林 睦晴

The study aimed to identify factors related to bone mineral density (BMD) among older patients with heart failure (HF). A total of 70 consecutive patients with HF aged 65 years or older who were admitted to an acute hospital due to worsening condition were enrolled before discharge. BMD of the femoral neck was evaluated using the DEXA method. Physical function, as well as echocardiographic and laboratory findings including biomarker of HF severity were collected. Bivariate and multiple regression analyses were employed to determine the association between BMD and the clinical variables. Bivariate analysis determined that age, grip strength, walking speed, serum albumin, and N-terminal pro B-type natriuretic peptide (NT-proBNP) were significantly correlated with BMD (P < 0.01), whereas other clinical parameters were not. The multiple regression analysis identified NT-proBNP as an independent related factor for BMD after adjusting with confounding clinical variables. NT-proBNP was independently related to BMD among older patients with HF. Our results suggest the inclusion of bone fracture prevention strategies in disease management programs, especially for older patients with HF.

The prognostic role of D-dimer in different types of heart failure (HF) is poorly understood. We investigated the prognostic value of D-dimer on admission, both independently and in combination with the Get With The Guidelines—Heart Failure (GWTG-HF) risk score and N-terminal pro-B-type natriuretic peptide (NT-proBNP), in patients with preserved left ventricular ejection fraction (LVEF) and acute decompensated HF (HFpEF) or reduced LVEF (HFrEF). Baseline D-dimer levels were measured on admission in 1670 patients (mean age: 75 years) who were hospitalized for worsening HF. Of those patients, 586 (35%) were categorized as HFpEF (LVEF ≥ 50%) and 1084 as HFrEF (LVEF &lt; 50%). During the 12-month follow-up period after admission, 360 patients died. Elevated levels (at least the highest tertile value) of D-dimer, GWTG-HF risk score, and NT-proBNP were all independently associated with mortality in all HFpEF and HFrEF patients (all p &lt; 0.05). Adding D-dimer to a baseline model with a GWTG-HF risk score and NT-proBNP improved the net reclassification and integrated discrimination improvement for mortality greater than the baseline model alone in all populations (all p &lt; 0.001). The number of elevations in D-dimer, GWTG-HF risk score, and NT-proBNP were independently associated with a higher risk of mortality in all study populations (HFpEF and HFrEF patients; all p &lt; 0.001). The combination of D-dimer, which is independently predictive of mortality, with the GWTG-HF risk score and NT-proBNP could improve early prediction of 12-month mortality in patients with acute decompensated HF, regardless of the HF phenotype.

OBJECTIVES: MicroRNAs (miRNA) are functional RNAs that have emerged as pivotal gene expression regulators in cardiac disease. Although several cardiomyocyte miRNAs have been reported to play roles in heart failure progression among patients with idiopathic dilated cardiomyopathy (DCM), the role of circulating miRNAs has not yet been well-examined. METHODS: After total RNA extraction from the peripheral blood samples of three control participants and six patients with DCM, miRNA profiling was performed using miRNA arrays. Based on the results of this initial screening, real-time polymerase chain reaction (RT-PCR) was used to perform a quantitative analysis of blood samples from a larger number of matched patients (DCM, n=20; controls, n=5). Finally, the correlations between specific miRNA expression levels and hemodynamic parameters were analyzed. RESULTS: A primary screening of 2,565 miRNAs resulted in the identification of nine miRNA candidates. Quantitative RT-PCR results revealed significantly increased miR-489 expression levels in the DCM group. Moreover, there was a significant positive correlation between miR-489 expression level and left ventricular ejection fraction. CONCLUSIONS: Our results suggest that circulating miR-489 could be a potential noninvasive diagnostic biomarker for DCM. Additionally, the quantification of circulating miR-489 may have value as a potential prognostic marker for patients with DCM.

OBJECTIVES: There are benefits of exercise-based cardiac rehabilitation (CR) in patients with heart failure (HF), but their underlying molecular mechanisms remain elusive. The effect of CR on the expression profile of circulating microRNAs (miRNAs), which are short noncoding RNAs that regulate posttranscriptional expression of target genes, is unknown. If miRNAs respond to changes following CR for HF, then serum profiling of miRNAs may reveal cardioprotective mechanisms of CR. METHODS: This study enrolled three hospitalized patients with progressed systolic HF and three normal volunteer controls. In patients, CR was initiated after improvement of HF, which included 2 weeks of bicycle ergometer and resistance exercises. Genome-wide expression profiling of circulating miRNAs was performed using microarrays for the patients (mean±SD age, 60.0±12.2 years) and controls (58.7±0.58 years). Circulating miRNA expression profiles were compared between patients with HF before and after CR and the controls. RESULTS: Expression levels of two miRNAs were significantly different in patients before CR compared with controls and patients after CR. The expression of hsa-miR-125b-1-3p was significantly downregulated and that of hsa-miR-1290 was significantly upregulated in patients before CR. CONCLUSIONS: When performing CR, expression of certain circulating miRNAs in patients with HF is restored to nonpathological levels. The benefits of CR for HF may result from regulation of miRNAs through multiple effects of gene expression.

Background: Anaerobic threshold (AT) during cardiopulmonary exercise testing (CPET) is not always determinable in patients with heart failure (HF). However, little is known about the clinical features of patients with HF who have indeterminable AT. Therefore, the present study aimed to clarify the clinical features of such patients. Methods: A total of 70 patients with HF (58 males; age: 68±12 years) who underwent CPET during hospitalization were divided into two groups: determinable AT (n=50) and indeterminable AT (n=20). Physical function, echocardiographic results, and laboratory findings were subsequently determined. Results: Univariate analyses showed that the indeterminable AT group had significantly higher age and left ventricular ejection fraction, and significantly lower body mass index, calf circumference, handgrip strength, walking speed, serum hemoglobin, and serum albumin than the determinable AT group. Multiple logistic regression analysis identified handgrip strength and walking speed as independent predictive factors for indeterminable AT. Receiver-operating characteristic analyses revealed that handgrip strength of 21.2 kg and walking speed of 0.97 m/s were optimal cutoff values for differentiating patients who were likely to experience indeterminable AT. Conclusions: The present study identified handgrip strength and walking speed as powerful predictors for indeterminable AT with HF.

The aim of this study was to determine whether early mobilization was associated with rehospitalization among elderly heart failure patients. We measured the time from admission to mobilization and other clinical characteristics for 190 heart failure patients (mean age, 80.7 years). The primary outcome was heart failure rehospitalization. Kaplan-Meier survival curves were plotted and the hazard ratios for rehospitalization were determined using Cox proportional hazards regression models. During a median follow-up period of 750 days, 58 patients underwent rehospitalization. The time from admission to mobilization was significantly longer for these patients than for those who were not rehospitalized. Univariate and multivariate Cox proportional hazards analyses showed that the time from admission to mobilization was an independent predictor of rehospitalization, and receiver-operating characteristic analysis determined an optimal cutoff value of 3 days for differentiating the patients more likely to experience a subsequent cardiac event (sensitivity, 76%; specificity, 69%; area under the curve, 0.667). Kaplan-Meier survival curve analysis showed a significantly lower event rate in the ≤ 3-day group (p = 0.001, log-rank test). In conclusion, the time from admission to mobilization may be one of the strongest predictors of rehospitalization in elderly heart failure patients. Early mobilization within 3 days may be an initial target for the acute phase treatment of heart failure.

We prospectively investigated the prognostic value of urinary liver-type fatty-acid-binding protein (L-FABP) levels on hospital admission, both independently and in combination with serum creatinine-defined acute kidney injury (AKI), to predict long-term adverse outcomes in 1119 heterogeneous patients (mean age; 68 years) treated at medical (non-surgical) cardiac intensive care units (CICUs). Patients with stage 5 chronic kidney disease were excluded from the study. Of these patients, 47% had acute coronary syndrome and 38% had acute decompensated heart failure. The creatinine-defined AKI was diagnosed according to the "Kidney Disease: Improving Global Outcomes" criteria. The primary endpoint was a composite of all-cause death or progression to end-stage kidney disease, indicating the initiation of maintenance dialysis therapy or kidney transplantation. Creatinine-defined AKI occurred in 207 patients, with 44 patients having stage 2 or 3 disease. During a mean follow-up period of 41 months after enrollment, the primary endpoint occurred in 242 patients. Multivariate Cox regression analyses revealed L-FABP levels as independent predictors of the primary endpoint (p < 0.001). Adding L-FABP to a baseline model with established risk factors further enhanced reclassification and discrimination beyond that of the baseline model alone, for primary-endpoint prediction (both; p < 0.01). On Kaplan-Meier analyses, increased L-FABP (≥4th quintile value of 9.0 ng/mL) on admission or presence of creatinine-defined AKI, correlated with an increased risk of the primary endpoint (p < 0.001). Thus, urinary L-FABP levels on admission are potent and independent predictors of long-term adverse outcomes, and they might improve the long-term risk stratification of patients admitted at medical CICUs, when used in combination with creatinine-defined AKI.

BACKGROUND: The purpose of this study was to identify the factors determining exercise capacity in elderly patients with heart failure (HF) with and without sarcopenia. METHODS: We studied 186 consecutive patients with HF who met the criteria of being >60 years, with no physical disability. During hospitalization, we measured the 6-min walking distance (6MWD) and other physical functional parameters and evaluated echocardiographic and laboratory measurements indicating the severity of HF. First, we divided patients into two groups (the sarcopenia group and the nonsarcopenia group) according to the presence of sarcopenia defined as fulfilling more than or equal to two criteria-body mass index <18.5, walking speed <0.8m/s, and grip strength <26kg in males, or <18kg in females. Then the association between the 6MWD and the clinical variables mentioned above was analyzed by univariate and multiple logistic regression analyses. RESULTS: The sarcopenia group comprised 77 patients (41.2%). In univariate analysis, age, grip strength, walking speed, and knee extensor muscle strength were significantly correlated with the 6MWD (p<0.05), whereas other clinical parameters were not. In multivariate analysis, walking speed was selected as an independent factor determining the 6MWD in both groups; however, knee extensor muscle strength was selected as an independent factor determining the 6MWD only in the sarcopenia group. CONCLUSION: We demonstrated that knee extensor muscle strength was an independent factor determining exercise capacity-especially in elderly patients with HF with sarcopenia, and provided useful information in terms of exercise prescription.

Additional risk stratification may provide more aggressive and focalized preventive treatment to high-risk hypertensive patients according to the Japanese hypertension guidelines. We prospectively investigated the predictive value of high-sensitivity troponin I (hsTnI), both independently and in combination with N-terminal pro-B-type natriuretic peptide (NT-proBNP), for incident heart failure (HF) in high-risk hypertensive patients with preserved left ventricular ejection fraction (LVEF). Baseline hsTnI and NT-proBNP levels and echocardiography data were obtained for 493 Japanese hypertensive outpatients (mean age, 68.5 years) with LVEF ae&lt;yen&gt; 50%, no symptomatic HF, and at least one of the following comorbidities: stage 3-4 chronic kidney disease, diabetes mellitus, and stable coronary artery disease. During a mean follow-up period of 86.1 months, 44 HF admissions occurred, including 31 for HF with preserved ejection fraction (HFpEF) and 13 for HF with reduced ejection fraction (HFrEF; LVEF &lt; 50%). Both hsTnI (p &lt; 0.01) and NT-proBNP (p &lt; 0.005) levels were significant independent predictors of HF admission. Furthermore, when the patients were stratified into 4 groups according to increased hsTnI (ae&lt;yen&gt;highest tertile value of 10.6 pg/ml) and/or increased NT-proBNP (ae&lt;yen&gt;highest tertile value of 239.7 pg/ml), the adjusted relative risks for patients with increased levels of both biomarkers versus neither biomarker were 13.5 for HF admission (p &lt; 0.0001), 9.45 for HFpEF (p = 0.0009), and 23.2 for HFrEF (p = 0.003). Finally, the combined use of hsTnI and NT-proBNP enhanced the C-index (p &lt; 0.05), net reclassification improvement (p = 0.0001), and integrated discrimination improvement (p &lt; 0.05) to a greater extent than that of any single biomarker. The combination of hsTnI and NT-proBNP, which are individually independently predictive of HF admission, could improve predictions of incident HF in high-risk hypertensive patients but could not predict future HF phenotypes.

Coronary artery calcification (CAC) is an independent predictor of cardiovascular morbidity and mortality in chronic kidney disease (CKD) patients. The aim of the present study was to evaluate the predictive value of CAC scores for the incidence of contrast-induced nephropathy (CIN) after cardiac catheterization in non-dialyzed CKD patients. The present study evaluated a total of 140 CKD patients who underwent cardiac catheterization. Patients were stratified into two groups based on the optimal cut-off value of the CAC score, which was graded by a non-triggered, routine diagnostic chest computed tomography scan: CAC score ae&lt;yen&gt;8 (high CAC group); and CAC score &lt; 8 (low CAC group). CIN was defined as an increase of &gt; 10 % in the baseline serum cystatin C level at 24 h after contrast administration. The mean estimated glomerular filtration rate levels were 41.1 mL/min/1.73 m(2), and the mean contrast dose administered was 37.5 mL. Patients with high CAC scores exhibited a higher incidence of CIN than patients with low CAC scores (25.5 vs. 3.2 %, p &lt; 0.001). After multivariate adjustment for confounders, the CAC score predicted CIN (odds ratio 1.68, 95 % confidence interval 1.28-2.21, p &lt; 0.001). Moreover, the C-index for CIN prediction significantly increased when the CAC scores were added to the Mehran risk score (0.855 vs. 0.760, p = 0.023). CAC scores, as evaluated using semi-quantitative methods, are a simple and powerful predictor of CIN. Incorporating the CAC score in the Mehran risk score significantly improved the predictive ability to predict CIN incidence.

Background: Diabetes is one of the risks for development of contrast-induced nephropathy (CIN). The percentage change in cystatin C (CyC), a recent new reliable marker for detecting subtle renal dysfunction, of &gt;= 10% for 24 h after procedure is an independent predictor for developing CIN. Urinary microalbumin is one of the Markers for preclinical nephropathy in diabetic patients. We investigated the relationship between pre-procedural urinary microalbumin and renal functional changes using CyC after coronary computed tomography angiography (CCTA) in diabetic patients. Methods: Two hundred and six patients with diabetes scheduled for CCTA were enrolled. The serum creatinine and CyC levels were measured before and 24 h after CCTA. The percentage change in CyC (%CyC) and absolute change in estimated glomerular filtration rate (eGFR) from pre- to post-procedure were calculated. The pre-procedural urinary microalbumin was measured. The patients were classified into 2 groups as follows: group A comprised 93 patients with pre-procedural urinary microalbumin of &gt;= 30 mg/g creatinine; and group B comprised 113 patients with one of &lt;30 mg/g creatinine. Results: The %CyC, fasting plasma glucose levels, and HbAl c were significantly greater in group A than in group B. The absolute change in eGFR was significantly less in group A than in group B. A significant correlation was seen between urinary microalbumin and %CyC (r = 0.49, p &lt; 0.0001). Multivariate regression analysis revealed that pre-procedural urinary microalbumin and HbAl c were independent predictors for a %CyC &gt;= 10% (OR: 1.030, 95% CI: 1.020-1.039, p = 0.008; and OR: 1.011, 95% CI: 1.0071.016, p = 0.004, respectively). The optimal cut-off value of a pre-procedural urinary microalbumin level was 64 mg/g creatinine for predicting a %CyC &gt;= 10% using receiver-operating characteristic curve analysis with a sensitivity, specificity, and area under the curve of 56%, 88%, and 0.72, respectively. Conclusions: Renal functional changes should be paid attention to after CCTA, particularly in diabetic patients exhibiting elevated pre-procedural urinary microalbumin even though they indicate preserved eGFR. 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Background: Poor physical ability and skeletal muscle wasting are common in chronic kidney disease (CKD) patients, who may experience a decline in daily activity and, in turn, increased mortality. The purpose of this study was to evaluate the effectiveness and safety of modest exercise in patients with stable CKD. Methods: Forty-seven CKD patients were enrolled in a 6-month group program for aerobic and resistance exercise by self-training. Parameters of physical function and clinical laboratory markers, including renal function, were measured. Results: The International Physical Activity Questionnaire score improved from a baseline of 36.6 ± 13.8 to 40.1 ± 14.8 after the exercise program (P &lt  0.001). The number of daily steps increased from 6141 ± 2620 to 7679 ± 3026 (P &lt  0.001). We detected significant changes in the 30-s chair stand test (from 20.7 ± 5.3 to 26.0 ± 5.9 repetitions P &lt  0.001), single-foot standing test (from 53.0 ± 44.3 to 68.4 ± 43.0 s P = 0.001) and 6-min walk (from 501.6 ± 63.8 to 528.7 ± 71.8 m P = 0.02). Moreover, body weight, waist circumference, and blood pressure were significantly reduced. No significant deterioration was observed in the estimated glomerular filtration rate. Proteinuria significantly decreased in 21 patients. Conclusion: Our modest exercise program improved the physical performance of CKD patients without deterioration of renal function. These results suggest that exercise rather than excess rest should be recommended for CKD patients to avoid muscle wasting.

Chronic kidney disease (CKD) is a cause of coronary artery calcification (CAC) and an independent predictor of major adverse cardiac and cerebrovascular events (MACCE). Cathepsin K (CatK) is a lysosomal cysteine protease which affects vascular calcification and glucose metabolism disorder. We investigated the relationships among CatK, CAC, diabetes mellitus (DM) and MACCE in CKD patients. 113 consecutive CKD patients were enrolled. Their CAC was evaluated by computed tomography. Their plasma CatK level was measured by ELISA. They were divided into two groups by CatK levels and followed up for up to 3 years. The impact of CatK was analyzed in all participants, diabetic patients and non-diabetic patients. Kaplan-Meier analysis demonstrated a significant higher incidence of MACCE in the high CatK group (P = 0.028). The CatK level was significantly higher in patients with MACCE compared to that in patients without MACCE (P = 0.034). Cox's model revealed the higher plasma CatK and BNP level as independent predictors of MACCE (P = 0.043 and P &lt; 0.01, respectively). Only in non-diabetic patients, there was a significant correlation between CatK and CAC score, and high CatK group had a significant higher level of LDL-C and LDL-C/HDL-C ratio (P &lt; 0.05 and P &lt; 0.001, respectively) than low CatK group. And these lipid disorders were independent predictors of CatK elevation. In CKD patients, our results indicated an impact of higher CatK level on their MACCE. The significant association among the CatK level, CAC and MACCE was found in non-diabetic CKD patients.

Background Accurate glomerular filtration rate (GFR) evaluation is significant for drug dosing of carboplatin, anticancer drug excreted mainly from kidney. Serum cystatin-C (sCys-C) is a GFR marker with little affected by body muscle mass volume. And GFR equations based on serum creatinine (eGFRcreat) and sCys-C (eGFRcys) were developed; however, accuracy of eGFRcys has not been elucidated fully among patients with cancer. Therefore, we analyzed the performance of GFR equations among patients with cancer whose GFR values were measured by inulin clearance (Cin). Methods Study design was a cross-sectional study. Subjects were 41 patients with cancer whose GFR values were measured by Cin for drug dosing studies of carboplatin or S-1 in Nagoya University Hospital from 2007 to 2010 and 29 non-cancer patients. Correlation with Cin and slope of regression line were evaluated in eGFRcreat and eGFRcys. Single and multiple regression analyses were analyzed to identify associating factors with eGFRcreat/Cin or eGFRcys/Cin. Results Age, body weight, body mass index (BMI) and sCr were different between cancer patients and non-cancer patients, but sCys-C and Cin were consistent in 2 groups. The slope of the regression line for Cin vs. eGFRcys with zero intercept in cancer patients was 1.10 (95 % CI: 1.02-1.17), which was significantly different from 1.0. In multiple regression analysis revealed that BMI and urinary creatinine excretion were significantly associated with eGFRcreat/Cin, and cancer was only associating factor with eGFRcys/Cin. Conclusion eGFRcys should not be used for evaluation of renal function in patients with cancer because it underestimates GFR.

心不全は冠動脈疾患や心筋症などの基礎疾患による左心室機能の低下に伴う循環不全のみでなく、中枢ならびに末梢の呼吸調節能の異常、骨格筋の構造変化、交感神経活性の亢進、慢性炎症など全身に波及した進行性の疾患と考えられる。運動療法はこれらの全身におよぶ病態を改善することが報告されており、薬物療法と同様に心不全に対する強力な治療法の一つである。心不全患者に対する運動療法の長期予後改善効果について、運動療法を中心に現在の知見をまとめた。

OBJECTIVE: The interaction between the renin-angiotensin system and toll-like receptors (TLRs) in the pathogenesis of advanced atherosclerotic plaques is not well understood. We studied the effects of the renin inhibitor aliskiren on the progression of advanced atherosclerotic plaque in apolipoprotein E-deficient (ApoE(-/-)) mice with a special focus on plaque neovessel formation. METHODS AND RESULTS: Four-wk-old ApoE(-/-) mice were fed a high-fat diet for 8 wks, and the mice were randomly assigned to one of three groups and administered a vehicle, hydralazine, or aliskiren for an additional 12 wks. Aliskiren reduced the atherosclerotic plaque area and plaque neovessel density. It increased the plaque collagen and elastin contents, and reduced plasma angiotensin II levels and plaque macrophage infiltration and cathepsin S (CatS) protein. Aliskiren also decreased the levels of AT1R, gp91phox, TLR2, monocyte chemotactic protein-1, and CatS mRNAs in the aortic roots. Hydralazine had no beneficial vascular effects, although its administration resulted in the same degree of blood pressure reduction as aliskiren. CatS deficiency mimicked the aliskiren-mediated vasculoprotective effect in the ApoE(-/-) mice, but aliskiren showed no further benefits in ApoE(-/-) CatS(-/-) mice. In vitro, TLR2 silencing reduced CatS expression induced by angiotensin II. Moreover, aliskiren or the inhibition of CatS impaired the endothelial cell angiogenic action in vitro or/and ex vivo. CONCLUSION: Renin inhibition appears to inhibit advanced plaque neovessel formation in ApoE(-/-) mice and to decrease the vascular inflammatory action and extracellular matrix degradation, partly by reducing AT1R/TLR2-mediated CatS activation and activity, thus regressing advanced atherosclerosis.

Eicosapentaenoic acid (EPA), a member of the omega-3 polyunsaturated fatty acid family, prevents cardiovascular disease. C-reactive protein (CRP) is a marker of inflammation, which promotes atherosclerosis. The aim of this study was to investigate the relationship among EPA, CRP, and the prevalence of peripheral artery disease (PAD), which is a manifestation of systemic atherosclerosis. A cross-sectional study was performed on 238 patients with coronary artery disease (CAD). Blood EPA and CRP levels and ankle-brachial pressure indices were measured. Cut-off values for plasma EPA levels and serum CRP levels were determined using receiver operating characteristic (ROC) analysis. Patients with ABIs a parts per thousand currency sign0.9 were defined as having PAD. EPA levels were significantly lower and CRP levels were significantly higher in patients with PAD than in those without [48 (26-77) vs. 58 (41-83) mu g/ml, p = 0.026 and 3.3 (0.64-14.0) vs. 0.70 (0.32, 2.4) mg/l, p = 0.004]. Multivariate analysis for PAD revealed that high CRP levels and low EPA levels were significant and independent predictors of PAD [odds ratio 3.1 (95 % CI 1.4-6.9), p = 0.006 and odds ratio 4.9 (95 % CI 1.5-9.7), p = 0.004]. Furthermore, to predict PAD, adding high CRP levels and low EPA levels to the established risk factors significantly improved the area under the ROC curves, from 0.66 to 0.78, of the PAD prediction model (p = 0.004). A significant relationship among EPA, CRP, and PAD was confirmed in patients with CAD.

Objective It has been reported that epicardial adipose tissue could locally modulate the coronary artery functions through secretion of proinflammatory and anti-inflammatory cytokines. Epicardial fat tissue is further implicated in the pathogenesis of coronary artery disease (CAD) because of its proximity to the adventitia of the major epicardial coronary arteries. We investigated the relationship between epicardial fat volume (EFV) and severity of CAD in nonobese patients using 64-slice multidetector computed tomography (MDCT). Methods One hundred and forty nonobese patients (BMI &lt;25 kg/m(2)) were enrolled. EFV and visceral fat area were measured by MDCT. Patients were classified according to the plaque components (noncalcified, mixed and calcified) and severity of CAD. Inflammatory biomarkers were also measured, and compared with each CT parameter. Results EFV was significantly correlated with the extent or severity of CAD. Patients with noncalcified or mixed plaque had a greater EFV than those with calcified plaque. Log-transferred high sensitivity C-reactive protein (CRP) was significantly correlated with EFV (r = 0.24, P = 0.04). Adiponectin level was significantly inversely correlated with visceral fat area (r = 0.38, P = 0.0001). Conclusion Increased EFV is associated with more severe CAD and noncalcified or mixed coronary plaques in nonobese patients.

Objectives: Diabetes mellitus (DM) and high fasting glucose levels are reportedly risk factors for contrast-induced nephropathy after invasive coronary angiography in patients with renal dysfunction. Cystatin C (CyC) is a sensitive marker for detecting early impairment of renal function. Using CyC, we investigated whether DM would be a risk for worsening renal function after coronary computed tomography angiography (CCTA) in patients with preserved renal function. Methods: Two hundred twenty-eight patients scheduled for CCTA were enrolled. The serum CyC at preprocedure and 1 day after procedure, urinary microalbumin at preprocedure, and oral fluid volume for 24 hours after procedure were measured. The percentage changes in CyC from preprocedure to 1 day after procedure (%CyC) were also calculated. Results: Ninety-eight patients had DM. The %CyC and urinary microalbumin were significantly greater in DM patients than in non-DM patients. The percentage of patients showing a %CyC of 10% or greater was significantly greater in DM patients than in non-DM patients (27% vs 8%, P &lt; 0.01). Using multivariate regression analysis, oral fluid volume and urinary microalbumin were independent predictors for a %CyC of 10% or greater in DM patients (beta = -0.428 [P &lt; 0.0001] and beta = 0.464 [P &lt; 0.0001], respectively). Conclusions: Diabetes mellitus is a risk factor for worsening changes in renal function after CCTA, even in patients with preserved renal function. In particular, elevated microalbuminuria and low oral fluid intake are high-risk factors for renal functional deterioration.

Background: The purpose of the present study was to compare the 5-year clinical outcomes after implantation of drug-eluting stent (DES) and bare-metal stent (BMS) in Japanese patients with acute myocardial infarction (AMI). Methods and Results: This study was a subgroup analysis of the Nagoya Acute Myocardial Infarction Study (NAMIS). It included 658 AMI patients, of which 280 were treated with a DES and 378 with a BMS. The major adverse cardiac event (MACE)-free rates during the 5-year follow-up period were similar between the 2 groups (95.7% vs. 96.8%, P=0.482). A significant difference was seen, however, in the target lesion revascularization (TLR) rates (7.9% vs. 17.7%, P<0.0001). Interestingly, there was no significant difference between the 2 groups from year 1 to 5 with regard to late TLR (2.5% vs. 2.1%, P=0.906), despite the markedly lower incidence of TLR within the first year in the DES group compared with the BMS group (5.4% vs. 15.6%, P<0.0001). Conclusions: In this long-term follow-up analysis of DES compared to BMS in Japanese patients with AMI, there was no significant difference in the incidence of MACE. Although a lower rate of TLR was observed in DES group within the first year, the superiority of DES in relation to the incidence of TLR disappeared after the first year following primary percutaneous coronary intervention.

Objective-Circulating endothelial progenitor cells (EPCs) contribute to postnatal angiogenesis. The number of circulating EPCs has an inverse correlation with coronary risk scores. However, the effect of smoking on the number of circulating EPCs is not well-known. Methods and Results-We examined the effects of chronic smoking and of smoking cessation on EPC levels. Circulating EPCs were quantified by flow cytometry as CD45(low)CD34(+)CD133(+) (progenitor cells [ PCs]) or CD45(low)CD34(+)CD133(+)VEGFR2(+) (EPCs) in 14 nonsmokers and in 15 smokers. All smokers quit smoking. Eight quit smoking with nicotine patch and 7 without nicotine patch. PC/EPC levels were inversely correlated with the number of cigarettes smoked. Circulating PCs/EPCs increased rapidly after cessation (P &lt; 0.0001) and decreased again after resumption of smoking to the level similar to that before cessation (P = 0.0031). The magnitude of increase in EPCs was greater in light smokers than in heavy smokers. Conclusions-The number of circulating PCs/EPCs was reduced in chronic smokers. Smoking cessation led to a rapid restoration of PC/EPC levels. The recovery of EPC levels was greater in light smokers than in heavy smokers. The decreased number of circulating EPCs would make smokers susceptible to cardiovascular disease, and even short-time cessation of smoking may be an effective means to reduce cardiovascular risk.