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1.  The efficacy and safety of co-administration of fimasartan and rosuvastatin to patients with hypertension and dyslipidemia 
Hypertension and dyslipidemia are major risk factors of cardiovascular disease (CVD) events. The objective of this study was to evaluate the efficacy and safety of the co-administration of fimasartan and rosuvastatin in patients with hypertension and hypercholesterolemia.
We conducted a randomized double-blind and parallel-group trial. Patients who met eligible criteria after 4 weeks of therapeutic life change were randomly assigned to the following groups.
1) co-administration of fimasartan 120 mg/rosuvastatin 20 mg (FMS/RSV), 2) fimasartan 120 mg (FMS) alone 3) rosuvastatin 20 mg (RSV) alone. Drugs were administered once daily for 8 weeks.
Of 140 randomized patients, 135 for whom efficacy data were available were analyzed. After 8 weeks of treatment, the FMS/RSV treatment group showed greater reductions in sitting systolic (siSBP) and diastolic (siDBP) blood pressures than those in the group receiving RSV alone (both p < 0.001). Reductions in siSBP and siDBP were not significantly different between the FMS/RSV and FMS alone groups (p = 0.500 and p = 0.734, respectively). After 8 weeks of treatment, FMS/RSV treatment showed greater efficacy in percentage reduction of low-density lipoprotein cholesterol (LDL-C) level from baseline than that shown by FMS alone treatment (p < 0.001). The response rates of siSBP with FMS/RSV, FMS alone, and RSV alone treatments were 65.22, 55.56, and 34.09%, respectively (FMS/RSV vs. RSV, p = 0.006). The LDL-C goal attainment rates with FMS/RSV, RSV alone, and FMS alone treatments were 80.43%, 81.82%, and 15.56%, respectively (FMS/RSV vs. FMS, p < 0.001). Incidence of adverse drug reactions with FMS/RSV treatment was 8.33%, which was similar to those associated with FMS and RSV alone treatments.
This study demonstrated that the co-administration of fimasartan and rosuvastatin to patients with both hypertension and hypercholesterolemia was efficacious and safe.
Trial registration Identifier: NCT02166814. 16 June 2014
Electronic supplementary material
The online version of this article (doi:10.1186/s40360-016-0112-7) contains supplementary material, which is available to authorized users.
PMCID: PMC5217661  PMID: 28057081
Fimasartan; Rosuvastatin; Hypertension; Hypercholesterolemia
2.  Effect of fixed‐dose combinations of ezetimibe plus rosuvastatin in patients with primary hypercholesterolemia: MRS‐ROZE (Multicenter Randomized Study of ROsuvastatin and eZEtimibe) 
Cardiovascular Therapeutics  2016;34(5):371-382.
We aimed to compare the effects of fixed‐dose combinations of ezetimibe plus rosuvastatin to rosuvastatin alone in patients with primary hypercholesterolemia, including a subgroup analysis of patients with diabetes mellitus (DM) or metabolic syndrome (MetS).
This multicenter eight‐week randomized double‐blind phase III study evaluated the safety and efficacy of fixed‐dose combinations of ezetimibe 10 mg plus rosuvastatin, compared with rosuvastatin alone in patients with primary hypercholesterolemia. Four hundred and seven patients with primary hypercholesterolemia who required lipid‐lowering treatment according to the ATP III guideline were randomized to one of the following six treatments for 8 weeks: fixed‐dose combinations with ezetimibe 10 mg daily plus rosuvastatin (5, 10, or 20 mg daily) or rosuvastatin alone (5, 10, or 20 mg daily).
Fixed‐dose combination of ezetimibe plus rosuvastatin significantly reduced LDL cholesterol, total cholesterol, and triglyceride levels compared with rosuvastatin alone. Depending on the rosuvastatin dose, these fixed‐dose combinations of ezetimibe plus rosuvastatin provided LDL cholesterol, total cholesterol, and triglyceride reductions of 56%–63%, 37%–43%, and 19%–24%, respectively. Moreover, the effect of combination treatment on cholesterol levels was more pronounced in patients with DM or MetS than in non‐DM or non‐MetS patients, respectively, whereas the effect of rosuvastatin alone did not differ between DM vs non‐DM or MetS vs non‐MetS patients.
Fixed‐dose combinations of ezetimibe and rosuvastatin provided significantly superior efficacy to rosuvastatin alone in lowering LDL cholesterol, total cholesterol, and triglyceride levels. Moreover, the reduction rate was greater in patients with DM or MetS.
PMCID: PMC5108468  PMID: 27506635
Cholesterol; Diabetes mellitus; Ezetimibe; Hypercholesterolemia; Metabolic syndrome; Rosuvastatin
3.  Coronary Computed Tomographic Angiography Does Not Accurately Predict the Need of Coronary Revascularization in Patients with Stable Angina 
Yonsei Medical Journal  2016;57(5):1079-1086.
To evaluate the ability of coronary computed tomographic angiography (CCTA) to predict the need of coronary revascularization in symptomatic patients with stable angina who were referred to a cardiac catheterization laboratory for coronary revascularization.
Materials and Methods
Pre-angiography CCTA findings were analyzed in 1846 consecutive symptomatic patients with stable angina, who were referred to a cardiac catheterization laboratory at six hospitals and were potential candidates for coronary revascularization between July 2011 and December 2013. The number of patients requiring revascularization was determined based on the severity of coronary stenosis as assessed by CCTA. This was compared to the actual number of revascularization procedures performed in the cardiac catheterization laboratory.
Based on CCTA findings, coronary revascularization was indicated in 877 (48%) and not indicated in 969 (52%) patients. Of the 877 patients indicated for revascularization by CCTA, only 600 (68%) underwent the procedure, whereas 285 (29%) of the 969 patients not indicated for revascularization, as assessed by CCTA, underwent the procedure. When the coronary arteries were divided into 15 segments using the American Heart Association coronary tree model, the sensitivity, specificity, positive predictive value, and negative predictive value of CCTA for therapeutic decision making on a per-segment analysis were 42%, 96%, 40%, and 96%, respectively.
CCTA-based assessment of coronary stenosis severity does not sufficiently differentiate between coronary segments requiring revascularization versus those not requiring revascularization. Conventional coronary angiography should be considered to determine the need of revascularization in symptomatic patients with stable angina.
PMCID: PMC4960372  PMID: 27401637
Multidetector computed tomography; coronary artery disease; myocardial revascularization
4.  Prognostic Value of Elevated Homocysteine Levels in Korean Patients with Coronary Artery Disease: A Propensity Score Matched Analysis 
Korean Circulation Journal  2016;46(2):154-160.
Background and Objectives
We sought to determine whether an elevated homocysteine (Hcy) level is associated with a worse prognosis in Korean patients with coronary artery disease (CAD).
Subjects and Methods
A total of 5839 patients (60.4% male, mean age 61.3±11.2 years) with CAD were enrolled from 2000 to 2010 at Gangnam Severance Hospital. CAD was diagnosed by invasive coronary angiography. Laboratory values including Hcy level were obtained on the day of coronary angiography and analyses were performed shortly after sampling. Patients were divided into two groups according to their Hcy levels. Baseline risk factors, coronary angiographic findings, length of follow-up, and composite endpoints including cardiac death (CD) and non-fatal myocardial infarction (NFMI) were recorded. 1:1 propensity score matched analysis was also performed.
Over a mean follow-up period of 4.4±2.5 years, there were 132 composite endpoints (75 CD and 57 NFMI) with an event rate of 2.3%. Mean Hcy level was 9.9±4.3 µmol/L (normal Hcy 7.9±1.5 µmol/L and elevated Hcy 13.9±5.1 µmol/L). Kaplan-Meier survival analysis showed an association of elevated Hcy level with worse prognosis (p<0.0001). In addition, a multivariate Cox regression analysis showed an association of elevated Hcy level with worse prognosis for both the entire cohort (hazard ratio [HR] 2.077, 95% confidence interval [CI] 1.467-2.941, p<0.0001) and the propensity score matched cohort (HR 1.982, 95% CI 1.305-3.009, p=0.001).
Elevated Hcy level is associated with worse outcomes in Korean patients with CAD.
PMCID: PMC4805559  PMID: 27014345
Homocysteine; Coronary artery disease; Prognosis
5.  Echo-Doppler–derived indexes of ventricular stiffness and ventriculo-arterial interaction as predictors of new-onset atrial fibrillation in patients with heart failure 
Atrial fibrillation (AF) is common in patients with heart failure (HF) and worsens their prognosis. Vulnerability to changes in loading is an important factor in the development of AF and is strongly influenced by ventricular stiffness and ventriculo-arterial interaction. The aim of this study was to investigate predictors of AF development in patients with HF.
We studied 349 patients with stable HF. The following parameters of ventricular stiffness and ventriculo-arterial interaction were derived from echo-Doppler measurements: left ventricular (LV) diastolic elastance (Ed), effective arterial elastance (Ea), LV end-systolic elastance (Ees) and ventricular–vascular coupling index (VVI).
AF occurred in 57 (16.3 %) patients over a median follow up of 30.3 months. Echo-Doppler–derived parameters of ventricular stiffness and ventriculo-arterial interaction were closely associated with HF severity. Ed was independently associated with AF after adjustment for age, hypertension, diabetes mellitus, and left atrial volume index (hazard ratio [HR] 5.49, p = 0.018). Ea and VVI were also associated with new-onset AF (HR 1.66, p = 0.027, and HR 1.06, p = 0.001, respectively).
Echo-Doppler indexes of ventricular stiffness are closely associated with HF severity. LV diastolic elastance (Ed) is the strongest predictor of new-onset AF in HF patients.
Electronic supplementary material
The online version of this article (doi:10.1186/s12947-016-0050-y) contains supplementary material, which is available to authorized users.
PMCID: PMC4743395  PMID: 26846527
Left ventricular stiffness; Atrial fibrillation; Heart failure; Diastolic dysfunction
6.  Circulating Microparticles and Coronary Plaque Components Assessed by Virtual Histology Intravascular Ultrasound of the Target Lesion in Patients with Stable Angina 
PLoS ONE  2016;11(1):e0148128.
High levels of microparticles (MPs) circulate in the blood of patients with atherosclerotic diseases where they can serve as potential biomarkers of vascular injury and cardiovascular outcome. We used virtual histology intravascular ultrasound (VH-IVUS) to evaluate the relationship between the levels of circulating MPs and the coronary plaque composition in patients with stable angina. We included 35 patients with stable angina (22 men, age 64 ± 9 years) and a de novo target lesion. Preintervention gray-scale and VH-IVUS analysis was performed across the target lesion. Volumetric analysis was performed over a 10-mm-long segment centered at the minimum luminal site. Blood samples were obtained from the femoral artery before coronary angioplasty. MPs were measured using a solid-phase capture assay from a commercial kit. We divided participants into either a low MPs group or high MPs group based on the median value of MPs. There was no significant difference in baseline characteristics between the groups. The plaque burden and remodeling index were similar between the groups. The presence of VH-IVUS-derived thin-cap fibroatheroma was not different between the groups. The percentage of the necrotic core (NC) was significantly higher in the high MPs group than in the low MPs group, both in planar (17.0 ± 8.8% vs. 24.1 ± 6.9%, p = 0.012) and volumetric analyses (17.0 ± 4.8% vs. 22.1 ± 4.3%, p = 0.002). Circulating MPs were positively correlated with the percentage of the NC area at the minimal luminal site (r = 0.491, p = 0.003) and the percentage of the NC volume (r = 0.496, p = 0.002). Elevated levels of circulating MPs were associated with the amount of NC in the target lesion in those with stable angina, suggesting a potential role of circulating MPs as a biomarker for detecting unstable plaque in patients with stable angina.
PMCID: PMC4727898  PMID: 26812147
7.  Carotid Artery End-Diastolic Velocity and Future Cerebro-Cardiovascular Events in Asymptomatic High Risk Patients 
Korean Circulation Journal  2016;46(1):72-78.
Background and Objectives
Prognostic value of additional carotid Doppler evaluations to carotid intima-media thickness (IMT) and plaque has not been completely evaluated.
Subjects and Methods
A total of 1119 patients with risk factors for, but without, overt coronary artery disease (CAD), who underwent both carotid ultrasound and Doppler examination were included in the present study. Parameters of interest included peak systolic and end-diastolic velocities, resistive indices of the carotid arteries, IMT, and plaque measurements. The primary end-point was all-cause cerebro-cardiovascular events (CVEs) including acute myocardial infarction, coronary revascularization therapy, heart failure admission, stroke, and cardiovascular death. Model 1 covariates comprised age and sex; Model 2 also included hypertension, diabetes and smoking; Model 3 also had use of aspirin and statin; and Model 4 also included IMT and plaque.
The mean follow-up duration was 1386±461 days and the mean age of the study population was 60±12 years. Amongst 1119 participants, 43% were women, 57% had a history of hypertension, and 23% had diabetes. During follow-up, 6.6% of patients experienced CVEs. Among carotid Doppler parameters, average common carotid artery end-diastolic velocity was the independent predictor for future CVEs after adjustments for all models variables (HR 0.95 per cm/s, 95% confident interval 0.91-0.99, p=0.034 in Model 4) and significantly increased the predictive value of Model 4 (global χ2=59.0 vs. 62.8, p=0.029).
Carotid Doppler measurements in addition to IMT and plaque evaluation are independently associated with future CVEs in asymptomatic patients at risk for CAD.
PMCID: PMC4720852  PMID: 26798388
Carotid arteries; Doppler; Events
8.  Left Ventricular Filling Pressure as Assessed by the E/e' Ratio Is a Determinant of Atrial Fibrillation Recurrence after Cardioversion 
Yonsei Medical Journal  2015;57(1):64-71.
Left ventricular (LV) filling pressure affects atrial fibrillation (AF) recurrence. We investigated the relationship between diastolic dysfunction and AF recurrence after cardioversion, and whether LV filling pressure was predictive of AF recurrence.
Materials and Methods
Sixty-six patients (mean 58±12 years) with newly diagnosed persistent AF were retrospectively enrolled. We excluded patients with left atrial (LA) diameters larger than 50 mm, thereby isolating the effect of LV filling pressure. We evaluated the differences between the patients with (group 1) and without AF recurrence (group 2).
Group 1 showed increased LA volume index (LAVI) and E/e' compared to group 2 (p<0.05). During a mean follow-up period of 25±19 months, AF recurrence after cardioversion was 60.6% (40/66). The area under the receiver operating characteristics curve of E/e' for AF recurrence was 0.780 [95% confidence interval (CI): 0.657-0.903], and the optimal cut-off value of the E/e' was 9.15 with 75.0% of sensitivity and 73.1% of specificity. A Kaplan-Meier survival curve showed that the cumulative recurrence-free survival rate was significantly lower in patients with higher LV filling pressure (E/e'>9.15) compared with patients with lower LV filling pressure (E/e'≤9.15) (log rank p=0.008). Cox regression analysis revealed that E/e' [hazards ratio (HR): 1.100, 95% CI: 1.017-1.190] and LAVI (HR: 1.042, 95% CI: 1.002-1.084) were independent predictors for AF recurrence after cardioversion.
LV filling pressure predicts the risk of AF recurrence in persistent AF patients after cardioversion.
PMCID: PMC4696974  PMID: 26632384
Diastolic dysfunction; left ventricular filling pressure; atrial fibrillation; cardioversion
9.  A Case of Acute Ventricular Capture Threshold Rise Associated with Flecainide Acetate 
Yonsei Medical Journal  2006;47(1):152-154.
Antiarrhythmic agents may increase capture threshold, but this is rarely of clinical significance. Flecainide acetate, a class IC agent, is reported to have a significant effect on the myocardial capture threshold. In this presentation, we report the case of a 72-year-old male, with a previously implanted VVI pacemaker due to sick sinus syndrome, who was treated with flecainide acetate for paroxysmal atrial arrhythmia control. During the fifteenth day of treatment, an abrupt rise in the ventricular capture threshold with ventricular pacing failure was noted. The capture threshold decreased two days after discontinuation of flecainide acetate.
PMCID: PMC2687576  PMID: 16502500
Flecainide acetate; capture threshold; pacing failure
10.  Lipoprotein-Associated Phospholipase A2 Is Related to Plaque Stability and Is a Potential Biomarker for Acute Coronary Syndrome 
Yonsei Medical Journal  2014;55(6):1507-1515.
Plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) binds to low-density lipoprotein. The levels of Lp-PLA2 reflect the plaque burden, and are upregulated in acute coronary syndrome (ACS). We investigated the diagnostic value of Lp-PLA2 levels and found that it might be a potential biomarker for ACS.
Materials and Methods
We classified 226 study participants into three groups: patients without significant stenosis (control group), patients with significant stenosis with stable angina (SA group), and patients with ACS (ACS group).
Lp-PLA2 and high-sensitivity C-reactive protein (hs-CRP) levels were significantly greater in the ACS group than in the SA group (p=0.044 and p=0.029, respectively). Multivariate logistic regression analysis revealed that Lp-PLA2 levels are significantly associated with ACS (odds ratio=1.047, p=0.013). The addition of Lp-PLA2 to the ACS model significantly increased the global χ2 value over traditional risk factors (28.14 to 35.602, p=0.006). The area under the receiver operating characteristic curve for Lp-PLA2 was 0.624 (p=0.004). The addition of Lp-PLA2 level to serum hs-CRP concentration yielded an integrated discrimination improvement of 0.0368 (p=0.0093, standard error: 0.0142) and improved the ability to diagnose ACS.
Lp-PLA2 levels are related to plaque stability and might be a diagnostic biomarker for ACS.
PMCID: PMC4205689  PMID: 25323886
Lp-PLA2; acute coronary syndrome; biomarker; coronary atherosclerotic plaque instability
11.  Diverse geometric changes related to dynamic left ventricular outflow tract obstruction without overt hypertrophic cardiomyopathy 
Dynamic left ventricular (LV) outflow tract (LVOT) obstruction (DLVOTO) is not infrequently observed in older individuals without overt hypertrophic cardiomyopathy (HCM). We sought to investigate associated geometric changes and then evaluate their clinical characteristics.
A total of 168 patients with DLVOTO, which was defined as a trans-LVOT peak pressure gradient (PG) higher than 30 mmHg at rest or provoked by Valsalva maneuver (latent LVOTO) without fixed stenosis, were studied. Patients with classical HCM, acute myocardial infarction, stress induced cardiomyopathy or unstable hemodynamics which potentially induce transient-DLVOTO were excluded.
Their mean age was 71 ± 11 years and 98 (58%) patients were women. Patients were classified as pure sigmoid septum (n = 14) if they have basal septal bulging but diastolic thickness less than 15 mm, sigmoid septum with basal septal hypertrophy for a thickness ≥15 mm (n = 85), prominent papillary muscle (PM) (n = 20) defined by visually large PMs which occluded the LV cavity during systole or 1/2 LVESD, or as having a small LV cavity with concentric remodelling or hypertrophy (n = 49). The prominent PM group was younger, had a higher S’ and lower E/e’ than other groups. In all groups, a higher peak trans-LVOT PG was related (p < 0.10) to higher E/e’, systolic blood pressure, relative wall thickness, and pulmonary arterial systolic pressure. In multivariate analysis, resting trans-LVOT PG correlated to pulmonary arterial pressure (ß = 0.226, p = 0.019) after adjustment for systolic blood pressure, relative wall thickness, and E/e’.
DLVOTO develops from various reasons, and patients with prominent PMs have distinct characteristics. We suggest to use DLVOTO-relieving medication might reduce pulmonary pressure in this group of patients.
PMCID: PMC4086991  PMID: 24993692
Dynamic left ventricular outflow tract obstruction; Sigmoid septum; Aging
12.  Multidetector Computed Tomography for the Evaluation of Coronary Artery Disease; The Diagnostic Accuracy in Calcified Coronary Arteries, Comparing with IVUS Imaging 
Yonsei Medical Journal  2014;55(3):599-605.
Contrast enhanced multidetector computed tomography (MDCT) has been used as an alternative to coronary angiography for the assessment of coronary artery disease in the patient of the intermediate risk group. However, coronary calcium is a known limiting factor for MDCT evaluation. We investigated the diagnostic accuracy of 64-channel MDCT with each coronary artery calcium score (CACS) by compared with intravascular ultrasound (IVUS) imaging.
Materials and Methods
A total of 54 symptomatic patients with intermediate-risk (10 females, mean age 59.9±6.9 years, Framingham point scores 9-20) with 162 sites who had a culprit lesion on 64-channel MDCT before performing coronary angiography with IVUS were enrolled. Patients were divided into 4 subgroups depending on CACS: 0, 1-99, 100-399, and >400. Lesion length, external elastic membrane (EEM) cross sectional area (CSA), minimal luminal area, and plaque area were measured and compared between IVUS and MDCT.
The correlation coefficients for the measurements of the EEM CSA, lumen CSA, and plaque area were r=0.514, r=0.837, and r=0.578, respectively. Furthermore, there were close correlation of plaque area between four subgroups of CACS (r=0.671, r=0.623, r=0.562, r=0.571, respectively).
Despite the increase in CACS, the geometric analysis of coronary arteries using with 64-channel MDCT was comparable with IVUS in symptomatic patient of the intermediate risk group.
PMCID: PMC3990095  PMID: 24719125
Coronary artery disease; coronary calcium score; computed tomography; intravascular ultrasound
13.  Antiplatelet Effect of Clopidogrel Can Be Reduced by Calcium-Channel Blockers 
Yonsei Medical Journal  2014;55(3):683-688.
Clopidogrel is metabolized by the hepatic cytochrome P450 (CYP) system into its active thiol metabolite. CYP3A4 is involved in the metabolism of both clopidogrel and dihydropyridine calcium channel blockers (CCBs). A few reports have suggested an inhibitory interaction between CCBs and clopidogrel. Accordingly, the aim of this study was to determine the effect of CCBs on the antiplatelet activity of clopidogrel by serial P2Y12 reaction unit (PRU) measurements.
Materials and Methods
We assessed changes in antiplatelet activity in patients receiving both clopidogrel and CCBs for at least 2 months prior to enrollment in the study. The antiplatelet activity of clopidogrel was measured by VerifyNow P2Y12 assay in the same patient while medicated with CCBs and at 8 weeks after discontinuation of CCBs. After discontinuation of the CCBs, angiotensin receptor blockers were newly administered to the patients or dosed up for control of blood pressure.
Thirty patients finished this study. PRU significantly decreased after discontinuation of CCBs (238.1±74.1 vs. 215.0±69.3; p=0.001). Of the 11 patients with high post-treatment platelet reactivity to clopidogrel (PRU≥275), PRU decreased in nine patients, decreasing below the cut-off value in seven of these nine patients after 8 weeks. Decrease in PRU was not related to CYP2C19 genotype.
CCBs inhibit the antiplatelet activity of clopidogrel.
PMCID: PMC3990098  PMID: 24719135
Calcium channel blockers; clopidogrel; platelet reactivity unit
14.  Different contribution of extent of myocardial injury to left ventricular systolic and diastolic function in early reperfused acute myocardial infarction 
We sought to investigate the influence of the extent of myocardial injury on left ventricular (LV) systolic and diastolic function in patients after reperfused acute myocardial infarction (AMI).
Thirty-eight reperfused AMI patients underwent cardiac magnetic resonance (CMR) imaging after percutaneous coronary revascularization. The extent of myocardial edema and scarring were assessed by T2 weighted imaging and late gadolinium enhancement (LGE) imaging, respectively. Within a day of CMR, echocardiography was done. Using 2D speckle tracking analysis, LV longitudinal, circumferential strain, and twist were measured.
Extent of LGE were significantly correlated with LV systolic functional indices such as ejection fraction (r = -0.57, p < 0.001), regional wall motion score index (r = 0.52, p = 0.001), and global longitudinal strain (r = 0.56, p < 0.001). The diastolic functional indices significantly correlated with age (r = -0.64, p < 0.001), LV twist (r = -0.39, p = 0.02), average non-infarcted myocardial circumferential strain (r = -0.52, p = 0.001), and LV end-diastolic wall stress index (r = -0.47, p = 0.003 with e’) but not or weakly with extent of LGE. In multivariate analysis, age and non-infarcted myocardial circumferential strain independently correlated with diastolic functional indices rather than extent of injury.
In patients with timely reperfused AMI, not only extent of myocardial injury but also age and non-infarcted myocardial function were more significantly related to LV chamber diastolic function.
PMCID: PMC3922533  PMID: 24512272
Acute myocardial infarction; Diastolic function; Cardiac magnetic resonance; Speckle tracking echocardiography
15.  Usefulness of metabolic syndrome score in the prediction of angiographic coronary artery disease severity according to the presence of diabetes mellitus: relation with inflammatory markers and adipokines 
It is a matter of debate whether metabolic syndrome (MS) improves cardiovascular risk prediction beyond the risk associated with its individual components. The present study examined the association of MS score with high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), resistin, adiponectin, and angiographic coronary artery disease (CAD) severity according to the presence of DM. In addition, the predictive value of various clinical and biochemical parameters were analyzed, including the MS score for angiographic CAD.
The study enrolled 363 consecutive patients (196 men, 62 ± 11 years of age) who underwent coronary angiography for evaluation of chest pain. Blood samples were taken prior to elective coronary angiography. MS was defined by the National Cholesterol Education Program criteria, with MS score defined as the numbers of MS components. CAD was defined as > 50% luminal diameter stenosis of at least one major epicardial coronary artery. CAD severity was assessed using the Gensini score.
Of the 363 patients studied, 174 (48%) had CAD and 178 (49%) were diagnosed with MS. When the patients were divided into 4 subgroups according to MS score (0–1, 2, 3, 4–5), IL-6 levels and the CAD severity as assessed by the Gensini score increased as MS scores increased. In contrast, adiponectin levels decreased significantly as MS scores increased. When subjects were divided into two groups according to the presence of DM, the relationships between MS score and IL-6, adiponectin, and Gensini score were maintained only in patients without DM. Age, smoking, DM, MS score, and adiponectin independently predicted angiographic CAD in the whole population. However, age is the only predictor for angiographic CAD in patients with DM.
In the presence of DM, neither adipokines nor MS score predicted angiographic CAD. However, in non-diabetic patients, IL-6 and adiponectin showed progressive changes according to MS score, and MS score was an independent predictor of CAD in patients without DM.
PMCID: PMC3850730  PMID: 24088407
Metabolic syndrome; Adipokines; Coronary artery disease; Diabetes mellitus
16.  Effect of Abciximab on the Levels of Circulating Microparticles in Patients with Acute Myocardial Infarction Treated by Primary Angioplasty 
Korean Circulation Journal  2013;43(9):600-606.
Background and Objectives
We investigated the effect of the additional use of abciximab during percutaneous coronary intervention (PCI) on the level of procoagulant microparticles (MPs) in patients with ST-segment elevation myocardial infarction (STEMI) who had undergone primary PCI.
Subjects and Methods
In this study, we studied 86 patients with STEMI (72 men, age 58±13) who had undergone primary PCI. The decision to administer abciximab immediately prior to PCI was left to the discretion of the operator. Blood samples for analysis of MPs were obtained from the femoral artery before and after PCI. MPs with procoagulant potential were measured using a commercial kit. The cellular origins of MPs were determined by antigenic capture with specific antibodies.
Procoagulant MPs captured onto annexin V were not changed significantly after PCI {13.4±13.2 nM vs. 13.2±16.1 nM phosphatidylserine equivalent (PS eq), p=0.479}. Abciximab was used in 30 of 86 patients (35%) immediately prior to PCI. In patients who had undergone PCI without abciximab, no significant change in the level of MPs was observed after PCI. However, in the abciximab group, the level of circulating MPs was significantly decreased after PCI (12.0±10.7 nM vs. 7.8±11.7 nM PS eq, p=0.018). Levels of endothelial- and platelet-derived MPs also showed a significant reduction after PCI in the abciximab group.
Primary PCI with additional abciximab significantly reduced the level of procoagulant MPs regardless of their cellular origins in patients with STEMI.
PMCID: PMC3808855  PMID: 24174960
Cell-derived microparticles; Myocardial infarction; Platelet aggregation inhibitors
17.  Correction with blood T1 is essential when measuring post-contrast myocardial T1 value in patients with acute myocardial infarction 
Post-contrast T1 mapping by modified Look-Locker inversion recovery (MOLLI) sequence has been introduced as a promising means to assess an expansion of the extra-cellular space. However, T1 value in the myocardium can be affected by scanning time after bolus contrast injection. In this study, we investigated the changes of the T1 values according to multiple slicing over scanning time at 15 minutes after contrast injection and usefulness of blood T1 correction.
Eighteen reperfused acute myocardial infarction (AMI) patients, 13 cardiomyopathy patients and 8 healthy volunteers underwent cardiovascular magnetic resonance with 15 minute-post contrast MOLLI to generate T1 maps. In 10 cardiomyopathy cases, pre- and post-contrast MOLLI techniques were performed to generate extracellular volume fraction (Ve). Six slices of T1 maps according to the left ventricular (LV) short axis, from apex to base, were consecutively obtained. Each T1 value was measured in the whole myocardium, infarcted myocardium, non-infarcted myocardium and LV blood cavity.
The mean T1 value of infarcted myocardium was significantly lower than that of non-infarcted myocardium (425.4±68.1 ms vs. 540.5±88.0 ms, respectively, p< 0.001). T1 values of non-infarcted myocardium increased significantly from apex to base (from 523.1±99.5 ms to 561.1±81.1 ms, p=0.001), and were accompanied by a similar increase in blood T1 value in LV cavity (from 442.1±120.7 ms to 456.8±97.5 ms, p<0.001) over time. This phenomenon was applied to both left anterior descending (LAD) territory (from 545.1±74.5 ms to 575.7±84.0 ms, p<0.001) and non-LAD territory AMI cases (from 501.2±124.5 ms to 549.5±81.3 ms, p<0.001). It was similarly applied to cardiomyopathy patients and healthy volunteers. After the myocardial T1 values, however, were adjusted by the blood T1 values, they were consistent throughout the slices from apex to base (from 1.17±0.18 to 1.25±0.13, p>0.05). The Ve did not show significant differences from apical to basal slices.
Post-contrast myocardial T1 corrected by blood T1 or Ve, provide more stable measurement of degree of fibrosis in non-infarcted myocardium in short- axis multiple slicing.
PMCID: PMC3564738  PMID: 23331480
Cardiovascular magnetic resonance; T1 mapping; Myocardium
18.  Spontaneous Sinus Conversion of Permanent Atrial Fibrillation During Treatment of Hyperkalemia 
Korean Circulation Journal  2012;42(1):65-68.
Hyperkalemia is a common adverse effect of treatment for heart failure and is associated with high mortality and morbidity. The cardiac manifestations of hyperkalemia include various electrocardiogram changes. We describe a case of a 74-year-old woman with heart failure and permanent atrial fibrillation who reverted to normal sinus rhythm during recovery from hyperkalemia.
PMCID: PMC3283759  PMID: 22363388
Hyperkalemia; Atrial fibrillation; Electrocardiography
19.  Impact of Metabolic Syndrome and Its Individual Components on the Presence and Severity of Angiographic Coronary Artery Disease 
Yonsei Medical Journal  2010;51(5):676-682.
Metabolic syndrome (MS) has been reported as a potential risk factor of coronary artery disease (CAD). The aims of this study were to assess whether there was a relationship between MS score and CAD angiographic severity, and to assess the predictive value of individual components of MS for CAD.
Materials and Methods
We retrospectively enrolled 632 patients who underwent coronary angiography for suspected CAD (394 men, 61.0 ± 10.6 years of age). MS was defined by the National Cholesterol Education Program criteria with the waist criterion modified into a body mass index (BMI) of more than 25 kg/m2. The MS score defined as the number of MS components. CAD was defined as > 50% luminal diameter stenosis of at least one major epicardial coronary artery. CAD angiographic severity was evaluated with a Gensini scoring system.
Of the patients, 497 (78.6%) had CAD and 283 (44.8%) were diagnosed with MS. The MS score was significantly related to the Gensini score. High fasting blood glucose (FBG) was the only predictive factor for CAD. A cluster including high FBG, high blood pressure (BP), and low high-density lipoprotein cholesterol (HDL-C) showed the highest CAD risk.
The MS score correlates with the angiographic severity of CAD. The predictive ability of MS for CAD was carried almost completely by high FBG, and individual traits with high BP and low HDL-C may act synergistically as risk factors for CAD.
PMCID: PMC2908873  PMID: 20635441
Metabolic syndrome; coronary artery disease; coronary angiography
20.  Evaluation of Reperfused Myocardial Infarction by Low-Dose Multidetector Computed Tomography Using Prospective Electrocardiography (ECG)-Triggering: Comparison with Magnetic Resonance Imaging 
Yonsei Medical Journal  2010;51(5):683-691.
To evaluate the potential of prospective electrocardiography (ECG)-gated 64-slice multidetector computed tomography (MDCT) for evaluation of myocardial enhancement, infarct size, and stent patency after percutaneous coronary intervention (PCI) with stenting in patients with myocardial infarction.
Materials and Methods
Seventeen patients who were admitted with acute myocardial infarction were examined with prospective ECG-gated 64-slice cardiac MDCT and magnetic resonance (MR) imaging after reperfusion using PCI with stenting. Cardiac MDCT was performed with two different phases: arterial and delayed phases. We evaluated the stent patency on the arterial phase, and nonviable myocardium on the delayed phase of computed tomography (CT) image, and they were compared with the results from the delayed MR images.
Total mean radiation dose was 7.7 ± 0.5 mSv on the two phases of CT images. All patients except one showed good patency of the stent at the culprit lesion on the arterial phase CT images. All patients had hyperenhanced area on the delayed phase CT images, which correlated well with those on the delayed phase MR images, with a mean difference of 1.6% (20 ± 10% vs. 22 ± 10%, r = 0.935, p = 0.10). Delayed MR images had a better contrast-to-noise ratio (CNR) than delayed CT images (27.1 ± 17.8% vs. 4.3 ± 2.1%, p < 0.001).
Prospective ECG-gated 64-slice MDCT provides the potential to evaluate myocardial viability on delayed phase as well as for stent patency on arterial phase with an acceptable radiation dose after PCI with stenting in patients with myocardial infarction.
PMCID: PMC2908876  PMID: 20635442
Prospective ECG-gated MDCT; magnetic resonance imaging; myocardial infarction; delayed enhancement imaging
21.  Potential role of HMG CoA reductase inhibitor on oxidative stress induced by advanced glycation endproducts in vascular smooth muscle cells of diabetic vasculopathy 
Experimental & Molecular Medicine  2009;41(11):802-811.
Advanced glycation endproducts (AGEs)-induced vascular smooth muscle cell (VSMCs) proliferation and formation of reactive oxygen species (ROS) are emerging as one of the important mechanisms of diabetic vasculopathy but little is known about the antioxidative action of HMG CoA reductase inhibitor (statin) on AGEs. We hypothesized that statin might reduce AGEs-induced intracellular ROS of VSMCs and analyzed the possible mechanism of action of statin in AGEs-induced cellular signaling. Aortic smooth muscle cell of Sprague-Dawley rat (RASMC) culture was done using the different levels of AGEs stimulation in the presence or absence of statin. The proliferation of RASMC, ROS formation and cellular signaling was evaluated and neointimal formation after balloon injury in diabetic rats was analyzed. Increasing concentration of AGEs stimulation was associated with increased RASMC proliferation and increased ROS formation and they were decreased with statin in a dose-dependent manner. Increased NF-κB p65, phosphorylated ERK, phosphorylated p38 MAPK, cyclooxygenase-2, and c-jun by AGEs stimulation were noted and their expression was inhibited by statin. Neointimal formation after balloon injury was much thicker in diabetic rats than the sham-treated group but less neointimal growth was observed in those treated with statin after balloon injury. Increased ROS formation, subsequent activation of MAPK system and increased VSMC proliferation may be possible mechanisms of diabetic vasculopathy induced by AGEs and statin may play a key role in the treatment of AGEs-induced diabetic atherosclerosis.
PMCID: PMC2788734  PMID: 19641377
cyclooxygenase 2; diabetes mellitus; extracellular signal-regulated MAP kinases; hydroxymethylglutaryl-CoA reductase inhibitors; muscle, smooth, vascular; NFκB; p38 mitogen-activated protein kinases; proto-oncogene proteins c-jun; reactive oxygen species
22.  Pathobiological role of advanced glycation endproducts via mitogen-activated protein kinase dependent pathway in the diabetic vasculopathy 
Experimental & Molecular Medicine  2008;40(4):398-406.
Advanced glycation endproducts (AGEs) have been reported to play a role in neointimal formation and increase the rate of in-stent restenosis (ISR) in the diabetic coronary artery disease patients treated with stents, but the potential pathogenic mechanisms of AGEs in vascular smooth muscle cell proliferation remain unclear. We sought to determine the AGEs related pathobiological mechanism of diabetic vasculopathy. Rat aortic smooth muscle cell (RAoSMC) culture was done with different concentrations of AGEs and proliferation was assessed. Immunohistochemistry for receptor of AGEs (RAGE) was performed with human carotid atheroma. Western blotting was performed to assess the activation of MAP kinase system in the cultured RAoSMC. AGEs increased RAoSMC proliferation and were associated with increased phosphorylation of ERK and p38 kinase by time and dose dependent manner. The MAP kinase activity was decreased by RNA interference for RAGE. AGEs stimulation increased reactive oxygen species (ROS) generation in cultured RAoSMC. From this study it is concluded that AGEs played a key role in RAoSMC proliferation via MAP kinase dependent pathways. Activation of vascular smooth muscle cell (VSMC) proliferation by MAP kinase system and increased formation of ROS may be the possible mechanisms of AGEs induced diabetic vasculopathy.
PMCID: PMC2679265  PMID: 18779652
atherosclerosis; blood vessels; diabetes mellitus; glycation end products, advanced; mitogen-activated protein kinases
23.  A Case of Noncompaction of the Ventricular Myocardium Combined with Situs Ambiguous with Polysplenia 
Yonsei Medical Journal  2007;48(6):1052-1055.
A 33-year-old man was admitted to our hospital with chest pain and exertional dyspnea. Two-dimensional echocardiography showed prominent trabeculations and deep intertrabecular recesses, findings consistent with noncompaction of the ventricular myocardium. Thoracoabdominal CT and cardiac magnetic resonance imaging (CMR) revealed situs ambiguous with polysplenia and noncompaction of the left ventricular myocardium. CMR also demonstrated delayed enhancement of the trabeculations located at the apical portion of the left ventricle. The coronary angiogram was normal. This is the first case of noncompaction of the ventricular myocardium associated with situs ambiguous with polysplenia.
PMCID: PMC2628179  PMID: 18159602
Noncompaction of the ventricular myocardium (NVM); situs ambiguous with polysplenia
24.  Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting in Patients with Coronary Artery Disease and Diabetic Nephropathy: A Single Center Experience 
Patients with diabetic nephropathy (DN) and coronary artery disease (CAD) represent a subset of patients with high cardiovascular morbidity and mortality. The optimal revascularization strategy using either percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) remains controversial. The purpose of this study was to compare the clinical outcomes of PCI to CABG in DN patients with CAD.
The clinical and angiographic records of DN patients with CAD who underwent either CABG (n=52) or PCI (n=48) were retrospectively analyzed.
The baseline characteristics were similar in the two groups except for the severity of the CAD. At 30 days, the death rate (PCI: 2.1% vs. CABG: 9.6%, p=0.21) and major adverse cardiac events (MACE) rate (PCI: 2.1% vs. CABG: 9.6%, p=0.21) were similar in comparisons between the PCI and CABG groups. At three years, the death rate (PCI: 18.8% vs. CABG: 19.2%, p=0.94) was similar between the PCI and CABG groups but the MACE rate (PCI: 47.9% vs. CABG: 21.2%, p=0.006) was higher in the PCI group compared to the CABG group. In addition, the repeat revascularization rate was higher in the PCI group compared to the CABG group (PCI: 12.5% vs. CABG: 1.9%, p=0.046).
The CABG procedure was associated with a lower incidence of MACE and repeat revascularization for up to three years of follow-up in DN patients with CAD. However, the overall survival rate was similar in the CABG and PCI groups. Therefore, CABG may be superior to PCI with regard to MACE and repeat revascularization.
PMCID: PMC2687692  PMID: 17939329
Diabetic Nephropathy; Coronary Artery Disease; Coronary Artery Bypass Grafting; Percutaneous Transluminal Coronary Angioplasty
25.  Significance of Small Dense Low-Density Lipoprotein as a Risk Factor for Coronary Artery Disease and Acute Coronary Syndrome 
Yonsei Medical Journal  2006;47(3):405-414.
Small dense LDL (sd-LDL) has recently emerged as an important coronary artery disease (CAD) risk factor. This study was performed to investigate how LDL particle size is related to CAD and acute coronary syndrome (ACS). Blood samples were collected from 504 patients that underwent coronary angiography to evaluate chest pain. The LDL particle size of these samples was measured. The mean LDL particle size was smaller in patients with angiographically proven CAD than in the controls (26.41 ± 0.95 vs 26.73 ± 0.64 nm, p < 0.001), and was negatively correlated with the Framingham risk score (r = -0.121, p = 0.007). Patients with more extensive CAD had smaller LDL particles. LDL particle size was also smaller in patients with acute coronary syndrome as compared to non-ACS patients (26.09 ± 1.42 vs 26.54 ± 0.63 nm, p = 0.011). These results suggest that sd-LDL is independently associated with the incidence and extent of CAD, and can be a risk factor for the development of ACS in the Korean population.
PMCID: PMC2688162  PMID: 16807992
Small dense LDL; coronary artery disease

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