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Background: This study aimed to investigate the association between proteinuria and long-term prognosis in patients with coronary artery disease., Methods: This was a single-center observational study. A total of 1351 patients were identified who underwent percutaneous coronary intervention, and whose urine data were available. Patients were divided into two groups according to the presence (n = 245) or absence (n = 1106) of proteinuria. All-cause and cardiovascular deaths were primarily evaluated., Results: The prevalence rates of hypertension and diabetes were significantly higher, and the baseline estimated glomerular filtration rate (eGFR) was lower in patients with proteinuria than in those without proteinuria. During the median follow-up of 4.1 years (interquartile range, 1.7-6.8 years), the occurrences of all-cause and cardiovascular deaths were significantly higher in patients with proteinuria. Multivariable Cox regression analysis indicated that the presence of proteinuria was a significant predictor of cardiovascular death as well as age, BMI, reduced eGFR, and left ventricular ejection fraction. When stratified into four groups based on eGFR category (eGFR <60 or ≥60 ml/min/1.73 m2) and absence or presence of proteinuria, the incidence rates of all-cause and cardiovascular deaths were highest in patients with proteinuria and eGFR less than 60 ml/min/1.73 m2. Furthermore, the incidence rates of all-cause and cardiovascular deaths were significantly higher in patients with proteinuria among both diabetic and nondiabetic patients., Conclusion: Proteinuria is associated with the long-term prognosis, and all-cause and cardiovascular deaths in patients with coronary artery disease, regardless of eGFR and the presence or absence of diabetes mellitus., (Copyright © 2023 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Insights from epidemiological, clinical and basic research are illuminating the interplay between metabolic disorders, cardiovascular disease (CVD) and kidney dysfunction, termed cardio-renal-metabolic (CRM) disease. Broadly defined, CRM disease involves multidirectional interactions between metabolic diseases such as type 2 diabetes (T2D), various types of CVD and chronic kidney disease (CKD). T2D confers increased risk for heart failure, which-although well known-has only recently come into focus for treatment, and may differ by ethnicity, whereas atherosclerotic heart disease is a well-established complication of T2D. Many people with T2D also have CKD, with a higher risk in Asians than their Western counterparts. Furthermore, CVD increases the risk of CKD and vice versa, with heart failure, notably, present in approximately half of CKD patients. Molecular mechanisms involved in CRM disease include hyperglycaemia, insulin resistance, hyperactivity of the renin-angiotensin-aldosterone system, production of advanced glycation end-products, oxidative stress, lipotoxicity, endoplasmic reticulum stress, calcium-handling abnormalities, mitochondrial malfunction and deficient energy production, and chronic inflammation. Pathophysiological manifestations of these processes include diabetic cardiomyopathy, vascular endothelial dysfunction, cardiac and renal fibrosis, glomerular hyperfiltration, renal hypoperfusion and venous congestion, reduced exercise tolerance leading to metabolic dysfunction, and calcification of atherosclerotic plaque. Importantly, recognition of the interaction between CRM diseases would enable a more holistic approach to CRM care, rather than isolated treatment of individual conditions, which may improve patient outcomes. Finally, aspects of CRM diseases may differ between Western and East Asian countries such as Japan, a super-ageing country, with potential differences in epidemiology, complications and prognosis that represent an important avenue for future research., (© 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

The number of patients with ischemic cardiovascular diseases is significantly increasing as populations age. Therapeutic angiogenesis has been developed as a new treatment strategy for such patients. In recent years, the presence of mesenchymal stem cells in adipose tissues was reported, and regenerative medicine using these cells has attracted attention worldwide. In this review, we describe how the transplantation of adipose-derived regenerative cells enhances angiogenesis and tissue regeneration because of their multilineage potential and cytokine secretion. Then, the current status of therapeutic angiogenesis using adipose-derived regenerative cells in the field of cardiovascular medicine was also described. These cells present great advantages over bone marrow mononuclear cells, as these need easier, shorter, and less invasive preparations as well as less ethical concerns and immunological problems. The efficacy of adipose-derived regenerative cell transplantation in the treatment of various diseases was examined in several clinical trials with favorable results. Currently, a multicenter study of therapeutic angiogenesis using these cells is being conducted in patients with critical limb ischemia. In conclusion, we expect that this method will soon be established as a treatment for cardiovascular diseases that have been refractory to conventional treatments., Competing Interests: The authors declare that there are no conflicts of interest.

Cerebral white matter hyperintensity (WMH) is highly prevalent among older adults. There is little information about the relationship among WMH extent, frailty status, and exercise capacity in older adults with cardiovascular disease (CVD). We assessed the association of WMH with frailty and exercise capacity in CVD patients.Seventy-eight stable older adults with CVD were evaluated for WMH, the Kihon Checklist (KCL), short physical performance battery score (SPPB), and cardiopulmonary exercise testing. WMH volume was quantified on brain magnetic resonance imaging. Patients were classified into 3 groups (using tertiles of 0.52% and 1.05%) according to WMH as a percentage of intracranial volume (ICV), and their KCL scores and exercise capacities were compared. The 3 WMH/ICV groups were mild (n = 26, 0.26% ± 0.14% of intracranial volume), moderate (n = 26, 0.70% ± 0.15%), and severe (n = 26, 1.75% ± 0.67%). Peak VO 2 was 15.2 ± 3.7 mL kg -1 minute -1 (mild group), 12.9 ± 3.5 mL kg -1 min -1 (moderate), and 11.4 ± 2.3 mL kg -1 minute -1 (severe) (mild versus moderate, P = 0.049; mild versus severe, P = 0.001). Multivariate regression analysis showed significant associations of severe WMH/ICV with peak VO 2 and SPPB. Cerebral WMH was strongly negatively associated with SPPB and peak VO 2 . WMH volume may be related to exercise capacity and frailty in stable older adult patients with CVD.

Objectives: Although there are 14 097 board-certified cardiologists in Japan, it is unknown whether the number of institutional board-certified cardiologists is related to the prognosis of cardiovascular disease patients., Design: Cross-sectional analysis., Setting: Data were collected from the nationwide database of acute care hospitals in Japan (2371 hospitals) between 2012 and 2013., Participants: A total of 1 422 703 consecutive patients were initially included in this study, but 518 610 patients were excluded due to age <18 years, missing data or prior hospitalisations; therefore, 896 171 patients comprised the final sample population., Main Outcome Measures: The primary outcome was in-hospital mortality due to any cause. For the per-hospital analysis, Poisson regression models were used to estimate the association of board-certified cardiologists with in-hospital mortality, adjusted for hospital facilitation. For the per-patient analysis, hierarchical logistic regression models were used to estimate the ORs of the number of institutional board-certified cardiologists, adjusted for patient demographics, diagnoses, therapies and hospital facilities., Results: The regression model of the per-hospital analysis indicated that the number of board-certified cardiologists was associated with a lower rate ratio of in-hospital mortality (rate ratio, 0.988; 95% CI 0.983 to 0.993; p<0.01). The per-patient analysis indicated that the median age was 73 years and the in-hospital mortality rate was 11.7%. The regression model indicated that the presence of more board-certified cardiologists was associated with a lower risk of in-hospital mortality (OR, 0.980; 95% CI 0.975 to 0.986; p<0.01) after adjustments for hospital facilities, patient characteristics and treatments., Conclusions: Among cardiovascular disease patients admitted to acute care hospitals in Japan, the presence of more board-certified cardiologists was associated with a lower risk of in-hospital mortality. These results have implications for national and institutional strategies for determining the required number of board-certified cardiologists., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Tobacco smoking continues to be a major risk factor for cardiovascular disease (CVD) and the leading avoidable cause of death worldwide. Tobacco smoking has declined in high-income countries, but the average smoking rate in Japan remains high: 29.4% for men and 7.2% for women in 2017. Of note, the average smoking rate among middle-aged men remains approximately 40%, indicating that a high incidence of smoking-related CVD will continue for a couple of decades in Japan. The adverse effects of tobacco smoking on CVD are more extensive than previously thought. Physicians should be particularly alert to the development and progression of heart failure, atrial fibrillation, and venous thromboembolism, as well as ischemic CVD among tobacco smokers. Increasing use of heat-not-burn tobacco as cigarette alternatives is an emerging issue. Harmful effects do not disappear just by changing the delivery system of tobacco.

Objectives: Follistatin-like 1 (FSTL1) is a glycoprotein secreted by skeletal muscle cells and cardiac myocytes. Previous studies showed that serum FSTL1 concentrations were increased in acute coronary syndrome and chronic heart failure. The aim of this study was to assess the associations among plasma FSTL1 concentration, clinical parameters, and whether FSTL1 concentration could predict cardiovascular events in patients with elective percutaneous coronary intervention (PCI)., Methods and Results: A consecutive series of 410 patients who underwent elective PCI with drug-eluting stents (DES) were enrolled between August 2004 and December 2006 at Juntendo University hospital. We measured plasma FSTL1 levels prior to elective PCI and assessed the association among FSTL1 levels, clinical parameters, and occurrence of major adverse cardiac or cerebrovascular events (MACCE) defined as cardiac death, nonfatal myocardial infarction, unstable angina, stroke, and hospitalization for heart failure. FSTL1 concentration was positively correlated with high-sensitivity C-reactive protein (hsCRP), serum creatinine, and N-terminal pro b-type natriuretic peptide (all P < 0.01). After excluding patients with creatinine clearance < 60 mL/min and hsCRP ≥ 0.2 mg/dL, the remaining 214 were followed for a median of 5.1 years. Twenty (9.3%) patients experienced MACCE. Receiver operating characteristics curve analysis estimated an FSTL1 cutoff of 41.1 ng/mL to predict MACCE occurrence. Kaplan-Meier analysis found a higher MACCE rate in patients with high (≥ 41.1 ng/mL) than with low (< 41.1 ng/mL) FSTL1 (P < 0.01). Multivariate Cox hazard analysis found that high FSTL1 was an independent predictor of MACCE (hazard ratio 4.54, 95% confidence interval: 1.45-20.07, P < 0.01)., Conclusion: High plasma FSTL1 may be a predictor of cardiovascular events in patients who underwent elective PCI with DES, especially with preserved renal function and low hsCRP., Competing Interests: K. Shimada has received lecture fees from Daiichi-Sankyo Pharmaceutical Company Ltd., and Takeda Pharmaceutical Company Ltd. Department of Molecular Medicine and Cardiology was endowed by Kowa Pharmaceutical Co Ltd (to N.O. and K.O.). H. Daida has received remuneration for lectures from Amgen Astellas Biopharma K.K., Astellas Pharma Inc., AstraZeneca Pharma Ltd., GlaxoSmithKline K.K., Sanofi K.K., Shionogi, Daiichi-Sankyo Pharmaceutical Company Ltd., Takeda Pharmaceutical Company Ltd., Terumo Corporation, Medtronic plc., Boehringer Ingelheim GmbH., Bayer AG., and MSD K.K., trust research and joint research funds from Kowa Pharmaceutical Company Ltd., Daiichi-Sankyo Company Ltd., Canon Medical Systems Corporation, Nihon Medi-Physics Company Ltd., Kaken Pharmaceutical Company Ltd., Kirin Holdings Company Ltd., Philips Respironics Ltd., Sanwa Kagaku Kenkyusho Company Ltd., and St. Jude Medical Japan Company Ltd., and scholarship fund from Astellas Pharma Inc., Abbott Laboratories, Otsuka Pharmaceutical Company Ltd., Sanofi K.K., Shionogi & Company Ltd., Sumitomo Dainippon Pharmaceutical Company Ltd., Boehringer Ingelheim GmbH., Bayer AG., Teijin Ltd., Daiichi-Sankyo Company Ltd., Takeda Pharmaceutical Company Ltd., MSD K.K., Tanabe Mitsubishi Pfizer Pharmaceutical Company Ltd., Philips Respironics Ltd., Bristol-Myers Squibb Company Ltd., Boston Scientific Ltd., St. Jude Medical Japan Company Ltd., and Actelion Pharmaceuticals Japan Ltd. He has been in affiliation with some endowed departments including VitalAire Japan Company K.K., Philips Respironics Ltd., Fukuda Denshi Company Ltd., ResMed Ltd. The remaining authors report no conflict of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Aims: To assess the benefits of intensive statin therapy on reducing cardiovascular (CV) events in patients with type 2 diabetes complicated with hyperlipidaemia and retinopathy in a primary prevention setting in Japan. In the intension-to-treat population, intensive therapy [targeting LDL cholesterol <1.81 mmol/L (<70 mg/dL)] was no more effective than standard therapy [LDL cholesterol ≥2.59 to <3.10 mmol/L (≥100 to <120 mg/dL)]; however, after 3 years, the intergroup difference in LDL cholesterol was only 0.72 mmol/L (27.7 mg/dL), and targeted levels were achieved in <50% of patients. We hypothesized that the intergroup difference in CV events would have been statistically significant if more patients had been successfully treated to target., Materials and Methods: This exploratory post hoc analysis focused on intergroup data from patients who achieved their target LDL cholesterol levels. The primary endpoint was the composite incidence of CV events. A Cox proportional hazards model was used to estimate hazard ratios (HRs) for incidence of the primary endpoint in patients who achieved target LDL cholesterol levels in each group., Results: Data were analysed from 1909 patients (intensive: 703; standard: 1206) who achieved target LDL cholesterol levels. LDL cholesterol at 36 months was 1.54 ± 0.30 mmol/L (59.7 ± 11.6 mg/dL) in the intensive group and 2.77 ± 0.46 mmol/L (107.1 ± 17.8 mg/dL) in the standard group (P < 0.05). After adjusting for baseline prognostic factors, the composite incidence of CV events or deaths associated with CV events was significantly lower in the intensive than the standard group (HR 0.48; 95% confidence interval 0.28-0.82; P = 0.007)., Conclusions: This post hoc analysis suggests that achieving LDL cholesterol target levels <1.81 mmol/L may more effectively reduce CV events than achieving target levels ≥2.59 to <3.10 mmol/L in patients with hypercholesterolaemia and diabetic retinopathy., (© 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Accumulating evidence suggests that pathologic interactions between the heart and the kidney can contribute to the progressive dysfunction of both organs. Recently, there has been an increase in the prevalence of cardiovascular disease (CVD) and chronic kidney disease (CKD) due to increasing obesity rates. It has been reported that obesity causes various heart and renal disorders and appears to accelerate their progression. Vascular endothelial growth factor-A (VEGF-A) is a major regulator of angiogenesis and vessel permeability, and is associated with CVD and CKD. It is now recognized that alternative VEGF-A gene splicing generates VEGF-A isoforms that differ in their biological actions. Proximal splicing that includes an exon 8a sequence results in pro-angiogenic VEGF-A 165 a, whereas distal splicing inclusive of exon 8b yields the anti-angiogenic isoform of VEGF-A (VEGF-A 165 b). This review highlights several recent preclinical and clinical studies on the role of VEGF-A 165 b in CVD and CKD as a novel function of VEGF-A. This review also discusses potential therapeutic approaches of the use of VEGF-A in clinical settings as a potential circulating biomarker for CVD and CKD., (© 2019 Elsevier Inc. All rights reserved.)

Background: Whether a dipeptidyl peptidase-4 (DPP-4) inhibitor can attenuate atherosclerosis is still controversial. Some clinical trials reported that DPP-4 inhibitors in diabetes patients without a previous history of cardiovascular (CV) events could reduce carotid intima-media thickness (IMT). However, in the PROLOGUE study, which enrolled diabetes patients both with and without previous CV events, sitagliptin failed to slow the progression of carotid IMT relative to conventional therapy., Aim and Methods: We hypothesized that the effect of DPP-4 inhibitors on carotid atherosclerosis might be different between the primary and secondary prevention groups. We performed a post hoc analysis of the PROLOGUE study and compared the effects of sitagliptin and conventional therapy on changes in carotid IMT in subgroups with or without previous CV events., Results: No significant difference in the IMT changes between the treatment groups was found in the secondary prevention subgroup (sitagliptin, N = 102; conventional, 111). However, in the primary prevention subgroup (sitagliptin, 120; conventional, 109), we found significant inhibitory effects of sitagliptin on mean and max internal carotid artery IMT [estimated group difference: -0.096 mm (95% CI -0.175 to -0.018, p = 0.017) and -0.162 mm (95% CI -0.272 to -0.052, p = 0.004), respectively], although there was no significant difference in the common carotid artery IMT., Conclusions: Our data suggest that there is a favorable effect of DPP-4 inhibitor treatment on carotid atherosclerosis in diabetes patients without previous CV events., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: Diabetes is associated with high risk of cardiovascular (CV) events, particularly in patients with dyslipidemia and diabetic complications. We investigated the incidence of CV events with intensive or standard lipid-lowering therapy in patients with hypercholesterolemia, diabetic retinopathy, and no history of coronary artery disease (treat-to-target approach)., Research Design and Methods: In this multicenter, prospective, randomized, open-label, blinded end point study, eligible patients were randomly assigned (1:1) to intensive statin therapy targeting LDL cholesterol (LDL-C) <70 mg/dL ( n = 2,518) or standard statin therapy targeting LDL-C 100-120 mg/dL ( n = 2,524)., Results: Mean follow-up was 37 ± 13 months. LDL-C at 36 months was 76.5 ± 21.6 mg/dL in the intensive group and 104.1 ± 22.1 mg/dL in the standard group ( P < 0.001). The primary end point events occurred in 129 intensive group patients and 153 standard group patients (hazard ratio [HR] 0.84 [95% CI 0.67-1.07]; P = 0.15). The relationship between the LDL-C difference in the two groups and the event reduction rate was consistent with primary prevention studies in patients with diabetes. Exploratory findings showed significantly fewer cerebral events in the intensive group (HR 0.52 [95% CI 0.31-0.88]; P = 0.01). Safety did not differ significantly between the two groups., Conclusions: We found no significant decrease in CV events or CV-associated deaths with intensive therapy, possibly because our between-group difference of LDL-C was lower than expected (27.7 mg/dL at 36 months of treatment). The potential benefit of achieving LDL-C <70 mg/dL in a treat-to-target strategy in high-risk patients deserves further investigation., (© 2018 by the American Diabetes Association.)

Background: The association between Helicobacter pylori infection and cardiovascular risk factors remains controversial. The high prevalence of H. pylori infection among Afghan patients warranted the investigation of this association. The aim of the present study was to determine the association between H. pylori infection and cardiovascular risk factors among patients visiting an outpatient clinic in Andkhoy, Afghanistan. Methods: We performed a cross-sectional study of 271 consecutive patients in an outpatient clinic in Andkhoy, Afghanistan from April 2017 to June 2017. The diagnosis of H. pylori infection was achieved using an enzyme-linked immunosorbent assay test. The patients were divided into H. pylori positive (n=189) and H. pylori negative (n=82) groups. The association between H. pylori infection and cardiovascular risk factors was analyzed. Results: Of the total 271 study participants, 102 (37.6%) were male and 169 (62.4%) female. The mean age ± standard deviation of the patients who were H. pylori-positive and H. pylori-negative was 51.0 ± 17.6 years and 51.6 ± 17.6 years, respectively. In multivariate logistic regression analyses, H. pylori infection was significantly associated with diabetes mellitus (DM) (odds ratio [OR] 3.16, 95% confidence interval [CI] 1.31-7.62, P = 0.011), and body mass index (BMI) levels (OR 1.17, 95% CI 108-1.26, P < 0.001). Conclusions: Our study indicated that H. pylori infection was significantly associated with DM and elevated BMI levels in patients from an outpatient clinic in Andkhoy, Afghanistan. More aggressive measures, including DM, obesity control, and H. pylori eradication are needed., (Creative Commons Attribution License)

Obesity leads to the development of cardiovascular diseases. Adipose tissue produces various bioactive molecules, also known as adipokines, and imbalanced production of adipokines contributes to the pathogenesis of obesity-linked metabolic and cardiovascular complications. Some adipokines such as adiponectin exert salutary actions on cardiovascular and metabolic disorders. Recent research has been conducted to identify poorly-characterized adipokines involved in cardiovascular regulation. In this review, we focus on the protective role of novel adipokines that are of current interest in the field of cardiology., (Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Purpose: We evaluated the effects of an alpha-glucosidase inhibitor, voglibose, on cardiovascular events in patients with a previous myocardial infarction (MI) and impaired glucose tolerance (IGT)., Methods: This prospective, randomized, open, blinded-endpoint study was conducted in 112 hospitals and clinics in Japan in 3000 subjects with both previous MI and IGT receiving voglibose (0.6 mg/day, n = 424) or no drugs (n = 435) for 2 years. The Data and Safety Monitoring Board (DSMB) recommended discontinuation of the study in June 2012 after an interim analysis when the outcomes of 859 subjects were obtained. The primary endpoint was cardiovascular events including cardiovascular death, nonfatal MI, nonfatal unstable angina, nonfatal stroke, and percutaneous coronary intervention/coronary artery bypass graft. Secondary endpoints included individual components of the primary endpoint in addition to all-cause mortality and hospitalization due to heart failure., Results: The age, ratio of males, and HbA 1 C were 65 vs. 65 years, 86 vs. 87%, and 5.6 vs. 5.5% in the groups with and without voglibose, respectively. Voglibose improved IGT; however, Kaplan-Meier analysis showed no significant between-group difference with respect to cardiovascular events [12.5% with voglibose vs. 10.1% without voglibose for the primary endpoint (95% confidence interval, 0.82-1.86)]; there were no significant differences in secondary endpoints., Conclusion: Although voglibose effectively treated IGT, no additional benefits for cardiovascular events in patients with previous MI and IGT were observed. Voglibose may not be a contributing therapy to the secondary prevention in patients with MI and IGT., Trial Registration: Clinicaltrials.gov number: NCT00212017.

Background: Sarcopenia is an aging and disease-related syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength, with the risk of frailty and poor quality of life. Sarcopenia is diagnosed by a decrease in skeletal muscle index (SMI) and reduction of either handgrip strength or gait speed. However, measurement of SMI is difficult for general physicians because it requires special equipment for bioelectrical impedance assay or dual-energy X-ray absorptiometry. The purpose of this study was, therefore, to explore a novel, simple diagnostic method of sarcopenia evaluation in patients with cardiovascular diseases (CVD)., Methods: We retrospectively investigated 132 inpatients with CVD (age: 72±12 years, age range: 27-93 years, males: 61%) Binomial logistic regression and correlation analyses were used to assess the associations of sarcopenia with simple physical data and biomarkers, including muscle-related inflammation makers and nutritional markers., Results: Sarcopenia was present in 29.5% of the study population. Serum concentrations of adiponectin and sialic acid were significantly higher in sarcopenic than non-sarcopenic CVD patients. Stepwise multivariate binomial logistic regression analysis revealed that adiponectin, sialic acid, sex, age, and body mass index were independent factors for sarcopenia detection. Sarcopenia index, obtained from the diagnostic regression formula for sarcopenia detection including the five independent factors, indicated a high accuracy in ROC curve analysis (sensitivity 94.9%, specificity 69.9%) and the cutoff value for sarcopenia detection was -1.6134. Sarcopenia index had a significant correlation with the conventional diagnostic parameters of sarcopenia., Conclusions: Our new sarcopenia index using simple parameters would be useful for diagnosing sarcopenia in CVD patients.

Protein-energy wasting (PEW) is highly prevalent in hemodialysis (HD) patients. We investigated the association of abnormal ankle brachial index (ABI), PEW, and chronic inflammation status with clinical prognosis in HD patients. A total of 973 HD patients were enrolled and were followed-up for 8 years. As a marker of the PEW, geriatric nutritional risk index (GNRI) was used. Cut-off levels were 91.2 for GNRI defined from previous studies and 1.9 mg/L for C-reactive protein (CRP) as median value, respectively. Abnormal ABI was seen in 332 (34.1%) patients. Declined GNRI and elevated CRP levels were independently associated with abnormal ABI (odds ratio (OR) 0.97, 95% confidence interval (CI) 0.96-0.99, p = 0.0009 and OR 1.40, 95% CI 1.07-1.83, p = 0.013, respectively). GNRI levels were also independently correlated with CRP levels (β = -0.126, p < 0.0001). During follow-up period, 283 (29.1%) patients died, including 123 (12.6%) due to cardiovascular disease (CVD). Abnormal ABI (adjusted hazard ratio (HR) 1.62, 95% CI 1.13-2.32, p = 0.0096), GNRI < 91.2 (adjusted HR 1.57, 95% CI 1.06-2.33, p = 0.023) and CRP > 1.9 mg/L (adjusted HR 1.89, 95% CI 1.31-2.77, p = 0.0007) independently predicted mortality due to CVD, respectively. In conclusion, abnormal ABI, GNRI, and CRP levels were closely associated with each other, and the combination of these variables increase their predictive values for the risk of mortality due to CVD and all-cause mortality in HD patients.

Obesity is a major risk factor for progression of cardiovascular disease. Adipose tissue is recognized as an endocrine organ producing various secretory molecules, also known as adipocytokines, and dysregulated production of adipocytokines participates in the pathogenesis of obesity complications, including metabolic dysfunction and cardiovascular disorders. Recent evidence indicates that skeletal muscle also functions as an endocrine organ capable of secreting a number of bioactive substances, also referred to as myokines. Several myokines are involved in metabolic and cardiovascular regulation. This review will discuss the clinical and experimental studies that have investigated the protective role of several adipocytokines and myokines in cardiovascular diseases. (Circ J 2016; 80: 2073-2080).

Background and Aims: Visceral adipose tissue (VAT), unlike subcutaneous adipose tissue (SAT), is highly correlated with cardiovascular risk factors. This study aimed to evaluate the predictive value of adipose tissue composition, as measured by computed tomography, for cardiovascular events in patients with stable coronary artery disease., Methods: 357 consecutive patients who underwent 64-slice computed tomography and elective percutaneous coronary intervention (PCI) were recruited. The ratio of visceral to subcutaneous adipose tissue (VAT/SAT) was calculated. Patients were divided into three groups in accordance with VAT/SAT (low VAT/SAT, <0.55 [<25th percentile]; moderate VAT/SAT, 0.55-1.03 [25th-75th percentile]; high VAT/SAT, ≥1.03 [≥75th percentile]). The investigated risk factors were hypertension, hyperglycaemia, and dyslipidaemia. We analysed the incidence of major adverse cardiovascular events (MACE), defined as the composite of cardiac death, myocardial infarction, and any revascularization., Results: The rate of patients with two or more concomitant risk factors was significantly higher in the high VAT/SAT group (p = 0.006). During 1480 person-years, 109 events were documented. There was a significant association between the incidence of MACE and VAT/SAT, with the worst event-free survival rate in the high VAT/SAT group (log-rank, p = 0.01). In Cox analysis, the hazard ratio of high VAT/SAT for MACE was 2.72 (95% confidence interval 1.04-7.09, p = 0.04) compared with the low VAT/SAT after adjustment for confounding factors., Conclusions: Increased VAT/SAT is independently associated with the incidence of MACE, indicating that adipose tissue composition is a useful predictor of cardiovascular outcome, after elective PCI., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: The presence of abdominal aortic calcification (AAC) can predict cardiovascular (CV) outcomes in hemodialysis patients. However, little is known about the predictive value of AAC for CV outcomes in chronic kidney disease (CKD) patients without hemodialysis. The aim of this study was to investigate the prevalence and the predictive value of AAC in asymptomatic CKD patients., Methods: We prospectively evaluated 347 asymptomatic CKD patients without hemodialysis [median estimated glomerular filtration rate (eGFR): 43.2 mL/min/1.73 m(2)]. A non-contrast computed tomography scan was used to determine the abdominal aortic calcification index (ACI) as a semi-quantitative measure of AAC. The patients were divided into three groups according to the tertiles of ACI., Results: Among the subjects, AAC was found (ACI > 0) in 296 patients (86.3%), and the median ACI was 11.4%. During the median follow-up of 41.5 months, a total of 33 CV events were observed. Patients with the highest tertile of ACI had the highest risk of CV outcomes compared with the other two groups (96.5%, 93.0%, and 74.3%, respectively; p < 0.001). The Cox proportional hazard models showed that ACI was an independent predictor of CV outcomes (hazard ratio 1.36, 95% confidence interval 1.17-1.60, p < 0.001). The C-index was also significantly increased by adding eGFR and ACI values to the model along with the other conventional risk factors (0.79 versus 0.66, p = 0.043)., Conclusion: Evaluation of the AAC provides useful information for predicting adverse clinical outcomes among asymptomatic CKD patients without hemodialysis., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Adipose tissue functions as an endocrine organ by producing bioactive secretory proteins, also known as adipokines, that can directly act on nearby or remote organs. Most of the adipokines are upregulated by obese conditions, and typically promote obese complications. In contrast, some adipokines, such as adiponectin, CTRP9 and omentin, are downregulated in obese states. These factors exert salutary actions on obesity-linked cardiovascular disorders. In this review, we focus on the significance of adiponectin, CTRP9 and omentin as therapeutic agents for cardiovascular disease., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Cardiovascular disease (CVD) is a leading cause of death in end-stage renal disease (ESRD) patients. Protein-energy wasting (PEW) or malnutrition is common in this population, and is associated with increasing risk of mortality. The geriatric nutritional risk index (GNRI) has been developed as a tool to assess the nutritional risk, and is associated with mortality not only in elderly patients but also in ESRD patients. However, whether the GNRI could predict the mortality due to CVD remains unclear in this population. We investigated the prognostic value of GNRI at initiation of hemodialysis (HD) therapy for CVD mortality in a large cohort of ESRD patients., Methods: Serum albumin, body weight, and height for calculating GNRI were measured in 1568 ESRD patients. Thereafter, the patients were divided into quartiles according to GNRI levels [quartile 1 (Q1): < 84.9; Q2: 85.0-91.1; Q3: 91.2-97.2; and Q4: >97.3], and were followed up for up to 10 years., Results: GNRI levels independently correlated with serum C-reactive-protein levels (β = -0.126, p < 0.0001). Rates of freedom from CVD mortality for 10 years were 57.9%, 73.3%, 80.8%, and 89.2% in Q1, Q2, Q3, and Q4, respectively (p < 0.0001). The GNRI was an independent predictor of CVD mortality (hazard ratio 3.42, 95% confidence interval 2.05-5.70, p < 0.0001 for Q1 vs. Q4). C-index was also greater in an established CVD risk model with GNRI (0.749) compared to that with albumin (0.730), body mass index (0.732), and alone (0.710). Similar results were observed for all-cause mortality., Conclusion: GNRI at initiation of HD therapy could predict CVD mortality with incremental value of the predictability compared to serum albumin and body mass index in ESRD patients., (Copyright © 2013 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Objective: To clarify whether the impact of normal and high-normal BP (BP) per se on cardiovascular disease (CVD) and all-cause death differs depending on smoking status., Methods and Results: A prospective observational cohort study (median follow-up period: 7.5 years) was performed among 25,077 healthy nondiabetic Japanese men aged 20-61 years (mean age 37.3 years), whose BP was less than 150/95 mmHg and who were not on medication. Hazard ratios (HRs), adjusted by known risk factors and a change in annual BP during the follow-up, were calculated by the Cox proportional model with less than 119/75 mmHg as a reference. Among smokers, CVD events increased significantly from a SBP of 120 mmHg, with HRs of 2.68 (120-129 mmHg), 4.28 (130-139 mmHg), and 11.7 (140-149 mmHg). The CVD events also increased from a DBP of 75 mmHg (P for trend less than 0.0001), with 75-79 mmHg and 90-94 mmHg considered statistically significant. Among noncurrent smokers, 110-149 mmHg (SBP) and 75-89 mmHg (DBP) were not associated with elevated HRs for CVD. The relation between BP and all-cause mortality was similar among both current and noncurrent smokers: 140-149 mmHg (SBP) and 90-94 mmHg (DBP) were significantly associated with elevated risk, and 130-139 mmHg (SBP) among noncurrent smokers associated with elevated risk., Conclusion: Young and middle-aged healthy Japanese individuals with normal and high-normal BP (120-139/75-89 mmHg) were at risk for CVD among smokers, even after adjusting for an annual change in BP.

Background: Cardiac valve calcification is seen frequently in patients undergoing dialysis. Serum C-reactive protein (CRP) level also is reported to predict future cardiovascular events. We investigated the association among valve calcification, CRP level, and mortality in patients with end-stage renal disease who were just beginning hemodialysis (HD) therapy., Study Design: Observational cohort., Setting & Participants: 1,290 consecutive patients who just started HD therapy were enrolled and were followed up to 10 years., Predictor: Patients were divided into 3 groups according to number of calcified valves: those without valve calcification, those with calcification in a single (aortic or mitral) valve, and those with calcification in both valves. They also were divided into tertiles according to CRP level., Outcomes: Cardiovascular and all-cause mortality., Measurements: Echocardiography and CRP measurement were performed within 1 month after beginning HD therapy., Results: During follow-up (median, 51 months), 335 (25.9%) patients died, including 156 (12.1%) of cardiovascular disease. The adjusted HR for cardiovascular mortality was 2.80 (95% CI, 1.63-4.81) for 2 calcifications versus 0 (P < 0.001). Furthermore, the risk of cardiovascular mortality was 3.66-fold higher in patients with calcifications in both valves (highest tertile of CRP) compared with patients without valve calcification (lowest tertile of CRP; P < 0.001)., Limitations: Precise medical treatments or therapeutic interventions were not evaluated., Conclusions: Valve calcification and elevated CRP levels were not only related to additively increased risk of mortality, but also improved the prediction of mortality in patients with end-stage renal disease who had just begun HD therapy., (Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Obesity is closely associated with an increased risk for metabolic and cardiovascular diseases. Adipose tissue produces a number of secretory bioactive substances, also known as adipocytokines or adipokines, which directly affect adjacent or distant organs. Most adipocytokines are pro-inflammatory, thereby promoting the obesity-linked disorders. In contrast, there are a small number of adipocytokines that exhibit antiinflammatory properties. It is now recognized that dysregulated production or secretion of adipocytokines caused by adipocyte dysfunction leads to the development of obesity-linked complications. In this review, we focus on the functional role of several adipocytokines in metabolic and cardiovascular diseases.

Background:  Body fat percentage (BF%) determined by bioelectrical impedance analysis is widely used at home and in medical check-ups. However, the clinical significance of measuring BF% has not been studied in detail., Methods and Results:  A cross-sectional study was carried out on a cohort of 10,774 middle-aged Japanese men who had undergone an annual check-up in 2008. Cut-off points were evaluated for body mass index (BMI), waist circumference (WC), and BF% for detecting participants with cardiovascular disease (CVD) risk factors (diabetes mellitus, hypertension, dyslipidemia), and effectiveness compared for each marker's cut-off point. Additionally, the effects of smoking on cut-off points were evaluated. The cut-off points of BMI, WC, and BF% for detecting participants with 1 or more CVD risk factors were 22.7kg/m(2), 81.4cm, and 20.3%, respectively. The cut-off points of BF% for 1 or more CVD risk factors classified 3.43% more subjects into correct categories than those of BMI (P<0.001). The cut-off points of BMI, WC, and BF% for detecting individuals with 3 CVD risk factors in current smokers were 24.9kg/m(2), 87.8cm, and 23.7%, while those in non-smokers were 23.3kg/m(2), 83.9cm, and 22.3%, respectively., Conclusions:  BF% could be more effective in detecting individuals with early stage CVD risk accumulation than BMI. The cut-off points for current smokers were lower than those for non-smokers in all markers.

Background: Ankle brachial pressure index (ABPI) and pulse wave velocity (PWV) have been widely recognized as a marker of systemic atherosclerosis. We examined whether ABPI and brachial-ankle PWV (baPWV) predict individual cardiovascular events in patients on maintenance hemodialysis (HD)., Methods: We prospectively followed-up 445 HD patients undergoing both ABPI and baPWV measurements for up to 5 years. They were divided into 2 groups [group with ABPI > 0.9 to ≤ 1.3 (n = 328) and group with ABPI ≤ 0.9 or >1.3 (n = 117)] and were also divided into tertiles according to the baPWV level (T1: <1850 cm/s; T2: 1850-2310 cm/s and T3: ≥ 2310 cm/s)., Results: During the follow-up period (mean 43 ± 17 months), 206 cardiovascular events [cardiac event: 125 (28.1%), cerebrovascular events: 39 (8.8%), and peripheral arterial events: 42 (9.4%)] occurred, and 36 (8.1%) and 42 (9.4%) patients experienced cardiovascular and non-cardiovascular deaths, respectively. Cox multivariable analysis showed that presence of ABPI ≤ 0.9 or >1.3 was a significant predictor of cardiac events [hazard ratio (HR) 1.78, 95% confidential interval (CI) 1.27-2.49, p = 0.0008], cerebrovascular event (HR 1.95, 95%CI 1.13-3.36, p = 0.017), peripheral arterial event (HR 3.64, 95%CI 2.10-6.29, p < 0.0001), composite endpoint of cardiovascular events (HR 2.22, 95%CI 1.64-2.99, p < 0.0001), cardiovascular mortality (HR 2.42, 95%CI 1.44-4.06, p = 0.0008) and all-cause mortality (HR 1.52, 95%CI 1.03-2.25, p = 0.037). However, baPWV did not predict cardiovascular events on multivariate analysis., Conclusion: ABPI but not baPWV is useful for risk stratification of systemic atherosclerotic morbidity and mortality in HD patients. Furthermore, ABPI could predict not only individual peripheral arterial events but also cardiac and cerebrovascular events., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Aim: The association between subjects with metabolic syndrome (MS) who were considered not to require medication by their attending physicians and all-cause mortality, ischemic heart disease (IHD) and cardiovascular disease (CVD) remains unknown and should be clarified., Methods and Results: This is an observational longitudinal cohort study with a median follow-up of 7.5 years performed for 25,471 Japanese men aged 20-61 years who were not on medication. We used a modified definition of MS from the Japanese Society of Internal Medicine and the NCEP ATPIII, both of which employed body mass index instead of waist circumference. MS was associated with increased rates of all-cause death (adjusted hazard ratio (HR): 4.88 [95% confidence interval, 2.96-7.66]), IHD (3.17 [1.06-7.65]), and CVD (2.63 [1.32-4.72]). In contrast, overweight subjects with no component or one component had similar rates to subjects of normal weight. Any combination of the three MS components was associated with significantly greater rates of all-cause mortality (HR: 3.18-11.2) and IHD (HR: 3.17-8.24), whereas blood pressure elevation plus dyslipidaemia was associated with a significantly higher rate of CVD (HR: 3.27). In any endpoint, MS defined by Japanese criteria had higher HRs than defined by NCEP ATP III criteria., Conclusion: Young and middle-aged Japanese men with MS who had been viewed as not needing medication already showed increased rates of all-cause mortality, IHD and CVD. Additionally, the event rate depended on the specific combination of metabolic syndrome components.

Background: Smoking is still a major health problem among males in Japan. The effects of smoking and quitting on mortality and cardiovascular disease (CVD) need updating., Methods and Results: This was a prospective cohort study with a median follow-up of 7.5 years of a total of 25,464 healthy male Japanese workers aged 20-61 years who were not on any medication. The adjusted hazard ratios (HR; 95% confidence interval) for all-cause death were 1.51 (0.73, 2.94), 1.68 (1.07, 2.70), 1.30 (0.70, 2.34), and those for total CVD events 1.91 (0.72, 4.67), 2.94 (1.65, 5.63), and 3.25 (1.69, 6.54) for light smokers (1-10 cigarettes/day), moderate smokers (11-20/day), and heavy smokers (≥ 21/day) compared to never-smokers, respectively. Total CVD events increased dose-dependently as the number of cigarettes/day increased. Acute myocardial infarction was increased at any level of smoking. Stroke was increased at a moderate level of smoking. Quitting for ≥ 4 years, compared with continuing smokers, reduced the HR for all-cause death to 0.64 (0.38, 1.01), and total CVD events to 0.34 (0.17, 0.62)., Conclusions: In healthy young- and middle-aged Japanese males, a significant increase in HR for total CVD events was confirmed for a smoking level of 11-20 cigarettes/day. Quitting reduced the HR for total CVD events, with quitting for ≥ 4 years being statistically significant. A similar trend was observed for all-cause mortality.

Background and Objectives: Cardiac failure is directly affected by left ventricular (LV) dysfunction, and particularly LV systolic dysfunction is strongly associated with survival in ESRD patients. The aim of this study was to determine the prognostic value of reduced LV ejection fraction (LVEF) measured at the time of initiation of hemodialysis (HD) in incident HD patients., Design, Setting, Participants, & Measurements: 1254 consecutive ESRD patients who electively started HD therapy were screened by echocardiography within 1 month after its inception. They were divided into five groups according to LVEF levels with a decrease of 0.1 each and were followed up for up to 7 years. Survival was examined with the Kaplan-Meier method and compared using the log-rank test., Results: Among the 1254 patients, LVEF levels ≥0.6, 0.5 to 0.6, 0.4 to 0.5, 0.3 to 0.4, and <0.3 were seen in 842 (67.1%), 247 (19.7%), 107 (8.5%), 41 (3.3%), and 17 (1.4%) patients, respectively. On Kaplan-Meier analysis, 7-year event-free rates from cardiovascular death were 84.2, 83.7, 73.6, 59.4, and 30.9% in order of groups with decreasing LVEF of 0.1 each, respectively. Seven-year event-free rates from all-cause death were 69.2, 61.7, 57.1, 45.9, and 23.1% in the respective groups. Even after adjustment for other risk factors, decreasing LVEF was a strong independent predictor for cardiovascular death., Conclusions: Reduced LVEF on starting HD therapy could stratify risk of cardiovascular and all-cause mortality in ESRD patients. Screening by echocardiography at start of HD therapy might be recommended to predict prognosis in patients with ESRD.

Objective: The Japan assessment of pitavastatin and atorvastatin in acute coronary syndrome (JAPAN-ACS) study demonstrated that aggressive lipid-lowering therapy with a statin resulted in a significant regression of coronary atherosclerotic plaques in patients with ACS. Adiponectin is an adipocyte-derived protein with anti-atherogenic properties. Here, we investigated the association between adiponectin levels and the change in the plaque volume in ACS patients., Methods: Intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) was undertaken, followed by the initiation of statin treatment, in 238 patients with ACS. Follow-up IVUS was performed between 8 and 12 months after the PCI. The percent change in the plaque volume (%PV) in a non-culprit coronary artery segment was evaluated. The serum adiponectin and lipid parameters were measured both at baseline and at the follow-up., Results: At baseline, adiponectin was correlated positively with HDL-cholesterol and negatively correlated with triglyceride, but no correlation was observed with the PV. Adiponectin levels increased significantly from 7.8+/-4.6 microg/mL at baseline to 10.3+/-6.9 microg/mL at the 8-12 months follow-up. The increase in adiponectin was also associated with an increase of HDL-cholesterol and decrease of triglyceride, however, no significant correlation was observed with the %PV. A significantly higher incidence of major adverse cardiac events (MACE) was observed in patients with hypo-adiponectinemia at baseline. A multiple logistic regression analysis identified adiponectin as a significant independent predictor of MACE., Conclusion: Adiponectin levels measured after PCI could serve as a marker of MACE in patients with ACS., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Objectives: Percutaneous coronary interventions for very small vessels are common in clinical practice despite an unavailability of the 2.25-mm sirolimus-eluting stent (SES) in some countries. We sought to evaluate the clinical and angiographic outcomes of 2.5-mm SES implantation at lower deployment pressures in very small coronary arteries., Methods: Between June 2004 and March 2007, a total of 244 patients underwent percutaneous coronary interventions in vessels with reference diameters less than 2.5 mm at our centers: outcomes in 126 consecutive patients undergoing 2.5-mm SES implantation at lower deployment pressures (< or =10 atmospheres) with predilatation and postdilatation were compared with those in 118 patients who received bare-metal stents (BMS)., Results: In the SES group, rates of predilatation and postdilatation were 73.8 and 81% respectively, and mean deployment pressure was 8.3+/-1.2 atmospheres. At follow-up, in-segment late loss was markedly lower in SES versus BMS (0.21+/-0.41 vs. 0.48+/-0.63 mm, P=0.001), resulting in significantly lower rates of restenosis (14.7 vs. 37.5%, P<0.001). At 1 year, SES versus BMS use was associated with similar rates of stent thrombosis (0.8 vs. 0.8%, P>0.999), but significantly lower rates of major adverse cardiac events (MACE) (11.9 vs. 27.1%, P=0.003), mainly driven by a significantly lower need for target-lesion revascularization (9.5 vs. 26.3%, P=0.001). Multivariable analysis identified the SES use as independently associated with a reduced 1-year MACE risk (hazard ratio: 0.32; 95% confidence interval: 0.15-0.66; P=0.002)., Conclusion: Implantation of 2.5-mm SES in vessels with reference diameters less than 2.5 mm using lower deployment pressures and predilatation and postdilatation may lead to reduced risks of restenosis and MACE without an increased risk of stent thrombosis up to 1 year.

Obstructive sleep apnea syndrome (OSAS) is associated with increases in cardiovascular morbidity and mortality. Vascular changes in individuals with OSAS have not been fully elucidated, however. The possible impact of OSAS on the extent of aortic pressure augmentation (AG), an indicator of cardiovascular risk, was investigated. Forty-five consecutive male patients aged 35 to 78 years (56.0+/-9.6 years) who were referred to the sleep clinic of Nagoya University Hospital for screening and treatment of OSAS and 71 age-matched healthy men were enrolled in the study. AG was derived from the pressure waveform measured at the radial artery by applanation tonometry. The number of apnea and hypopnea episodes per hour (apnea-hypopnea index [AHI]) was determined by standard polysomnography. AG was significantly greater in OSAS patients than in controls (9.0+/-4.1 vs. 6.4+/-3.4 mmHg, p<0.001), and it was significantly reduced in 19 OSAS patients treated with continuous positive airway pressure. AG was also significantly correlated with the AHI (r=0.562, p<0.001) and age (r=0.356, p=0.016) but not with the serum concentrations of low and high density lipoprotein-cholesterol, triglyceride, or glycosylated hemoglobin. Stepwise multiple regression analysis revealed that the AHI was the most significant contributing factor to the increased AG in OSAS patients (beta=0.109, r=0.530, p<0.001). OSAS may thus have an adverse effect on vascular function that can be ameliorated by appropriate treatment.

Background: Despite a close association of adiponectin with metabolic syndrome (MetS), its usefulness as an additional MetS factor has not been well investigated., Methods: We studied 2327 apparently healthy Japanese male office workers aged 35 to 66 years old and investigated cross-sectionally whether categorization by serum adiponectin distinguished participants' levels of high-sensitivity C-reactive protein (CRP) beyond the conventional MetS., Results: In a linear regression analysis, adiponectin was associated with CRP independently of all MetS factors (beta=-0.192, P<0.001). Furthermore, a graded decrease in CRP level was observed with elevation of adiponectin in every stratum characterized by the presence or absence of each MetS component (trend P<0.05 in all strata except those of decreased high-density lipoprotein cholesterol or hyperglycemia). Similarly, geometric means of CRP levels (mg/l) decreased as adiponectin increased from the lowest to the highest tertile in all strata classified by the number of MetS components, though a P value did not reach statistical significance in those with 3 MetS components (the stratum of 0 MetS component: 0.41 [95% confidence interval, 0.34-0.49], 0.32 [0.28-0.37] and 0.26 [0.23-0.30], trend P<0.001; 1 component: 0.45 [0.39-0.52], 0.38 [0.34-0.43], and 0.32 [0.28-0.36], trend P<0.001; 2 components: 0.58 [0.50-0.67], 0.51 [0.44-0.60], and 0.46 [0.38-0.55], trend P=0.043; 3 components: 0.80 [0.66-0.96], 0.69 [0.55-0.87], and 0.58 [0.39-0.85], trend P=0.139)., Conclusions: Adiponectin evaluation provides additional inflammatory information on conventional MetS, supporting the potential of hypoadiponectinemia as an additional MetS component for identifying high-risk individuals for cardiovascular disease.

Objective: An inverse association between adiponectin and C-reactive protein (CRP) has been shown in certain pathological states including obesity, diabetes, and coronary artery disease, which themselves might have confounded this association. This study investigated the association between adiponectin and CRP among substantially healthy subjects., Methods and Results: A population of 2347 middle-aged Japanese men with no medical history of cardiovascular disease, cancer, diabetes, hypertension, or hyperlipidemia was evaluated. Those with some metabolic syndrome components from serological and anthropometric tests were excluded, leaving 714 men for analysis. Serum adiponectin and CRP were significantly correlated (r = -0.21, P < 0.001). After categorization into quartiles from the lowest to the highest adiponectin concentration (Q1 to Q4), the CRP level was found to be significantly higher in Q1 than in Q2, Q3 and Q4 (0.41 mg/L versus 0.30, 0.25 and 0.24 mg/L, P = 0.043, P < 0.001 and P < 0.001, respectively). These associations remained significant even after adjustment for covariates. Moreover, multiple linear regression analysis revealed that adiponectin contributed more strongly to CRP than other factors, including the index of insulin resistance., Conclusions: An inverse and strong association between adiponectin and CRP in substantially healthy subjects implies that decreased serum adiponectin might be fundamentally associated with the early stage of low-grade inflammation.

Ischemic heart disease and peripheral artery disease mainly develop as a consequence of atherosclerotic lesion formation. Angiogenesis, the formation of new blood vessels from the preexisting vascular bed, is of paramount importance in the maintenance of vascular integrity both in the repair process of damaged tissue (wound healing) and in the formation of collateral vessels in response to tissue ischemia. Angiogenesis is a complex process that is orchestrated by a multitude of cytokines/chemokines and growth factors. In its broadest sense, angiogenesis cannot be viewed as a single process. It is likely that different mediators are involved in different phases of angiogenesis. Vascular endothelial cells produce nitric oxide (NO), an endothelium-derived labile molecule, which maintains vascular homeostasis and thereby prevents vascular atherosclerotic changes. In patients with ischemic heart disease and peripheral artery disease, the release of endothelium-derived NO is decreased, which plays an important role in the atherosclerotic disease progression. In recent years, endothelium-derived NO has been shown to modulate angiogenesis in vitro and in vivo. In this review, we summarize recent progress in the field of the NO-mediated regulation of postnatal angiogenesis.

The utility of abdominal aortic calcification (AAC) for prediction of cardiovascular events (CVEs) in patients with acute coronary syndrome (ACS) remains to be determined. The aim of this prospective study was to determine the predictive value of the abdominal aortic calcification index (ACI), a semi-quantitative measure of AAC, for CVEs in patients with ACS. We evaluated 314 patients with ACS. All patients underwent successful percutaneous coronary intervention to the culprit coronary vessel without in-hospital adverse events. ACI was calculated on non-contrast computed tomography images. CVEs were defined as a composite of cardiovascular death, ACS recurrence, and stroke. During a median follow-up period of 19.1 months, CVEs occurred in 29 patients (9.2%). Multivariable regression analysis after adjustment for age and gender showed a significantly higher baseline ACI in patients with CVEs than in those without [median (interquartile ranges), 42.1 (25.9–60.2) vs. 20.8 (8.8–38.6) %; P = 0.021]. The cutoff value of ACI for prediction of CVEs, estimated by receiver-operating characteristic analysis, was 29.2%, with sensitivity of 76% and specificity of 64% (area under the curve, 0.69). After adjustment for conventional cardiovascular risk factors, Cox analysis showed high ACI (≥29.2%) to be significantly associated with increased risk of CVEs (P = 0.011; hazard ratio, 1.82). Multivariate analysis identified high ACI as an independent predictor of CVEs (P = 0.012; hazard ratio, 1.80). Stepwise forward selection procedure also showed that high ACI was a significant independent determinant of CVEs (P = 0.004; R2, 0.089). Both net reclassification improvement (0.64; P = 0.001) and integrated discrimination improvement (0.04; P < 0.001) improved significantly after the addition of high ACI to conventional risk factors. Evaluation of ACI using CT seems to provide valuable clinical information for proper assessment of mid-term CVEs in patients with ACS after percutaneous coronary intervention. [ABSTRACT FROM AUTHOR]