Impact of abdominal and epicardial fat on the association between plasma adipocytokine levels and coronary atherosclerosis in non-obese patients.

OBJECTIVE: Ectopic fat accumulation is associated with coronary artery disease. Visceral adipose tissue has paracrine and systemic effects and is a source of adipocytokines. It has been implicated in the pathogenesis of coronary atherosclerosis; however, nothing is known about whether increases in epicardial fat have the same effect on coronary atherosclerosis as increases in abdominal visceral fat. METHODS: We examined 216 consecutive patients suspected to have coronary artery disease. Individuals with acute coronary syndrome and inadequate computed tomography (CT) imaging were excluded. We enrolled 164 patients (65 ± 10 years old; 70% men; body mass index [BMI], 23.8 ± 3.6 kg/m(2)). The plasma concentrations of adiponectin, interleukin-6 (IL-6), plasminogen activator inhibitor-1, and vascular endothelial growth factor were measured. The characteristics of coronary plaque, abdominal visceral fat area, and epicardial fat volume (EFV) were determined by 64-slice CT imaging. RESULTS: EFV was greater in subjects with noncalcified plaque than in those with no plaque or with calcified plaque (126 ± 39 mL vs. 98 ± 34 mL and 97 ± 45 mL, respectively; P = 0.010). EFV was significantly correlated with BMI, triglycerides, and the triglyceride/high-density lipoprotein cholesterol ratio (r = 0.51, 0.19, and 0.20, respectively) but not with plasma levels of adipocytokines. The plasma adiponectin and IL-6 concentration was significantly correlated with abdominal visceral fat area in coronary plaque patients (r = -0.49 and 0.20). CONCLUSIONS: In non-obese Japanese patients, epicardial fat may have unique mechanisms affecting the development of coronary atherosclerosis, which is different from abdominal visceral fat.

The different association of epicardial fat with coronary plaque in patients with acute coronary syndrome and patients with stable angina pectoris: analysis using integrated backscatter intravascular ultrasound.

OBJECTIVES: We assessed the hypothesis that the epicardial fat is associated with coronary lipid plaque. BACKGROUND: Epicardial fat volume (EFV) is increased in patients with acute coronary syndrome (ACS), and lipid-rich plaques have been associated with acute coronary events. METHODS: We enrolled 112 individuals who underwent percutaneous coronary intervention (PCI) (66 with ACS; 46 with stable angina pectoris [SAP]) and classified plaque components using integrated backscatter intravascular ultrasound as calcified, fibrous, or lipid. Possible effects of PCI on plaque data were minimized by assessing 10-mm vessel lengths proximal to the culprit lesions. Total plaque volume and percentage volumes of individual plaque components were calculated. EFV and abdominal visceral fat area were measured using 64-slice computed tomography. RESULTS: ACS patients had significantly higher EFV than did SAP patients (118 ± 44 vs.101 ± 41 mL, p = 0.019). In ACS patients, EFV was correlated with total plaque volume and percentage of lipid plaque (r = 0.27 and 0.31, respectively; p < 0.05). Moreover, an independent interaction between EFV and lipid-rich plaque (odds ratio, 1.04; 95% confidence interval, 1.00-1.07) were revealed. In contrast, in SAP patients, EFV was positively correlated with body mass index and abdominal visceral fat area but not with plaque characteristics. CONCLUSIONS: EFV was associated with lipid-rich plaque in patients with ACS, whereas no correlation between EFV and coronary plaque profile was apparent in SAP patients. Epicardial fat may have a role in the development of lipid plaque, which contributes to the pathogenesis of ACS.

Comparison of tissue characteristics between acute coronary syndrome and stable angina pectoris. An integrated backscatter intravascular ultrasound analysis of culprit and non-culprit lesions.

BACKGROUND: Patients with acute coronary syndrome (ACS) have multiple complex coronary plaques associated with plaque vulnerability. The present study assessed the tissue characteristics of coronary plaques between ACS and stable angina pectoris (SAP) of culprit and non-culprit lesions using integrated backscatter intravascular ultrasound (IB-IVUS). METHODS AND RESULTS: IVUS was performed in 165 patients (40 patients with ACS) with 225 culprit (65 lesions in ACS) and 171 non-culprit lesions (42 lesions in ACS). The percentage of fibrous area (fibrous area/plaque area, %FIB) and the percentage of lipid area (lipid area/plaque area, %LIP) at the segment with minimal luminal area were calculated using IB-IVUS system. Culprit and non-culprit lesions with ACS showed a significant increase in %LIP (38±18 vs. 30±15%, P=0.002, and 38±21 vs. 32±17%, P=0.03, respectively) and a significant decrease in %FIB (59±15 vs. 63±12 %, P=0.04, and 57±18 vs. 62±14%, P=0.04, respectively) compared to those with SAP. On logistic regression analysis, not only culprit lesions but also non-culprit lesions with ACS patients were significantly associated with the lipid-rich plaque. CONCLUSIONS: Non-culprit coronary lesions with ACS patients are associated with the lipid-rich plaque, suggesting the extensive development of plaques instability in these patients.

Sirolimus-eluting stents vs bare metal stents for coronary intervention in Japanese patients with renal failure on hemodialysis.

BACKGROUND: Accelerated atherosclerosis is a major risk for long-term survivors receiving hemodialysis (HD), with coronary events being the leading cause of mortality. METHODS AND RESULTS: A total of 88 consecutive patients on HD (121 lesions) who underwent percutaneous coronary intervention (PCI) with sirolimus-eluting stents (SES) were compared with 78 patients on HD (95 lesions) who received bare metal stents (BMS) in the preceding 1 year. The primary endpoint was angiographic restenosis defined as > or =50% diameter stenosis at 6-8 months follow-up after PCI. The angiographic restenosis rate at follow-up was 22.2% in the SES group and 24.4% in the BMS group. No difference was detected in the restenosis rate between the 2 groups (p=0.73). When including both HD and non-HD patients, the independent predictors for restenosis after SES implantation were treatment with HD (hazard ratio (HR) 3.12; 95% confidence interval (CI) 1.23-7.95; p=0.016), incidence of hyperlipidemia (HR 3.93; 95%CI 1.12-13.7; p=0.032), coronary calcification (HR 2.78; 95%CI 1.12-6.91; p=0.027), and implantation of multi-stents (HR 4.14; 95%CI 1.70-10.1; p=0.0017). CONCLUSIONS: Even if treated with SES, patients with end-stage renal failure on HD are at high risk of restenosis after PCI.

Heart slice NMR.

Nuclear magnetic resonance (NMR) spectroscopy of the heart is normally carried out using whole heart preparations under coronary perfusion. In such preparations, either radical changes in ionic composition of the perfusate or applications of numerous drugs would affect coronary microcirculation. This report communicates the first (31)P NMR spectroscopy study using a heart slice preparation (left ventricular slices) superfused with extracellular medium. The ratio of phosphocreatine concentration to ATP concentration was approximately 2.1. Also, intracellular pH and Mg(2+) concentration ([Mg(2+)](i)), estimated from the chemical shifts of inorganic phosphate and ATP, were comparable with those under retrograde perfusion. [Mg(2+)](i) was significantly increased by the removal of extracellular Na(+), supporting the essential role of Na(+)-coupled Mg(2+) transport in Mg(2+) homeostasis of the heart. Heart slice preparation could also be used to evaluate the potency of cardiac drugs, regardless of their possible effects on coronary microcirculation.

Ca2+-dependent modulation of intracellular Mg2+ concentration with amiloride and KB-R7943 in pig carotid artery.

It has long been recognized that magnesium is associated with several important diseases, including diabetes, hypertension, cardiovascular, and cerebrovascular diseases. In the present study, we measured the intracellular free Mg2+ concentration ([Mg2+]i) using 31P nuclear magnetic resonance (NMR) in pig carotid artery smooth muscle. In normal solution, application of amiloride (1 mm) decreased [Mg2+]i by approximately 12% after 100 min. Subsequent washout tended to further decrease [Mg2+]i. In contrast, application of amiloride significantly increased [Mg2+]i (by approximately 13% after 100 min) under Ca2+-free conditions, where passive Mg2+ influx is facilitated. The treatments had little effect on intracellular ATP and pH (pHi). Essentially the same Ca2+-dependent changes in [Mg2+]i were produced with KB-R7943, a selective blocker of reverse mode Na+-Ca2+ exchange. Application of dimethyl amiloride (0.1 mM) in the presence of Ca2+ did not significantly change [Mg2+]i, although it inhibited Na+-H+ exchange at the same concentration. Removal of extracellular Na+ caused a marginal increase in [Mg2+]i after 100-200 min, as seen in intestinal smooth muscle in which Na+-Mg2+ exchange is known to be the primary mechanism of maintaining a low [Mg2+]i against electrochemical equilibrium. In Na+-free solution (containing Ca2+), neither amiloride nor KB-R7943 decreased [Mg2+]i, but they rather increased it. The results suggest that these inhibitory drugs for Na+-Ca2+ exchange directly modulate Na+-Mg2+ exchange in a Ca2+-dependent manner, and consequently produce the paradoxical decrease in [Mg2+]i in the presence of Ca2+.

Mechanisms for monovalent cation-dependent depletion of intracellular Mg2+:Na(+)-independent Mg2+ pathways in guinea-pig smooth muscle.

It has been suggested that magnesium deficiency is correlated with many diseases. 31P NMR experiments were carried out in order to investigate the effects of Na+ substitution on Mg2+ depletion in smooth muscle under divalent cation-free conditions. In the taenia of guinea-pig caeci, the intracellular free Mg2+ concentration ([Mg2+]i) was estimated from the chemical shifts of (1) the beta-ATP peak alone and (2) beta- and gamma-ATP peaks. Both estimations indicated that [Mg2+]i decreased only very slowly in Mg(2+)-free, Ca(2+)-free solutions in which Na+ was substituted with large cations such as NMDG (N-methyl-D-glucamine) and choline. Furthermore, the measurements of tension development supported the suggestion of preservation of intracellular Mg2+ with NMDG substitution. Substituting extracellular Na+ with the small cation, Li+, also shifted the beta-ATP peak towards a lower frequency, but the frequency shift was significantly less than that seen upon Na+ substitution with K+. The estimated [Mg2+]i depletion was, however, comparable with that seen after Na+ substitution with K+ using the titration curves of metal-free and Mg(2+)-bound ATP obtained in Li(+)-based model solutions. It was concluded that Mg2+ rapidly decreases only when small cations were the major electrolyte of the extracellular medium. Na+ substitutions with NMDG, choline or Li+ had little effect on intracellular ATP concentration after 100 min treatment.