Estrogen signaling pathways may play a significant role in the pathogenesis of non-small cell lung cancers (NSCLC) as evidenced by the expression of aromatase and estrogen receptors (ERα and ERβ) in many of these tumors. Here we examine whether ERα and ERβ levels in conjunction with aromatase define patient groups with respect to survival outcomes and possible treatment regimens. Immunohistochemistry was performed on a high-density tissue microarray with resulting data and clinical information available for 377 patients. Patients were subdivided by gender, age and tumor histology, and survival data was determined using the Cox proportional hazards model and Kaplan-Meier curves. Neither ERα nor ERβ alone were predictors of survival in NSCLC. However, when coupled with aromatase expression, higher ERβ levels predicted worse survival in patients whose tumors expressed higher levels of aromatase. Although this finding was present in patients of both genders, it was especially pronounced in women ≥ 65 years old, where higher expression of both ERβ and aromatase indicated a markedly worse survival rate than that determined by aromatase alone. Conclusion: Expression of ERβ together with aromatase has predictive value for survival in different gender and age subgroups of NSCLC patients. This predictive value is stronger than each individual marker alone. Our results suggest treatment with aromatase inhibitors alone or combined with estrogen receptor modulators may be of benefit in some subpopulations of these patients.

Background and Objectives

Predictive factors of mortality in acute coronary syndrome (ACS) patients with left ventricular dysfunction were analyzed during 5-year clinical follow-up after percutaneous coronary intervention (PCI).

Subjects and Methods

A total of 329 ACS consecutive patients (64.6±11.3 years, 227 males) who underwent PCI from January 2001 to March 2006 were followed for 5 years. All patients had lower than 40% of left ventricular ejection fraction (LVEF). Patients were divided into Group I (survived longer than 5-years: n=130, 101 males) and Group II (survived shorter than 5 years: n=199, 126 males).

Results

The cumulative survival rate was 88.0% at 1 month, 78.0% at 6 months, 75.0% at 1 year, 67.0% at 2 years, 62.0% at 3 years, 57.0% at 4 years and 40% at 5-years. Group II was older (61.6±11.2 years vs. 66.4±11.4 years, p<0.001), and showed higher prevalence of female gender (28.4% vs. 36.7%, p=0.006) and lower LVEF (35.3±5.2 vs. 33.6±5.6) than Group I. The independent predictors for mortality were LVEF <30% {odds ratio (OR)=1.793, 95% confidence interval (CI): 1.234-2.452, p=0.002}, serum creatinine >3.0 mg/dL (OR=2.455, 95% CI: 1.306-4.614, p=0.005), older than 65 years (OR=1.594, 95% CI: 1.152-2.206, p=0.005), and female gender (OR=1.524, 95% CI: 1.090-2.130, p=0.014).

Conclusion

Five-year survival rate was 40% in ACS patients with left ventricular dysfunction, and the predictors for mortality were low LVEF, high serum creatinine, old age, and female gender.

Colorectal cancer (CRC) is among the leading causes of cancer deaths and can be caused by environmental factors as well as genetic factors. Therefore, we developed a prediction model of CRC using genetic risk scores (GRS) and evaluated the effects of conventional risk factors, including family history of CRC, in combination with GRS on the risk of CRC in Koreans. This study included 187 cases (men, 133; women, 54) and 976 controls (men, 554; women, 422). GRS were calculated with most significantly associated single-nucleotide polymorphism with CRC through a genomewide association study. The area under the curve (AUC) increased by 0.5% to 5.2% when either counted or weighted GRS was added to a prediction model consisting of age alone (AUC 0.687 for men, 0.598 for women) or age and family history of CRC (AUC 0.692 for men, 0.603 for women) for both men and women. Furthermore, the risk of CRC significantly increased for individuals with a family history of CRC in the highest quartile of GRS when compared to subjects without a family history of CRC in the lowest quartile of GRS (counted GRS odds ratio [OR], 47.9; 95% confidence interval [CI], 4.9 to 471.8 for men; OR, 22.3; 95% CI, 1.4 to 344.2 for women) (weighted GRS OR, 35.9; 95% CI, 5.9 to 218.2 for men; OR, 18.1, 95% CI, 3.7 to 88.1 for women). Our findings suggest that in Koreans, especially in Korean men, GRS improve the prediction of CRC when considered in conjunction with age and family history of CRC.

Flow mediated brachial dilatation (FMD) and carotid intima-media thickness (IMT) have been a surrogate for early atherosclerosis. Slow coronary flow in a normal coronary angiogram is not a rare condition, but its pathogenesis remains unclear. A total of 85 patients with angina were evaluated of their brachial artery FMD, carotid IMT and conventional coronary angiography. Coronary flow was quantified using the corrected thrombosis in myocardial infarction (TIMI) frame count method. Group I was a control with normal coronary angiography (n = 41, 56.1 ± 8.0 yr) and group II was no significant coronary stenosis with slow flow (n = 44, 56.3 ± 10.0 yr). Diabetes was rare but dyslipidemia and family history were frequent in group II. Heart rate was higher in group II than in group I. White blood cells, especially monocytes and homocysteine were higher in group II. The FMD was significantly lower in group II than in group I. Elevated heart rate, dyslipidemia and low FMD were independently related with slow coronary flow in regression analysis. Therefore, endothelial dysfunction may be an earlier vascular phenomenon than increased carotid IMT in the patients with slow coronary flow.

Background and Objectives

Prehypertension according to JNC7 is common and is associated with increased vascular mortality. The importance of management in high-normal blood pressure (BP) is underemphasized.

Subjects and Methods

We analyzed major adverse cardiac events (MACEs) in the Korea Acute Myocardial Infarction Registry in normal BP (group I) and high-normal BP (group II) patients.

Results

Among 14871 patients, 159 (61±12.3 years, 122 males) satisfied the study indication. Six-month and one-year clinical follow-up rate was 88.9% and 85.8%, respectively. Group I had 78 patients (60.9±12.4 years). Group II had 81 patients (61.6±12.5 years). Demographics of patients were not different between groups. Treatment strategy was not different. Initial Thrombolysis in Myocardial Infarction flow grade 0 was less frequent in group II (n=32, 47.1%) than in group I (n=16, 21.9%) (p=0.001). Successful intervention rate was not different between group II (93.8%) and group I (97.1%) (p=0.590). Six-month MACE occurred in 3 patients in group I (4.4%) and 10 in group II (15.6%) (p=0.031). Compared with normal BP, the odds ratio for patients with high-normal BP was 1.147 (p=0.045, 95% confidence interval 1.011-1.402) for 6-month MACE.

Conclusion

Even though high-normal BP patients had a better baseline clinical status, the prognosis was poorer than patients with normal BP. Therapeutic BP target goal for the patients with acute myocardial infarction should be <140/90 mm Hg, which is recommended in JNC7.

Despite an increasing prevalence and burden of disease in the elderly, little is known about the management and outcomes of acute coronary syndromes in this group. We report the case of a 101-year-old female patient with a non-ST segment elevation myocardial infarction. Coronary angiography showed a total occlusion of the proximal right coronary artery (RCA), and a significant stenosis in the proximal to mid left anterior descending artery (LAD). Despite a very poor initial clinical status, a percutaneous coronary intervention was successfully performed for the total occlusion in the RCA. The LAD lesion was treated with medical therapy only, on account of the age and general condition of the patient. She was discharged after recovering to a good health status, free of chest pain or dyspnea.

The aim of the present study was to evaluate the plaque components and the predictors of thin-cap fibroatheroma (TCFA) in anemic patients with acute coronary syndrome using virtual histology-intravascular ultrasound (VH-IVUS). Anemia was defined according to criteria of the World Health Organization, (i.e. , hemoglobin levels < 13 g/dL in men and < 12 g/dL in women) and we compared VH-IVUS findings between anemia group (171 patients, 260 lesions) and non-anemia group (569 patients, 881 lesions). Anemia group had greater % necrotic core (NC) volume (21% ± 9% vs 19% ± 9%, P = 0.001) compared with non-anemia group. Hemoglobin level correlated negatively with absolute NC volume (r = -0.235, P < 0.001) and %NC volume (r = -0.209, P < 0.001). Independent predictors of TCFA by multivariate analysis were diabetes mellitus (odds ratio [OR], 2.213; 95% confidence interval [CI], 1.403-3.612, P = 0.006), high-sensitivity C-reactive protein (OR, 1.143; 95% CI, 1.058-1.304, P = 0.012), microalbuminuria (albumin levels of 30 to 300 mg/g of creatinine) (OR, 2.124; 95% CI, 1.041-3.214, P = 0.018), and anemia (OR: 2.112; 95% CI 1.022-3.208, P = 0.028). VH-IVUS analysis demonstrates that anemia at the time of clinical presentation is associated with vulnerable plaque component in patients with acute coronary syndrome.

One of the single anomalous origins of coronary artery that has rarely been reported is a congenital anomaly of coronary circulation that occurs in the left coronary artery originating from the right coronary sinus of valsalva. We report a 49-year-old male patient with non-ST segment elevated myocardial infarction that was identified to have an anomalous origin of the left coronary artery from the right coronary artery (RCA) with thrombotic total occlusion of RCA by coronary angiography and cardiac computed tomography. The patient underwent successful percutaneous coronary intervention in total occlusion of the RCA and was discharged after uneventful recovery.

The present study aimed to investigate the clinical characteristics and 1-year outcomes of acute myocardial infarction (AMI) patients without significant stenosis on a coronary angiogram comparison with the clinical characteristics and outcomes of patients with significant coronary artery stenosis. A total of 1,220 patients with AMI were retrospectively classified into Group I (≥50% diameter stenosis, n=1,120) and Group II (<50%, n=100). Group II was further divided into two subgroups according to the underlying etiology: cryptogenic (Group II-a, n=54) and those with possible causative factors (Group II-b, n=46). Patients in Group II were younger, were more likely to be women, and were less likely to smoke and to have diabetes mellitus than were patients in Group I. The levels of cardiac enzymes, LDL-cholesterol levels, and the apo-B/A1 ratio were lower in Group II. However, 1-month and 12-month rates of major adverse cardiac events (MACE) were not significantly different between the two groups. The Group II-b subgroup comprised 29 patients with vasospasm, 11 with myocardial bridge, and 6 with spontaneous thrombolysis. Left ventricular ejection fraction and creatinine clearance were lower and levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hs-CRP) were higher in Group II-a than in Group II-b. However, outcomes including MACE and mortality at 12 months were not significantly different between the two subgroups. The 1-year outcomes of patients in Group II were similar to those of patients in Group I. The clinical outcomes in Group II-a were also similar to those of Group II-b, although the former group showed higher levels of NT-proBNP and hs-CRP.

The GATA family members are zinc finger transcription factors involved in cell differentiation and proliferation. GATA3 in particular is necessary for mammary gland maturation, and its loss has been implicated in breast cancer development. Our goal was to validate the ability of GATA3 expression to predict survival in breast cancer patients. Protein expression of GATA3 was analyzed on a high density tissue microarray consisting of 242 cases of breast cancer. We associated GATA3 expression with patient outcomes and clinicopathological variables. Expression of GATA3 was significantly increased in breast cancer, in situ lesions, and hyperplastic tissue compared to normal breast tissue. GATA3 expression decreased with increasing tumor grade. Low GATA3 expression was a significant predictor of disease-related death in all patients, as well as in subgroups of estrogen receptor positive or low grade patients. Additionally, low GATA3 expression correlated with increased tumor size and estrogen and progesterone receptor negativity. GATA3 is an important predictor of disease outcome in breast cancer patients. This finding has been validated in a diverse set of populations. Thus, GATA3 expression has utility as a prognostic indicator in breast cancer.

The protein 14-3-3σ is involved in the regulation of cellular processes such as apoptosis, cell cycle progression and proliferation. Disruption of protein expression has been implicated in a number of malignancies. Here we examine the expression pattern of 14-3-3σ in breast cancer and specifically consider whether expression in ductal carcinoma in situ (DCIS) lesions is predictive of disease outcome. We examined 14-3-3σ protein expression and localization using immunohistochemical staining on a high-density tissue microarray consisting of 157 invasive breast cancer patients. Statistical analyses were used to assess the correlation of 14-3-3σ expression with clinico-pathological parameters and patient outcome. We observed a statistically significant increase in 14-3-3σ protein expression in ductal hyperplasia, DCIS, and invasive ductal carcinoma (IDC) as compared normal glandular epithelium. In IDC, lower expression of 14-3-3σ tended to predicted poorer survival time while in DCIS lesions, there was a stronger correlation between relatively higher levels of 14-3-3σ predicting shorter survival time. Further, of patients who had concurrent DCIS and IDC lesions, those that exhibited a decrease of 14-3-3σ expression from DCIS to IDC had significantly shorter survival time. Our findings indicate that 14-3-3σ expression may be a useful prognostic indicator for survival in patients with breast cancer with an elevated 14-3-3σ in earlier disease predicting a less favorable disease outcome. To our knowledge this is the first published study associating 14-3-3σ protein expression with breast cancer survival.

Background/Aims

A controversy exists about which statin is preferable for patients with acute myocardial infarction (AMI), and clinical impacts of different statins according to lipophilicity have not been established.

Methods

The 1,124 patients with AMI included in the present study were divided into hydrophilic- and lipophilic-statin groups. In-hospital complications (defined as death, cardiogenic shock, ventricular arrhythmia, infection, bleeding, and renal insufficiency, and other fatal arrhythmias), major adverse cardiac events (MACE), all-cause death, re-myocardial infarction, re-percutaneous coronary intervention (re-PCI), and surgical revascularization were analyzed during a 1-year clinical follow-up.

Results

Baseline characteristics were similar between the two groups, and in-hospital complication rates showed no between-group differences (11.7% vs. 12.8%, p = 0.688). Although MACE at the 1- and 6-month clinical follow-ups occurred more in hydrophilic statin group I (1 month: 10.0% vs. 4.4%, p = 0.001; 6 month: 19.9% vs. 14.2%, p = 0.022), no significant difference in MACE was observed at the 1-year follow-up (21.5% vs. 17.9%, p = 0.172). Both statin groups showed similar efficacy for reducing serum lipid concentrations. A Cox-regression analysis showed that the use of a hydrophilic statin did not predict 1-year MACE, all-cause death, AMI, or re-PCI.

Conclusions

Although short-term cardiovascular outcomes were better in the lipophilic-statin group, 1-year outcomes were similar in patients with AMI who were administered hydrophilic and lipophilic statins. In other words, the type of statin did not influence 1-year outcomes in patients with AMI.

Background and Objectives

The renin-angiotensin-aldosterone system has been implicated in the pathogenesis of neointimal hyperplasia, and a role for angiotensin II in the migration and proliferation of vascular smooth muscle cells in restenotic lesions has been proposed. The aim of this study was to determine the anti-proliferative and anti-inflammatory effects of ramiprilat-coated stents in a porcine coronary overstretch restenosis model.

Subjects and Methods

Pigs were randomized into two groups in which the coronary arteries {16 pigs (16 coronaries in each group)} had a 3.0×17 mm ramiprilat-coated MAC stent or a 3.0×17 mm control MAC stent (AMG, Munich, Germany) implanted with oversizing (stent-to-artery ratio, 1.3 : 1) in porcine coronary arteries, and histopathologic analysis was assessed 28 days after stenting.

Results

There were no significant differences in the injury and inflammation scores between the two groups (1.20±0.43 vs. 1.23±0.57, p=0.8; and 1.21±0.39 vs. 1.25±0.49, p=0.6, respectively). Within the neointima, most inflammatory cells were lymphohistiocytes. Significant positive correlations existed between inflammatory cell counts and the neointima areas (r=0.567, p<0.001), and between inflammatory cell counts and the percent area stenosis (r=0.478, p<0.001). There was no significant difference in the inflammatory cell counts normalized to the injury (110±89 vs. 123±83, p=0.4) and fibrin scores (0.15±0.06 vs. 0.17±0.07, p=0.8) between the 2 groups. There were trends toward a smaller neointima area (1.06±0.51 mm2 vs. 1.28±0.35 mm2, p=0.083) and a smaller percent area stenosis (18.9±8.7% vs. 21.8±7.2%, p=0.088) in the ramiprilat-coated stent group.

Conclusion

Although the ramiprilat-coated stent did not show significant inhibitory effects on neointimal hyperplasia, the ramiprilat-coated stent showed good effects on the inflammatory reaction and arterial healing similar to the control stent in a porcine coronary restenosis model.

Background and Objectives

We used virtual histology-intravascular ultrasound (VH-IVUS) to evaluate the relationship between high-sensitivity C-reactive protein (hs-CRP) levels and plaque components in 279 acute coronary syndrome (ACS) patients.

Subjects and Methods

We divided patients into three groups according to their hs-CRP levels {lowest tertile <0.07 mg/dL (n=93), middle tertile ≥0.07, <0.4 mg/dL (n=93), and highest tertile ≥0.4 mg/dL (n=93)}. Thin-cap fibroatheroma (TCFA) was defined as focal, necrotic core (NC)-rich (≥10% of the cross-sectional area) plaques in contact with the lumen in a plaque burden ≥40%.

Results

The highest tertile group was mostly diabetics (20%, 27%, 40%, p=0.009), and had the greatest plaque plus media volume (163±139/mm3 vs. 201±155/mm3 vs. 232±176/mm3, p=0.013). The highest tertile group had the greatest absolute and % NC volumes (13.6±15.1 mm3 vs. 14.8±14.2 mm3 vs. 23.7±24.3 mm3, p<0.001, and 14.9±8.7% vs. 16.0±8.7% vs. 19.5±10.2%, p=0.024, respectively). The culprit lesion TCFA was observed most frequently in the highest tertile group (28% vs. 35% vs. 55%, p=0.006). By multivariable analysis, absolute NC volume was an independent predictor of hs-CRP elevation {odds ratio (OR); 1.03, 95% confidence interval (CI)=1.06-1.21, p=0.004}, and hs-CRP was an independent predictor of TCFA (OR; 1.86, 95% CI=1.11-2.90, p=0.010).

Conclusion

VH-IVUS analysis has demonstrated that ACS patients with elevated hs-CRP have more vulnerable plaque component (NC-rich plaques and higher frequency of culprit lesion TCFA), compared with ACS patients with normal hs-CRP.

Stent thrombosis is a fatal complication in patients who have undergone percutaneous coronary intervention, and discontinuation of anti-platelet agent is a major risk factor of stent thrombosis. We report a rare case of very late stent thrombosis (VLST) following discontinuation of anti-platelet agents in a patient who experienced acute myocardial infarction and essential thrombocytosis. She had undergone implantation of a drug eluting stent (DES) and a bare metal stent (BMS) two and half years prior to her presentation. VLST developed in DES, not in BMS, following interruption of anti-platelet therapy.

Background

Raf-1 kinase inhibitor protein (RKIP) has been reported to negatively regulate signal kinases of major survival pathways. RKIP activity is modulated in part by phosphorylation on Serine 153 by protein kinase C, which leads to dissociation of RKIP from Raf-1. RKIP expression is low in many human cancers and represents an indicator of poor prognosis and/or induction of metastasis. The prognostic power has typically been based on total RKIP expression and has not considered the significance of phospho-RKIP.

Methods

The present study examined the expression levels of both RKIP and phospho-RKIP in human lung cancer tissue microarray proteomics technology.

Results

Total RKIP and phospho-RKIP expression levels were similar in normal and cancerous tissues. phospho-RKIP levels slightly decreased in metastatic lesions. However, the expression levels of phospho-RKIP, in contrast to total RKIP, displayed significant predictive power for outcome with normal expression of phospho-RKIP predicting a more favorable survival compared to lower levels (P = 0.0118); this was even more pronounced in more senior individuals and in those with early stage lung cancer.

Conclusions

This study examines for the first time, the expression profile of RKIP and phospho-RKIP in lung cancer. Significantly, we found that phospho-RKIP was a predictive indicator of survival.

Background

Tissue microarray (TMA) data are commonly used to validate the prognostic accuracy of tumor markers. For example, breast cancer TMA data have led to the identification of several promising prognostic markers of survival time. Several studies have shown that TMA data can also be used to cluster patients into clinically distinct groups. Here we use breast cancer TMA data to cluster patients into distinct prognostic groups.

Methods

We apply weighted correlation network analysis (WGCNA) to TMA data consisting of 26 putative tumor biomarkers measured on 82 breast cancer patients. Based on this analysis we identify three groups of patients with low (5.4%), moderate (22%) and high (50%) mortality rates, respectively. We then develop a simple threshold rule using a subset of three markers (p53, Na-KATPase-β1, and TGF β receptor II) that can approximately define these mortality groups. We compare the results of this correlation network analysis with results from a standard Cox regression analysis.

Results

We find that the rule-based grouping variable (referred to as WGCNA*) is an independent predictor of survival time. While WGCNA* is based on protein measurements (TMA data), it validated in two independent Affymetrix microarray gene expression data (which measure mRNA abundance). We find that the WGCNA patient groups differed by 35% from mortality groups defined by a more conventional stepwise Cox regression analysis approach.

Conclusions

We show that correlation network methods, which are primarily used to analyze the relationships between gene products, are also useful for analyzing the relationships between patients and for defining distinct patient groups based on TMA data. We identify a rule based on three tumor markers for predicting breast cancer survival outcomes.

Background/Aims

Carvedilol is an antioxidant that inhibits smooth muscle cell proliferation and migration. The aim of this study was to investigate the beneficial effects of carvedilol-loaded stents on 2-year clinical outcomes after stent implantation in patients with coronary artery disease.

Methods

We performed a prospective trial with male subjects to compare the safety and effects of carvedilol-loaded BiodivYsio® stents implanted into 20 patients with those of bare-metal BiodivYsio® stents implanted into 21 patients for de novo coronary lesions. The primary end point was the degree of neointimal hyperplasia, which was measured by intravascular ultrasound (IVUS) 6 months after the procedure; the secondary end point was major adverse cardiac events (MACE) at 2 years after implantation. All carvedilol and control stents were deployed successfully.

Results

A 2-year follow-up was completed for 19 patients (95%) in the carvedilol stent group and 20 patients (95%) in the control stent group. IVUS showed a trend toward a larger luminal area (6.86 ± 2.59 vs. 5.47 ± 1.52 mm2, p = 0.267), smaller neointimal area (1.34 ± 0.70 vs. 2.40 ± 1.73 mm2, p = 0.18), and reduced net decrease in luminal area (-0.78 ± 0.97 vs. -1.89 ± 1.78 mm2, p = 0.106) in the carvedilol stent group compared with the control stent group, respectively. There were no significant differences in the incidence of MACE (10.5 vs. 30.0%, respectively, p = 0.132) between the groups at 2 years after stent implantation. Stent thrombosis did not occur in either group after 2 years.

Conclusions

The carvedilol-loaded stents tended to inhibit neointimal hyperplasia without the occurrence of cardiac death, myocardial infarction, or stent thrombosis at 2-year follow-up.

Background/Aims

The aim of this study was to assess the effects of a usual dose of simvastatin (20 mg/day) on plaque regression and vascular remodeling at the peri-stent reference segments after bare-metal stent implantation.

Methods

We retrospectively investigated serial intravascular ultrasound (IVUS) findings in 380 peri-stent reference segments (184 proximal and 196 distal to the stent) in 196 patients (simvastatin group, n = 132 vs. non-statin group, n = 64). Quantitative volumetric IVUS analysis was performed in 5-mm vessel segments proximal and distal to the stent.

Results

IVUS follow-up was performed at a mean of 9.4 months after stenting (range, 5 to 19 months). No significant differences were observed in the changes in mean plaque plus media (P&M) area, mean lumen area, and mean external elastic membrane (EEM) area from post-stenting to follow-up at both proximal and distal edges between the simvastatin and non-statin group. Although lumen loss within the first 3 mm from each stent edge was primarily due to an increase in P&M area rather than a change in EEM area, and lumen loss beyond 3 mm from each stent edge was due to a combination of increased P&M area and decreased EEM area, no significant differences in changes were observed in P&M, EEM, and lumen area at every 1-mm subsegment between the simvastatin and non-statin group.

Conclusions

A usual dose of simvastatin does not inhibit plaque progression and lumen loss and does not affect vascular remodeling in peri-stent reference segments in patients undergoing bare-metal stent implantation.

Background and Objectives

An elevated concentration of lipoprotein(a) {Lp(a)} is associated with an increased prevalence and increased severity of coronary artery disease. However, the relationship between Lp(a) levels and outcomes after acute myocardial infarction (AMI) is unclear.

Subjects and Methods

Between October 2005 and June 2007, we measured serum Lp(a) levels in 832 consecutive AMI patients (age, 62.8±12.4 years, 600 men) on admission. They were divided into tertiles according to their serum Lp(a) levels {Tertile 1 (n=276), Lp(a)<13.8 mg/dL; Tertile 2 (n=279), Lp(a)=13.8-30.6 mg/dL; Tertile 3 (n=277), Lp(a)>30.6 mg/dL}.

Results

There were no differences in baseline clinical characteristics among Tertiles 1, 2, and 3, except for proportions of Killip class III-IV patients (5.8% vs. 10.0% vs. 18.8%, respectively, p<0.001). There were significant differences in left ventricular ejection fractions (57.3±11.4% vs. 55.9±12.3% vs. 53.1±13.1%, p<0.001). Among the laboratory findings, there were significant differences in total cholesterol (173.3±37.2 vs. 183.5±38.9 vs. 185.3±43.8 mg/dL, p=0.001), low density lipoprotein-cholesterol (111.3±34.3 vs. 122.9±34.7 vs. 123.3±39.4 mg/dL, p<0.001), apolipoprotein B (92.8±25.4 vs. 100.8±26.0 vs. 101.9±28.8 mg/dL, p<0.001), and amino-terminal pro-brain natriuretic peptide levels (1805.2±4343.3 vs. 2607.9±5216.3 vs. 3981.5±7689.7 pg/mL, p<0.001). After adjusting for multiple variables in the high Killip class (III-IV) subgroup, the risk estimate for major adverse cardiovascular events (MACE) at 1-year follow-up was significantly higher in Tertile 3 than in Tertiles 1 or 2 (hazard ratio 6.723, 95% confidence interval 1.037-43.593, p=0.046).

Conclusion

In patients in high Killip classes, high serum levels of Lp(a) were significantly associated with long-term adverse outcomes after AMI.

Background/Aims

The usefulness of global longitudinal peak systolic strain (GLPSS) measurement by automated function imaging (AFI) in the prediction of perfusion status of infarct-related artery (IRA) before percutaneous coronary intervention (PCI) was evaluated.

Methods

Sixty-nine patients with acute myocardial infarction (AMI) who underwent successful primary PCI were divided into two groups; the patients with occlusion of IRA (Group I, 41 patients, 63.0 ± 14.9 years of age, 31 males) versus the patients with patent IRA (Group II, 28 patients, 63.8 ± 11.2 years of age, 15 males). GLPSS by AFI and wall-motion score index (WMSI) were analyzed in both groups.

Results

GLPSS was significantly decreased in Group I compared with Group II (-11.2 ± 3.7 vs. -14.1 ± 4.7%, p = 0.005), but WMSI (1.49 ± 0.28 vs. 1.35 ± 0.32, p = 0.062) did not differ between groups. GLPSS of infarct segments was significantly lower (-3.7 ± 5.4 vs. -11.4 ± 4.8%, p < 0.001), and WMSI of infarct segments was significantly higher (2.13 ± 0.57 vs. 1.66 ± 0.57, p = 0.001) in Group I compared with Group II. By receiver operation curve analysis, the area under the curve to predict IRA occlusion was 0.850 in GLPSS of infarct segments and 0.719 in WMSI of infarct segments. The optimal cut-off value to predict IRA occlusion was -9.4% in GLPSS of infarct segments (sensitivity, 85.4%; specificity, 67.9%) and 1.68 in WMSI of infarct segments (sensitivity, 78.0%; specificity, 60.7%).

Conclusions

The present study suggested that GLPSS measured by AFI is a more sensitive predictor of IRA occlusion than is WMSI before PCI. Routine measurement of GLPSS by AFI can be a very useful tool in risk stratification of AMI.

Background

MED28 (also known as EG-1 and magicin) has been implicated in transcriptional control, signal regulation, and cell proliferation. MED28 has also been associated with tumor progression in in vitro and in vivo models. Here we examined the association of MED28 expression with human breast cancer progression.

Methods

Expression of MED28 protein was determined on a population basis using a high-density tissue microarray consisting of 210 breast cancer patients. The association and validation of MED28 expression with histopathological subtypes, clinicopathological variables, and disease outcome was assessed.

Results

MED28 protein expression levels were increased in ductal carcinoma in situ and invasive ductal carcinoma of the breast compared to non-malignant glandular and ductal epithelium. Moreover, MED28 was a predictor of disease outcome in both univariate and multivariate analyses with higher expression predicting a greater risk of disease-related death.

Conclusions

We have demonstrated that MED28 expression is increased in breast cancer. In addition, although the patient size was limited (88 individuals with survival information) MED28 is a novel and strong independent prognostic indicator of survival for breast cancer.

Oxidative damage is thought to be a major cause of the progression of dopamine (DA)rgic neurodegeneration as in Parkinson's disease. We have previously reported that tetrahydrobiopterin (BH4), an endogenous molecule required for DA synthesis, exerts oxidative stress to DA-producing cells and facilitates the production of DA quinone. It is known that aconitase, present in both mitochondrial and cytosolic forms, act as an reactive oxygen species (ROS) sensor, and that their inactivation leads to further generation of ROS. In the present study we investigated whether the BH4-associated vulnerability of DA cells might involve aconitase. In DArgic cell line CATH.a, BH4 treatment caused reduction of activity of both mitochondrial and cytosolic aconitases, and this appeared to be due to direct inactivation of the pre-existing enzyme molecules. Although most of the activity reduced by BH4 was increased upon reactivation reaction under a reducing condition, the restoration was not complete, suggesting that irreversible and covalent modification has occurred. The aconitase inactivation was exacerbated in the presence of DA and attenuated in the presence of tyrosine hydroxylase inhibitor a-methyl-p-tyrosine, suggesting the involvement of DA. The degree of inactivation increased when the cells were treated with the quinone reductase inhibitor dicoumarol and decreased in the presence of quinone reductase inducer sulforaphane. Taken together, BH4 appeared to lead to both reversible and irreversible inactivation of aconitase and that this is facilitated by the presence of DA and accumulation of DA quinone.

Background

The lack of epidemiologic information on osteoporotic hip fractures hampers the development of preventive or curative measures against osteoporosis in South Korea. We conducted a population-based study to estimate the annual incidence of hip fractures. Also, we examined factors associated with post-fracture mortality among Korean elderly to evaluate the impact of osteoporosis on our society and to identify high-risk populations.

Methods

The Korean National Health Insurance (NHI) claims database was used to identify the incidence of hip fractures, defined as patients having a claim record with a diagnosis of hip fracture and a hip fracture-related operation during 2003. The 6-month period prior to 2003 was set as a 'window period,' such that patients were defined as incident cases only if their first record of fracture was observed after the window period. Cox's proportional hazards model was used to investigate the relationship between survival time and baseline patient and provider characteristics available from the NHI data.

Results

The age-standardized annual incidence rate of hip fractures requiring operation over 50 years of age was 146.38 per 100,000 women and 61.72 per 100,000 men, yielding a female to male ratio of 2.37. The 1-year mortality was 16.55%, which is 2.85 times higher than the mortality rate for the general population (5.8%) in this age group. The risk of post-fracture mortality at one year is significantly higher for males and for persons having lower socioeconomic status, living in places other than the capital city, not taking anti-osteoporosis pharmacologic therapy following fracture, or receiving fracture-associated operations from more advanced hospitals such as general or tertiary hospitals.

Conclusion

This national epidemiological study will help raise awareness of osteoporotic hip fractures among the elderly population and hopefully motivate public health policy makers to develop effective national prevention strategies against osteoporosis to prevent hip fractures.

Background and Objectives

Left ventricular (LV) remodeling (LVR) after an acute myocardial infarction (AMI) has important clinical implications. We have investigated the prognostic relevance of ventricular systolic dyssnchrony as an indicator of LVR after an AMI.

Subjects and Methods

We enrolled 92 patients (males, 72.8%; mean age, 61.0±13.0 years) with an AMI who underwent successful percutaneous coronary intervention. We analyzed the baseline characteristics, the laboratory and echocardiographic findings, and we performed follow-up echocardiography 6 months after the AMI. The patients were divided into two groups: 1) the presence of LVR, which was defined as an increment of LV end systolic volume (LVESV) >20% compared with the baseline examination; and 2) the absence of LVR.

Results

Twenty-seven patients (29.3%) developed LVR after a 6 month follow-up. There was no statistically significant difference in the clinical and angiographic findings between the two groups. With respect to the laboratory findings, the LVR group had a higher peak creatine kinase MB (CK-MB) (149.9±155.0 vs. 74.6±69.7 U/L, p=0.001) and troponin-I (70.2±73.3 vs. 43.2±39.5 ng/mL, p=0.024) level than the group without LVR. With respect to echocardiographic findings, the baseline LV ejection fraction (EF) and LVESV were not significantly different (LVESV, 73.0±37.3 vs. 91.3±52.0 mL, p=0.013; and EF, 58.3±13.3 vs. 55.6±11.8%, p=0.329) between the groups with and without LVR, respectively. The degree of LV dyssynchrony, which was assessed by tissue Doppler imaging, was significantly higher in the LVR group than the group without LVR (75.2±43.4 vs. 38.3±32.5 ms), and the degree of LV dyssynchrony was an independent predictor for LVR based on multivariate analysis {hazard ratio (HR)=0.097, p<0.001}. In receiver operating characteristics (ROC) curve analysis, the area under the curve (AUC) was 0.754 and a cutoff value of 45.9 predicted the development of LVR with 74.1% sensitivity and 72.3% specificity.

Conclusion

The presence of LV dyssynchroncy immediately after a myocardial infarction is an important predictive factor for development LVR.