Clinical features, future cardiac events, and prognostic factors following percutaneous coronary intervention in young female patients.

BACKGROUND: The proportion of young females among the patients who undergo percutaneous coronary intervention (PCI) is relatively small, and information on their clinical characteristics is limited. This study investigated the clinical characteristics and prognostic factors for future cardiac events in young females who underwent PCI. METHODS: This multicenter observational study included 187 consecutive female patients aged < 60 years who underwent PCI in seven hospitals. The primary composite endpoint was the incidence of cardiac death, nonfatal myocardial infarction, and target vessel revascularization. RESULTS: The mean patient age was 52.1 ± 6.1 years and 89 (47.6%) had diabetes, and renal dysfunction (an estimated glomerular filtration rate < 60 mL/min/1.73 m2) was observed in 38 (20.3%). During a median follow-up of 3.3 years, the primary endpoint occurred in 28 patients. The Cox proportional hazards models showed that renal dysfunction was an independent predictor for the primary endpoint (hazard ratio 3.04, 95% confidence interval 1.25-7.40, p = 0.01), as well as multivessel disease (hazard ratio 2.79, 95% confidence interval 1.12-6.93, p = 0.03). Patients with renal dysfunction had a significantly higher risk for the primary endpoint than those without renal dysfunction. CONCLUSIONS: Renal dysfunction was strongly associated with future cardiac events in young females who underwent PCI.

Impact of right coronary artery dominance on the long-term mortality in the patients with acute total/subtotal occlusion of unprotected left main coronary artery.

BACKGROUND: Patients with a right dominant coronary artery anatomy account for a significant proportion of acute myocardial infarction cases, and this condition is associated with a better prognosis. However, there are limited data on the impact of coronary dominance on patients with acute total/subtotal occlusion of unprotected left main coronary artery (ULMCA). METHODS: This study aimed to assess the impact of right coronary artery (RCA) dominance on long-term mortality in patients with acute total/subtotal occlusion of the ULMCA. From a multicenter registry, 132 cases of consecutive patients who had undergone emergent percutaneous coronary intervention (PCI) due to acute total/subtotal occlusion of the ULMCA were reviewed. RESULTS: Patients were classified into two groups according to the size of their RCA (dominant RCA group, n = 29; non-dominant RCA group, n = 103). Long-term outcomes were examined according to the presence of dominant RCA. Cardiopulmonary arrest (CPA) occurred in 52.3 % of patients before revascularization. All-cause death was significantly lower in the dominant RCA group than in the non-dominant RCA group. In the Cox regression model, dominant RCA was an independent predictor of all-cause death, as well as total occlusion of ULMCA, collateral from RCA, chronic kidney disease, and CPA. Patients were further analyzed according to the degree of stenosis of the ULMCA; patients with non-dominant RCA and total occlusive ULMCA had the worst outcome compared with the other groups. CONCLUSIONS: A dominant RCA might improve long-term mortality in patients with acute total/subtotal occlusion of the ULMCA who were treated with PCI.

Long-term outcomes of percutaneous revascularization for internal mammary artery-left anterior descending artery bypass failure.

Despite the excellent long-term results of internal mammary artery (IMA)-left anterior descending (LAD) bypass, percutaneous revascularization of IMA is sometimes required for IMA-LAD bypass failure. However, its clinical outcomes have not been fully elucidated. The aim of this study was to investigate the long-term clinical outcomes, including target lesion revascularization (TLR) following contemporary percutaneous revascularization of failed IMA bypass graft. We examined data of 59 patients who had undergone percutaneous revascularization of IMA due to IMA-LAD bypass failure at nine hospitals. Patients with IMA graft used for Y-composite graft or sequential bypass graft were excluded. The incidence of TLR was primarily examined, whereas other clinical outcomes including cardiac death, myocardial infarction, and target vessel revascularization were also evaluated. Mean age of the enrolled patients was 67.4 ± 11.3 years, and 74.6% were men. Forty patients (67.8%) had anastomotic lesions, and 17 (28.8%) underwent revascularization within three months after bypass surgery. Procedural success was achieved in 55 (93.2%) patients. Stent implantation was performed in 13 patients (22.0%). During a median follow-up of 1401 days (interquartile range, 282-2521 days), TLR was required in six patients (8.5% at 1, 3, and 5 years). Patients who underwent percutaneous revascularization within 3 months after surgery tended to have a higher incidence of TLR. Clinical outcomes of IMA revascularization for IMA-LAD bypass failure were acceptable.

The ridge line of left pulmonary vein isolation from left atrial appendage can subsequently increase the completion rate of the mitral isthmus block line.

BACKGROUND AND OBJECTIVES: Mitral isthmus (MI) ablation for mitral flutter is technically difficult, and incomplete block line is not uncommon. The objective of this study is to investigate the effect of the ridge line of left pulmonary vein isolation (LPVI) from left atrial appendage (LAA) on completion rate of mitral isthmus (MI) block line and recurrence rate of atrial tachycardia (AT) or atrial flutter (AFL) after the first MI ablation. METHODS: We identified 611 patients who underwent first MI ablation for mitral flutter during the study period. Finally, 559 patients were enrolled and divided into two groups according to the method of ridge line ablation of LPVI (LAA group, n = 467, conventional group, n = 92). Outcome measures were the completion of MI block line by first MI ablation, the recurrence of AT/AFL, and repeat MI ablation after the first MI ablation. RESULTS: The first MI block line completion rate was significantly higher in the LAA group than the conventional group (95% vs. 85%, p < 0.001). The recurrence rate of AT/AFL after 3 months from first MI ablation was significantly lower in the LAA group. The requirement of additional MI ablation tended to be lower in the LAA group. CONCLUSIONS: Our novel approach of ablating LPV-LAA ridge from the LAA side during PVI can increase the success rate of MI block line completion, and reduce the recurrence rate of AT/AFL and the need for additional MI block line ablation. Graphical abstract Ablation of the left pulmonary vein-left atrial appendage ridge from the left atrial appendage side during PVI increased the success rate of mitral isthmus block line completion.

Comparison of the empirical linear ablation and low voltage area-guided ablation in addition to pulmonary vein isolation in patients with persistent atrial fibrillation: a propensity score-matched analysis.

BACKGROUND: The efficacy of pulmonary vein isolation (PVI) alone is not guaranteed for persistent atrial fibrillation (PeAF), and it is unclear which type of ablation approach should be applied in addition to PVI. This study aimed to compare outcomes and prognosis between empirical linear ablation and low-voltage area (LVA) ablation after PVI for PeAF. METHODS: We enrolled 128 patients with PeAF who were assigned to the linear ablation group (n = 64) and the LVA ablation group (n = 64) using a propensity score-matched model. After PVI and cardioversion, the patients underwent either empirical linear ablation or LVA ablation during sinus rhythm. All patients in the linear ablation group underwent both roof line and mitral valve isthmus (MVI) ablations. An electrical-guided ablation targeting LVA (< 0.5 mV) was performed in the LVA group. When there was no LVA in the LVA group, only PVI was applied. We compared the procedural outcomes and recurrence after ablation between the two groups. RESULTS: The baseline characteristics were well-balanced between the two groups. Fifty patients had LVA (22 and 28 patients in the linear and LVA groups). The roof and MVI lines were completed in 100% and 96.9% of the patients. During the mean follow-up of 279.5 ± 161.3 days, the LVA group had significantly lower recurrence than the linear group (15 patients [23%] vs. 29 patients [45%], p = 0.014). Thirty-five patients were prescribed antiarrhythmic drugs during the follow-up period (linear group, n = 17; LVA group, n = 18); amiodarone and bepridil were administered to most of the patients (15 and 17 patients, respectively). The difference in the prognosis was relevant among the patients with LVA, while this trend was not observed in those without LVA. The LVA ablation group demonstrated significantly lower radiofrequency energy and shorter procedural time compared to the linear ablation group. The recurrence of atrial flutter was more likely to occur in the linear group than in the LVA group (14 [22%] vs. 6 [9.4%], p = 0.052). CONCLUSION: The electrophysiological-guided LVA ablation is more effective than empirical linear ablation in PeAF patients with LVA. Unnecessary empirical linear ablation might have a risk of iatrogenic gap and atrial flutter recurrence.

＜Editors' Choice＞ Prevalence of acute coronary syndrome during the pandemic of COVID-19 in the Tokai Region of Japan.

The outbreak of coronavirus disease 19 (COVID-19) has had a great impact on medical care. During the COVID-19 pandemic, the rate of hospital admissions has been lower and the rate of in-hospital mortality has been higher in patients with acute coronary syndrome (ACS) in Western countries. However, in Japan, it is unknown whether the COVID-19 pandemic has affected the incidence of ACS. In the study, eleven hospitals in the Tokai region participated. Among enrolled hospital, we compared the incidence of ACS during the COVID-19 pandemic (April and May, 2020) with that in equivalent months in the preceding year as the control. During the study period; April and May 2020, 248 patients with ACS were admitted. Compared to April and May 2019, a decline of 8.1% [95% confidence interval (CI) 5.2-12.1; P = 0.33] in admissions for ACS was observed between April and May 2020. There was no significant difference in the strategy for revascularization and in-hospital deaths between 2019 and 2020. In conclusion, the rate of admission for ACS slightly decreased during the COVID-19 pandemic, compared to the same months in the preceding year. Moreover, degeneration of therapeutic procedures for ACS did not occur.

Clinical Outcomes Following Emergent Percutaneous Coronary Intervention for Acute Total/Subtotal Occlusion of the Left Main Coronary Artery.

BACKGROUND: Data regarding the clinical features, outcomes and prognostic factors in patients presenting with acute total/subtotal occlusion of the unprotected left main coronary artery (LMCA) remain limited.Methods and Results:From a multi-center registry, 134 patients due to acute total/subtotal occlusion of the unprotected LMCA were reviewed. Emergency room (ER) status classification was defined according to the presence of cardiogenic shock and cardiopulmonary arrest (CPA) in the ER (class 1=no cardiogenic shock; class 2= cardiogenic shock but not CPA; and class 3=CPA). In-hospital mortality and cerebral performance category (CPC) as the endpoints were evaluated. One-half (67/134) of the enrolled patients presented with total occlusion of the unprotected LMCA. Regarding ER status classification, class 1, 2, and 3 were observed in 30.6%, 45.5%, and 23.9% of the patients, respectively. In-hospital mortality occurred in 73 (54.5%) patients; of the remaining patients, 52 (85.3%) could be discharged with a CPC 1 or 2. ER status classification (odds ratio 4.4 [95% confidence interval: 2.33-10.67]; P<0.001) and total occlusion of the unprotected LMCA (odds ratio 8.29 [95% confidence interval 2.93-23.46]; P<0.001) were strong predictors of in-hospital mortality. CONCLUSIONS: Acute total/subtotal occlusion involving the unprotected LMCA appeared to be associated with high in-hospital mortality. ER status classification and initial flow in the unprotected LMCA were significant predictive factors of in-hospital mortality.

Clinical characteristics and treatment of Spontaneous Coronary Artery Dissection in Young Women Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) has recently been recognized as a cause of acute coronary syndrome (ACS), especially in young women. However, the characteristics, optimal treatment, and prognosis of patients who experience SCAD have not been fully described. METHODS: Data were retrospectively collected from a multicenter registry. Among 187 young women less than 60 years of age who underwent percutaneous coronary intervention, 19 (10.2%) with SCAD were identified through coronary angiography. Clinical characteristics and outcomes were investigated. RESULTS: Those with SCAD less frequently exhibited coronary risk factors, such as diabetes, dyslipidemia, and smoking, than those without SCAD. Intense emotional and/or physical stress was more frequently observed as a prominent precipitating factor in cases of SCAD. All 19 SCAD patients presented with ACS, 7 of whom were treated using stents, and the other 12 treated without stents. During a median follow-up of 960 days (interquartile range, 686-1504 days), two recurrent coronary artery dissections occurred within 7 days, both of which occurred in a vessel other than that in which primary dissection occurred. There were no deaths or recurrent dissection after 1 week. CONCLUSION: SCAD was not uncommon among young Japanese women requiring percutaneous coronary intervention. Patients with SCAD exhibited fewer coronary risk factors and more precipitating factors than those without SCAD, and long-term clinical outcomes after an early period appeared to be favorable.

A case of extensive encircling pulmonary vein isolation in a patient with severe scoliosis.

The patient was a 62-year-old man with atrial fibrillation and severe scoliosis. Scoliosis may impair cardiorespiratory function. Enhanced computed tomography (CT) was helpful for the Brockenbrough method. Three-dimensional (3D) mapping also demonstrated clockwise rotation of the heart. We successfully isolated extensive encircling pulmonary vein in this patient using enhanced CT and 3D mapping. The CT venous images revealed appropriate localization of the vein and heart. CT and 3D mapping may ensure a more stable and safer procedure.

Efficacy and safety of radiofrequency catheter ablation for atrial fibrillation in chronic hemodialysis patients.

BACKGROUND: Radiofrequency catheter ablation (RFCA) is increasingly performed for the treatment of atrial fibrillation (AF), but it is problematic because the use of anti-arrhythmic agents is largely restricted in patients undergoing hemodialysis (HD) therapy. However, little is known about the long-term clinical outcomes of AF after RFCA in HD patients. METHODS: Between 2002 and 2008, 16 HD patients (age: 63.8 ± 7.4 years, 75.0% men) underwent RFCA for AF at the Toyota Kosei Hospital. We investigated the long-term results and mortality of RFCA for AF in HD patients and compared them with those of 111 non-HD patients (age: 58.6 ± 10.0 years, 78.3% male) who received the same procedures. RESULTS: During the follow-up (64.3 ± 25.4 months in HD patients, 70.5 ± 20.2 months in non-HD patients) after the initial RFCA procedure, sinus rhythm was restored in 4 HD patients (25%) and in 45 non-HD patients (40.5%). Multiple procedures were performed in 12 HD patients and in 57 non-HD patients. After the final procedure, 13 HD patients (81.3%) and 92 non-HD patients (82.9%) were free of atrial arrhythmia and symptoms. Of importance, Kaplan-Meier analysis did not demonstrate any significant differences in the atrial arrhythmia-free rate after the last procedure between HD patients and the control group matched after propensity-score analysis despite higher all-cause mortality in HD patients than in non-HD patients. CONCLUSIONS: During 5-years of follow-up, the use of multiple RFCA procedures for AF in patients undergoing HD was favorable, whereas the use of a single procedure was disappointing. Multiple RFCA procedures can be an efficient approach to the treatment of AF in HD patients.

Impact of pitavastatin on high-sensitivity C-reactive protein and adiponectin in hypercholesterolemic patients with the metabolic syndrome: the PREMIUM Study.

BACKGROUND: Inflammatory reactions and oxidative stress, which are important in progression of atherosclerosis, are reported to be increased in individuals with metabolic syndrome (MetS). On the other hand, adiponectin levels are lowered. Since effects of pitavastatin on these parameters have not been reported in hypercholesterolemic patients with MetS, the present study was conducted. PURPOSE: To evaluate the effects of pitavastatin on inflammatory reaction, oxidative stress, and plasma adiponectin levels in hypercholesterolemic MetS patients in a multicenter trial. METHODS: This open-label, single group study was performed at 7 hospitals in Japan. Pitavastatin (2mg/day) was administered to 103 consecutive patients with hypercholesterolemia, subdivided into MetS and non-MetS for 12 weeks. Blood samples were collected after overnight fasting at the start of treatment (baseline) and after 12 weeks. RESULTS: In the patients with MetS (n=69), mean values of plasma high-sensitivity C-reactive protein (hs-CRP) were significantly higher and mean values of plasma high-molecular-weight (HMW)-adiponectin significantly lower than in their counterparts without MetS (n=34). The baseline HMW-adiponectin and high-density lipoprotein cholesterol (HDL-C) values significantly correlated only in the MetS patients (r=0.318; p=0.01). In an effectiveness analysis including 94 patients (62 with MetS, 32 without MetS), the level of hs-CRP was significantly decreased in patients with MetS during the drug treatment, whereas HMW-adiponectin did not change. When patients with MetS were divided into two subgroups according to the percent changes in HDL-C, significantly greater increase in HMW-adiponectin by pitavastatin treatment was observed in the HDL-C ≥10% increase subgroup than in the HDL-C <10% increase subgroup (p=0.009). CONCLUSION: Twelve weeks administration of pitavastatin, in addition to the antihyperlipidemic effects, may be beneficial as an anti-atherosclerotic therapy in hypercholesterolemic patients with MetS, taking changes in hs-CRP and HMW-adiponectin into consideration. ClinicalTrials.gov identifier: NCT00444717.

Adiponectin ameliorates doxorubicin-induced cardiotoxicity through Akt protein-dependent mechanism.

Accumulating evidence shows that obesity is associated with doxorubicin cardiac toxicity in the heart, but the molecular mechanisms that contribute to this pathological response are not understood. Adiponectin is an adipose-derived, cardioprotective factor that is down-regulated in obesity. Here, we investigated the effect of adiponectin on doxorubicin (DOX)-induced cardiotoxicity and assessed the mechanisms of this effect. A single dose of DOX was intraperitoneally injected into the abdomen of adiponectin knock-out (APN-KO) and wild-type (WT) mice. APN-KO mice had increased mortality and exacerbated contractile dysfunction of left ventricle compared with WT mice. APN-KO mice also showed increased apoptotic activity and diminished Akt signaling in the failing myocardium. Systemic delivery of adenoviral vector expressing adiponectin improved left ventricle dysfunction and myocardial apoptosis following DOX injection in WT and APN-KO mice but not in Akt1 heterozygous KO mice. In cultured rat neonatal cardiomyocytes, adiponectin stimulated Akt phosphorylation and inhibited DOX-stimulated apoptosis. Treatment with sphingosine kinase-1 inhibitor or sphingosine 1-phosphate receptor antagonist diminished adiponectin-induced Akt phosphorylation and reversed the inhibitory effects of adiponectin on myocyte apoptosis. Pretreatment with anti-calreticulin antibody reduced the binding of adiponectin to cardiac myocytes and blocked the adiponectin-stimulated increase in Akt activation and survival in cardiomyocytes. Interference of the LRP1/calreticulin co-receptor system by siRNA or blocking antibodies diminished the stimulatory actions of adiponectin on Akt activation and myocyte survival. These data show that adiponectin protects against DOX-induced cardiotoxicity by its ability to promote Akt signaling.

Correlation between circulating adiponectin levels and coronary plaque regression during aggressive lipid-lowering therapy in patients with acute coronary syndrome: subgroup analysis of JAPAN-ACS study.

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.

Evidence for the importance of adiponectin in the cardioprotective effects of pioglitazone.

The favorable effects of the peroxisome proliferator-activated receptor-gamma ligand pioglitazone on glucose metabolism are associated with an increase in the fat-derived hormone adiponectin in the bloodstream. A recent clinical trial, Prospective Pioglitazone Clinical Trial in Macrovascular Events, demonstrated that pioglitazone improved cardiovascular outcomes in patients with type 2 diabetes mellitus. However, the functional role of adiponectin in cardioprotection by pioglitazone has not been examined experimentally. Here we investigated the effect of pioglitazone on angiotensin II (Ang II)-induced cardiac hypertrophy and assessed the potential contribution of adiponectin to the action of pioglitazone on the heart. Wild-type or adiponectin-deficient mice were treated with pioglitazone as food admixture at a concentration of 0.01% for 1 week followed by 2 weeks of infusion with Ang II at 3.2 mg/kg per day. Ang II infusion in wild-type mice resulted in exacerbated myocyte hypertrophy and increased interstitial fibrosis, which were accompanied by elevated phosphorylation of extracellular signal-regulated kinase and expression of transforming growth factor-beta1 in the heart. Treatment of wild-type mice with pioglitazone attenuated cardiac hypertrophy and fibrosis, extracellular signal-regulated kinase phosphorylation, and transforming growth factor-beta1 expression in response to Ang II. Pioglitazone also increased the plasma adiponectin level and phosphorylation of cardiac AMP-activated protein kinase in wild-type mice in the presence of Ang II. The suppressive effects of pioglitazone on Ang II-induced cardiac hypertrophy and fibrosis were diminished in adiponectin-deficient mice. Furthermore, pioglitazone had no effects on the phosphorylation of extracellular signal-regulated kinase and AMP-activated protein kinase in the Ang II-infused heart of adiponectin-deficient mice. These data provide direct evidence that pioglitazone protects against Ang II-induced pathological cardiac remodeling via an adiponectin-dependent mechanism.

Impact of renal function on coronary plaque composition.

BACKGROUND: Recent studies have demonstrated that patients with chronic kidney disease are at high risk of atherosclerosis. Recently it has been found that coronary plaque components can be evaluated by integrated backscatter intravascular ultrasound (IB-IVUS), and lipid-rich plaque is associated with vulnerable plaque. The aim of the study was to investigate the relationship between renal function and tissue characterization of coronary plaque composition at the target stenotic site for percutaneous coronary intervention (PCI). METHODS: We prospectively performed IB-IVUS before elective PCI in 89 consecutive patients with stable angina. According to estimated glomerular filtration rate (eGFR), they were divided into two groups (eGFR <60 ml/min/ 1.73 m(2) or eGFR > or =60 ml/min/1.73 m(2)). The tissue characteristics of the coronary plaque at each target stenotic site were evaluated by three-dimensional (3D) IB-IVUS just before PCI procedure. RESULTS: The patients with eGFR <60 ml/min/1.73 m(2) had higher percentage of lipid volume and lower percentage of fibrous volume compared to the patients with eGFR > or = 60 ml/min/1.73 m(2) on the 3D IB-IVUS images (36.7 +/- 10.6% versus 28.7 +/- 9.3%, P < 0.001 and 59.1 +/- 8.7% versus 66.3 +/- 8.3%, P < 0.001, respectively). eGFR showed a significant negative correlation with lipid volume and had a significant positive correlation with fibrous volume in coronary plaques (r = -0.44, P < 0.0001, and r = 0.46, P < 0.0001, respectively). CONCLUSIONS: Impaired renal function was related to higher percentage of lipid volume and lower percentage of fibrous volume in coronary plaque. Our findings may explain the increasing risk of cardiovascular events in patients with renal dysfunction.

Impact of long-term statin treatment on coronary plaque composition at angiographically severe lesions: a nonrandomized study of the history of long-term statin treatment before coronary angioplasty.

BACKGROUND: Studies have found an association between treatment with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ("statins") and reductions in procedure-related complications in percutaneous coronary intervention (PCI). OBJECTIVE: This study investigated the effects of long-term statin treatment before elective PCI on coronary plaque composition at the angiographically severe target stenotic lesions. METHODS: This nonrandomized, observational study was conducted at Nagoya University Hospital, Nagoya, Japan. Data were collected from the electronic medical records of patients with stable angina pectoris who underwent PCI guided by intravascular ultrasound (IVUS). Patients were stratified into 2 groups: those who received long-term statin treatment for > or =6 months before PCI (statin group) and those who did not (nonstatin group). The tissue characteristics of the coronary plaque at each target stenotic site were analyzed using 3-dimensional integrated backscatter IVUS immediately before PCI. RESULTS: Data from 100 patients were included (91 men, 9 women; mean [SD] age, 67 [10] years; statin group, 44 patients; nonstatin group, 56). The clinical characteristics of the 2 groups were not significantly different, with the exception of the prevalence of hyperlipidemia (statin vs nonstatin, 100% vs 51.8%; P < 0.001). There were no significant between-group differences in serum lipid profiles. The statin group had a significantly greater mean (SD) percentage decrease in lipid volume (28.7% [10.0%] vs 34.7% [9.8%]; P = 0.003) and a significantly greater increase in fibrous volume (66.5% [8.5%] vs 60.9% [8.6%]; P = 0.001) compared with the nonstatin group. CONCLUSION: This study found a significant difference in lipid and fibrous volumes in angiographically severe coronary stenotic lesions in these patients with stable angina who received long-term statin treatment before PCI versus those who did not.

Caloric restriction stimulates revascularization in response to ischemia via adiponectin-mediated activation of endothelial nitric-oxide synthase.

Caloric restriction (CR) can extend longevity and modulate the features of obesity-related metabolic and vascular diseases. However, the functional roles of CR in regulation of revascularization in response to ischemia have not been examined. Here we investigated whether CR modulates vascular response by employing a murine hindlimb ischemia model. Wild-type (WT) mice were randomly divided into two groups that were fed either ad libitum (AL) or CR (65% of the diet consumption of AL). Four weeks later, mice were subjected to unilateral hindlimb ischemic surgery. Body weight of WT mice fed CR (CR-WT) was decreased by 26% compared with WT mice fed AL (AL-WT). Revascularization of ischemic hindlimb relative to the contralateral limb was accelerated in CR-WT compared with AL-WT as evaluated by laser Doppler blood flow and capillary density analyses. CR-WT mice had significantly higher plasma levels of the fat-derived hormone adiponectin compared with AL-WT mice. In contrast to WT mice, CR did not affect the revascularization of ischemic limbs of adiponectin-deficient (APN-KO) mice. CR stimulated the phosphorylation of endothelial nitric-oxide synthase (eNOS) in the ischemic limbs of WT mice. CR increased plasma adiponectin levels in eNOS-KO mice but did not stimulate limb perfusion in this strain. CR-WT mice showed enhanced phosphorylation of AMP-activated protein kinase (AMPK) in ischemic muscle, and administration of AMPK inhibitor compound C abolished CR-induced increase in limb perfusion and eNOS phosphorylation in WT mice. Our observations indicate that CR can promote revascularization in response to tissue ischemia via an AMPK-eNOS-dependent mechanism that is mediated by adiponectin.

Usefulness of adiponectin to predict myocardial salvage following successful reperfusion in patients with acute myocardial infarction.

Adiponectin is an adipose-derived plasma protein that demonstrates beneficial actions on myocardial injury under ischemic conditions. Circulating endothelial progenitor cells are reported to associate with rescue of cardiac damage after acute myocardial infarction (AMI). We examined whether circulating adiponectin level affects myocardial function and injury in patients with AMI. A total of 48 patients who underwent successful reperfusion treatment after AMI were enrolled. Cardiac function and perfusion defect were assessed by scintigraphic images of iodine-123 beta-methyl iodophenyl pentadecanoic acid in the acute phase and technetium-99m tetrofosmin in the long-term phase. Plasma adiponectin levels were measured by enzyme-linked immunosorbent assay at day 7 after AMI. Plasma adiponectin levels associated positively with myocardial salvage index representing the proportion of initial perfusion defect rescued by reperfusion and recovery of ejection fraction in the long-term phase and negatively with final infarct size. A positive correlation was also observed between adiponectin levels and number of circulating CD34(+) cells as determined by flow cytometry and between myocardial salvage index and recovery of ejection fraction independently associated with circulating CD34(+) cell levels. In conclusion, plasma adiponectin levels predict improvement of cardiac damage and function after reperfusion therapy in patients with AMI, suggesting that adiponectin could serve as a biomarker for assessment of myocardial injury after AMI.

Adiponectin promotes endothelial progenitor cell number and function.

Obesity-linked diseases are associated with suppressed endothelial progenitor cell (EPC) function. Adiponectin is an adipose-derived protein that is downregulated in obese and diabetic subjects. Here, we investigated the effects of adiponectin on EPCs. EPC levels did not increase in adiponectin deficient (APN-KO) in response to hindlimb ischemia. Adenovirus-mediated delivery of adiponectin increased EPC levels in both WT and APN-KO mice. Incubation of human peripheral blood mononuclear cells with adiponectin led to an increase of the number of EPCs. Adiponectin induced EPC differentiation into network structures and served as a chemoattractant in EPC migration assays. These data suggest that hypoadiponectinemia may contribute to the depression of EPC levels that are observed in patients with obesity-related cardiovascular disorders.