[Show abstract][Hide abstract] ABSTRACT: Blood transcriptome reflects the status of diseases, and characteristic molecular signature provides a novel window on gene expression preceding acute coronary events. We aim to determine blood transcriptome-based molecular signature of acute coronary syndrome (ACS), and to identify novel serum biomarkers for early stage ST-segment-elevation myocardial infarction (STEMI). We obtained peripheral blood from the patients with ACS who visited emergency department within 4 hours after the onset of chest pain: STEMI (n = 10), Non-ST-segment-elevation MI (NSTEMI, n = 10) and unstable angina (UA, n = 11). Blood transcriptome scans revealed that a characteristic gene expression change exists in STEMI, resulting in 531 outlier genes as STEMI molecular signature (Welch's t test, P < 0.05). Another analysis with a set of blood samples of patients with STEMI (n = 7) before and 7 days after the primary percutaneous coronary intervention (n = 7) and normal control (n = 10) evidenced that STEMI molecular signature directly reflects the onset of STEMI pathogenesis. From the two sets of transcriptome-based STEMI signatures, we identified 10 genes encoding transmembrane or secretory proteins that are highly expressed in STEMI. We validated blood protein expression levels of these 10 putative biomarkers in 40 STEMI and 32 healthy subjects by ELISA. Data suggested that PGLYRP1, IRAK3 and VNN3 are more specific and sensitive diagnostic biomarkers for STEMI than traditional CK-MB or troponin.Blood transcriptome scans of ACS evidenced early stage molecular markers for STEMI. Here, we report novel biomarkers to diagnose STEMI at emergency department in hospitals by a simple ELISA method.
[Show abstract][Hide abstract] ABSTRACT: Cystatin-C, a marker of mild renal dysfunction, has been reported to be associated with cardiovascular diseases including vasospastic angina (VSA). We aimed to investigate the impact of cystatin-C level on the prevalence and angiographic characteristics of VSA in Korean patients.A total of 549 patients in the VA-KOREA (Vasospastic Angina in KOREA) registry who underwent ergonovine provocation tests were consecutively enrolled. Estimated glomerular filtration rate (eGFR) and levels of serum creatinine (Cr) and cystatin-C were assessed before angiography.The patients were classified into two groups: the VSA group (n = 149, 27.1%) and the non-VSA group (n = 400). Although eGFR and Cr levels were similar between the two groups, the VSA group had a significantly higher level of cystatin-C (P < 0.05). A high level of cystatin-C (second tertile, hazard ratio 1.432; 95% confidence interval [1.1491.805]; P = 0.026, third tertile, 1.947 [1.132-2.719]; P = 0.003) and current smoking (2.710 [1.415-4.098]; P < 0.001) were independently associated with the prevalence of VSA. Furthermore, the highest level of cystatin-C (> 0.96 ng/mL) had a significant impact on the incidence of multivessel spasm (2.608 [1.061-4.596]; P = 0.037).A high level of cystatin-C was independently associated with the prevalence of VSA and with a high-risk type of VSA in Korean patients, suggesting that proactive investigation of VSA should be considered for patients with mild renal dysfunction indicated by elevated cystatin-C.
International Heart Journal 01/2015; 56(1):49-55. DOI:10.1536/ihj.14-213 · 1.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background/aims:
Atrial fibrillation (AF) often coexists with acute myocardial infarction (AMI), and chronic kidney disease (CKD) is a major risk for AMI. However, the combined impact of CKD and AF on the mortality and morbidity in AMI population has not been determined.
Between January 2004 and December 2009, a total of 4,738 AMI patients were enrolled prospectively. Patients were divided into four groups according to the combined status of CKD and AF. The primary endpoint was a combination of 5-year major adverse cardiac and cerebrovascular events (MACCE).
The prevalence of AF was significantly higher in CKD patients than in non-CKD patients (6.76 vs. 3.31%, p < 0.001). The highest cumulative event rate of MACCE and death was observed in patients with both CKD and AF (68.5 and 64.0%), respectively. In multivariable analyses, compared with patients with neither AF nor CKD, hazard ratios (HR) for composite of MACCE were 1.66 (95% CI, 1.14-2.41), 1.24 (95% CI, 1.06-1.46), and 2.10 (95% CI, 1.42-3.13) for patients with AF only, those with CKD only, and those with both CKD and AF, respectively (p for interaction = 0.935). Patients with both CKD and AF had a greatest risk for all-cause mortality (HR 2.54; 95% CI, 1.60-4.53), and the significant synergistic interaction was observed between CKD and AF (p for interaction = 0.015).
The combined effect of AF and CKD on the risk of MACCE after an AMI is stronger than any separate condition, and it confers a synergistic effect on the all-cause mortality risk.
American Journal of Nephrology 10/2014; 40(4):345-352. DOI:10.1159/000368422 · 2.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: AimsThe Korean Acute Heart Failure registry (KorAHF) aims to evaluate the clinical characteristics, management, hospital course, and long-term outcomes of patients hospitalized for acute heart failure syndrome (AHFS) in Korea.Methods and resultsThis is a prospective observational multicentre cohort study funded by the Korea National Institute of Health. Patients hospitalized for AHFS in 10 tertiary university hospitals across the country have been consecutively enrolled since March 2011. The study is expected to complete the scheduled enrolment of 5000 patients some time in 2014, and follow-up is planned through 2016. As of April 2012, the interim analysis of 2066 consecutive subjects was performed to understand the baseline characteristics of the population. The mean age was 69 ± 14 years; 55% were male; and 50% were de novo heart failure. The mean left ventricular ejection fraction (LVEF) was 40 ± 18%. Ischaemia was both the leading cause (38%) and the most frequent aggravating factor (26%) of AHFS. ACE inhibitors/ARBs and beta-blockers were prescribed at discharge in 65% and 51% of the patients, respectively. In-hospital mortality was 5.2%, and 0.9% of patients received urgent heart transplantation. Low blood pressure and azotaemia were the most important predictors of in-hospital mortality. The post-discharge 30-day and 180-day all-cause mortality were 1.2% and 9.2%, respectively.Conclusions
Our analysis reveals that the prognosis of AHFS in Korea is poor and that there are specific features, including lower blood pressures at admission and lower rates of heart failure related to hypertension, compared with other registries. Adherence to current guidelines should be improved.
European Journal of Heart Failure 06/2014; 16(6). DOI:10.1002/ejhf.91 · 6.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Heart failure (HF) complicating acute myocardial infarction (AMI) is common and is associated with poor clinical outcome. Limited data exist regarding the incidence and in-hospital mortality of AMI with HF (AMI-HF). We retrospectively analyzed 1,427 consecutive patients with AMI in the five major university hospitals in Korea at two time points, 1998 (n = 608) and 2008 (n = 819). Two hundred twenty eight patients (37.5%) in 1998 and 324 patients (39.5%) in 2008 of AMI patients complicated with HF (P = 0.429). AMI-HF patients in 2008 were older, had more hypertension, previous AMI, and lower systolic blood pressure than those in 1998. Regarding treatments, AMI-HF patients in 2008 received more revascularization procedures, more evidence based medical treatment and adjuvant therapy, such as mechanical ventilators, intra-aortic balloon pulsation compared to those in 1998. However, overall in-hospital mortality rates (6.4% vs 11.1%, P = 0.071) of AMI-HF patients were unchanged and still high even after propensity score matching analysis, irrespective of types of AMI and revascularization methods. In conclusion, more evidence-based medical and advanced procedural managements were applied for patients with AMI-HF in 2008 than in 1998. However the incidence and in-hospital mortality of AMI-HF patients were not significantly changed between the two time points.
Journal of Korean medical science 04/2014; 29(4):544-9. DOI:10.3346/jkms.2014.29.4.544 · 1.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abstract Morning blood pressure (BP) surge (MS) has been known to be a predictor of cardiovascular events. Currently, few studies have evaluated the underlying mechanism underlying MS, which may include neurohormonal factors and the renin-angiotensin-aldosterone system (RAAS). This study aimed to examine plasma aldosterone concentration (PAC) and plasma renin activity (PRA) and BP parameters with or without MS in never-treated subjects with essential hypertension. This cross-sectional study included a total of 261 patients (mean age: 48.8 years; 60.5% male) with never-treated essential hypertension who were registered in a working group at The Catholic University of Korea. The patients were divided into the MS group, which was defined as having the highest quartile of morning BP increase from sleep (>31 mmHg; n = 66) and the non-MS group (≤31 mmHg; n = 195). We collected 24-h ambulatory BP, pulse wave velocity, ankle brachial index, PAC and PRA from all patients. The measured PAC and PRA were lower in the MS group than in the non-MS group (PAC: 9.0 ± 5.4 ng/dl versus 12.2 ± 8.7 ng/dl, p < 0.001; PRA: 1.7 ± 1.3 ng/ml/h versus 2.6 ± 3.6 ng/ml/h, p = 0.002). The MS group had greater variations in daytime, nighttime and 24-h systolic blood pressure (SBPs) than the non-MS group (24-h SBP: 15.6 ± 4.4 mm Hg for the non-MS group and 18.9 ± 4.9 mmHg for the MS group; p < 0.001 for each). It is generally accepted that the sympathetic nervous system plays a major role in the regulation of BP variability. Therefore, further studies on sympathetic nervous system activation in hypertensives with extreme MS are needed. MS in enrolled patients who were at relatively low risk in this study may be less affected by the RAAS.
[Show abstract][Hide abstract] ABSTRACT: Stent length has been considered an important predictor of adverse events after percutaneous coronary intervention, even with the first-generation drug-eluting stents (DESs). The introduction of newer-generation DES has further reduced the rates of adverse clinical events such as restenosis, myocardial infarction, and stent thrombosis. The aim of this study was to compare the impact of stent length on the long-term clinical outcomes between first- and newer-generation DESs. The effects of stent length (≥32 vs <32 mm) on the clinical outcomes were evaluated in 8,445 patients who underwent percutaneous coronary intervention using either a first-generation DES (sirolimus- and paclitaxel-eluting stents, n = 6,334) or a newer-generation DES (everolimus- and zotarolimus-eluting stents, n = 2,111) from January 2004 to December 2009. The 3-year adverse outcomes (composite of all-cause death, nonfatal myocardial infarction, target vessel revascularization, and stent thrombosis) were compared using the inverse probability of treatment-weighted method according to the stent length. After adjustment for differences in the baseline risk factors, a stent length of ≥32 mm was significantly associated with higher cumulative rates of target vessel revascularization and stent thrombosis in the patients treated with a first-generation DES (adjusted hazard ratio 1.875, 95% confidence interval 1.531 to 2.297, p <0.001; adjusted hazard ratio 2.964, 95% confidence interval 1.270 to 6.917, p = 0.012), but it was not associated with the clinical outcomes in patients treated with a newer-generation DES. In conclusion, stent length might not be associated with long-term clinical outcomes in newer-generation DES era, whereas stent length might be associated with long-term clinical outcomes in the first-generation DESs.
The American journal of cardiology 11/2013; 113(3). DOI:10.1016/j.amjcard.2013.10.029 · 3.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The impact of the CYP2C19*17 polymorphism on the clinical outcome in Asians undergoing percutaneous coronary intervention (PCI) is unknown. We sought to assess the long-term impact of CYP2C19*17 on the risk for adverse clinical events in 2188 Korean patients taking clopidogrel after PCI. The prevalence of the CYP2C19*17 allele [*wt/*17: 2.4% (n=53), *17/*17: 0%] was very low. The 2-year cumulative event rates for bleeding [*wt/*17 vs. *wt/*wt: 2 vs. 2.3%; adjusted hazard ratio (HR), 1.23; 95% confidence interval (CI), 0.16-9.45], stent thrombosis (2 vs. 1.1%; HR, 3.98; 95% CI, 0.49-31.6) or composite of any death, and myocardial infarction or stroke (5.4 vs. 7.1%; HR, 1.37; 95% CI, 0.32-5.73) did not differ on the basis of the presence of CYP2C19*17. In conclusion, in our study population of Asian patients, the CYP2C19*17 polymorphism was not associated with adverse clinical outcomes after PCI because of its low prevalence, the rarity of homozygotes, and the relatively low rate of adverse clinical events.
Pharmacogenetics and Genomics 08/2013; 23(10). DOI:10.1097/FPC.0b013e328364eb92 · 3.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Clinical features of acute myocarditis range from a subclinical state to a fulminant state. Fulminant myocarditis with ventricular arrhythmia or atrioventricular block is associated with a high mortality rate. In cases in which aggressive medical therapy for fulminant myocarditis is not likely to be successful, intensive and emergency mechanical circulatory support, such as extracorporeal membrane oxygenation (ECMO) or intra-aortic balloon pump, should be considered. We report life salvage of acute fulminant myocarditis in a 53-year-old woman presented with malignant arrhythmia and cardiogenic shock supported by ECMO.
Korean Circulation Journal 08/2013; 43(8):565-8. DOI:10.4070/kcj.2013.43.8.565 · 0.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aim:
We assessed the relationship between the level of high-sensitivity C-reactive protein (hsCRP) and cardiovascular risk factors in Korean adults.
We reviewed 1,561 patients with cardiovascular disease or diabetes mellitus with hsCRP levels measured within the past year. Four cardiovascular risk groups were determined: low (<10%, 0-1 risk), moderate (<10%, >2 risk), high (10-20%) and very high (>20%) risk, according to the number of risk factors and the Framingham/NCEP ATP III risk score. The correlations between the hsCRP level and cardiovascular risk factors (age, smoking, hypertension, lipid profiles and familial history of premature coronary heart disease) were investigated.
The mean and median hsCRP (mg/L) levels were 1.32 ± 9.69 and 0.29 (range: 0.01-7.48), respectively. Men had a higher median level of hsCRP than women (p<0.001). The levels of hs CRP significantly increased from the low to the very high risk group (0.15, 0.23, 0.27 and 0.47, respectively) and were significantly correlated with age, the level of glycosylated hemoglobin, body mass index (BMI), the level of high-density lipoprotein cholesterol (HDL-C), the low-density lipoprotein cholesterol (LDL-C)/HDL-C ratio, the LDL-C/total cholesterol (TC) ratio, the HDL-C/TC ratio, the HDL-C/triglyceride (TG) ratio and the TC/TG ratio. Neither smoking, the LDL-C level nor the TG level affected the hsCRP level. In a multivariate regression analysis, age, the HDL-C level, the LDL-C/TC ratio and BMI were found to be independently correlated with the hsCRP level.
There is a significant relationship between the degree of cardiovascular risk and the hsCRP level in Korean adults with cardiovascular disease or diabetes mellitus. Assessing the hsCRP levels may thus provide additive value in predicting cardiovascular risks.
Journal of atherosclerosis and thrombosis 05/2013; 20(7). DOI:10.5551/jat.16089 · 2.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The association between microalbuminuria (MAU) and the indices of macrovascular complication in patients with newly diagnosed type 2 diabetes (D) or essential hypertension (H) was evaluated. Total 446 patients were classified into four groups according to the urinary albumin-to-creatinine ratio: MAU-D (n = 104), normoalbuminuria (NAU)-D (n = 114), MAU-H (n = 116), and NAU-H (n = 112). The indices of macrovascular complication including arterial stiffness evaluated by pulse-wave-velocity (PWV), carotid intima-media thickness (IMT), and vascular inflammation marked by high-sensitivity C-reactive protein (hsCRP) were assessed. PWV, IMT, and hsCRP were higher in patients with MAU than in those with NAU in both diabetes and hypertension groups. In both MAU-D and MAU-H groups, PWV and hsCRP levels were positively correlated with MAU level (MAU-D: r = 0.47, 0.41, MAU-H: r = 0.36, 0.62, respectively, P < 0.05). Additionally, PWV and hsCRP were independent factors predicting MAU (diabetes group: OR 1.85, 1.54, hypertension group: OR 1.38, 1.51, respectively, P < 0.001), but not IMT. MAU is independently associated with arterial stiffness and vascular inflammation but not with IMT in patients with newly diagnosed type 2 diabetes or essential hypertension, which emphasizes the importance of proactive clinical investigations for atherosclerotic complications in patients with MAU, even in newly diagnosed diabetes or hypertension.
Journal of Korean medical science 02/2013; 28(2):252-60. DOI:10.3346/jkms.2013.28.2.252 · 1.27 Impact Factor