapy, a holistic soothing warmth therapy, showed clinical advantages in safety and efficacy among patients with advanced HF.

Nationwide distribution of cardiovascular practice in Japan - results of Japanese circulation society 2010 annual survey.

BACKGROUND: The geographic distribution of cardiovascular (CV) health-care services has not been assessed systematically. METHODS AND RESULTS: Data of the Japanese Circulation Society (JCS) annual survey were provided to the JCS working group with the permission of the JCS Scientific Committee. The status of CV practice in 2010 was then assessed in 47 prefectures retrospectively, along with national census and gross domestic product (GDP) data. The surveyed indices included resources (hospitals, beds and cardiologists), burden (number of inpatients), and outcome (CV mortality and autopsy) in each prefecture, which correlated well with respective populations or GDP. Inequality of geographic distribution was evident for pediatrics among the 47 prefectures, according to Lorenz curve, Gini coefficient or the maximum/minimum ratio for each index. According to the Gini coefficients, only the number of inpatients (medical or acute myocardial infarction) and beds for the total number of general hospitals or the hospitals surveyed in the present JCS study were lower than expected with regard to GDP. CONCLUSIONS: Geographic disparity of CV resources or burden was larger in pediatrics than in CV medicine or surgery. Improvement of equality in CV practice with regard to appropriateness and quality are the coming challenges for the JCS.

Effects of Waon therapy on chronic fatigue syndrome: a pilot study.

OBJECTIVE: Chronic fatigue syndrome (CFS) is a disabling condition of unknown etiology, and no definitive therapy has been identified to date. We developed Waon therapy, a form of thermal therapy using a far-infrared dry sauna, and in this study herein examined its feasibility and safety in patients with CFS. METHODS: Ten consecutive inpatients with CFS stayed in a 60°C sauna for 15 minutes and then rested on a bed under a blanket for an additional 30 minutes outside the sauna room. The treatments were performed once a day, five days a week for four weeks. Perceived fatigue, the primary outcome measure, was evaluated using a numerical rating scale before, during (two weeks after the commencement of therapy) and after therapy. The pain level, evaluated using a numerical rating scale, mood, assessed using the Profile of Mood States questionnaire, and performance status, assessed using a scale developed for CFS patients were also examined before and after therapy. RESULTS: Perceived fatigue significantly decreased after therapy, although no significant reductions were observed during therapy. In addition, a negative mood, including anxiety, depression and fatigue, and the performance status significantly improved after therapy. However, the levels of pain and vigor did not change significantly. No patients reported any adverse effects during the therapy. CONCLUSION: These findings suggest that Waon therapy may be a useful and safe treatment for CFS.

The incidence of asymptomatic cerebral microthromboembolism after atrial fibrillation ablation: comparison of warfarin and dabigatran.

BACKGROUND: Cerebral microthromboembolism after atrial fibrillation (AF) ablation has been reported in 4-20% with perioperative warfarin. Dabigatran is a new anticoagulant in patients with nonvalvular AF. We investigated the incidence of asymptomatic cerebral microthromboembolism after AF ablation with perioperative warfarin or dabigatran using diffusion-weighted and T2-weighted magnetic resonance imaging (MRI). METHODS AND RESULTS: Our study included 210 consecutive patients with AF (111 paroxysmal and 99 persistent) who underwent complex fractionated atrial electrogram-guided ablation (combined with pulmonary vein isolation, n = 110). Catheter irrigation was performed in all cases. Uninterrupted warfarin therapy was used in 180 patients (warfarin group) and interrupted only on the morning of the procedure with dabigatran in 30 (dabigatran group). All patients underwent cerebral MRI the day after ablation. New microthromboemboli were detected in 10.0% of the warfarin group and 26.7% of the dabigatran group (P < 0.05). The incidence of hemopericardium treated with pericardiocentesis was lower in the warfarin group than in the dabigatran group (2.5% vs 11.1%, P < 0.05). In multivariate analysis, the use of cardioversion was a predictor of new microthromboembolism development after AF ablation. CONCLUSIONS: The incidence of asymptomatic cerebral microthromboembolism and hemopericardium after AF ablation was significantly lower with perioperative warfarin therapy than with dabigatran therapy. Dabigatran may not be an effective alternative to warfarin for AF ablation, especially in patients who undergo cardioversion.

Atrial fibrillation-induced endothelial dysfunction improves after restoration of sinus rhythm.

BACKGROUND: Recent evidence suggests that atrial fibrillation (AF) adversely affects endothelial function. The goal of this study was to assess endothelial function in patients with AF before and after restoration of sinus rhythm by catheter ablation (ABL). METHODS: Reactive hyperemia peripheral arterial tonometry (RH-PAT) measurements reflecting endothelial function were conducted with Endo-PAT2000 (Itamar Medical, Caesarea, Israel) in 27 patients with persistent AF before ABL and in 21 control subjects with sinus rhythm (SR). According to cardiac rhythm on the morning after ABL, patients were divided into two groups: day 1-restored SR group (n=19) and day 1-recurred AF group (n=8). Based on the cardiac rhythm at 6 months after ABL, the restored SR group was further subdivided into the month 6-maintained SR group (n=11) and the month 6-recurred AF group (n=6). RESULTS: Loge RH-PAT index (RHI) was significantly lower in the persistent AF group than in the control (SR) group (0.52 ± 0.20; 0.69 ± 0.24, p<0.01). Multivariate logistic regression analysis revealed that persistent AF was the only independent predictor of impaired endothelial function defined as loge RHI<0.6 (odds ratio, 4.96; 95% CI, 1.2 to 21.3; p<0.05). Loge RHI was significantly higher after ABL than before ABL (0.53±0.20; 0.73 ± 0.25; p<0.01) in the day 1-restored SR group. Loge RHI of the month 6-maintained SR group was comparable to that of the day 1-restored SR group. CONCLUSIONS: These results suggest that AF is associated with impairment of endothelial dysfunction and that this impairment is reversed by restoration of sinus rhythm.

Cardiac tamponade due to rupture of coronary artery fistula to the coronary sinus with giant aneurysm of coronary artery: usefulness of transthoracic echocardiography.

A 68-year-old woman was admitted to our hospital because of back pain and syncope. Transthoracic echocardiography revealed pericardial effusion, a collapsed right ventricle, a giant aneurysm connected to the coronary sinus, a dilated left main trunk coronary artery, and a dilated left circumflex artery (LCx). Furthermore, there was a coronary artery fistula arising from the LCx that drained into the coronary sinus. We diagnosed cardiac tamponade due to rupture of the coronary artery fistula or giant aneurysm, and successful emergency surgery was performed. Rupture of coronary artery aneurysm or coronary artery fistula is very rare. Transthoracic two-dimensional echocardiography was very useful in our case for the diagnosis of cardiac tamponade, giant coronary aneurysm, and coronary artery fistula.

Characterization of the effect of serum bilirubin concentrations on coronary endothelial function via measurement of high-sensitivity C-reactive protein and high-density lipoprotein cholesterol.

Bilirubin can prevent oxidation of low-density lipoprotein (LDL) and may protect against atherosclerosis and coronary heart disease (CHD). The goal of this study was to characterize the relationship between bilirubin and CHD through measurements of bilirubin concentration, coronary endothelial function, and markers of oxidative stress, inflammation, and lipid/glucose metabolism. The study population consisted of 141 patients without CHD who underwent Doppler flow study. Vascular reactivity was examined by intracoronary administration of papaverine, acetylcholine (ACh) and nitroglycerin using a Doppler guide wire. Serum bilirubin, high-sensitivity C-reactive protein (hsCRP), malondialdehyde-modified LDL, LDL cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting plasma glucose (FPG), and immunoreactive insulin were also measured. Homeostasis model assessment insulin resistance index and estimated glomerular filtration rate (eGFR) were calculated. Univariate analysis revealed that both percent change in coronary blood flow (CBF) and coronary artery diameter induced by ACh correlated positively with log-transformed bilirubin (r = 0.22, P < 0.05; r = 0.20, P < 0.05, respectively). Percent change in CBF in response to ACh correlated positively with eGFR (r = 0.24, P < 0.05) and correlated inversely with age, LDL-C, and log-transformed FPG (r = -0.24, P < 0.05; r = -0.17, P < 0.05, r = -0.22, P < 0.05, respectively). Multivariate analysis revealed that log-transformed bilirubin was the only independent predictor of percent change in CBF in response to ACh. Multivariate analysis revealed that log-transformed hsCRP and HDL-C were independent predictors of log-transformed bilirubin. These results suggest that a high level of bilirubin is associated with favorable coronary endothelial function, which may be mediated via the effect of bilirubin on inflammation and HDL-C.