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1.  A Polymorphism of the Renin Gene rs6682082 Is Associated with Essential Hypertension Risk and Blood Pressure Levels in Korean Women 
Yonsei Medical Journal  2014;56(1):227-234.
The aim of the present study was to investigate associations between the renin gene (REN) and the risk of essential hypertension and blood pressure (BP) levels in Koreans.
Materials and Methods
To outline the functional role of a single nucleotide polymorphism in the transcription of the REN gene, we conducted a case-control study of 1975 individuals: 646 hypertension (HT) patients and 1329 ethnically and age-matched normotensive subjects.
Logistic regression analysis indicated that the genotypes AA/AG were strongly associated with risk of HT (odds ratio, 1.493; 95% confidence interval, 1.069-2.086, p=0.018) in female subjects. The genotypes AA/AG also showed significant association with higher blood pressure levels, both systolic and diastolic, in postmenopausal HT women (p=0.003 and p=0.017, respectively). Analysis of the promoter containing rs6682082 revealed a 2.4±0.01-fold higher activity in the A variant promoter than the G variant promoter, suggesting that rs6682082 is itself a functional variant.
We suggest that the A allele of rs6682082 is a positive genetic marker for predisposition to essential hypertension and high BP in Korean women and may be mediated through the transcriptional activation of REN.
PMCID: PMC4276760  PMID: 25510769
Essential hypertension; renin; polymorphism; association
2.  Impact of Statin Treatment on Strut Coverage after Drug-Eluting Stent Implantation 
Yonsei Medical Journal  2014;56(1):45-52.
To evaluate the effect of statin treatment on strut coverage after drug-eluting stent (DES) implantation.
Materials and Methods
In this study, 60 patients were randomly assigned to undergo sirolimus-eluting stent (SES) or biolimus-eluting stent (BES) implantation, after which patients were randomly treated with pitavastatin 2 mg or pravastatin 20 mg for 6 months. The degree of strut coverage was assessed by 6-month follow-up optical coherence tomography, which was performed in 52 DES-implanted patients.
The percentages of uncovered struts were 19.4±14.7% in pitavastatin-treated patients (n=25) and 19.1±15.2% in pravastatin-treated patients (n=27; p=0.927). A lower percentage of uncovered struts was significantly correlated with a lower follow-up low-density lipoprotein (LDL) cholesterol level (r=0.486; p=0.009) and a greater decline of the LDL cholesterol level (r=-0.456; p=0.015) in SES-implanted patients, but not in BES-implanted patients. In SES-implanted patients, the percentage of uncovered struts was significantly lower among those with LDL cholesterol levels of less than 70 mg/dL after 6 months of follow-up (p=0.025), but no significant difference in this variable according to the follow-up LDL cholesterol level was noted among BES-implanted patients (p=0.971).
Lower follow-up LDL cholesterol levels, especially those less than 70 mg/dL, might have a protective effect against delayed strut coverage after DES implantation. This vascular healing effect of lower LDL cholesterol levels could differ according to the DES type.
PMCID: PMC4276777  PMID: 25510746
Stent; optical coherence tomography; statin
3.  Serial Changes of Neointimal Tissue after Everolimus-Eluting Stent Implantation in Porcine Coronary Artery: An Optical Coherence Tomography Analysis 
BioMed Research International  2014;2014:851676.
Purposes. The serial changes in neointimal tissues were compared between everolimus-eluting stent (EES) and bare-metal stent (BMS) in the porcine coronary artery using optical coherence tomography (OCT). Methods. Serial (1, 3, and 6 month follow-up after stent implantation) OCT examinations were performed in 15 swine with 15 BMS- and 15 EES-treated lesions in porcine coronary arteries. Results. In BMS-implanted lesions, neointimal volume decreased from 7.3 mm3 to 6.9 mm3 and 6.4 mm3 at 1, 3, and 6 months follow-up without statistical significance (P = 0.369). At the time points of 1, 3, and 6 months, neointimal tissue appearance was mainly a homogeneous pattern (80.0%, 93.3%, and 100%, resp.), while the other pattern was layered. In contrast, in EES-implanted lesions, neointimal volume significantly increased from 4.8 mm3 to 9.8 mm3 between 1 and 3 months but significantly decreased to 8.6 mm3 between 3 and 6 months (P < 0.001). Between 1 and 3 months, the layered pattern of neointimal tissue increased from 26.7% to 66.7% but decreased to 20.0% between 3 and 6 months. Conclusions. EES had a biphasic pattern of neointimal amounts that correlated with changes in neointimal morphology.
PMCID: PMC4182891  PMID: 25309929
4.  Multidisciplinary Team Approach for Identifying Potential Candidate for Transcatheter Aortic Valve Implantation 
Yonsei Medical Journal  2014;55(5):1246-1252.
We sought to evaluate the clinical usefulness of decision making by a multidisciplinary heart team for identifying potential candidates for transcatheter aortic valve implantation (TAVI) in patients with symptomatic severe aortic stenosis.
Materials and Methods
The multidisciplinary team consisted of two interventional cardiologists, two cardiovascular surgeons, one cardiac imaging specialist, and two cardiac anesthesiologists.
Out of 60 patients who were screened as potential TAVI candidates, 31 patients were initially recommended as appropriate for TAVI, and 20 of these 31 eventually underwent TAVI. Twenty-two patients underwent surgical aortic valve replacement (AVR), and 17 patients received only medical treatment. Patients who underwent TAVI and medical therapy were older than those who underwent surgical AVR (p<0.001). The logistic Euroscore was significantly highest in the TAVI group and lowest in the surgical AVR group (p=0.012). Most patients in the TAVI group (90%) and the surgical AVR group (91%) had severe cardiac symptoms, but only 47% in the medical therapy group had severe symptoms. The cumulative percentages of survival without re-hospitalization or all-cause death at 6 months for the surgical AVR, TAVI, and medical therapy groups were 84%, 75%, and 28%, respectively (p=0.007, by log-rank).
TAVI was recommended in half of the potential candidates following a multidisciplinary team approach and was eventually performed in one-third of these patients. One-third of the patients who were initially considered potential candidates received surgical AVR with favorable clinical outcomes.
PMCID: PMC4108808  PMID: 25048481
Endovascular procedures; aortic stenosis; clinical outcomes
5.  Blockade of TGF- by Catheter-based Local Intravascular Gene Delivery Does Not Alter The In-Stent Neointimal Response, But Enhances Inflammation in Pig Coronary Arteries 
International journal of cardiology  2010;145(3):468-475.
Extracellular matrix (ECM) accumulation significantly contributes to in-stent restenosis. In this regard, transforming growth factor (TGF)-β, a positive regulator of ECM deposition, may be implicated in in-stent restenosis. The goal of this study was to assess the effect of blockade of TGF-β on stent-induced restenosis in porcine coronary arteries.
An adenovirus expressing the ectodomain of the TGF-β type II receptor (AdTβ-ExR) was applied onto a coronary arterial segment of a pig (n=10) using an Infiltrator™, followed by stent deployment. Controls consisted of adenoviruses expressing β-galactosidase (AdLacZ) or phosphate-buffered saline (PBS) applied onto the other segment (n=10) of the same pig.
Computer-based pathological morphometric analysis of stented coronary arteries, performed 4 weeks after stenting, demonstrated no significant difference in morphometric parameters such as in-stent neointimal area and % area stenosis between the AdTβ-ExR group and control (n=7 for each). However the AdTβ-ExR group had increased neointimal cell density, infiltration of inflammatory cells mostly consisting of CD3+ T cell, accumulation of hyaluronan, cell proliferation rate, and adventitial matrix metalloproteinase-1 (MMP-1) expression compared with control. The expression of connective tissue growth factor mRNA, measured by reverse transcription PCR, in cultured rat arterial smooth muscle cells was inhibited by AdTβ-ExR at moi 60.
Blockade of TGF-β by catheter based local intravascular gene delivery does not reduce stent-induced neointima formation 4 weeks after stenting in spite of modest inhibition of ECM accumulation, but it induces vascular inflammation and associated pathological changes that may potentially aggravate lesion progression.
PMCID: PMC4100469  PMID: 20053468
hyaluronan; inflammation; restenosis; stents; transforming growth factor-β
6.  Fasting Glucose Level and the Risk of Incident Atherosclerotic Cardiovascular Diseases 
Diabetes Care  2013;36(7):1988-1993.
Although diabetes increases the risk of cardiovascular disease (CVD) and mortality, the dose-response relationship between fasting glucose levels below those diagnostic of diabetes with cardiovascular events has not been well characterized.
A prospective cohort study of more than one million Koreans was conducted with a mean follow-up of 16 years. A total of 1,197,384 Korean adults with no specific medical conditions diagnosed were classified by baseline fasting serum glucose level. Associations of fasting glucose level with CVD incidence and mortality, stroke incidence and mortality, and all-cause mortality were analyzed using multivariate proportional hazards regression.
The relationships between fasting glucose levels and CVD risks generally followed J-shape curves, with lowest risk in the glucose range of 85–99 mg/dL. As fasting glucose levels increased to >100 mg/dL, risks for CVD, ischemic heart disease, myocardial infarction, and thrombotic stroke progressively increased, but risk for hemorrhagic stroke did not. Fasting glucose levels <70 mg/dL were associated with increased risk of all stroke (hazard ratio 1.06, 95% CI 1.01–1.11) in men and (hazard ratio 1.11, 1.05–1.17) in women.
Both low glucose level and impaired fasting glucose should be considered as predictors of risk for stroke and coronary heart disease. The fasting glucose level associated with the lowest cardiovascular risk may be in a narrow range.
PMCID: PMC3687304  PMID: 23404299
7.  Optical Coherence Tomographic Observation of Morphological Features of Neointimal Tissue after Drug-Eluting Stent Implantation 
Yonsei Medical Journal  2014;55(4):944-952.
The impacts of different time courses and the degree of neointimal growth on neointimal morphology have not yet been sufficiently investigated. Therefore, we evaluated the morphological features of neointimal tissue after drug-eluting stent (DES) implantation using optical coherence tomography (OCT).
Materials and Methods
The morphological features of neointimal tissue in stented segments with a maximal percentage of cross-sectional area (CSA) stenosis of neointima were evaluated in 507 DES-treated lesions with >100 µm mean neointimal thickness on follow-up OCT. Neointimal tissue was categorized as homogeneous, heterogeneous, layered, or neoatherosclerotic.
In lesions with <50% of neointimal CSA stenosis, homogeneous neointima (68.2%) was predominant, followed by heterogeneous neointima (14.1%) and layered neointima (14.1%). In lesions with ≥50% of neointimal CSA stenosis, layered neointima was most frequently observed (68.3%), followed by neoatherosclerotic neointima (25.2%). In subgroup analysis of lesions with ≥50% of neointimal CSA stenosis, 89.5% of the lesions with a stent age <30 months were layered neointima, while 62.3% of the lesions with a stent age ≥30 months were neoatherosclerotic neointima.
This study suggests that the OCT-detected morphology of DES neointimal tissue was different according to the follow-up time course and degree of neointimal hyperplasia.
PMCID: PMC4075398  PMID: 24954322
Optical coherence tomography; stent; coronary artery disease
8.  A coronary heart disease prediction model: the Korean Heart Study 
BMJ Open  2014;4(5):e005025.
The objectives of this study were to develop a coronary heart disease (CHD) risk model among the Korean Heart Study (KHS) population and compare it with the Framingham CHD risk score.
A prospective cohort study within a national insurance system.
18 health promotion centres nationwide between 1996 and 2001 in Korea.
268 315 Koreans between the ages of 30 and 74 years without CHD at baseline.
Outcome measure
Non-fatal or fatal CHD events between 1997 and 2011. During an 11.6-year median follow-up, 2596 CHD events (1903 non-fatal and 693 fatal) occurred in the cohort. The optimal CHD model was created by adding high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol and triglycerides to the basic CHD model, evaluating using the area under the receiver operating characteristic curve (ROC) and continuous net reclassification index (NRI).
The optimal CHD models for men and women included HDL-cholesterol (NRI=0.284) and triglycerides (NRI=0.207) from the basic CHD model, respectively. The discrimination using the CHD model in the Korean cohort was high: the areas under ROC were 0.764 (95% CI 0.752 to 0.774) for men and 0.815 (95% CI 0.795 to 0.835) for women. The Framingham risk function predicted 3–6 times as many CHD events than observed. Recalibration of the Framingham function using the mean values of risk factors and mean CHD incidence rates of the KHS cohort substantially improved the performance of the Framingham functions in the KHS cohort.
The present study provides the first evidence that the Framingham risk function overestimates the risk of CHD in the Korean population where CHD incidence is low. The Korean CHD risk model is well-calculated alternations which can be used to predict an individual's risk of CHD and provides a useful guide to identify the groups at high risk for CHD among Koreans.
PMCID: PMC4039825  PMID: 24848088
9.  Soluble CD93 Levels in Patients with Acute Myocardial Infarction and Its Implication on Clinical Outcome 
PLoS ONE  2014;9(5):e96538.
Inflammation plays a key role in the pathogenesis of acute myocardial infarction (MI). However, it is unclear whether marker of immune activation will provide prognostic information in these patients. We hypothesized that circulating levels of soluble CD93 (sCD93), a soluble form of transmembrane glycoprotein CD93, is increased in acute MI patients and its level would be associated with clinical outcomes in patients with acute MI.
We measured circulating levels of sCD93 in 120 patients with acute MI (63±13 yrs, M∶F = 85∶35) and in 120 age, sex-matched control subjects. In patients with acute MI, clinical characteristics, echocardiographic and laboratory findings were assessed at the time of initial enrollment. The primary outcome was defined as all-cause and cardiovascular death.
Circulating sCD93 levels were significantly higher in patients with acute MI than in control subjects (552.1±293.7 vs. 429.8±114.2 ng/mL, p<0.0001). Upon in vitro inflammatory stimulation, increased CD93 shedding was demonstrated in acute MI patients but not in control subjects. During follow up period (median 208 days, 3-1058 days), the primary outcome occurred in 18 (15%) patients (9 cardiovascular deaths). Circulating levels of sCD93 were associated with all cause (p<0.0001) and cardiovascular (p<0.0001) mortality in patients with acute MI. Multivariate Cox regression analysis revealed that initial sCD93 level was found to be an independent predictor of all cause (p = 0.002) and cardiovascular mortality (p = 0.033) when controlled for age and left ventricular ejection fraction.
Circulating levels of sCD93 are elevated in patients with acute MI and their levels were associated with adverse clinical outcomes.
PMCID: PMC4011875  PMID: 24801400
10.  Comparison of Full Lesion Coverage versus Spot Drug-Eluting Stent Implantation for Coronary Artery Stenoses 
Yonsei Medical Journal  2014;55(3):584-591.
The aim of this study was to evaluate and compare the long-term clinical outcomes of the spot drug-eluting stent (DES) implantation strategy, which is used to minimize implanted stent length and the number of stents, versus full lesion coverage for treatment of coronary artery stenoses.
Materials and Methods
We evaluated 1-year clinical outcomes of 1619 patients with stent implantation for a single coronary lesion. They were divided into two groups: those treated by full lesion coverage (n=1200) and those treated with the spot stenting strategy (n=419). The combined occurrence of 1-year target vessel failure (TVF), including cardiac death, target-vessel related myocardial infarction, or ischemia-driven target-vessel revascularization was evaluated.
The spot DES implantation group had a shorter stent length (23.14±9.70 mm vs. 25.44±13.24 mm, respectively; p<0.001) and a fewer number of stents (1.09±0.30 vs. 1.16±0.41, respectively; p<0.001), even though the average lesion length was similar to the full lesion coverage group (21.36±10.30 mm vs. 20.58±10.97 mm, respectively; p=0.206). Spot DES implantation was superior to full DES coverage with respect to 1-year TVF (1.4% vs. 3.3%, p=0.044). Cox proportional hazard model analysis showed that the risk for 1-year TVF was almost 60% lower among patients who received spot DESs compared to those who received full DES coverage after adjustment for other risk factors (HR=0.40, 95% confidence interval=0.17-0.98; p=0.046).
Minimizing stent length and the number of stents with overlapping by spot DES implantation may result in reduced rates of 1-year TVF, compared with full DES coverage.
PMCID: PMC3990086  PMID: 24719123
Drug-eluting stents; percutaneous coronary intervention; coronary artery disease
11.  Retrograde Distal Superficial Femoral Artery Approach in the Supine Position for Chronic Superficial Femoral Artery Occlusion 
Korean Circulation Journal  2014;44(3):184-188.
Subintimal angioplasty is an effective method for the treatment of long superficial femoral artery (SFA) occlusions. One of the major limiting factors for the success of this procedure is the failure to re-enter the true lumen. The recently introduced luminal re-entry devices provide a high technical success rate, but failures can occur. In such cases, a retrograde popliteal approach can serve as a potential backup option. However, the need to reposition the patient remains a drawback. Here, we report a case of an 81-year-old male with a long SFA occlusion treated using a retrograde distal SFA approach in the supine position after the initial failure of antegrade angioplasty.
PMCID: PMC4037641  PMID: 24876860
Peripheral arterial disease; Femoral artery; Angioplasty
12.  Prospective and Systematic Analysis of Unexpected Requests for Non-Cardiac Surgery or Other Invasive Procedures during the First Year after Drug-Eluting Stent Implantation 
Yonsei Medical Journal  2014;55(2):345-352.
Unexpected requests for non-cardiac surgery requiring discontinuation of dual antiplatelet therapy (DAPT) frequently occur in daily clinical practice. The objectives of this study were to evaluate prevalence, timing and clinical outcomes of such unexpected requests for non-cardiac surgery or other invasive procedures during the first year after drug-eluting stents (DESs) implantation.
Materials and Methods
We prospectively investigated the prevalence, timing and clinical outcomes of unexpected requests for non-cardiac surgery or other procedures during the first year after DESs implantation in 2117 patients.
The prevalence of requested non-cardiac surgery or invasive procedures was 14.6% in 310 requests and 12.3% in 261 patients. Among 310 requests, those were proposed in 11.3% <1 month, 30.0% between 1 and 3 months, 36.8% between 4 and 6 months and 21.9% between 7 and 12 months post-DES implantation. The rates of actual discontinuation of DAPT and non-cardiac surgery or procedure finally performed were 35.8% (111 of 310 requests) and 53.2% (165 of 310 requests), respectively. On multivariate regression analysis, the most significant determinants for actual discontinuation of DAPT were Endeavor zotarolimus-eluting stent implantation with 3-month DAPT (OR=5.54, 95% CI 2.95-10.44, p<0.001) and timing of request (OR=2.84, 95% CI 1.97-4.11, p<0.001). There were no patients with any death, myocardial infarction, or stent thrombosis related with actual discontinuation of DAPT.
Those unexpected requests with premature discontinuation of DAPT were relatively common and continuously proposed during the first year following DES implantation. No death, myocardial infarction or stent thrombosis occurred in patients with actual discontinuation of DAPT.
PMCID: PMC3936620  PMID: 24532502
Antiplatelet therapy; drug-eluting stents; coronary artery disease
13.  Prognostic Usefulness of Metabolic Syndrome Compared with Diabetes in Korean Patients with Critical Lower Limb Ischemia Treated with Percutaneous Transluminal Angioplasty 
Yonsei Medical Journal  2013;55(1):46-52.
Metabolic syndrome (MS) is a clinical condition that shares many common characteristics with diabetes. However, unlike diabetes, the usefulness of MS as a prognostic entity in peripheral arterial disease is uncertain. This study evaluated the prognostic usefulness of MS in critical lower limb ischemia (CLI) patients.
Materials and Methods
We compared the 2-year clinical outcomes in 101 consecutive CLI patients (66±14 years; 78% men) with 118 affected limbs treated with percutaneous transluminal angioplasty (PTA) according to the presence of MS and diabetes.
The number of MS patients was 53 (52%), of which 45 (85%) had diabetes. During a 2-year follow-up, the incidence of clinical outcomes, including reintervention, major amputation, minor amputation, and survival, was not significantly different between MS and non-MS patients; however, the incidence of minor amputation was significantly higher in diabetic than in non-diabetic patients (42% vs. 17%; p=0.011). Cox regression analysis for the 2-year primary patency demonstrated no association between MS and 2-year primary patency [hazard ratio (HR), 1.02; 95% confidence interval (CI), 0.45-2.30; p=0.961], whereas there was a significant association between diabetes and 2-year primary patency (HR, 2.81; 95% CI, 1.02-7.72; p=0.046). Kaplan-Meier analysis revealed no significant difference in the 2-year primary patency between MS and non-MS patients; however, the 2-year primary patency was lower in diabetic than in non-diabetic patients (p=0.038).
As a prognostic concept, MS might conceal the adverse impact of diabetes on the prognosis of CLI patients treated with PTA.
PMCID: PMC3874905  PMID: 24339286
Metabolic syndrome; diabetes; critical limb ischemia; angioplasty
14.  Association between CDH13 Variants and Cardiometabolic and Vascular Phenotypes in a Korean Population 
Yonsei Medical Journal  2013;54(6):1305-1312.
Although some CDH13 single nucleotide polymorphisms (SNPs) have been shown to be determinants of blood adiponectin levels, the clinical implications of CDH13 variants are not yet completely understood. The purpose of this study was to evaluate the effects of SNPs of CDH13 on metabolic and vascular phenotypes.
Materials and Methods
We included 238 hypertensive subjects and 260 age- and sex-matched controls. Seven tagging-SNPs were identified in the CDH13 gene by whole gene sequencing. The association between these SNP variants and the risk of hypertension, metabolic traits, and carotid intima-media thickness (IMT) was examined.
Minor allele carriers of rs12444338 had a lower risk of hypertension, but the association turned out just marginal after adjusting confoudners. Blood glucose levels were higher in the minor allele carriers of c.1407C>T (p=0.01), whereas low-density lipoprotein-cholesterol levels were greater in those of rs6565105 (p=0.02). The minor allele of rs1048612 was associated with a higher body mass index (p=0.01). In addition, the mean carotid IMT was significantly associated with rs12444338 (p=0.02) and rs1048612 (p=0.02).
These results provide evidence that CDH13 variants are associated with metabolic traits and carotid atherosclerosis in Koreans. This study shows the multifaceted effects of CDH13 variants on cardiometabolic risk.
PMCID: PMC3809859  PMID: 24142632
CDH13 protein; human; hypertension; atherosclerosis; glucose; cholesterol
15.  Preventive Effect of Pretreatment with Intravenous Nicorandil on Contrast-Induced Nephropathy in Patients with Renal Dysfunction Undergoing Coronary Angiography (PRINCIPLE Study) 
Yonsei Medical Journal  2013;54(4):957-964.
To investigate the effect of pretreatment with intravenous nicorandil on the incidence of contrast-induced nephropathy (CIN) in patients with renal dysfunction undergoing coronary angiography.
Materials and Methods
This randomized controlled multicenter study enrolled a total of 166 patients (nicorandil n=81; control n=85) with an estimated glomerular filtration rate <60 mL/min. Nicorandil 12 mg dissolved in 100 mL of 0.9% saline was administered intravenously for 30 minutes just prior to coronary angiography in the nicorandil group. The same volume of only saline was given to the control group. The primary end-point was the incidence of CIN, defined as >0.5 mg/dL increase or >25% rise in serum creatinine (SCr) concentration within 48 hours of contrast exposure compared to baseline.
The final analysis included 149 patients (nicorandil n=73; control n=76). The baseline characteristics and the total volume of the used contrast (Iodixanol, 125.6±69.1 mL vs. 126.9±74.6 mL, p=0.916) were similar between the two groups. The incidence of CIN also did not differ between the nicorandil and control groups (6.8% vs. 6.6%, p=0.794). There was no difference between the two groups in the relative change in SCr from baseline to peak level within 48 hours after coronary angiography (-1.58±24.07% vs. 0.96±17.49%, p=0.464), although the nicorandil group showed less absolute change in SCr than the control group (-0.01±0.43 mg/mL vs. 0.02±0.31 mg/mL, p=0.005).
Prophylactic intravenous infusion of nicorandil did not decrease the incidence of CIN in patients with renal dysfunction undergoing coronary angiography.
PMCID: PMC3663233  PMID: 23709432
Contrast media; acute kidney injury; coronary artery disease
16.  Comparison of Early Clinical Outcomes Following Transcatheter Aortic Valve Implantation versus Surgical Aortic Valve Replacement versus Optimal Medical Therapy in Patients Older than 80 Years with Symptomatic Severe Aortic Stenosis 
Yonsei Medical Journal  2013;54(3):596-602.
Transcatheter aortic valve implantation (TAVI) has become an attractive therapeutic strategy for severe aortic stenosis (AS) in elderly patients due to its minimally-invasive nature. Therefore, early results of its clinical outcomes in elderly Korean patients were evaluated.
Materials and Methods
We compared early clinical outcomes of TAVI, surgical aortic valve replacement (SAVR), and optimal medical therapy (OMT) in patients aged ≥80 years with symptomatic severe AS. Treatment groups were allocated as follows: TAVI (n=10), SAVR (n=14), and OMT (n=42).
Baseline clinical characteristics including predicted operative mortality were similar among the three groups. However, patients with New York Heart Association functional class III or IV symptoms and smaller aortic valve area were treated with TAVI or SAVR rather than OMT. In-hospital combined safety endpoints (all-cause mortality, major stroke, peri-procedural myocardial infarction, life-threatening bleeding, major vascular complication, and acute kidney injury) after TAVI or SAVR were significantly lower in the TAVI group than in the SAVR group (10.0% vs. 71.4%, respectively, p=0.005), along with an acceptable rate of symptom improvement and device success. During the follow-up period, the TAVI group showed the lowest rate of 3-month major adverse cardiovascular and cerebrovascular events, a composite of all-cause mortality, myocardial infarction, major stroke, and re-hospitalization (TAVI 0.0% vs. SAVR 50.0% vs. OMT 42.9%, p=0.017).
Treatment with TAVI was associated with lower event rates compared to SAVR or OMT. Therefore, TAVI may be considered as the first therapeutic strategy in selected patients aged ≥80 years with symptomatic severe AS.
PMCID: PMC3635628  PMID: 23549802
Aortic stenosis; transcatheter aortic valve implantation; treatment outcome
17.  Effects of aging and menopause on serum interleukin-6 levels and peripheral blood mononuclear cell cytokine production in healthy nonobese women 
Age  2011;34(2):415-425.
Inappropriate interleukin-6 production is thought to play a role in the development of several age-related conditions including atherosclerosis. This study aimed to determine whether aging affects circulating interleukin-6 (IL-6) levels. Healthy, nonobese women (n = 208, 44.5 ± 0.70 years, 22.4 ± 0.17 kg/m2) were categorized into four age groups (22–31, 32–41, 42–51, and 52–63 years; cross-sectional study). Cytokine levels in serum and those produced from peripheral blood mononuclear cell (PBMC) were measured. The oldest group had the highest circulating levels of IL-6 and oxidized low-density lipoprotein (ox-LDL) and higher PBMC production of IL-6, tumor necrosis factor-α (TNF-α), and interleukin-1 alpha (IL-1β). Additionally, significant interactions between age and menopause were found for serum IL-6 (P = 0.024), and TNF-α (P = 0.011) and IL-1β (P < 0.001) produced from PBMCs. Serum IL-6 levels positively correlated with age, waist–hip ratio (WHR), systolic blood pressure, circulating levels of TNF-α, IL-1β, and ox-LDL, and urinary 8-epi-prostaglandin F2α. Multiple stepwise regression models identified the following factors for contributing to serum IL-6 levels: serum IL-1β, menopause status, WHR, and serum TNF-α in mode I (R2 = 0.302); serum IL-1β, age, serum TNF-α, and WHR (β = 0.197; P = 0.006) in model II (R2 = 0.283). Sub-analysis was performed according to menopausal status. Serum IL-6 levels were positively associated with levels of IL-6, TNF-α, and IL-1β in PBMC supernatants (unstimulated) from postmenopausal women, whereas these were negatively associated in premenopausal women. In conclusion, circulating IL-6 levels may be interactively influenced by age and menopause. Additionally, estrogen deprivation after menopause may enhance PBMC cytokine production in postmenopausal women, resulting in increased IL-6 levels which are closely related to oxidative stress.
PMCID: PMC3312621  PMID: 21487705
Serum interleukin-6; Cytokines; Peripheral mononuclear cells; Oxidative stress; Menopause
18.  Differential impact of metabolic syndrome on subclinical atherosclerosis according to the presence of diabetes 
Metabolic syndrome (MS) is associated with increased risks of diabetes and atherosclerotic cardiovascular disease. However, data on the impact of MS and its individual components on subclinical atherosclerosis (SCA) according to diabetes status are scarce.
Surrogate markers of SCA, brachial–ankle pulse wave velocity (baPWV), and carotid intima–medial thickness (IMT) and plaque were assessed in 2,560 subjects (60 ± 8 years, 33% men) who participated in baseline health examinations for a community-based cohort study.
The participants included 2,149 non-diabetics (84%) and 411 diabetics (16%); 667 non-diabetics (31%) and 285 diabetics (69%) had MS, respectively. Diabetics had significantly higher baPWV and carotid IMT, and more plaques than non-diabetics (p < 0.001, respectively). Individuals with MS had significantly higher baPWV and carotid IMT than those without MS only among non-diabetics (p < 0.001, respectively). Among MS components, increased blood pressure was significantly associated with the exacerbation of all SCA markers in non-diabetics. The number of MS components was significantly correlated with both baPWV and carotid IMT in non-diabetics (baPWV: r = 0.302, p < 0.001; carotid IMT: r = 0.217, p < 0.001). Multiple regression showed both MS and diabetes were significantly associated with baPWV (p < 0.001, respectively), carotid IMT (MS: p < 0.001; diabetes: p = 0.005), and the presence of plaque (MS: p = 0.041; diabetes: p = 0.002).
MS has an incremental impact on SCA in conditions without diabetes. The identification of MS and its individual components is more important for the risk stratification of CVD in non-diabetic individuals.
PMCID: PMC3599532  PMID: 23452437
Metabolic syndrome; Diabetes; Atherosclerosis
19.  Dorsal-Plantar Loop Technique Using Chronic Total Occlusion Devices via Anterior Tibial Artery 
Yonsei Medical Journal  2013;54(2):534-537.
The effectiveness of below-the-knee (BTK) percutaneous transluminal angioplasty to obtain successful revascularization in patients with critical limb ischemia has been well established, and many of these patients with chronic lower-extremity disease have been treated by endovascular intervention as the firstline treatment. Dorsal-plantaer loop technique is one of the new BTK interventional techiniques, and includes recanalization of both pedal and plantar arteries and their anatomical anastomoses. This method generally needs two approaches simultaneously, including antegrade and retrograde. In this report, however, we describe a case in which dorsal-plantar loop technique with only one antegrade approach, using chronic total occlusion devices via anterior tibial artery, was used to successfully recanalize BTK arteries. We think that this new technique, which may represent a safe and feasible endovascular option to avoid more invasive, time-consuming, and riskier surgical procedures, especially in end-stage renal disease and diabetes, should be considered whenever the foot is at risk, and results of above-the-ankle percutaneous transluminal angioplasty remain unsatisfactory or insufficient to achieve limb salvage.
PMCID: PMC3575960  PMID: 23364993
Ischemia; peripheral arterial disease; angioplasty
20.  Trans-Radial versus Trans-Femoral Intervention for the Treatment of Coronary Bifurcations: Results from Coronary Bifurcation Stenting Registry 
Journal of Korean Medical Science  2013;28(3):388-395.
Trans-radial (TR) approach is increasingly recognized as an alternative to the routine use of trans-femoral (TF) approach. However, there are limited data comparing the outcomes of these two approaches for the treatment of coronary bifurcation lesions. We evaluated outcomes of TR and TF percutaneous coronary interventions (PCI) in this complex lesion. Procedural outcomes and clinical events were compared in 1,668 patients who underwent PCI for non-left main bifurcation lesions, according to the vascular approach, either TR (n = 503) or TF (n = 1,165). The primary outcome was major adverse cardiac events (MACE), including cardiac death, myocardial infarction (MI), and target lesion revascularization (TLR) in all patients and in 424 propensity-score matched pairs of patients. There were no significant differences between TR and TF approaches for procedural success in the main vessel (99.6% vs 98.6%, P = 0.08) and side branches (62.6% vs 66.7%, P = 0.11). Over a mean follow-up of 22 months, cardiac death or MI (1.8% vs 2.2%, P = 0.45), TLR (4.0% vs 5.2%, P = 0.22), and MACE (5.2% vs 7.0%, P = 0.11) did not significantly differ between TR and TF groups, respectively. These results were consistent after propensity score-matched analysis. In conclusion, TR PCI is a feasible alternative approach to conventional TF approaches for bifurcation PCI ( number: NCT00851526).
PMCID: PMC3594602  PMID: 23486858
Bifurcation; Percutaneous Coronary Intervention; Trans-Radial Approach
21.  Relationship between Angiographic Late Loss and 5-Year Clinical Outcome after Drug-Eluting Stent Implantation 
Yonsei Medical Journal  2012;54(1):41-47.
Currently, insufficient data exist to evaluate the relationship between angiographic late loss (LL) and long-term clinical outcome after drug-eluting stent (DES) implantation. In this study, we hypothesized that angiographic LL between 0.3 and 0.6 mm correlate with favorable long-term clinical outcomes.
Materials and Methods
Patients were enrolled in the present study if they had undergone both DES implantation in single coronary vessel and a subsequent follow-up angiogram (n=634). These individuals were then subdivided into three groups based on their relative angiographic LL: group I (angiographic LL <0.3 mm, n=378), group II (angiographic LL between 0.3 and 0.6 mm, n=124), and group III (angiographic LL >0.6 mm, n=134). During a 5-year follow-up period, all subjects were tracked for critical events, defined as any cause of death or myocardial infarction, which were then compared among the three groups.
Mean follow-up duration was 63.0±10.0 months. Critical events occurred in 25 subjects in group I (6.6%), 5 in group II (4.0%), and 17 in group III (12.7%), (p=0.020; group I vs. group II, p=0.293; group II vs. group III, p=0.013). In a subsequent multivariate logistic regression analysis, chronic renal failure [odds ratio (OR)=3.29, 95% confidence interval (CI): 1.48-7.31, p=0.003] and long lesion length, defined as lesion length >28 mm (OR=1.88, 95% CI: 1.02-3.46, p=0.042) were independent predictors of long-term critical events.
This retrospective analysis fails to demonstrate that post-DES implantation angiographic LL between 0.3 and 0.6 mm is protective against future critical events.
PMCID: PMC3521267  PMID: 23225797
Coronary artery disease; stents; outcome assessment
22.  Migration of a sirolimus-eluting stent from the ostium of the left main coronary artery to the right deep femoral artery 
PMCID: PMC3543952  PMID: 23346008
Sirolimus-eluting stent; Left main coronary artery; Angioplasty
23.  Association between Serine/Threonine Kinase 39 Gene Polymorphism, Hypertension, and Other Cardiovascular Risk Factors in Koreans 
Korean Circulation Journal  2013;43(1):13-22.
Background and Objectives
Although the association between single nucleotide polymorphisms (SNPs) of Serine/Threonine Kinase 39 (STK39) and hypertension has been reported, the prior studies have been inconsistent. The aim of this study is to evaluate the association between rs3754777 and rs6749447, the two SNPs of STK39, and hypertension and other cardiovascular risk factors in Koreans, residing in the Republic of Korea.
Subjects and Methods
We included 238 hypertensive patients and 260 controls. The associations between genotype and haplotype combination and hypertension were examined. In addition, possible SNP-related differences in the adjusted blood pressure and other cardiovascular risk factors were analyzed.
There was no significant association between the two SNPs and hypertension. However, the carriers of AA genotype of rs3754777 showed lower blood glucose and cholesterol levels, particularly in females. Genotype of rs6749447 was associated with the waist circumference, triglyceride, and high density lipoprotein-cholesterol levels, only in gender-stratified analysis. The effects of haplotype combinations on risk factors were compatible with genotype effects of each SNP.
Associations between the two SNPs of STK39, rs3754777 and rs6749447, and hypertension were not significant. However, the two SNPs showed genotype-related differences in blood glucose, lipids, and waist circumference, especially in women. Further studies are needed to clarify the effect of STK39 variants in these cardiovascular risk factors.
PMCID: PMC3569562  PMID: 23408757
STK39 protein, human; Hypertension; Cholesterol; Waist circumference; Glucose
24.  Association of CYP2C19*2 and *3 Genetic Variants with Essential Hypertension in Koreans 
Yonsei Medical Journal  2012;53(6):1113-1119.
The cytochrome P450 2C19 (CYP2C19) metabolizes arachidonic acid to produce epoxyicosanoid acids, which are involved in vascular tone and regulation of blood pressure. Recent findings suggest that CYP2C19 gene might be considered as a novel candidate gene for treatment of cardiovascular disease. The aim of the present study was to evaluate the association between two variants, CYP2C19*2 (681G>A) and CYP2C19*3 (636G>A) and the development of essential hypertension (EH) in Koreans.
Materials and Methods
We carried out an association study in a total of 1190 individuals (527 hypertensive subjects and 663 unrelated healthy controls). The CYP2C19 polymorphisms were genotyped using the SNaPShot™ assay.
The distribution of alleles and genotypes of CYP2C19*3 showed significant difference between hypertensive patients and normal controls (p=0.011 and p=0.013, respectively). Logistic regression analysis indicated that the CYP2C19*3 (636A) allele carriers were significantly associated with EH [odds ratio, 0.691; 95% confidence interval (CI), 0.512-0.932, p=0.016], in comparison to wild type homozygotes (CYP2C19*1/*1). Neither genotype nor allele distribution of CYP2C19*2 polymorphism showed significant differences between hypertensive and control groups (p>0.05).
Our present findings strengthen the evidence of an association between CYP2C19 gene polymorphism and EH prevalence. In particular, the CYP2C19*3 defective allele may contribute to reduced risk for the development of EH.
PMCID: PMC3481368  PMID: 23074110
Essential hypertension; CYP2C19; polymorphism; association study; Koreans
25.  Arterial Occlusive Disease Complicating Radiation Therapy of Cervical Cancer 
Yonsei Medical Journal  2012;53(6):1220-1223.
Radiation-induced arterial disease is caused by significant atherosclerosis in the circumjacent vessels being irradiated. Even though this has been recognized as survival of cancer patients treated with radiotherapy improves, it is a problem that is often under-reported. We present a case of chronic thromboembolic occlusion of right common iliac artery in a 53-year-old woman who was treated with radiation therapy for cervical cancer 13 years ago. We initially performed percutaneous transluminal angioplasty with thrombolytic therapy, but had to cease thrombolytic therapy due to upper gastrointestinal bleeding of Dieulafoy's lesion, nevertheless, achieved good results after revascularization by Fogarty embolectomy.
PMCID: PMC3481387  PMID: 23074126
Radiation-induced arterial disease; thromboembolic occlusion; atherosclerosis

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