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Kee-Sik Kim - Top 30 Publications

Comparison of Fixed-Dose Combinations of Amlodipine/Losartan Potassium/Chlorthalidone and Amlodipine/Losartan Potassium in Patients With Stage 2 Hypertension Inadequately Controlled With Amlodipine/Losartan Potassium: A Randomized, Double-blind, Multicenter, Phase III Study.

The goal of this study was to compare the efficacy and safety of fixed-dose combinations of amlodipine/losartan potassium/chlorthalidone (A/L/C) and A/L in Korean patients with stage 2 hypertension inadequately controlled by A/L.

Evaluation of the impact of statin therapy on the obesity paradox in patients with acute myocardial infarction: A propensity score matching analysis from the Korea Acute Myocardial Infarction Registry.

The phenomenon of obesity paradox after acute myocardial infarction (AMI) has been reported under strong recommendation of statin therapy. However, the impact of statin therapy on this paradox has not been investigated. This study investigated the impact of statin therapy on 1-year mortality according to obesity after AMI. A total of 2745 AMI patients were included from the Korea Acute Myocardial Infarction Registry after 1:4 propensity score matching analysis (n = 549 for nonstatin group and n = 2196 for statin group). Primary and secondary outcomes were all-cause and cardiac death, respectively. During 1-year follow-up, the incidence of all-cause (8.4% vs 3.7%) and cardiac (6.2% vs 2.3%) death was higher in nonstatin group than in statin (P < .001, respectively). In nonstatin group, the incidence of all-cause (7.2% vs 9.0%) and cardiac (5.5% vs 6.5%) death did not differ significantly between obese and nonobese patients. However, in statin group, obese patients had lower 1-year rate of all-cause (1.7% vs 4.8%) and cardiac (1.2% vs 2.9%) death (P < .05, respectively), and lower cumulative rates by Kaplan-Meier analysis of all-cause and cardiac death compared with nonobese patients (log-rank P < .05, respectively). The overall risk of all-cause death was significantly lower in obese than in nonobese patients only in statin group (hazard ratio: 0.35; P = .001). After adjusting for confounding factors, obesity was independently associated with decreased risk of all-cause death in statin group. In conclusion, the greater benefit of statin therapy for survival in obese patients is further confirmation of the obesity paradox after AMI.

Epicardial Fat Thickness is Correlated with Vagal Hyperactivity in Patients with Neurally-Mediated Syncope.

Epicardial fat tissue has unique endocrine and paracrine functions that affect the cardiac autonomic system. The head-up tilt test (HUTT) is a simple non-invasive measurement that assesses autonomic nervous system dysfunction. We investigated the association between epicardial fat thickness (EFT) and autonomic neural tone, such as vagal tone.

Efficacy and safety of pitavastatins in patients with acute myocardial infarction: Livalo in Acute Myocardial Infarction Study (LAMIS) II.

We evaluated the efficacy and safety and influence on glucose tolerance by different doses of pitavastatins in acute myocardial infarction (AMI) patients.

Impact of low high-density lipoprotein-cholesterol level on 2-year clinical outcomes after acute myocardial infarction in patients with diabetes mellitus.

It is still unclear whether low high-density lipoprotein cholesterol (HDL-C) affects cardiovascular outcomes after acute myocardial infarction (AMI), especially in patients with diabetes mellitus.

Blood Pressure and Cholesterol-lowering Efficacy of a Fixed-dose Combination With Irbesartan and Atorvastatin in Patients With Hypertension and Hypercholesterolemia: A Randomized, Double-blind, Factorial, Multicenter Phase III Study.

A fixed-dose combination of a stain and an antihypertensive drug may be useful for the treatment of patients with hypertension and hyperlipidemia. It may also improve patient drug compliance to help control risk factors of cardiovascular disease. This study was designed to evaluate the blood pressure-lowering and cholesterol-lowering effect of a fixed-dose combination of irbesartan-atorvastatin compared with monotherapy by either agent over an 8-week treatment period.

The changes of individual carotid artery wall layer by aging and carotid intima-media thickness value for high risk.

It is still unclear which layer (intima or media) is mainly involved in increased carotid intima-media thickness (CIMT) by aging and also unclear regarding CIMT value suggesting high cardiovascular risk, although 75th percentile value of CIMT is known as a high risk in asymptomatic adults. We sought to find the changes of carotid intima thickness (CIT) and carotid media thickness (CMT) by aging and the 75th percentile value of CIMT in asymptomatic Korean adults.

Geographic variations in the PARADIGM-HF heart failure trial.

The globalization of clinical trials has highlighted geographic variations in patient characteristics, event rates, and treatment effects. We investigated these further in PARADIGM-HF, the largest and most globally representative trial in heart failure (HF) to date.

Comparison of 2-year clinical outcomes between diabetic versus nondiabetic patients with acute myocardial infarction after 1-month stabilization: Analysis of the prospective registry of DIAMOND (DIabetic acute myocardial infarctiON Disease) in Korea: an observational registry study.

This study assessed the 2-year clinical outcomes of patients with diabetes mellitus (DM) after acute myocardial infarction (AMI) in a cohort of the DIAMOND (DIabetic Acute Myocardial infarctiON Disease) registry. Clinical outcomes were compared between 1088 diabetic AMI patients in the DIAMOND registry after stabilization of MI and 1088 nondiabetic AMI patients from the KORMI (Korean AMI) registry after 1 : 1 propensity score matching using traditional cardiovascular risk factors. Stabilized patients were defined as patients who did not have any clinical events within 1 month after AMI. Primary outcomes were the 2-year rate of major adverse cardiac events (MACEs), a composite of all-cause death, recurrent MI (re-MI), and target vessel revascularization (TVR). Matched comparisons revealed that diabetic patients exhibited significantly lower left ventricular ejection fraction (LVEF) and estimated glomerular filtration rate and smaller stent size. Diabetic patients exhibited significantly higher 2-year rates of MACE (8.0% vs 3.7%), all-cause death (3.9% vs 1.4%), re-MI (2.8% vs 1.2%), and TVR (3.5% vs 1.3%) than nondiabetic patients (all P < 0.01), and higher cumulative rates in Kaplan-Meier analyses of MACE, all-cause death, and TVR (all P < 0.05). A multivariate Cox regression analysis revealed that chronic kidney disease, LVEF < 35%, and long stent were independent predictors of MACE, and large stent diameter and the use of drug-eluting stents were protective factors against MACE. The 2-year MACE rate beyond 1 month after AMI was significantly higher in DM patients than non-DM patients, and this rate was associated with higher comorbidities, coronary lesions, and procedural characteristics in DM.

Comparison of 2-year mortality according to obesity in stabilized patients with type 2 diabetes mellitus after acute myocardial infarction: results from the DIAMOND prospective cohort registry.

After acute myocardial infarction (AMI), the replicated phenomenon of obesity paradox, i.e., obesity appearing to be associated with increased survival, has not been evaluated in stabilized (i.e., without clinical events within 1 month post AMI) Asian patients with diabetes mellitus (DM).

Contemporary Trends of Optimal Evidence-Based Medical Therapy at Discharge for Patients Surviving Acute Myocardial Infarction From the Korea Acute Myocardial Infarction Registry.

Temporal trends of evidence-based optimal medical therapy (OMT) at discharge after acute myocardial infarction (AMI) have not been investigated in recent years.

Prognostic value of the age, creatinine, and ejection fraction score for 1-year mortality in 30-day survivors who underwent percutaneous coronary intervention after acute myocardial infarction.

Few simple and effective tools are available for determining the prognosis of 30-day survivors after acute myocardial infarction. We aimed to assess whether the simple age, creatinine, and ejection fraction (ACEF) score could predict 1-year mortality of 12,000 post-myocardial infarction 30-day survivors who underwent percutaneous coronary intervention. The ACEF score was computed as follows: (age/ejection fraction)+1, if the serum creatinine was >2 mg/dl. Accuracy was defined through receiver-operating characteristics analysis and area under the curve (AUC) evaluation. Twelve risk factors were selected and ranked according to their AUC value. Age, ejection fraction, and serum creatinine levels indicated the best AUC value. The ACEF score was significantly higher in the nonsurvivors (1.95±0.82 vs 1.28±0.50; p<0.001) and was an independent predictor of 1-year mortality (adjusted hazard ratio 2.26; p<0.001). The best accuracy was achieved by a prediction model including 12 risk factors (AUC=0.80), but this did not significantly differ compared with the AUC (0.79) of the ACEF score (p=ns). Adjusted hazard ratios for 1-year mortality were 1 (reference), 3.11 (p<0.001), and 10.38 (p<0.001) for the ACEFLOW (ACEF score<1.0), ACEFMID (ACEF score 1.0 to 1.39), and ACEFHIGH (ACEF score≥1.4) groups, respectively. The ACEF score may be a novel valid model to stratify the 1-year mortality risk in 30-day survivors who underwent percutaneous coronary intervention after acute myocardial infarction.

Apamin inhibits PDGF-BB-induced vascular smooth muscle cell proliferation and migration through suppressions of activated Akt and Erk signaling pathway.

The increased proliferation and migration of vascular smooth muscle cells (VSMC) are key process in the development of atherosclerosis lesions. Platelet-derived growth factor (PDGF) initiates a multitude of biological effects that contribute to VSMC proliferation and migration. Apamin, a component of bee venom, has been known to block the Ca(2+)-activated K(+) channels. However, the effects of apamin in the regulation PDGF-BB-induced VSMC proliferation and migration has not been identified. In this study, we investigate the inhibitory effect of apamin on PDGF-BB-induced VSMC proliferation and migration. Apamin suppressed the PDGF-BB-induced VSMC proliferation and migration with no apparent cytotoxic effect. In accordance with these findings, apamin induced the arrest of cell cycle progression at G0/G1 phase. Apamin also decreased the expressions of G0/G1 specific regulatory proteins including proliferating cell nuclear antigen (PCNA), cyclin D1, cyclin-dependent kinases (CDK) 4, cyclin E and CDK2, as well as increased the expression of p21(Cip1) in PDGF-BB-induced VSMC. Moreover, apamin inhibited PDGF-BB-induced phosphorylation of Akt and Erk1/2. These results suggest that apamin plays an important role in prevention of vascular proliferation and migration through the G0/G1 cell cycle arrest by PDGF signaling pathway. Thus, apamin may be a promising candidate for the therapy of atherosclerosis.

Usefulness of the Doppler flow of the ophthalmic artery in the evaluation of carotid and coronary atherosclerosis.

There is little information about the relationship between the Doppler flow of the ophthalmic artery (OA) and carotid and coronary atherosclerosis. The aim of the investigation was to assess the clinical usefulness of the Doppler flow of the OA to estimate the severity of carotid and coronary atherosclerosis.

Response to letter regarding article, "optimal duration of dual antiplatelet therapy after drug-eluting stent implantation: a randomized, controlled trial".

A putative placebo analysis of the effects of LCZ696 on clinical outcomes in heart failure.

Although active-controlled trials with renin–angiotensin inhibitors are ethically mandated in heart failure with reduced ejection fraction, clinicians and regulators often want to know how the experimental therapy would perform compared with placebo. The angiotensin receptor-neprilysin inhibitor LCZ696 was compared with enalapril in PARADIGM-HF. We made indirect comparisons of the effects of LCZ696 with putative placebos.

Angiotensin receptor neprilysin inhibition compared with enalapril on the risk of clinical progression in surviving patients with heart failure.

Clinical trials in heart failure have focused on the improvement in symptoms or decreases in the risk of death and other cardiovascular events. Little is known about the effect of drugs on the risk of clinical deterioration in surviving patients.

Impact of statin usage patterns on outcomes after percutaneous coronary intervention in acute myocardial infarction: Korea Working Group on Myocardial Infarction registry (KorMI) study.

The benefit of statin use after acute ST-segment elevation myocardial infarction (STEMI) has been well established, however, the influence of the timing of statin administration has not been elucidated. The objective of this study focused on early clinical outcomes after percutaneous coronary intervention (PCI).

Comparison of biolimus A9-eluting (Nobori) and everolimus-eluting (Promus Element) stents in patients with de novo native long coronary artery lesions: a randomized Long Drug-Eluting Stent V trial.

Procedural and clinical outcomes still remain unfavorable for patients with long coronary lesions who undergo percutaneous coronary intervention. The current study, therefore, evaluated 2 innovative drug-eluting stents for the management of long-lesion coronary artery disease.

Gender Difference in Arterial Stiffness in a Multicenter Cross-Sectional Study: The Korean Arterial Aging Study (KAAS).

Elevated arterial stiffness has emerged as an important risk factor for future cardiovascular (CV) events in men and women. However, gender-related differences in arterial stiffness have not been clearly demonstrated. We thus determine whether gender affects arterial stiffness in subjects with and without CV risk factors. We consecutively enrolled 1,588 subjects aged 17-87 years (mean age: 46.5; 51% women) from the Korean Arterial Aging Study (KAAS), which is a multicenter registry from 13 university hospitals in Korea for the evaluation of arterial stiffness. We compared markers of arterial stiffness - central augmentation index (AIx), aortic pulse wave velocity (PWV), and pulse pressure (PP) amplification - in apparently healthy men and women without risk factors with those in high-risk subjects with a smoking habit, hypertension, diabetes, and dyslipidemia but without drug treatment. Aortic PWV and PP amplification were significantly higher in men than in women (7.78 ± 1.16 vs. 7.64 ± 1.15 m/s, p = 0.015, and 1.39 ± 0.22 vs. 1.30 ± 0.18, p < 0.001, respectively). However, women had a significantly higher central AIx than men (23.5 ± 11.9 vs. 16.1 ± 12.6%, p < 0.001). The central AIx and aortic PWV values were significantly higher in the high-risk group than in the healthy group for both men and women. In men, central AIx and aortic PWV were associated positively with age and blood pressure, and negatively with body mass index. In women, central AIx was positively related to age, diastolic blood pressure, and serum cholesterol levels. Aortic PWV was positively related to age, systolic blood pressure, fasting glucose, and heart rate. PP amplification was associated negatively with age and blood pressure and positively with heart rate in both men and women. In conclusion, arterial stiffness is mainly determined by sex, age, and blood pressure. Markers of arterial stiffness differ between men and women. Dyslipidemia and glucose contribute to a modest increase in arterial stiffness only in women. Therefore, the arteries of women may be more vulnerable to CV risk factors than those of men.

Efficacy and safety of antiplatelet-combination therapy after drug-eluting stent implantation.

Combination single-pill therapy can improve cost-effectiveness in a typical medical therapy. However, there is a little evidence about the efficacy and tolerability of combination single-pill antiplatelet therapy after percutaneous coronary intervention (PCI) with drug-eluting stents (DES).

Free Floating Left Atrial Thrombus Disappearing during Echocardiography.

Optimal duration of dual antiplatelet therapy after drug-eluting stent implantation: a randomized, controlled trial.

The risks and benefits of long-term dual antiplatelet therapy remain unclear.

Ambulatory blood pressure response to once-daily fimasartan: an 8-week, multicenter, randomized, double-blind, active-comparator, parallel-group study in Korean patients with mild to moderate essential hypertension.

Fimasartan, a selective angiotensin II type 1 receptor blocker, was approved in Korea for the treatment of patients with mild to moderate hypertension.

Benidipine has effects similar to losartan on the central blood pressure and arterial stiffness in mild to moderate essential hypertension.

Central blood pressure (BP) is pathophysiologically more important than peripheral BP for the pathogenesis of cardiovascular disease. Arterial stiffness is also a good predictor of cardiovascular morbidity and mortality. The effects of benidipine, a unique dual L-/T-type calcium channel blocker, on central BP have not been reported. This study aimed to compare the effect of benidipine and losartan on the central BP and arterial stiffness in mild to moderate essential hypertensives.

Anomalous origin of the left coronary artery from the pulmonary artery initially visualized by echocardiography and multidetector computed tomography coronary angiography.

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital anomaly associated with very high mortality during infancy. We report a 35-year-old female patient with ALCAPA initially visualized by echocardiography. She visited outpatient department presenting with intermittent chest discomfort for 3 weeks. Transthoracic echocardiography showed left coronary artery arising from main pulmonary artery and abundant septal color flow Doppler signals. Transesophageal echocardiography clearly revealed markedly dilated and tortuous right coronary artery showing windsock appearance. Multidetector computed tomography and coronary angiography enabled visualization of anomalous left coronary artery originating from left side of main pulmonary trunk. After treadmill exercise test which showed ST-segment depression presenting inducible myocardial ischemia, patient underwent direct re-implantation of the anomalous coronary artery into the aorta without any complication.

Effects of chimeric decoy oligodeoxynucleotide in the regulation of transcription factors NF-κB and Sp1 in an animal model of atherosclerosis.

Atherosclerosis is a multifactorial and progressive disease in which the inflammatory reaction and inflammation-related factors play important roles at all stages. Modulation of NF-κB and Sp1 expression may be important targets for the prevention and treatment of atherosclerotic vascular disease. To develop a novel therapeutic approach in atherosclerosis, we examined the simultaneous suppression of the transcription factors NF-κB and Sp1 which regulate inflammation. We employed chimeric decoy oligodeoxynucleotide (ODN) containing the consensus of NF-κB and Sp1-binding sites to suppress these transcription factors simultaneously and to test chimeric decoy for anti-atherogenic effects in an atherogenic diet-induced atherosclerotic mouse model with inflammatory stimulation. C57BL/6 mice were fed with an atherogenic diet (15% fat, 1.25% cholesterol and 0.5% cholic acid) for 12 weeks to induce atherosclerosis; lipopolysaccharide (LPS, 2 mg/kg) was intraperitoneally injected in the first week of study to simulate underlying infectious burden during development of atherosclerosis. Decoy ODNs were injected into tail vein at 2, 4, 6, 8, 10 and 12 weeks after only three LPS injections in mice fed the atherogenic diet. Chimeric decoy ODN alleviated atherosclerotic changes and reduced serum cholesterol and inflammatory cytokines. In accordance with these results, the expressions of atherosclerotic markers were inhibited by chimeric decoy ODN. Chimeric decoy ODN modulates multiple pathogenic aspects of an atherogenic diet-induced atherosclerosis with inflammatory stimulation: hypercholesterolaemia and inflammation. Therefore, this study demonstrates the efficacy of chimeric decoy ODN on atherosclerosis with immunological complication.

Outcomes after unrestricted use of everolimus-eluting and sirolimus-eluting stents in routine clinical practice: a multicenter, prospective cohort study.

It remains unclear whether there are differences in the safety and efficacy outcomes between everolimus-eluting stents (EES) and sirolimus-eluting stents (SES) in contemporary practice.

Effect of pitavastatin treatment on changes of plaque volume and composition according to the reduction of high-sensitivity C-reactive protein levels.

There are few data regarding the effect of statins on regression and compositional changes of plaque according to the reduction in high-sensitivity C-reactive protein (hs-CRP) levels in acute myocardial infarction (AMI) patients.

Apamin inhibits THP-1-derived macrophage apoptosis via mitochondria-related apoptotic pathway.

The development of atherosclerotic lesions is mainly due to macrophage death. The oxidative stresses of monocytes/macrophages play a vital role in the initiation and amplification of atherosclerosis. Apamin, a component of bee venom, exerts an anti-inflammatory effect, and selectively inhibits the Ca(2+)-activated K(+) channels. The mechanisms involved in the inhibition of macrophage apoptosis have been fully elucidated. We induced oxidized low-density lipoprotein (oxLDL) in THP-1-derived macrophage and studied the effect of apamin on intercellular lipid levels, mitochondria-related apoptotic pathway and numbers of apoptotic cells. Oil-red O staining indicates that the inhibition of apamin in the condition significantly prevents intracellular lipid deposition. Treatment with apamin significantly decreased the apoptotic macrophages by decreasing the expression of pro-apoptotic genes Bax, caspase-3 and PARP protein levels, as well as through increasing expression of anti-apoptotic genes Bcl-2 and Bcl-xL protein levels in the absence and presence of oxLDL. In vivo, with apamin treatment reduced apoptotic cells death by TUNEL staining. These results indicate that apamin plays an important role in monocyte/macrophage apoptotic processing, which may provide a potential drug for preventing atherosclerosis.