Assessment and diagnostic relevance of novel serum biomarkers for early decision of ST-elevation myocardial infarction.

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.

Comparative assessment of angiotensin II type 1 receptor blockers in the treatment of acute myocardial infarction: surmountable vs. insurmountable antagonist.

BACKGROUND: The mechanisms of antagonism vary between the angiotensin II type 1 receptor blockers (ARBs): insurmountable antagonism and surmountable antagonism. Recent retrospective observational studies suggest that ARBs may not have equivalent benefits in various clinical situations. The aim of this study was to compare the effect of two categories of ARBs on the long-term clinical outcomes of patients with acute myocardial infarction (AMI). METHODS: We analyzed the large-scale, prospective, observational Korea Acute Myocardial Infarction Registry study, which enrolled 2740 AMI patients. They divided by the prescription of surmountable ARBs or insurmountable ARBs at discharge. Primary outcome was major adverse cardiac events (MACEs), defined as a composite of cardiac death, nonfatal MI, and re-percutaneous coronary intervention, coronary artery bypass graft surgery. RESULTS: In the overall population, the MACEs rate in 1 year was significantly higher in the surmountable ARB group (14.3% vs. 11.2%, p=0.025), which was mainly due to increased cardiac death (3.3% vs. 1.9%, p=0.031). Matching by propensity-score showed consistent results (MACEs rate: 14.9% vs. 11.4%, p=0.037). In subgroup analysis, the insurmountable ARB treatment significantly reduced the incidence of MACEs in patients with left ventricular ejection fraction greater than 40%, with a low killip class, with ST segment elevation MI, and with normal renal function. CONCLUSIONS: In our study, insurmountable ARBs were more effective on long-term clinical outcomes than surmountable ARBs in patients with AMI.

Noninvasive assessment of myocardial inflammation by cardiovascular magnetic resonance in a rat model of experimental autoimmune myocarditis.

BACKGROUND: Limited availability of noninvasive and biologically precise diagnostic tools poses a challenge for the evaluation and management of patients with myocarditis. METHODS AND RESULTS: The feasibility of cardiovascular magnetic resonance (CMR) imaging with magneto-fluorescent nanoparticles (MNPs) for detection of myocarditis and its effectiveness in discriminating inflammation grades were assessed in experimental autoimmune myocarditis (EAM) (n=65) and control (n=10) rats. After undergoing CMR, rats were administered with MNPs, followed by a second CMR 24 hours later. Head-to-head comparison of MNP-CMR with T(2)-weighted, early and late gadolinium enhancement CMR was performed in additional EAM (n=10) and control (n=5) rats. Contrast-to-noise ratios were measured and compared between groups. Flow cytometry and microscopy demonstrated that infiltrating inflammatory cells engulfed MNPs, resulting in altered myocardial T(2)* effect. Changes in contrast-to-noise ratio between pre- and post-MNP CMR were significantly greater in EAM rats (1.08 ± 0.10 versus 0.48 ± 0.20; P<0.001). In addition, contrast-to-noise ratio measurement in MNP-CMR clearly detected the extent of inflammation (P<0.001) except for mild inflammation. Compared with conventional CMR, MNP-CMR provided better image contrast (CNR change 8% versus 46%, P<0.001) and detectability of focal myocardial inflammation. Notably, MNP-CMR successfully tracked the evolution of myocardial inflammation in the same EAM rats. CONCLUSIONS: Magneto-fluorescent nanoparticle CMR permitted effective visualization of myocardial inflammatory cellular infiltrates and distinction of the extent of inflammation compared with conventional CMR in a preclinical model of EAM. Magneto-fluorescent nanoparticle CMR performs best in EAM rats with at least moderate inflammatory response.

Reaching C-reactive protein and low-density lipoprotein cholesterol goals in dyslipidemic patients (from the Lipid Treatment Assessment Project [L-TAP] 2).

The purpose of the present substudy of the Lipid Treatment Assessment Project 2 was to assess dual C-reactive protein (CRP) and low-density lipoprotein (LDL) cholesterol goal attainment across a spectrum of low-, moderate-, and high-risk patients with dyslipidemia in 8 countries in North America, Latin America, Europe, and Asia. Of the 9,518 patients studied overall, 45% were women, 64% had hypertension, 31% had diabetes, 14% were current smokers, 60% were high risk, and 79% were taking a statin. The median CRP level was 1.5 mg/L (interquartile range 0.2 to 2.8). On multivariate analysis, higher CRP levels were associated with older age, female gender, hypertension, current smoking, greater body mass index, larger waist circumference, LDL cholesterol level, and triglyceride/high-density lipoprotein cholesterol ratio. In contrast, being from Asia or taking a statin was associated with lower levels. Across all risk groups, 59% of patients attained the CRP target of <2 mg/L, and 33% had <1 mg/L. Overall, 44% of patients attained both their National Cholesterol Education Program Adult Treatment Panel III LDL cholesterol target and a CRP level of <2 mg/L, but only 26% attained their LDL cholesterol target and a CRP level of <1 mg/L. In the very high-risk group with coronary heart disease and ≥2 risk factors, only 19% attained both their LDL cholesterol goal and a CRP level of <2 mg/L and 12% their LDL cholesterol goal and a CRP level of <1 mg/L. In conclusion, with current treatment, most dyslipidemic patients do not reach the dual CRP and LDL cholesterol goals. Smoking cessation, weight reduction, and the greater use of more potent statins at higher doses might be able to improve these outcomes.

Hospital discharge risk score system for the assessment of clinical outcomes in patients with acute myocardial infarction (Korea Acute Myocardial Infarction Registry [KAMIR] score).

Assessment of risk at time of discharge could be a useful tool for guiding postdischarge management. The aim of this study was to develop a novel and simple assessment tool for better hospital discharge risk stratification. The study included 3,997 hospital-discharged patients with acute myocardial infarction who were enrolled in the nationwide prospective Korea Acute Myocardial Infarction Registry-1 (KAMIR-1) from November 2005 through December 2006. The new risk score system was tested in 1,461 hospital-discharged patients who were admitted from January 2007 through January 2008 (KAMIR-2). The new risk score system was compared to the Global Registry of Acute Coronary Events (GRACE) postdischarge risk model during a 12-month clinical follow-up. During 1-year follow-up, all-cause death occurred in 228 patients (5.7%) and 81 patients (5.5%) in the development and validation cohorts, respectively. The new risk score (KAMIR score) was constructed using 6 independent variables related to the primary end point using a multivariable Cox regression analysis: age, Killip class, serum creatinine, no in-hospital percutaneous coronary intervention, left ventricular ejection fraction, and admission glucose based on multivariate-adjusted risk relation. The KAMIR score demonstrated significant differences in its predictive accuracy for 1-year mortality compared to the GRACE score for the developmental and validation cohorts. In conclusion, the KAMIR score for patients with acute myocardial infarction is a simpler and better risk scoring system than the GRACE hospital discharge risk model in prediction of 1-year mortality.

Gender differences in clinical features and in-hospital outcomes in ST-segment elevation acute myocardial infarction: from the Korean Acute Myocardial Infarction Registry (KAMIR) study.

BACKGROUND: Studies have suggested that women are biologically different and that female gender itself is independently associated with poor clinical outcome after an acute myocardial infarction (AMI). HYPOTHESIS: We analyzed data from the Korean Acute Myocardial Infarction Registry (KAMIR) to assess gender differences in in-hospital outcomes post ST-segment elevation myocardial infarction (STEMI). METHODS: Between November 2005 and July 2007, 4037 patients who were admitted with STEMI to 41 facilities were registered into the KAMIR database; patients admitted within 72 hours of symptom onset were selected and included in this study. RESULTS: The proportion of patients who had reperfusion therapy within 12 hours from chest pain onset was lower in women. Women had higher rates of in-hospital mortality (8.6% vs 3.2%, P < .01), noncardiac death (1.5% vs 0.4%, P < .01), cardiac death (7.1% vs 2.8%, P < .01), and stroke (1.2% vs 0.5%, P < .05) than men. Multivariate logistic regression analysis identified age, previous angina, hypertension, a Killip class > or = II, a left ventricular ejection fraction (LVEF) < 40%, and a thrombolysis in myocardial infarction flow (TIMI) grade < or = 3 after angioplasty as independent risk factors for in-hospital death for all patients; however, female gender itself was not an independent risk factor. CONCLUSIONS: The results of this study show that although women have a higher in-hospital mortality than men, female gender itself is not an independent risk factor for in-hospital mortality.

A new risk score system for the assessment of clinical outcomes in patients with non-ST-segment elevation myocardial infarction.

BACKGROUND AND OBJECTIVES: Prediction for long-term clinical outcomes in patients with non-ST elevation acute coronary syndrome is important as well as early risk stratification. The aim of this study is to develop a simple assessment tool for better early bedside risk stratification for both short- and long-term clinical outcomes. SUBJECTS AND METHODS: 2148 patients with non-ST-segment elevation myocardial infarction (NSTEMI) (64.9±12.2 years, 35.0% females) were enrolled in a nationwide prospective Korea Acute Myocardial Infarction Registry (KAMIR). A new risk score was constructed using the variables related to one year mortality: TIMI risk index (17.5-30: 1 point, >30: 2 points), Killip class (II: 1 point, >II: 2 points) and serum creatinine (≥1.5 mg/dL: 1 point), based on the multivariate-adjusted risk relationship. The new risk score system was compared with the Global Registry of Acute Coronary Events (GRACE) and TIMI risk scores during a 12-month clinical follow-up. RESULTS: During a one year follow-up, all causes of death occurred in 362 patients (14.3%), and 184 (8.6%) patients died in the hospital. The new risk score showed good predictive value for one year mortality. The accuracy for in-hospital and one year post-discharge mortality rates, the new risk score demonstrated significant differences in predictive accuracy when compared with TIMI and GRACE risk scores. CONCLUSION: A new risk score in the present study provides simplicity with accuracy simultaneously for early risk stratification, and also could be a powerful predictive tool for long-term prognosis in NSTEMI.

Direct comparison of B-type natriuretic peptide and N-terminal pro-BNP for assessment of cardiac function in a large population of symptomatic patients.

BACKGROUNDS: B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NTproBNP) levels showed frequent discrepancies in individual patients. OBJECTIVES: The aims were 1) to compare the abilities of BNP and NTproBNP for the detection of left ventricular systolic dysfunction (LVSD) or diastolic dysfunction (LVDD) in the symptomatic patients, and 2) to assess the direct correlation and its independent determinants between them. METHODS: 1032 patients with dyspnea underwent BNP and NTproBNP measurements simultaneously. 967/1032 (93.7%) patients underwent echocardiography. Using the receiver operation characteristic curve analyses for the detection of LVSD (EF<45%) or advanced LVDD, the area under the curves (AUC) of both biomarkers was compared according to age, gender, body mass index (BMI), hemoglobin (Hb), and glomerular filtration rate (eGFR). Using multiple regression analysis, the direct correlation and its independent determinants were identified between them. RESULTS: In the entire population, the AUCs of BNP and NTproBNP had no significant differences (LVSD: 0.909 vs. 0.893, p=0.20; advanced LVDD: 0.897 vs. 0.879, p=0.13). In patients with BMI<25, the AUCs of BNP were significantly higher than those of NTproBNP (LVSD: 0.897 vs. 0.869, p=0.03; advanced LVDD: 0.916 vs. 0.885, p=0.02). They had strong correlation (r=0.895, p<0.001) and LVEF, eGFR<60 ml/min, Hb<12 g/dl and use of diuretics were the independent determinants between them. CONCLUSION: BNP and NTproBNP displayed strong correlation and near-identical performances for the screening of cardiac dysfunction. However, LVEF, renal function, Hb and use of diuretics should be considered for clinical interpretation.

Lipid treatment assessment project 2: a multinational survey to evaluate the proportion of patients achieving low-density lipoprotein cholesterol goals.

BACKGROUND: Information about physicians' adherence to cholesterol management guidelines remains scant. The present survey updates our knowledge of lipid management worldwide. METHODS AND RESULTS: Lipid levels were determined at enrollment in dyslipidemic adult patients on stable lipid-lowering therapy in 9 countries. The primary end point was the success rate, defined as the proportion of patients achieving appropriate low-density lipoprotein cholesterol (LDL-C) goals for their given risk. The mean age of the 9955 evaluable patients was 62+/-12 years; 54% were male. Coronary disease and diabetes mellitus had been diagnosed in 30% and 31%, respectively, and 14% were current smokers. Current treatment consisted of a statin in 75%. The proportion of patients achieving LDL-C goals according to relevant national guidelines ranged from 47% to 84% across countries. In low-, moderate-, and high-risk groups, mean LDL-C was 119, 109, and 91 mg/dL and mean high-density lipoprotein cholesterol was 62, 49, and 50 mg/dL, respectively. The success rate for LDL-C goal achievement was 86% in low-, 74% in moderate-, and 67% in high-risk patients (73% overall). However, among coronary heart disease patients with > or =2 risk factors, only 30% attained the optional LDL-C goal of <70 mg/dL. In the entire cohort, high-density lipoprotein cholesterol was <40 mg/dL in 19%, 40 to 60 mg/dL in 55%, and >60 mg/dL in 26% of patients. CONCLUSIONS: Although there is room for improvement, particularly in very-high-risk patients, these results indicate that lipid-lowering therapy is being applied much more successfully than it was a decade ago.

A serial ultrasound assessment of neoaneurysm following paclitaxel-eluting stent implantation.

We present a case of serial regression of aneurysm of coronary artery complicating paclitaxel-eluting Taxus stent implantation in the mid anterior descending artery evaluated by intravascular ultrasound in a 55-year-old woman.