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Because of paucity of published data, we evaluated the 2-year major clinical outcomes between early invasive (EI) and delayed invasive (DI) strategies according to the stage of chronic kidney disease (CKD) in patients with non-ST-segment elevation myocardial infarction (NSTEMI), who underwent a successful newer-generation drug-eluting stent (DES) implantation.A total of 8241 NSTEMI patients were recruited from the Korea Acute Myocardial Infarction Registry (KAMIR). Based on baseline estimated glomerular filtration rate (eGFR; ≥90, 60-89, 30-59, and30 mL/min/1.73 mAfter multivariable-adjusted and propensity score-adjusted analyses, the cumulative incidence of MACE (group A, p = 0.139 and p = 0.103, respectively; group B, p = 0.968 and p = 0.608, respectively; group C, p = 0.111 and p = 0.196, respectively; group D, p = 0.882 and p = 0.571, respectively), all-cause death, re-MI, and any repeat revascularization was similar between the EI and DI groups in the 4 different renal function groups.In the era of newer-generation DES, EI and DI strategies showed comparable major clinical outcomes in patients with NSTEMI and CKD during a 2-year follow-up period. However, to confirm these results, further randomized, large-scale, long-term follow-up studies are needed.

Plasma membrane repair defects cause human muscle and heart diseases. In the early stage of membrane repair, TRIM72/MG53 nucleates vesicles to the damaged site within seconds. Despite the therapeutic potential of TRIM72/MG53, the molecular mechanisms are poorly understood. Here, we present the structure of TRIM72, the first complete model of a TRIM E3 ligase. Structure-guided functional analysis revealed a unique phospholipid recognition mode in which a pair of PRYSPRY domains interacts with negatively charged membranes. In subsequent biochemical analyses, the interaction between TRIM72 and the phosphatidylserine-enriched membrane was shown to be critical for both the oligomeric assembly and ubiquitination activity of TRIM72. We elucidated a higher-order model of TRIM72 assembly on the phospholipid bilayer using cryogenic electron tomography followed by subtomogram averaging. We developed a working molecular model of TRIM72 through integrated structural and biochemical techniques. The findings provide a fundamental basis for the study of TRIM E3 ligases, which share a conserved molecular architecture, and provide further insights into the general regulation of RING-type E3 ligases through the cooperation of multiple domains like those in higher-order assemblies.

The cellular glucose level has to be tightly regulated by a variety of cellular processes. One of them is the degradation of gluconeogenic enzymes such as Fbp1, Icl1, Mdh2, and Pck1 by GID (glucose-induced degradation deficient) E3 ubiquitin ligase. The Gid4 component of the GID ligase complex is responsible for recognizing the N-terminal proline residue of the target substrates under normal conditions. However, an alternative N-recognin Gid10 controls the degradation process under stressed conditions. Although Gid10 shares a high sequence similarity with Gid4, their substrate specificities are quite different. Here, we report the structure of Gid10 from Saccharomyces cerevisiae in complex with Pro/N-degron, Pro-Tyr-Ile-Thr, which is almost identical to the sequence of the natural substrate Art2. Although Gid10 shares many structural features with the Gid4 protein from yeast and humans, the current structure explains the unique structural difference for the preference of bulky hydrophobic residue at the second position of Pro/N-degron. Therefore, this study provides a fundamental basis for understanding of the structural diversity and substrate specificity of recognition components in the GID E3 ligase complex involved in the Pro/N-degron pathway.

In eukaryotic cells, mitochondria are closely tethered to the endoplasmic reticulum (ER) at sites called mitochondria‐associated ER membranes (MAMs). Ca(2+) ion and phospholipid transfer occurs at MAMs to support diverse cellular functions. Unlike those in yeast, the protein complexes involved in phospholipid transfer at MAMs in humans have not been identified. Here, we determine the crystal structure of the tetratricopeptide repeat domain of PTPIP51 (PTPIP51_TPR), a mitochondrial protein that interacts with the ER‐anchored VAPB protein at MAMs. The structure of PTPIP51_TPR shows an archetypal TPR fold, and an electron density map corresponding to an unidentified lipid‐like molecule probably derived from the protein expression host is found in the structure. We reveal functions of PTPIP51 in phospholipid binding/transfer, particularly of phosphatidic acid, in vitro. Depletion of PTPIP51 in cells reduces the mitochondrial cardiolipin level. Additionally, we confirm that the PTPIP51–VAPB interaction is mediated by the FFAT‐like motif of PTPIP51 and the MSP domain of VAPB. Our findings suggest that PTPIP51 is a phospholipid transfer protein with a MAM‐tethering function.

The structure of dCMP hydroxymethylase from bacteriophage T4 in complex with the substrate dCMP and cofactor THF was determined at 1.9 Å resolution, providing the first view of the ternary complex of a pyrimidine hydroxymethylase., To protect viral DNA against the host bacterial restriction system, bacterio­phages utilize a special modification system – hydroxymethylation – in which dCMP hydroxymethylase (dCH) converts dCMP to 5-hydroxymethyl-dCMP (5hm-dCMP) using N5,N10-methylenetetrahydrofolate as a cofactor. Despite shared similarity with thymidylate synthase (TS), dCH catalyzes hydroxylation through an exocyclic methylene intermediate during the last step, which is different from the hydride transfer that occurs with TS. In contrast to the extensively studied TS, the hydroxymethylation mechanism of a cytosine base is not well understood due to the lack of a ternary complex structure of dCH in the presence of both its substrate and cofactor. This paper reports the crystal structure of the ternary complex of dCH from bacteriophage T4 (T4dCH) with dCMP and tetrahydrofolate at 1.9 Å resolution. The authors found key residues of T4dCH for accommodating the cofactor without a C-terminal tail, an optimized network of ordered water molecules and a hydrophobic gating mechanism for cofactor regulation. In combination with biochemical data on structure-based mutants, key residues within T4dCH and a substrate water molecule for hydroxymethylation were identified. Based on these results, a complete enzyme mechanism of dCH and signature residues that can identify dCH enzymes within the TS family have been proposed. These findings provide a fundamental basis for understanding the pyrimidine modification system.

In addition to essential roles in protein synthesis, lysyl–tRNA synthetase (KRS) is secreted to trigger a proinflammatory function that induces macrophage activation and TNF-α secretion. KRS has been associated with autoimmune diseases such as polymyositis and dermatomyositis. In this study, we investigated the immunomodulatory effects of KRS on bone marrow–derived dendritic cells (DCs) of C57BL/6 mice and subsequent polarization of Th cells and analyzed the underlying mechanisms. KRS-treated DCs increased the expression of cell surface molecules and proinflammatory cytokines associated with DC maturation and activation. Especially, KRS treatment significantly increased production of IL-12, a Th1-polarizing cytokine, in DCs. KRS triggered the nuclear translocation of the NF-κB p65 subunit along with the degradation of IκB proteins and the phosphorylation of MAPKs in DCs. Additionally, JNK, p38, and ERK inhibitors markedly recovered the degradation of IκB proteins, suggesting the involvement of MAPKs as the upstream regulators of NF-κB in the KRS-induced DC maturation and activation. Importantly, KRS-treated DCs strongly increased the differentiation of Th1 cells when cocultured with CD4+ T cells. The addition of anti–IL-12–neutralizing Ab abolished the secretion of IFN-γ in the coculture, indicating that KRS induces Th1 cell response via DC-derived IL-12. Moreover, KRS enhanced the OVA-specific Th1 cell polarization in vivo following the adoptive transfer of OVA-pulsed DCs. Taken together, these results indicated that KRS effectively induced the maturation and activation of DCs through MAPKs/NF-κB–signaling pathways and favored DC-mediated Th1 cell response.

The hydroxymethylation of cytosine bases plays a vital role in the phage DNA protection system inside the host Escherichia coli. This modification is known to be catalyzed by the dCMP hydroxymethylase from bacteriophage T4 (T4dCH); structural information on the complexes with the substrate, dCMP and the co-factor, tetrahydrofolate is currently available. However, the detailed mechanism has not been understood clearly owing to a lack of structure in the complex with a reaction intermediate. We have applied the X-ray free electron laser (XFEL) technique to determine a high-resolution structure of a T4dCH D179N active site mutant. The XFEL structure was determined at room temperature and exhibited several unique features in comparison with previously determined structures. Unexpectedly, we observed a bulky electron density at the active site of the mutant that originated from the physiological host (i.e., E. coli). Mass-spectrometric analysis and a cautious interpretation of an electron density map indicated that it was a dTMP molecule. The bound dTMP mimicked the methylene intermediate from dCMP to 5′-hydroxymethy-dCMP, and a critical water molecule for the final hydroxylation was convincingly identified. Therefore, this study provides information that contributes to the understanding of hydroxymethylation.

The coiled-coil (CC) domain is a very important structural unit of proteins that plays critical roles in various biological functions. The major oligomeric state of CCs is a dimer, which can be either parallel or antiparallel. The orientation of each α-helix in a CC domain is critical for the molecular function of CC-containing proteins, but cannot be determined easily by sequence-based prediction. We developed a biochemical method for assessing differences between parallel and antiparallel CC homodimers and named it ACCORD (Assessment tool for homodimeric Coiled-Coil ORientation Decision). To validate this technique, we applied it to 15 different CC proteins with known structures, and the ACCORD results identified these proteins well, especially with long CCs. Furthermore, ACCORD was able to accurately determine the orientation of a CC domain of unknown directionality that was subsequently confirmed by X-ray crystallography and small angle X-ray scattering. Thus, ACCORD can be used as a tool to determine CC directionality to supplement the results of in silico prediction.

Ski7 (superkiller protein 7) plays a critical role in the mRNA surveillance pathway. The C-terminal fragment of Ski7 (residues 520–747) fromSaccharomyces cerevisiaewas heterologously expressed inEscherichia coliand purified to homogeneity. It was successfully crystallized and preliminary X-ray data were collected to 2.0 Å resolution using synchrotron radiation. The crystal belonged to a trigonal space group, eitherP3121 orP3221, with unit-cell parametersa=b= 73.5,c= 83.6 Å. The asymmetric unit contains one molecule of the C-terminal fragment of Ski7 with a corresponding crystal volume per protein mass (VM) of 2.61 Å3 Da−1and a solvent content of 52.8% by volume. The mergingRfactor is 6.6%. Structure determination by MAD phasing is under way.

Cystathionine β-synthase (CBS) domains are small intracellular modules that can act as binding domains for adenosine derivatives, and they may regulate the activity of associated enzymes or other functional domains. Among these, the single CBS domain-containing proteins, CBSXs, from Arabidopsis thaliana, have recently been identified as redox regulators of the thioredoxin system. Here, the crystal structure of CBSX2 in complex with adenosine monophosphate (AMP) is reported at 2.2Å resolution. The structure of dimeric CBSX2 with bound-AMP is shown to be approximately flat, which is in stark contrast to the bent form of apo-CBSXs. This conformational change in quaternary structure is triggered by a local structural change of the unique α5 helix, and by moving each loop P into an open conformation to accommodate incoming ligands. Furthermore, subtle rearrangement of the dimer interface triggers movement of all subunits, and consequently, the bent structure of the CBSX2 dimer becomes a flat structure. This reshaping of the structure upon complex formation with adenosine-containing ligand provides evidence that ligand-induced conformational reorganization of antiparallel CBS domains is an important regulatory mechanism.

Background— The optimal duration of dual antiplatelet therapy (DAPT) after implantation of drug-eluting coronary stents remains undetermined. We aimed to test whether 6-month DAPT would be noninferior to 12-month DAPT after implantation of drug-eluting stents. Methods and Results— We randomly assigned 1443 patients undergoing implantation of drug-eluting stents to receive 6- or 12-month DAPT (in a 1:1 ratio). The primary end point was a target vessel failure, defined as the composite of cardiac death, myocardial infarction, or ischemia-driven target vessel revascularization at 12 months. Rates of target vessel failure at 12 months were 4.8% in the 6-month DAPT group and 4.3% in the 12-month DAPT group (the upper limit of 1-sided 95% confidence interval, 2.4%; P =0.001 for noninferiority with a predefined noninferiority margin of 4.0%). Although stent thrombosis tended to occur more frequently in the 6-month DAPT group than in the 12-month group (0.9% versus 0.1%; hazard ratio, 6.02; 95% confidence interval, 0.72–49.96; P =0.10), the risk of death or myocardial infarction did not differ in the 2 groups (2.4% versus 1.9%; hazard ratio, 1.21; 95% confidence interval, 0.60–2.47; P =0.58). In the prespecified subgroup analysis, target vessel failure occurred more frequently in the 6-month DAPT group than in the 12-month group (hazard ratio, 3.16; 95% confidence interval, 1.42–7.03; P =0.005) among diabetic patients. Conclusions— Six-month DAPT did not increase the risk of target vessel failure at 12 months after implantation of drug-eluting stents compared with 12-month DAPT. However, the noninferiority margin was wide, and the study was underpowered for death or myocardial infarction. Our results need to be confirmed in larger trials. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00698607.

Objectives The goal of this study was to compare the angiographic outcomes of everolimus-eluting stents (EES) and sirolimus-eluting stents (SES) in a head-to-head manner. Background EES have been shown to be superior to paclitaxel-eluting stents in inhibiting late loss (LL) and clinical outcome. Whether EES may provide similar angiographic and clinical outcomes compared with SES is undetermined. Methods This was a prospective, randomized, open-label, multicenter trial to demonstrate the noninferiority of EES compared with SES in preventing LL at 9 months. A total of 1,443 patients undergoing percutaneous coronary intervention were randomized 3:1 to receive EES or SES. Routine follow-up angiography was recommended at 9 months. The primary endpoint was in-segment LL at 9 months, and major secondary endpoints included in-stent LL at 9 months, target lesion failure, cardiac death, nonfatal myocardial infarction, target lesion revascularization, and stent thrombosis at 12 months. Data were managed by an independent management center, and clinical events were adjudicated by an independent adjudication committee. Results Clinical follow-up was available in 1,428 patients and angiographic follow-up in 924 patients (1,215 lesions). The primary endpoint of the study (in-segment LL at 9 months) was 0.11 ± 0.38 mm and 0.06 ± 0.36 mm for EES and SES, respectively (p for noninferiority = 0.0382). The in-stent LL was also noninferior (EES 0.19 ± 0.35 mm; SES 0.15 ± 0.34 mm; p for noninferiority = 0.0121). The incidence of clinical endpoints was not statistically different between the 2 groups, including target lesion failure (3.75% vs. 3.05%; p = 0.53) and stent thrombosis (0.37% vs. 0.83%; p = 0.38). Conclusions EES were noninferior to SES in inhibition of LL after stenting, which was corroborated by similar rates of clinical outcomes. (Efficacy of Xience/Promus Versus Cypher in Reducing Late Loss After Stenting [EXCELLENT]; NCT00698607 )

Spinocerebellar ataxia type 1 (SCA1), an autosomal-dominant neurodegenerative disorder, is caused by expansion of the polyglutamine tract within ataxin-1 (ATXN1). The AXH domain of ATXN1 can mediate neurodegeneration through its interaction with other proteins. We have previously showed that the ubiquitin-conjugating enzyme UbcH6 modulates the transcriptional repression activity of ATXN1 through ubiquitylation. In the present study, we sought to identify sites in the AXH domain that are ubiquitylated by UbcH6. Systematic replacement of each lysine residue in the AXH domain revealed that the lysine at 589 (K589) of ATXN1 is essential for its ubiquitylation by UbcH6. Mass spectrometry studies further confirmed the ubiquitylation site. Interestingly, protein aggregation was significantly enhanced in mutant AXH K589R, implying that the aggregation is strongly associated with the level of ATXN1 expression. Our study may suggest a therapeutic potential of UbcH6 in the treatment of SCA1.

Obesity is one of the well-known risk factors of vascular disorders; however, the molecular mechanisms underlying the association between the two remain undetermined. Previous studies have demonstrated that the plasma levels of adiponectin, an adipose-derived hormone, are reduced in obese subjects, and that this hypoadiponectinemia is associated with ischemic heart disease. In this study, we sought to identify the primary determinants of plasma adiponectin levels in healthy premenopausal women.We analyzed the plasma adiponectin concentrations in age-matched healthy obese premenopausal women [n=37, body mass index (BMI)or= 25 kg/m(2)] and in healthy nonobese premenopausal women (n = 23, BMI25 kg/m(2)). Visceral and subcutaneous fat (VCF and SCF) areas were determined by abdominal computed tomography (CT) scan. Plasma levels of adiponectin in obese subjects were lower than in nonobese subjects (3.24 +/- 1.08 vs. 4.90 +/- 2.06 ug/ml, P0.01). Significant, univariate inverse correlations were observed between adiponectin levels and visceral fat areas (r = -0.643, p0.001), subcutaneous fat areas (r = -0.407, p0.01), and hsCRP (r = -0.36, p = 0.007). Plasma levels of adiponectin correlated positively with insulin sensitivity [quantitative insulin sensitivity check index (QUICKI): r = 0.38, p = 0.005] and high-density lipoprotein (HDL) cholesterol (r = 0.44, p = 0.001), and negatively with low-density lipoprotein (LDL) cholesterol (r = -0.29, p = 0.028), triglyceride (r = -0.33, p = 0.013), and BMI (r = -0.48, p0.001). By multivariate analysis, only visceral fat areas affected adiponectin plasma levels (beta = -0.016, p0.05, R(2) = 0.504). Plasma levels of HDL cholesterol remained significantly correlated to plasma adiponectin concentrations in multivariate analysis (beta = 0.067, p0.05).These results collectively indicate that plasma HDL cholesterol levels and visceral fat masses are independently associated with plasma adiponectin concentrations.

We performed this study in order to compare the immediate and mid-term outcomes of sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) in lesions of the unprotected left main coronary artery (LMCA). We assessed 54 patients from 5 centers who had undergone unprotected LMCA stenting (35 SES and 19 PES). The procedural success rates were 100 and 95%, respectively, in the SES and PES patients (p = 0.19). At the 6-month clinical follow-up, the event-free probability was 100% in the SES group, and 88% in the PES group (p = 0.07). At the 6-month angiographic follow-up (n = 24), the SES group exhibited a slightly lower late loss than did the PES group (0.24 ± 0.44 vs. 0.65 ± 0.60 mm, p = 0.09), and the restenosis rates were 8 and 9% (p = 0.94) in the SES and PES patients, respectively. In conclusion, both groups exhibited excellent in-hospital and 6-month outcomes with no significant differences between them.

Background The key biological determinants that promote restenosis in the setting of diabetes have not been elucidated. There is no accepted animal model to study restenosis in diabetes. Methods and Results We evaluated 2 models of diabetes mellitus: (1) streptozotocin (STZ)-treated Sprague-Dawley rats (type I diabetes) versus regular Sprague-Dawley rats and (2) obese Zucker rats (type II diabetes) versus lean Zucker rats. Neointimal hyperplasia was assessed after carotid balloon injury at 21 days by computerized morphometry. There was no difference in neointimal area in the STZ-treated rats compared with controls, irrespective of insulin administration or dose of STZ. Neointimal area was increased >2-fold in obese Zucker rats compared with lean Zucker rats (0.21±0.06 versus 0.08±0.03 mm 2 , P 2 , P Conclusions The type II diabetic rat model, typifying insulin resistance, is associated with a propensity for neointima. The obese Zucker rat model may be an ideal diabetic model to further characterize the diabetic vascular response to injury.

The single cystathionine β-synthase (CBS) pair proteins from Arabidopsis thaliana have been identified as being a redox regulator of the thioredoxin (Trx) system. CBSX1 and CBSX2, which are two of the six Arabidopsis cystathione β-synthase domain-containing proteins that contain only a single CBS pair, have close sequence similarity. Recently, the crystal structure of CBSX2 was determined and a significant portion of the internal region was disordered. In this study, crystal structures of full-length CBSX1 and the internal loop deleted (Δloop) form are reported at resolutions of 2.4 and 2.2A, respectively. The structures of CBSX1 show that they form anti-parallel dimers along their central twofold axis and have a unique ∼155° bend along the side. This is different from the angle of CBSX2, which is suggestive of the flexible nature of the relative angle between the monomers. The biochemical data that were obtained using the deletion as well as point mutants of CBSX1 confirmed the importance of AMP-ligand binding in terms of enhancing Trx activity.

Background and Objectives Statin prevents atherosclerotic progression and helps to stabilize the plaque. According to a recent study, statin reduces inflammation in blood vessels. However, it has not been demonstrated to have any anti-inflammation reaction in patients who have been diagnosed as having a triple-vessel coronary artery disease (CAD). Subjects and Methods This study included a total of thirty (30) patients who had been diagnosed by coronary angiogram as having a triple-vessel CAD. Patients who already had been taking statin were given doubled dosage. An interview, physical examination and blood test were performed at the beginning of this study and three months later. Results After doubling the dose of statin, there was no statistically significant decrease in total cholesterol, low density lipoprotein-cholesterol, (increase in) high density lipoprotein-cholesterol and triglyceride in the blood test. C-reactive protein (CRP), an acute phase reactant, significantly decreased from 0.34 mg/dL at the beginning of the study to 0.12 mg/dL at the end of study (p

The number of hypertensive patients achieving treatment targets is not ideal with therapies that engage a single mechanism of action, and combination therapies using different mechanisms of action can increase drug efficacy in a synergistic way.This noninferiority study compared the clinical efficacy and safety profile of fixed-dose combination of amlodipine/losartan 5/50 mg and amlodipine 10 mg monotherapy in essential hypertensive patients who respond poorly to amlodipine 5 mg monotherapy.This was a double-blind, multicenter, randomized trial of hypertensive patients (N = 185) aged ≥18 years taking amlodipine 5 mg during the run-in treatment period but failed to achieve sitting diastolic blood pressure (DBP)90 mm Hg. After randomization into the amlodipine/losartan 5/50 mg fixed-dose combination group (n = 92) and the amlodipine 10 mg monotherapy group (n = 93), treatment was maintained without dose escalation for 8 weeks. The noninferiority margin was prespecified as 4 mm Hg after 8 weeks of treatment for the difference of the average change in DBP between treatments. The primary efficacy evaluation of noninferiority was tested using a confidence interval approach with a 97.5% 1-sided lower confidence limit using the average difference in DBP measured at baseline and 8 weeks.After 8 weeks, the DBP of both groups decreased from baseline by 8.9 (6.1) and 9.4 (7.5) mm Hg, respectively (difference = -0.5 [6.9] mm Hg, 95% CI: -2.5 to 1.5). Secondary end points of reductions in DBP after 4 weeks (-8.1 [6.7] vs -9.9 [7.3] mm Hg, difference = -1.8 mm Hg, 95% CI: -3.9 to 0.2) and sitting systolic blood pressure after 4 (-10.2 [11.8] vs -12.8 [10.2] mm Hg, difference = -2.6 mm Hg, 95% CI: -5.9 to 0.6) and 8 weeks (-12.2 [11.0] vs -13.4 [11.3] mm Hg, difference = -1.2 mmHg, 95% CI: -4.4 to 2.1) were comparable between the 2 treatment groups. There were 38 adverse events in 20 patients (21.7%) in the amlodipine/losartan 5/50 mg fixed-dose combination group and 31 in 24 patients (26.1%) in the amlodipine 10 mg monotherapy group; most were mild. There were 7 adverse events in 6 patients (6.5%) related to treatment in the fixed-dose combination group and 13 in 10 patients (10.9%) in the monotherapy group (P = 0.30).Fixed-dose combination amlodipine/losartan 5/50 mg was not inferior in terms of reductions in DBP after 8 weeks of treatment and had comparable safety profile to amlodipine 10 mg in patients who did not respond to amlodipine 5 mg monotherapy. ClinicalTrials.gov identifier: NCT00940667.

Background: Korean Panax Red Ginseng (KPRG) is known to enhance endothelium-dependent vasorelaxation by activating eNOS. Activation of Rho-associated kinase (ROCK) is implicated in endothelial dysfunction in part through destabilization of eNOS mRNA. This study, a randomized, double-blind, placebo-controlled, crossover trial, is aimed to analyze the effect of KPRG on endothelial function, arterial stiffness, and ROCK activity of peripheral blood mononuclear cells (PBMC) in patients with coronary artery disease (CAD). Methods: Patients (n=20, 12 males, 62.5 yrs) with stable angina (multi-vessel disease: n=10) were treated alternatively with either KPRG (3g/d) or placebo (starch, 3g/d) for 10 weeks (washout period for 4 wks). Measurements of flow mediated dilation (FMD) and nitroglycerine mediated dilation (NMD) on the brachial artery and collection of peripheral venous blood for the biochemical study were performed at day 0 (baseline) and after completion (endpoint) of each treatment. Activity of ROCK of PBMC was assessed by analyzing phospho-Thr853 in the myosin binding subunit (MBS) of myosine light chain phosphatase with use of Western blot, and was expressed as the % ratio of phospho-Thr853-MBS/total MBS at endpoint versus baseline. Patients were classified into low (5%) FMD group (n=9). Results: Treatment with KPRG significantly increased FMD in low FMD group (3.49±0.35% vs 5.50±0.72%, p=0.013), but not in high FMD group. Brachial ankle pulse wave velocity (ba-PWV), measured by VP2000, tends to be decreased by KPRG (1770±185 vs. 1499±95, p=0.05. There was no significant changes in nitroglycerine mediated dilation after each drug treatment in both patient groups. Treatment with KPRG significantly decreased ROCK activity in PBMC of CAD patients (n=6) by 23.9±3.01 as compared with the baseline (p

Background: There is some controversy on long-term cardiac outcomes between sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) in diabetes mellitus (DM). We compared cardiac adverse events after SES and PES implantation in patients with DM over a period of 3 year. Methods: A total of 634 patients with DM treated with SES (n 5 428) or PES (n 5 206) were consecutively enrolled in the KOMATE registry from 2003 to 2004. We assessed major adverse cardiac events (MACEs, cardiovascular death, nonfatal myocardial infarction, ischemia driven target vessel revascularization) and stent thrombosis (ST) according to the definitions set by the Academic Research Consortium. Results: Propensity score (PS) analysis was performed to adjust different baseline characteristics. The mean follow-up duration was 38 6 8 month (at least 36 month and up to 53 month). The 3-year MACE rate did not show a significant difference between the two groups [52 (12.1%) in SES vs. 29 (14.1%) in PES, P 5 0.496]. The definite and probable ST at 3 year were similar in both SES and PES [12 (2.8%) in SES vs. 7 (3.4%) in PES, P 5 0.681]. There were no differences in hazard ratio for MACE and ST between two stents [MACE, crude: 0.844 (0.536–1.330) and adjusted for PS: 0.858 (0.530–1.389); ST, crude: 0.820 (0.323–2.083) and adjusted for PS: 0.960 (0.357–2.587)]. Conclusions: The present study demonstrated that long-tem cardiac outcomes including ST were not significantly different between SES and PES in patients with DM. ' 2008 Wiley-Liss, Inc.

Background: Although previous studies have examined the efficacy of pitavastatin, its tolerability and effects on lipid concentrations have not been compared with those of atorvastatin in a multicenter, randomized study. Objective: This trial compared the efficacy and tolerability of pitavastatin and atorvastatin in hypercholesterolemic Korean adults. Methods: This 8-week, multicenter, randomized, open-label, dose-titration study was conducted at 18 clinical centers in Korea between May 2005 and February 2006. After a 4-week dietary lead-in period, patients with hypercholesterolemia were randomized to receive either pitavastatin 2 mg/d or atorvastatin 10 mg/d. Patients who had not reached the low-density lipoprotein cholesterol (LDL-C) goal by week 4 received a double dose of the assigned medication for an additional 4 weeks. Efficacy was evaluated in terms of achievement of the National Cholesterol Education Program Adult Treatment Panel III LDL-C goals and changes from baseline in other lipids and high-sensitivity C-reactive protein (hs-CRP). The tolerability profile was assessed by physical and electro-cardiographic examinations, laboratory tests, and recording adverse reactions at all visits. Results: A total of 268 patients were randomized to treatment, and 222 (82.8%) completed the study (149 women, 73 men; mean age, 59 years; mean weight, 63.5 kg). At the end of the study, there was no significant difference between the pitavastatin and atorvastatin groups in the proportion of patients achieving the LDL-C goal (92.7% [102/110] vs 92.0% [103/112], respectively). In addition, there were no significant differences between groups in terms of the percent changes from baseline in LDL-C, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), or hs-CRP. Twenty-six of 136 patients (19.1%) taking pitavastatin reported 35 treatment-emergent adverse reactions; 33 of 132 patients (25.0%) taking atorvastatin reported 39 treatment-emergent adverse reactions. Elevations in creatine kinase were observed in 6 patients (4.4%) in the pitavastatin group and 7 patients (5.3%) in the atorvastatin group. There were no serious adverse drug reactions in either group. Conclusions: In these adult Korean patients with hypercholesterolemia, pitavastatin and atorvastatin did not differ significantly in terms of the proportions of patients achieving the LDL-C goal; reductions in LDL-C, total cholesterol, and triglycerides; or increases in HDL-C. Both drugs were well tolerated.

Because obesity is frequently complicated by other cardiovascular risk factors, the impact of a reduction in visceral adiposity on vascular endothelial dysfunction (VED) in obese patients is difficult to determine. In the present study, we evaluated the impact of a reduction in visceral adiposity on VED in obese women. Thirty-six premenopausal obese women (BMI/= 25 kg/m2) without complications were enrolled in the study. VED was evaluated by determining the augmentation index (AIx) from radial artery pulse waves obtained by applanation tonometry. Changes in AIx in response to nitroglycerin- induced endothelium-independent vasodilatation (DeltaAIx-NTG) and in response to salbutamol administration (DeltaAIx-Salb) were determined before and after weight reduction. After a 12-week weight reduction program, the average weight loss was 7.96 +/- 3.47 kg, with losses of 21.88 +/- 20.39 cm2 in visceral fat areas (p0.001). Pulse wave analysis combined with provocative pharmacological testing demonstrated preserved endothelium-independent vasodilation in healthy premenopausal obese women (DeltaAIx-NTG: 31.36 +/- 9.80% before weight reduction vs. 28.25 +/- 11.21% after weight reduction, p0.1) and an improvement in endothelial-dependent vasodilation following weight reduction (DeltaAIx-Salb: 10.03 +/- 6.49% before weight reduction vs. 19.33 +/- 9.28% after reduction, p0.001). A reduction in visceral adipose tissue was found to be most significantly related to an increase in DeltaAIx-Salb (beta=-0.57, p0.001). A reduction in visceral adiposity was significantly related to an improvement in VED. This finding suggests that reduction of visceral adiposity may be as important as the control of other major risk factors in the prevention of atherosclerosis in obese women.

Aneurysms of the left main coronary arteries are found in 0.1% of angiograms. This case involves an athlete with a left main coronary artery aneurysm, which was combined with chronic total occlusion of the proximal left anterior descending and proximal left circumflex coronary arteries. The extraordinary clinical presentation in this patient may be associated with good coronary collaterals, which may have developed in the patient in response to chronic total occlusion of the coronary artery by the aneurysm, and repeat myocardial hypoxia during high levels of performance as a soccer player. Keywords: coronary aneurysm; left main coronary disease; intravascular ultrasonography; electron beam computed tomography

Dissections after percutaneous transluminal coronary angioplasty (PTCA) are risk factors for acute or subacute vessel closures. Intracoronary stenting was developed to avoid these complications by pressing the intimal and medial flaps against the vessel wall, thus reducing the risk of acute closure from thrombus formation. Thirty three coil (Gianturco-Roubin) stents were implanted into the coronary arteries of 32 patients with dissections after PTCA during the period of March 1993 to December 1993. The indications for stent implantation were acute closure in 6 (18.8%), threatened closure in 6 (18.8%) and suboptimal result in 20 (62.4%) patients. Stent insertion were successful in 30 (94%) patients. The diameter stenosis in an immediate angiographic findings after stenting was decreased from 87% to 18% by caliper estimation. Emergency coronary artery bypass graft surgery was required in 1 (3%) patient. A non-Q wave myocardial infarction occurred in 1 (3%) patient. Complications included hematoma of the arterial access site requiring blood transfusion in 4 (12.5%) patients and hemopericardium in 1 (3%) patient. Our initial clinical experience of flexible coil coronary stent imply that stenting is efficacious treatment for acute dissections that are causing acute or threatened closure following angioplasty. The long term follow-up result in all groups of patient who received coronary stents is needed for better evaluation of new devices and prognosis.

Background —The optimal duration of dual antiplatelet therapy (DAPT) after implantation of drug-eluting coronary stents (DES) remains undetermined. We aimed to test whether 6-month DAPT would be noninferior to 12-month DAPT after implantation of DES. Methods and Results —We randomly assigned 1443 patients undergoing implantation of DES to receive 6-month or 12-month DAPT (in a 1:1 ratio). The primary end point was a target vessel failure (TVF) defined as the composite of cardiac death, myocardial infarction, or ischemia-driven target vessel revascularization at 12 months. Rates of TVF at 12 months were 4.8% in the 6-month DAPT group and 4.3% in the 12-month DAPT group (the upper limit of one-sided 95% confidence interval [CI], 2.4%; P =0.001 for noninferiority with a pre-defined noninferiority margin of 4.0%). Although stent thrombosis tended to occur more frequently in the 6-month DAPT group than in 12-month one (0.9% versus 0.1%; hazard ratio 6.02, 95% CI 0.72-49.96; P =0.10), the risk of death or myocardial infarction did not differ in the 2 groups (2.4% versus 1.9%; hazard ratio 1.21, 95% CI 0.60-2.47; P=0.58). In the prespecified subgroup analysis, TVF occurred more frequently in the 6-month DAPT group than in the 12-month one (hazard ratio 3.16; 95% CI 1.42-7.03; P=0.005) among diabetic patients. Conclusions —Six-month DAPT did not increase the risk of TVF at 12 months after implantation of DES compared with 12-month DAPT. However, noninferiority margin was wide, and the study was underpowered for death or myocardial infarction. Our results need to be confirmed in larger trials.

Background and Objectives: The aim of this study was to evaluate the efficacy of lacidipine in reducing blood pressure (BP) and to determine its effect on endothelial function in mild-to-moderate hypertensive patients with type 2 diabetes mellitus (DM). Subjects and Methods: This was a prospective, multicenter, open-label, single-arm study, enrolling 290 patients with mild-to-moderate hypertension and type 2 DM. Patients were initially treated with 2 mg lacidipine orally once daily for 4 weeks, which was then increased as necessary every 4 weeks to a maximal dose of 6 mg daily. The primary endpoint was the mean change in systolic blood pressure (SBP) from baseline after 12 weeks of treatment. Secondary endpoints included mean changes in diastolic blood pressure (DBP), flow-mediated vasodilatation (FMD), and serum concentrations of biochemical markers such as high-sensitivity C-reactive protein (hs-CRP), monocyte chemo-attractant protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9), and plasminogen activator inhibitor-1 (PAI-1). Results: Lacidipine treatment significantly reduced SBP by -13.4±13.0 mmHg (p

Background and Objectives：Previous studies have demonstrated that adipokines can have positive and/or negative effects on vascular function. In this study, we attempted to characterize the association of adipokines with endothelium-dependent vasodilation in healthy premenopausal women. Subjects and Methods：Noninvasive pulse wave analysis coupled with provocative pharmacological testing with salbutamol was used to measure endotheliumdependent vasodilation in 60 healthy premenopausal women [37 obese women; body mass index (BMI) ≥25 kg/m 2 , 23 age-matched non-obese women; BMI

Background and Objectives：An ischemic brain stroke following acute myocardial infarction (AMI) has a poor clinical prognosis, which primarily results from a thromboembolism. We determined the risk factors of acute cardioembolic brain stroke events that developed concurrently with, or soon after, the onset of AMI. Subjects and Methods：We evaluated 38 AMI patients, who developed subsequent acute cardioembolic brain stroke during their index admission, by comparing their clinical and angiographic characteristics with those of 1,443 consecutive patients that had not experienced a brain stroke. Strokes that occurred between the onset of the AMI and patient discharge were analyzed. The incidences of cardiovascular risk factors, and the clinical and angiographic characteristics, of patients admitted to Ewha Womans University Mokdong Hospital, with a diagnosis of AMI over a 10-year period, were compared. Results：In the univariate analysis, the frequencies of atrial fibrillation (21% vs. 4%, p=0.011) and hypertension (71% vs. 48%, p=0.030), and a left ventricular ejection fraction

Background and Objectives:Stent thrombosis (ST) after a successful drug-eluting stent (DES) implantation has been reported in around 1% of clinical trials. However, the incidence of ST with a DES in practice is not well known. Here, we evaluated the possible causes of ST encountered in four Korean hospitals. Subjects and Methods:Between March 2003 and December 2003, 450 patients were treated using a DES in the four study hospitals. We reviewed the clinical and procedural characteristics of 8 patients that experienced ST after a successful DES implantation. Results:Eight patients (1.8%), who were administered antiplatelet medication, experienced ST, with a mortality of 50% at the 2 month follow-up. ST occurred within 7 days in all patients, with the exception of one, with an occurrence 37 days after intervention. Initially, all patients were diagnosed as having acute coronary syndrome. Direct PTCA was performed in 3 patients (38%). Severe calcification or a thrombus was noted in 6 (67%) of 9 lesions. In all cases, no GPIIbIIIa inhibitors were used prior to the DES implantation. Incomplete lesion coverage and incomplete stent expansion appeared in 7 (88%) cases. Conclusion:Our study demonstrated that full expansion of the DES and complete lesion coverage must be accomplished, with high pressure inflation or use of cutting balloon preferably under IVUS guidance, for the prevention of ST. Those patients with acute coronary syndrome might warrant intensive antiplatelet therapy, including GPIIbIIIa inhibitors. (Korean Circulation J 2005;35:163-171)

We successfully treated a case of in-stent restenosis, which presented on 6 occasions, resulting in frequent acute inferior wall myocardial infarctions, using a drug-eluting stent. This case demonstrates that drug-eluting stents offer the promise of an effective treatment for frequent in-stent restenosis, and importantly, that the underexpansion of a drug-eluting stent heightens the risk of acute or subacute stent thrombosis. (Korean Circulation J 2005;35:480-483)

In the era before reperfusion therapy, ventricular septal rupture complicated 1approximate3% of acute myocardial infarctions (AMI) usually 3-5 days after onset. Studies have reported a positive correlation between the incidence of septal perforation and total occlusion of the coronary arteries. A 70-year old female patient was referred to the emergency room with the diagnosis of acute anterior myocardial infarction (MI) and recent cerebral infarction. The coronary angiogram showed a 90% stenosis at the mid-portion of the left anterior descending artery (LAD), and the lesion was successfully treated by percutaneous coronary intervention (PCI) with stent implantation. After PCI, the anterior wall motion improved on the follow-up echocardiogram. However, on the 20th hospital day, the patient condition deteriorated suddenly with pulmonary congestion. The echocardiography revealed a 1.3 cm ventricular septal defect at the apical septum with a left-to-right shunt. We report this rare case of delayed septal rupture in a patient with patent LAD after PCI and recovery of wall motion.

Although very rare, the incidence of tricuspid valve regurgitation after blunt chest trauma has risen in line with the increasing rate of car accidents and steering wheel trauma. It is easy to miss the diagnosis of tricuspid valve regurgitation following blunt chest trauma because most patients feel no symptoms at trauma, and the condition is sometimes overlooked for a long period of time due to its mild symptoms. A 49-year-old man suffered dyspnea on exertion for 1 month due to right heart failure 8 years after accidentally falling from a third floor. Preoperative echocardiography revealed severe tricuspid valve regurgitation resulting from prolapse of the anterior leaflet with annular dilatation. The patient underwent tricuspid valvuloplasty with a 36-mm Carpentier tricuspid ring. Intraoperative transesophageal echocardiography showed mild tricuspid valve regur - gitation. We report a case of successful native valve salvage of ruptured tricuspid valve after blunt chest trauma, and present a review of the relevant literature. (Korean Circulation J 2004;34(4):415-419)

Background and Objectives：The purpose of the present study was to investigate the diagnostic accuracy of coronary stenoses in patients with ischemic heart disease using multidetector CT coronary angiography (MDCT) in the assessment of coronary artery disease. Subjects and Methods：Forty-three patients (49-72yrs) undergoing conventional coronary angiography (CCA) were included in this study. All patients were premedicated with oral propranolol, 40-80 mg, to achieve an acceptable heart rate of less than 65 bpm, 1hr before the MDCT. All coronary arteries, including the distal segments and side branches, were assessed with respect to assessability and the presence of significant stenosis (>50%) and the results compared with those of CCA. Results：Of the 645 coronary artery segments scanned, 540 were assessable (84%). A total 44 significant stenoses were detected by CCA and 49 lesions by MDCT. The overall sensitivity and specificity were 77 and 97%, respectively. The overall accuracy for the LAD, RCA and LCX was 94, 98 and 95%, respectively, and there were no differences in the accuracies in each vessel. The sensitivity in the proximal segments was much higher than in the distal segments. A total 15 segments were overestimated by the MDCT due to calcification and the small vessel size. Conclusion：MDCT, with improved spatial and temporal resolutions, and pre-treated with oral beta-blocker, permits the detection of coronary artery stenoses with a high degree

Although myocardial stunning occurs in coronary artery disease, it has rarely been reported with hyperthyroidism. A 72-year-old woman presented with general weakness, shortness of breath and febrile sensation of 10 days duration. The serum thyroid hormone level was elevated. Serial EKGs showed significant ST elevation suggesting transmural ischemia, but coronary angiography was not significant. Echocardiography showed regional wall motion abnormality of apical hypokinesia, which was improved after medication for hyperthyroidism. We report this case as an example of myocardial stunning associated with hyperthyroidism. (Korean Circulation J 2004; 34(5):516-519)

Background and Objectives:The beneficial effects of statins in preventing cardiovascular events may depend, in part, on their anti-inflammatory action. We previously reported that low dose statin therapy has cholesterol lowering effects, but no effect on inflammation, and proposed that a sufficient dose of therapy might be needed to achieve anti-inflammatory action. The aims of this study were to confirm the suggestions made in our previous study. Subjects and Methods:Fifteen unstable angina patients who were enrolled in our previous study were evaluated. The usual dose (20 mg) of simvastatin was administrated for 26 weeks, blood samples collected following the administration and tested for their lipid profiles and inflammatory markers (IL-6, CRP). The changes in the lipid profiles and inflammatory markers, from baseline levels, to the usual and low doses of statin therapy were evaluated. Results:The changes in the IL-6 and hsCRP levels after the usual dose simvastatin therapy compared with the baseline levels were -72.8 and -59.6% (p

Background and Objectives：Cardiovascular mortality in patients with atherosclerosis can be reduced by treatment with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA reductase inhibitors. This proven effect is probably due, not only to the cholesterol lowering effect, but also to the non-lipid-lowering mechanisms elicited by the action of statins. These results, however, were achieved with high or usual doses of statin therapy, whereas similar results with low dose statins are rare. The aims of this study wereas to investigate the changes ofin cholesterol level and the inflammatory markers, Interleukin-6 (IL-6, and C-Reactive protein (CRP, in unstable angina patients with hypercholesterolemia, using low dose simvastatin therapy. Subjects and Methods：Eighteen unstable angina patients (55±6 years, M：F＝10：8, Baunwald class IIIb with hypercholesterolemia (a LDL-cholesterol level over 100 mg/dLwere evaluated. A Llow dose of simvastatin (5 mg was administrated for 4 weeks. The changes of total cholesterol, LDL-cholesterol, triglyceride, HDL-cholesterol and the inflammatory markers, IL-6, and CRP, were all elevated from the baseline following 4 weeks of treatment. Results：The baseline mean values of total cholesterol, LDL-cholesterol, triglyceride, and HDL-cholesterol were 237.1±56.9 mg/dL, 131.9±39.0 mg/dL, 168.3±20.4 mg/dL, and 50.0±3.8 mg/dL, respectively. The baseline mean values of IL-6 and hs CRP were 6.842±6.661 pg/mL, and 0.866±1.083 mg/dL, respectively. Following the 4 weeks of simvastatin treatment, the levels of total cholesterol, LDL- cholesterol, triglyceride, and HDL-cholesterol were 200.8±47.5 mg/dL, 101.6±35.4 mg/dlL, 155.8±18.6 mg/dL, and 47.0±2.3 mg/dL, respectively, giving percentage changes of -17.6% (p 0.05, and -2.1% (p>0.05, respectively. Following the 4 weeks of treatment, the levels of IL-6 and hs CRP were 6.955±5.555 pg/mL, and 0.753±0.571 mg/dL, respectively, giving percentage changes of 51.8 (p>0.05, and 36.5% (p>0.05, respectively. There was no significant correlation between the level of LDL-cholesterol and the levels of IL-6, or hs CRP at the baseline, or post-treatment. There was also no significant correlation between the change of LDL-cholesterol and the changes of IL-6 or hs CRP levels during the simvastatin therapy. There was no significant correlation between the levels of IL-6 and hs CRP at the baseline or ost-treatment. Conclusion：Our data showed that in patients with unstable

Background and Objectives:Transradial percutaneous coronary intervention enables early ambulation and causes less complications at the puncture site. This study was performed in order to evaluate the safety of transradial coronary intervention with early discharge in selected patients. Materials and Method:Thirty patients were studied retrospectively. Twenty-five patients experienced transradial percutaneous coronary int- ervention with next morning discharge and 5 patients underwent transradial percutaneous coronary intervention on an outpatient basis. Each patient was checked for cardiovascular complications and other problems at the puncture site immediately following, 2 weeks after and 1 month after the procedure. Results:The study group consisted of 30 patients with a mean age of 60 years. The indications for intervention were unstable angina (63.3%, stable angina (20.0%, and restenosis at the 6-month follow-up after intervention. A total of 21 stents were implanted at 40 lesions. No major cardiovascular complication nor puncture site complication was reported at the 1 month follow-up. Conclusion:Early discharge at least 5 hours after intervention is safe for those with optimal angiographic results and no clinical problems. (Korean Circulation J 2001;31(10 :1013-1018

Background：It has not been completely understood whether acute phase responses of unstable angina result from a disruption of coronary plaques or from an instability & hypersensitivity of the plaque itself. Plasma IL6 can be affected by several systemic factors, so it is difficult to conclude that IL-6 level in the peripheral blood always reflects the level of the coronary sinus blood. Methods：We measured the IL-6 level in coronary sinus blood and peripheral blood of 14 patients (11 men, 3 women, mean age 55±6 years, range 43 to 65 years with unstable angina before, and 4, 8, 16, 24, and 36 hours after undergoing percutaneous coronary intervention (PCI, respectively. Results：A statistically significant increase of all IL-6 levels in both coronary sinus blood and peripheral blood following PCI was noted. There was also a correlation between IL-6 levels in coronary sinus blood and peripheral blood following PCI (correlation coefficient r＝0.416, p＝0.01, although the difference of the concentration of IL-6 between coronary sinus blood and peripheral blood following PCI was increased as time passed. There was no statistically significant relationship between the number of coronary lesions treated with PCI and the amount of elevation of plasma IL-6 level. Conclusion：It is difficult to infer that the IL-6 level in peripheral blood exactly reflects the level found in the coronary sinus blood and the plaque rupture induced by PCI is the main cause of the elevated plasma IL-6.(Korean Circulation J 2001;31(8 :773-779

Background and Objectives:Thrombin and its interaction with platelets play a pivotal role in arterial thro- mbus formation. Hirudin, an anticoagulant agent derived from medicinal leeches(Hirudo medicinalis ), is a unique and specific thrombin inhibitor with no effect on other serine protease. We investigated the inhibitory effect of hirudin on platelet deposition in a rabbit carotid artery eversion model of acute arterial thrombosis. Materials and Methods:The everted arterial segments were perfused with 111Indium-labeled human pla- telets only (control, n=8, and a mixed solution of 111Indium-labeled human platelets and hirudin (30, 45, 60, 90 μg/ml, n=3, respectively. Platelet deposition was calculated by a gamma-counter and confirmed by scanning electron microscopy. Results:1 Indium-111 labeling efficiency of platelets was 87.0±6.6%, and the aggre-gation of platelets was not changed after labeling. The number of platelets perfused through each arterial segment was 4.3±0.2×10 8 platelets/ml. 2 The control group showed a platelet deposition rate of 23.9±7.0 % and a num-ber of platelet deposition of 9.8±2.5×10 8 platelets/cm 2 . 3 Platelet deposition of arteries perfused with hirudin (60 μ g/ml was significantly decreased compared with that of the control group (2.9±0.6 vs 9.8 ±2.5×10 8 /cm 2 , p

Background and Objectives:Insulin resistance is associated with hyperlipidemia. Recently, visceral fat adiposity is reported to be associated with insulin resistance and hyperlipidemia. We investigated insulin resistance and visceral fat adiposity in hyperlipidemic patients. Materials and Method:Hyperlipidemic group included 14 hyperlipidemic patients (total cholesterol ≥ 220 mg/dl and triglyceride ≤ 400 mg/dl without hypertension, angina, impaired glucose tolerance and diabetes mellitus (DM. Control group included age, sex and body mass index (BMI matched 25 healthy volunteers. We measured plasma lipid profiles and the insulin and glucose during the oral glucose tolerance test. We measured visceral fat area and abdominal subcutaneous fat area with computed tomography (CT. Results:There were no differences of age, sex and BMI in both group. Total cholesterol, LDL cholesterol and triglyceride increased significantly in hyperlipi- demic group. Fasting plasma glucose, insulin, area under curve (AUC of the glucose and insulin and the Insulin/Glucose (IG ratio increased significantly in hyperlipidemic group. Significant positive correlations were demonstrated between visceral fat area and the fasting plasma glucose, AUC of glucose and insulin at 120 minutes after glucose load. However, there was no difference in visceral fat area between both groups. After adjustment of visceral fat area, fasting plasma glucose, insulin, area under curve (AUC of the glucose and insulin and the Insulin/Glucose (IG ratio still remained increased significantly in hyperlipidemic group. Conclusion:We observed significantly increased insulin resistance in hyperlipidemic group. There was partial relationship between visceral fat area and the glucose and insulin profile. However, we did not find increased visceral fat area in hyperlipidemic group. (Korean Circulation J 1999;29(7 :673-679