13 results on '"Sang Hak Lee"'
Search Results
2. Metabolic phenotyping of human atherosclerotic plaques: Metabolic alterations and their biological relevance in plaque-containing aorta
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Hyun-Chel Joo, Sang Hak Lee, Seung-Hyun Lee, Sak Lee, Gijong Yi, Suk-Won Song, Do Hyun Ryu, Eun Jeong Cheon, Se Hoon Kim, Eui-Young Choi, Sunhee Jung, Soo jin Ann, and Geum-Sook Hwang
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Male ,0301 basic medicine ,Purine ,Spectrometry, Mass, Electrospray Ionization ,Pathology ,medicine.medical_specialty ,Aortic Diseases ,Inflammation ,030204 cardiovascular system & hematology ,medicine.disease_cause ,Cell Line ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Metabolomics ,Tandem Mass Spectrometry ,medicine.artery ,Lipidomics ,Animals ,Humans ,Medicine ,Aorta ,Aged ,business.industry ,Macrophages ,Glutathione ,Middle Aged ,Atherosclerosis ,Plaque, Atherosclerotic ,Oxidative Stress ,Phenotype ,030104 developmental biology ,chemistry ,Case-Control Studies ,cardiovascular system ,Female ,medicine.symptom ,Energy Metabolism ,Cardiology and Cardiovascular Medicine ,business ,Biomarkers ,Oxidative stress ,Kynurenine ,Chromatography, Liquid - Abstract
Atherosclerosis is a chronic inflammatory disease characterized by thickening of the arterial wall. However, a limited number of studies have been conducted on metabolic profiling of human aortic tissue.We applied liquid chromatography/mass spectrometry to perform global and targeted profiling of plaque-containing aortic tissue. The aorta samples included plaque-containing (n = 18) and control plaque-free (n = 24) aortic tissue from patients undergoing aortic surgery.The metabolic patterns of atherosclerotic and control vessels were significantly different. Metabolites in the purine and glutathione pathways showed dysregulation of oxidative stress in plaques, and levels of glucosylceramide, tryptophan, and kynurenine, which are related to inflammation, were also altered. Interestingly, an increased level of quinic acid was observed in plaques (p 0.000), and we demonstrated an inhibitory effect of quinic acid on inflammatory activation and oxidative stress in macrophages.Our study provides insight into the disease mechanism and potential markers of atherosclerosis through comprehensive metabolic profiling of human aortic tissue samples containing plaque.
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- 2018
3. Statin and clinical outcomes of primary prevention in individuals aged75 years: The SCOPE-75 study
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Hyuk Jae Chang, Kyu Yeun Kim, Chan Joo Lee, Jung Sun Kim, Sungha Park, Donghoon Choi, Jong-Won Ha, Chi Young Shim, Byeong Keuk Kim, Yangsoo Jang, Young Guk Ko, Myeong Ki Hong, Seok Min Kang, Sang Hak Lee, and Geu Ru Hong
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0301 basic medicine ,Male ,medicine.medical_specialty ,Statin ,medicine.drug_class ,Population ,030204 cardiovascular system & hematology ,Lower risk ,Coronary artery disease ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,cardiovascular diseases ,Myocardial infarction ,education ,Propensity Score ,Aged ,Retrospective Studies ,Aged, 80 and over ,education.field_of_study ,business.industry ,Hazard ratio ,Age Factors ,Retrospective cohort study ,medicine.disease ,Primary Prevention ,Cerebrovascular Disorders ,030104 developmental biology ,Treatment Outcome ,Cardiovascular Diseases ,Propensity score matching ,Female ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background and aims Limited data is available on the benefit of statin for primary prevention in the elderly. The aim of this study is to investigate whether statin for primary prevention is effective in lowering the cardiovascular risk and all-cause death in individuals aged >75 years. Methods This was a retrospective, propensity score-matched study and data were acquired between 2005 and 2016 in a tertiary university hospital. Of the 6414 patients screened, 1559 statin-naive patients without a history of atherosclerotic cardiovascular disease before the index visit were included. After propensity score matching, 1278 patients (639 statin users, 639 statin non-users) were finally analyzed. Primary outcome variables included major adverse cardiovascular and cerebrovascular events (MACCE) and all-cause death. MACCE included cardiovascular death, nonfatal myocardial infarction, coronary revascularization, and nonfatal stroke or transient ischemic attack. Results At a median follow-up of 5.2 years, statin users had lower rates of MACCE (2.15 vs. 1.25 events/100 person-years; hazard ratio, 0.59; p = 0.005) and all-cause death (1.19 vs. 0.65 events/100 person-years; hazard ratio, 0.56; p = 0.02), as well as lower levels of low-density lipoprotein-cholesterol than did non-users. The Kaplan-Meier curves revealed lower event rates in statin users (hazard ratio: 0.59 for MACCE and 0.56 for all-cause death). The incidence of myocardial infarction and coronary revascularization were lower in statin users. Conclusions Statin therapy for primary prevention was clearly associated with lower risk of cardiovascular events and all-cause death in individuals aged >75 years. These results support more active statin use in this population.
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- 2018
4. Novel association between CDKAL1 and cholesterol efflux capacity: Replication after GWAS-based discovery
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Heon Yung Gee, Sungha Park, Sang Hak Lee, Sung Kweon Cho, Hye Min Noh, Seok Min Kang, Eun Jeong Cheon, and Do Hyeon Cha
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0301 basic medicine ,Oncology ,Male ,medicine.medical_specialty ,Genome-wide association study ,Coronary Artery Disease ,030204 cardiovascular system & hematology ,Biology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Linear regression ,Genetic model ,medicine ,Humans ,CDKAL1 ,tRNA Methyltransferases ,Cholesterol ,Confounding ,Cholesterol, HDL ,Genetic Variation ,Middle Aged ,030104 developmental biology ,chemistry ,cardiovascular system ,Female ,Cardiology and Cardiovascular Medicine ,Body mass index ,Lipoprotein ,Genome-Wide Association Study - Abstract
Background and aims Although the importance of the functional properties of high-density lipoprotein (HDL) has been increasingly emphasized, studies on the genetic factors associated with HDL function are highly limited. The aim of this study was to identify genetic variants associated with an individual's cholesterol efflux capacity (CEC) using a genome-wide association study approach. Methods This study included a discovery group of 607 subjects with coronary artery disease and an independent replication group of 158 subjects. CEC was assessed using a radioisotope and ApoB-depleted serum. Genome-wide associations between the adjusted CEC and genotyped and imputed variants were examined with linear regression, assuming an additive genetic model. Finally, adjustments were made for confounding parameters to assess the independence of associations and to determine R2 of overall model on CEC. Results In the discovery group, 631 variants showed significant association with CEC, and five of them were found to correlate with CEC in the replication group. One of them was located near LOC541471 in 2q13, whereas the other four (rs117835232, rs117252933, rs118064592, and rs150434350) were located in CDKAL1 in 6p22.3. The association between the presence of any CDKAL1 variant and CEC was significant after adjustment for clinical and laboratory variables. High-density lipoprotein-cholesterol levels also showed a very significant association with CEC. Body mass index, current alcohol use, triglycerides levels, low-density lipoprotein-cholesterol levels and statin use showed borderline associations with CEC. Conclusions We identified and replicated genetic variants associated with CEC using a genome-wide association study-based approach. CDKAL1 variants showed correlations with CEC independent of HDL-cholesterol levels and other clinical characteristics.
- Published
- 2017
5. Irisin, a novel myokine is an independent predictor for sarcopenia and carotid atherosclerosis in dialysis patients
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Sungha Park, Sang Hak Lee, Sul A Lee, Dong Ryeol Ryu, Young Eun Kwon, Han Jak Ryu, Seung Hyeok Han, Shin Wook Kang, Mi Jung Lee, Yung Ly Kim, Jung Tak Park, Hyung Jung Oh, Bo Young Nam, Tae Hyun Yoo, and Kyoung Sook Park
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Adult ,Carotid Artery Diseases ,Male ,Sarcopenia ,medicine.medical_specialty ,medicine.medical_treatment ,Enzyme-Linked Immunosorbent Assay ,Inflammation ,Disease ,Carotid Intima-Media Thickness ,Body Mass Index ,Peritoneal dialysis ,Cohort Studies ,Internal medicine ,Myokine ,medicine ,Humans ,Aged ,Anthropometry ,business.industry ,Case-control study ,Middle Aged ,medicine.disease ,Fibronectins ,Endocrinology ,Case-Control Studies ,Arm ,Kidney Failure, Chronic ,Female ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Peritoneal Dialysis ,Body mass index ,Cohort study - Abstract
In end-stage renal disease, deleterious effect of sarcopenia on cardiovascular disease has been explained mainly by chronic inflammation. However, evidence emerged that skeletal muscles mediate their protective effect against sarcopenia by secreting myokines. Therefore, we sought to investigate the effect of irisin, a recently introduced myokine, on the association between sarcopenia and cardiovascular disease in peritoneal dialysis (PD) patients.Serum irisin concentrations were assessed by enzyme-linked immunosorbent assay in 102 prevalent PD patients and 35 age- and sex-matched controls. To determine sarcopenia and cardiovascular disease, anthropometric indices including mid-arm muscle circumference (MAMC) and carotid intima-media thickness (cIMT) were measured.Serum irisin concentrations were significantly lower in PD patients than in controls (184.2 ± 88.0 vs. 457.2 ± 105.5 ng/mL, P0.001). In PD patients, univariate linear regression analysis showed that serum irisin was positively correlated with MAMC and thigh circumference, but negatively correlated with residual renal function and cIMT. Multivariate analysis revealed that MAMC (per 1 cm increase, B = 8.78, 95% confidence interval [CI] = 0.77-16.79, P = 0.03) had an independent association with serum irisin. In addition, serum irisin was a significant independent predictor for carotid atherosclerosis even after adjustment for high-sensitivity C-reactive protein in PD patients (per 1 g/mL increase, odds ratio = 0.990, 95% CI = 0.982-0.997, P = 0.007).This study demonstrated that serum irisin was significantly associated with sarcopenia and carotid atherosclerosis in PD patients. Additional studies to provide a confirmation and examine possible mechanisms are warranted.
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- 2015
6. PPARα agonists inhibit inflammatory activation of macrophages through upregulation of β-defensin 1
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Byung Hee Park, Ji Young Jang, Soo Hyuk Kim, Soo jin Ann, Sang Hak Lee, Seok Min Kang, Ji Hyung Chung, and Sungha Park
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Lipopolysaccharides ,MAPK/ERK pathway ,medicine.medical_specialty ,Chemokine ,beta-Defensins ,Anti-Inflammatory Agents ,Inflammation ,Pharmacology ,Transfection ,Cell Line ,Mice ,Fenofibrate ,Downregulation and upregulation ,Internal medicine ,medicine ,Animals ,PPAR alpha ,Secretion ,Oxazoles ,Dose-Response Relationship, Drug ,biology ,Macrophages ,Macrophage Activation ,Up-Regulation ,Toll-Like Receptor 4 ,CXCL2 ,Endocrinology ,Culture Media, Conditioned ,Chemokine secretion ,biology.protein ,TLR4 ,Tyrosine ,RNA Interference ,Gemfibrozil ,Inflammation Mediators ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,Signal Transduction - Abstract
Background Effects of peroxisome proliferator-activated receptor alpha (PPARα) agonists on cardiovascular outcome have been controversial. Although these agents primarily affect lipoprotein metabolism, their pleiotropic anti-inflammatory effect is one of the potential anti-atherosclerotic mechanisms. This study aimed to evaluate the effect of fenofibrate and gemfibrozil on inflammation in macrophages and reveal pathways these agents may affect. Methods and results The two PPARα agonists inhibited secretion of CXCL2, TNF-α, IL-6, activation of p65 of NF-κB, ERK, and TLR4 expression. These changes occurred simultaneously with upregulation and secretion of β-defensin 1, an inflammation-modulating peptide. To demonstrate the role of β-defensin 1, it was knocked-down by target-specific siRNA. The effects of PPARα agonists on TLR4 expression and chemokine secretion were obviously abrogated with this treatment. In experiments investigating whether β-defensin 1 acts extracellularly, inflammatory chemokines decreased significantly after the addition of recombinant β-defensin 1 or conditioned media to cells. In experiments designed to clarify if the effects of the two agents are PPARα-dependent, induction of mRNA and secretion β-defensin 1 and inhibition of chemokine release were clearly reduced with GW6471, a PPARα blocker. Conclusions Our results reveal the pathways by which fenofibrate and gemfibrozil inhibit LPS-induced inflammatory activation of macrophages. This study elucidated a novel anti-inflammatory mechanism that acts through PPARα, β-defensin 1, and TLR4 pathways.
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- 2015
7. FADS gene polymorphisms in Koreans: Association with ω6 polyunsaturated fatty acids in serum phospholipids, lipid peroxides, and coronary artery disease
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Jung Hyun Kwak, Yangsoo Jang, Sang Hak Lee, Oh Yoen Kim, Jose M. Ordovas, Jean Kyung Paik, and Jong Ho Lee
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Adult ,Fatty Acid Desaturases ,Male ,Lipid Peroxides ,medicine.medical_specialty ,FADS1 ,FADS2 ,Linoleic acid ,Coronary Artery Disease ,Biology ,Body Mass Index ,chemistry.chemical_compound ,Delta-5 Fatty Acid Desaturase ,Fatty Acids, Omega-6 ,Internal medicine ,Hyperlipidemia ,medicine ,Humans ,Phospholipids ,Aged ,chemistry.chemical_classification ,Korea ,Polymorphism, Genetic ,Lipid peroxide ,Middle Aged ,Malondialdehyde ,medicine.disease ,Lipoproteins, LDL ,C-Reactive Protein ,Endocrinology ,chemistry ,Case-Control Studies ,Female ,lipids (amino acids, peptides, and proteins) ,Arachidonic acid ,Cardiology and Cardiovascular Medicine ,Polyunsaturated fatty acid - Abstract
Objective We investigated the association of polymorphisms in FADS genes with polyunsaturated fatty acids (PUFAs) in serum phospholipids, lipid peroxides, and coronary artery disease (CAD) in Koreans. Methods In this case–control study, CAD patients ( n =756, 40–79 years) and healthy controls ( n =890) were genotyped for rs174537 near FADS1 ( FEN1 rs174537G>T), FADS2 (rs174575, rs2727270), and FADS3 (rs1000778). We calculated the odds ratios (ORs) for CAD risk and measured serum PUFA composition and lipid peroxide. Results Among four SNPs, only rs174537G>T differed in allele frequencies between controls and CAD patients after adjustment for age, BMI, cigarette smoking, alcohol consumption, hypertension, diabetes mellitus, and hyperlipidemia ( P =0.017). The minor T allele was associated with a lower risk of CAD [OR 0.75 (95%CI 0.61–0.92), P =0.006] after adjustment. rs174537T carriers had a significantly higher proportion of linoleic acid (LA, 18:2ω6), lower arachidonic acid (AA, 20:4ω6), and lower ratios of AA/dihomo-γ-linolenic acid (DGLA, 20:3ω6) and AA/LA than G/G subjects in both control and CAD groups. In the control group, 174537T carriers had significantly lower levels of total- and LDL-cholesterol, malondialdehyde, and ox-LDL. In CAD patients, rs174537T carriers showed a larger LDL particle size than G/G subjects. The proportion of AA in serum phospholipids positively correlated with LDL-cholesterol, ox-LDL, and malondialdehyde in controls and with 8-epi-prostaglandin F 2α in both control and CAD groups. Conclusion The rs174537T is associated with a lower proportion of AA in serum phospholipids and reduced CAD risk, in association with reduced total- and LDL-cholesterol and lipid peroxides.
- Published
- 2011
8. Visceral adiposity and the severity of coronary artery disease in middle-aged subjects with normal waist circumference and its relation with lipocalin-2 and MCP-1
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Sang Hak Lee, Yangsoo Jang, Donghoon Choi, Eun Suk Jung, Chi Young Shim, Young Guk Ko, Namsik Chung, Jong-Won Ha, Jung Sun Kim, and Yong Ho Lee
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Adult ,Male ,medicine.medical_specialty ,Waist ,Adipokine ,Adipose tissue ,Coronary Artery Disease ,Disease ,Intra-Abdominal Fat ,Coronary artery disease ,Internal medicine ,medicine ,Humans ,Chemokine CCL2 ,business.industry ,Vascular disease ,Middle Aged ,medicine.disease ,Obesity ,Lipocalins ,Endocrinology ,Cardiology ,Waist Circumference ,Tomography, X-Ray Computed ,Cardiology and Cardiovascular Medicine ,business ,Body mass index - Abstract
Visceral adipose tissue has emerged as a key organ contributing to the development of coronary artery disease (CAD). However, defining central obesity by waist circumference (WC) may underestimate visceral adiposity in lean patients. The aim of this study was to investigate the relationship between visceral adiposity and severity of CAD in subjects with normal WC.Among 365 patients with documented CAD, 90 male subjects with normal WC (90 cm) were selected and their visceral fat areas (VFA) were examined using computed tomography. Lipid profiles and levels of adipokines including lipocalin-2, high molecular weight adiponectin, and monocyte chemoattractant protein (MCP)-1 were measured. Patients were divided into tertiles based on VFA at the L4 vertebra level.Patients with single-vessel disease had significantly lower VFA than those with multi-vessel disease (P0.05; 86.0 vs. 97.5 vs. 99.6 cm(2) for single- , double- , and triple-vessel diseases, respectively). Positive association between the extent of CAD and VFA was clearly demonstrated and logistic regression analysis showed that subjects in the upper tertile for VFA had a 4.5-fold higher risk of having multi-vessel disease compared with those in the lowest tertile (P0.05; odds ratio=4.51; 95% confidence interval=1.10-18.45). Circulating levels of lipocalin-2 and MCP-1 were significantly higher in the upper tertiles of VFA.Increased visceral adiposity is significantly associated with the severity of CAD, even in subjects without central obesity as determined by WC measurements. Abnormalities in adipokine regulation may provide a novel mechanistic connection between visceral adiposity and associated cardiovascular complications.
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- 2010
9. Independent inverse relationship between serum lycopene concentration and arterial stiffness
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Ju Yeon Park, Hyae Jin Kim, Yangsoo Jang, Jong Ho Lee, Ji-Young Kim, Jin Hee Lee, Kang Pyo Lee, Hyun Yang Yoe, Sang Hak Lee, and Oh Yoen Kim
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Adult ,medicine.medical_specialty ,alpha-Tocopherol ,medicine.disease_cause ,chemistry.chemical_compound ,Lycopene ,Internal medicine ,Bayesian multivariate linear regression ,medicine ,Humans ,Pulse wave velocity ,Aged ,Inflammation ,business.industry ,Arteries ,Middle Aged ,beta Carotene ,medicine.disease ,Carotenoids ,Lipoproteins, LDL ,Oxygen ,Menopause ,Oxidative Stress ,Blood pressure ,Endocrinology ,chemistry ,Cardiovascular Diseases ,Low-density lipoprotein ,Arterial stiffness ,Regression Analysis ,Female ,Cardiology and Cardiovascular Medicine ,business ,Oxidative stress - Abstract
Emerging evidence suggests a role of lycopene in the primary prevention of cardiovascular disease. This study aimed to investigate the association of serum lycopene concentration with brachial-ankle pulse wave velocity (baPWV), a marker of arterial stiffness and markers of oxidative stress and inflammation.healthy women (n=264, 31-75 yrs) were classified into tertiles according to serum lycopene concentration. Multivariate linear regression analyses were used to assess the relationship between serum lycopene and baPWV.Subjects in middle tertile (T2) and upper tertile (T3) had lower baPWV (1263+/-23 and 1265+/-14 cm/s vs. 1338+/-21 cm/s; p=0.009) and lower oxidized LDL (oxLDL) (53+/-3 and 55+/-3 U/L vs. 66+/-3 U/L; p0.001) than those in lower tertile (T1). Subjects in T3 showed higher LDL particle size (24.3+/-0.08 nm vs. 24.0+/-0.07 nm, p=0.005) and lower C-reactive protein (hs-CRP) (0.80+/-0.25mg/dL vs. 1.27+/-0.24 mg/dL, p=0.015), compared with those in T1. Logistic regression analysis showed that baPWV decreased with the increment of lycopene concentration; log baPWV decreased by 0.21 cm/s (95% CI -0.168;-0.045, p=0.001) per unit change in lycopene. After adjustment for age, BMI, smoking, drinking, menopause and blood pressure, the estimated effect was attenuated by 35%, but remained statistically significant [-0.13 cm/s (95% CI -0.112;-0.018, p=0.006)]. Further adjustment for beta-carotene, alpha-tocopherol, oxLDL, LDL particle size, and hs-CRP increased the strength of the association [beta=-0.221 (95% CI -0.215;-0.012, p=0.029)].This study supports the presence of an independent inverse relationship between circulating lycopene and baPWV. Additionally, reduced oxidative modification of LDL may be one of mediators on the mechanisms how lycopene reduces arterial stiffness.
- Published
- 2010
10. Clinical features of familial hypercholesterolemia in Korea: Predictors of pathogenic mutations and coronary artery disease - A study supported by the Korean Society of Lipidology and Atherosclerosis
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Young Keun Ahn, Dong Geum Shin, Sang Hak Lee, Jeong Taek Woo, Seung Ho Hur, Byung Ryul Cho, Doo Il Kim, Ji Hyun Lee, Jin Ok Jeong, Byoung Kwon Lee, Soo Min Han, Moo Yong Rhee, and Yangsoo Jang
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Adult ,Male ,Pathology ,medicine.medical_specialty ,Mutation rate ,Population ,Familial hypercholesterolemia ,Coronary Artery Disease ,Xanthoma ,Sensitivity and Specificity ,Coronary artery disease ,Hyperlipoproteinemia Type II ,Risk Factors ,Internal medicine ,Republic of Korea ,medicine ,Humans ,Family history ,education ,Aged ,Apolipoproteins B ,education.field_of_study ,business.industry ,PCSK9 ,Serine Endopeptidases ,Cholesterol, LDL ,Middle Aged ,medicine.disease ,Atherosclerosis ,Phenotype ,ROC Curve ,Receptors, LDL ,Mutation (genetic algorithm) ,Mutation ,Regression Analysis ,lipids (amino acids, peptides, and proteins) ,Female ,Proprotein Convertases ,Proprotein Convertase 9 ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background Proper screening and diagnosis of familial hypercholesterolemia (FH) is of critical importance for cardiovascular prevention. However, the clinical diagnosis of FH remains difficult partly because its phenotype can vary between different ethnicities. The aim of this study was to determine the clinical features and the best diagnostic approach in Korean FH patients. The predictors of putative pathogenic mutations and coronary artery disease (CAD) were also identified. Methods and Results Ninety-seven patients with low-density lipoprotein-cholesterol >190 mg/dL and xanthoma or FH-compatible family history were included. Putative pathogenic mutations in LDLR , APOB , or PCSK9 genes were identified in 32% of the enrolled patients. The subjects were classified according to four sets of clinical criteria (Simon Broome, Dutch, MEDPED, Japanese). The mutation rates in definite type FH of Simon Broome or Dutch criteria were 35%–37% and lower in our patients than in those of other countries. The mutation detection rate by MEDPED criteria was 67%–75% and higher than those based on other criteria. The best low-density lipoprotein-cholesterol (LDL-C) threshold for predicting mutations was 225 mg/dL. LDL-C was found to be the only independent predictor of mutation carriers, while hypertension and low high-density lipoprotein-cholesterol were predictive of CAD. Conclusions The conventional clinical criteria showed limited mutation detection power and low specificities in Korean FH patients, in whom the best LDL-C threshold for putative mutation was 225 mg/dL. Traditional cardiovascular risk factors were also significantly associated with CAD risk in this population.
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- 2015
11. Evaluation of polygenic cause in Korean patients with familial hypercholesterolemia - A study supported by Korean Society of Lipidology and Atherosclerosis
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Moo Yong Rhee, Byoung Kwon Lee, Ji Hyun Lee, Manjae Kwon, Do Il Kim, Jeong Taek Woo, Sang Hak Lee, Jin Ok Jeong, Seung Ho Hur, Young Keun Ahn, Byung Ryul Cho, Yangsoo Jang, and Soo Min Han
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Adult ,Male ,medicine.medical_specialty ,Multifactorial Inheritance ,Apolipoprotein B ,Genotype ,Single-nucleotide polymorphism ,Familial hypercholesterolemia ,Comorbidity ,Bioinformatics ,Polymorphism, Single Nucleotide ,Hyperlipoproteinemia Type II ,Asian People ,Risk Factors ,Internal medicine ,Statistical significance ,Republic of Korea ,Diabetes Mellitus ,Medicine ,SNP ,Humans ,Triglycerides ,Aged ,Genes, Dominant ,biology ,business.industry ,PCSK9 ,Cholesterol, HDL ,Serine Endopeptidases ,Cholesterol, LDL ,Middle Aged ,medicine.disease ,Receptors, LDL ,Cardiovascular Diseases ,LDL receptor ,Apolipoprotein B-100 ,Mutation ,biology.protein ,Female ,Proprotein Convertases ,Proprotein Convertase 9 ,Cardiology and Cardiovascular Medicine ,business ,Lipidology - Abstract
Background/Objective Familial hypercholesterolemia (FH) is an autosomal dominant disorder caused by mutations in LDLR, APOB, or PCSK9 . Polygenicity is a plausible cause in mutation-negative FH patients based on LDL cholesterol (LDL-C)-associated single nucleotide polymorphisms (SNPs) identified by the Global Lipids Genetics Consortium (GLGC). However, there are limited data regarding the polygenic cause of FH in Asians. Methods We gathered data from 66 mutation-negative and 31 mutation-positive Korean FH patients, as well as from 2274 controls who participated in the Korean Health Examinee (HEXA) shared control study. We genotyped the patients for six GLGC SNPs and four East Asian LDL-C-associated SNPs and compared SNP scores among patient groups and controls. Results Weighted mean 6- and 4-SNP scores (0.67 [SD = 0.07] and 0.46 [0.11], respectively) were both significantly associated with LDL-C levels in controls ( p = 2.1 × 10 −4 , R 2 = 0.01 and p = 5.0 × 10 −12 , R 2 = 0.02, respectively). Mutation-negative FH patients had higher 6-SNP (0.72 [0.07]) and 4-SNP (0.49 [0.08]) scores than controls ( p = 1.8 × 10 −8 and p = 3.6 × 10 −3 , respectively). We also observed higher scores in mutation-positive FH patients compared with controls, but the difference did not reach statistical significance. Conclusion The present study demonstrates the utility of SNP score analysis for identifying polygenic FH in Korean patients by showing that small-effect common SNPs may cumulatively elevate LDL-C levels.
- Published
- 2015
12. The association between social network betweenness and coronary calcification: A baseline study on patients with a high risk of cardiovascular disease
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In-Cheol Kim, Won Tak Joo, Sang Hak Lee, Sungha Park, Seok Min Kang, Chan Joo Lee, Yoosik Youm, Jaewon Oh, and Hyeon Chang Kim
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medicine.medical_specialty ,Baseline study ,Social network ,Betweenness centrality ,business.industry ,Coronary artery calcification ,Internal medicine ,Cardiology ,medicine ,Disease ,Cardiology and Cardiovascular Medicine ,business ,Association (psychology) - Published
- 2017
13. Non-lipid effects of rosuvastatin-fenofibrate combination therapy in high-risk Asian patients with mixed hyperlipidemia
- Author
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Si Wan Choi, Sang Hak Lee, Young Keun Ahn, Jang Young Kim, Sang Hong Baek, Dong Woon Jeon, Dong-Ju Choi, Pil-Ki Min, Seung-Woon Rha, Kyoung Im Cho, Yong-Jin Kim, Young Sup Byun, Yangsoo Jang, Yun Seok Choi, and Kwon Sam Kim
- Subjects
Blood Glucose ,Male ,Time Factors ,Pharmacology ,Gastroenterology ,Rhabdomyolysis ,Blood Urea Nitrogen ,chemistry.chemical_compound ,Hemoglobins ,Fenofibrate ,Risk Factors ,Medicine ,Rosuvastatin Calcium ,Blood urea nitrogen ,Homocysteine ,Hypolipidemic Agents ,Sulfonamides ,Middle Aged ,Lipids ,Enzymes ,Drug Combinations ,Treatment Outcome ,Liver ,Cardiovascular Diseases ,Creatinine ,Population study ,Female ,Chemical and Drug Induced Liver Injury ,Cardiology and Cardiovascular Medicine ,medicine.drug ,medicine.medical_specialty ,Combination therapy ,Hyperlipidemias ,Risk Assessment ,Asian People ,Internal medicine ,Republic of Korea ,Humans ,Rosuvastatin ,Adverse effect ,Muscle, Skeletal ,Aged ,business.industry ,Patient Selection ,nutritional and metabolic diseases ,Fluorobenzenes ,Pyrimidines ,chemistry ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,business ,Biomarkers - Abstract
Objective The aim of this study is to compare the non-lipid effects of rosuvastatin–fenofibrate combination therapy with rosuvastatin monotherapy in high-risk Asian patients with mixed hyperlipidemia. Methods A total of 236 patients were initially screened. After six weeks of diet and life style changes, 180 of these patients were randomly assigned to receive one of two regimens: rosuvastatin 10mg plus fenofibrate 160mg or rosuvastatin 10mg. The primary outcome variables were the incidences of muscle or liver enzyme elevation. The patients were followed for 24 weeks during drug treatment and for an additional four weeks after drug discontinuation. Results The rates of the primary outcome variables were similar between the two groups (2.8% and 3.9% in the combination and the rosuvastatin groups, respectively, p =1.00). The combination group had more, but not significantly, common treatment-related adverse events (AEs) (13.3% and 5.6%, respectively) and drug discontinuation due to AEs (10.0% and 3.3%, respectively) than the rosouvastatin group. Combination therapy was associated with higher elevations in homocysteine, blood urea nitrogen, and serum creatinine, whereas elevation in alanine aminotransferase was greater in the rosuvastatin group. Leukocyte count and hemoglobin level decreased to a greater extent in the combination group. The combination group showed greater reductions in TG and elevation in HDL-cholesterol. Conclusion In our study population, the rosuvastatin–fenofibrate combination resulted in comparable incidences of myo- or hepatotoxicity as rosuvastatin monotherapy. However, this combination may need to be used with caution in individuals with underlying pathologies such as renal dysfunction (NCT01414803).
- Published
- 2011
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