Kugel's Artery: Silent Bystander or Savior?

Kugel's artery is defined as a rare anatomical variant of the coronary artery vascular bed consisting of an anastomotic connection between branches of the right coronary artery (RCA) and/or left circumflex artery (LCX). Kugel's artery has been reported to have an incidence of 6% in the general population. The presence of this anastomotic communication may play a pathophysiological role in a patient with a right dominant coronary circulation and an underlying coronary artery disease (CAD) affecting the right coronary system. Understanding the existence and significance of Kugel's artery and the anastomotic network cannot be overemphasized. The presence of an anomalous vascular connection bypassing an area of epicardial vessel occlusion may be a lifesaving pathophysiological finding that maintains myocardial perfusion and viability. Herein, we present a case with multivessel occlusion myocardial infarction found to have anomalous vascular anastomosis between the proximal RCA and distal segment of the same artery.

Red cell distribution width (RDW) as a predictor of long-term mortality in patients undergoing percutaneous coronary intervention.

Red cell distribution width (RDW) has been shown to be an independent predictor of mortality in patients with coronary artery disease and in patients with heart failure. The current study evaluated the prognostic utility of RDW in patients undergoing percutaneous coronary intervention (PCI). We evaluated 859 patients who underwent PCI during January 2003 to August 2005. After a median follow up of four (interquartile range 3.1 to 4.4) years, there were a total of 95 (11%) deaths. RDW was analysed as a categorical variable with empirically determined cut points of 13.3 and 15.7 (low RDW <13.3, medium RDW > or = 13.3 to <15.7, high RDW > or = 15.7) based on differences in hazard ratio (HR) for death among RDW deciles. In univariate analysis, higher RDW was a significant predictor of mortality (p < 0.001). In multivariate analysis there was a significant two-way interaction between RDW and haemoglobin (Hgb). RDW was not an independent predictor of mortality in patients with Hgb <10.4. However, among patients with Hgb >10.4, high RDW was a strong and independent predictor of mortality. For patients with Hgb > or = 10.4 to <12.7, HR for death in patients with high RDW relative to low RDW was 5.2 (95% confidence intervals [CI]: 2.0-13.3). For patients with Hgb > or = 12.7, HR for death in patients with high RDW relative to low RDW was 8.6 (CI:2.8-28.6). Higher RDW was a strong and independent predictor of long-term mortality in patients undergoing PCI who were not anaemic at baseline.

Long-term mortality after bolus-only administration of abciximab, eptifibatide, or tirofiban during percutaneous coronary intervention.

OBJECTIVE: To evaluate the long-term mortality after bolus-only administration of abciximab, eptifibatide, and tirofiban during percutaneous coronary intervention (PCI). BACKGROUND: Studies on platelet glycoprotein IIb/IIIa receptor inhibitors (GPI) administered as bolus-only during PCI suggest that this strategy may be similar in efficacy, safer, and more cost-effective compared to a bolus plus infusion of GPI. METHODS: We evaluated 864 patients (abciximab = 274, eptifibatide = 361, and tirofiban = 229) who underwent PCI with a bolus-only regimen during January 2003 to August 2005. RESULTS: After a median follow up of four (interquartile range, 3-4.5) years, there were a total of 95 (11%) deaths. The survival rate was 83% in the abciximab group, 91% in the eptifibatide group, and 93% in the tirofiban group (P = 0.003 by log-rank test). After adjustment for baseline clinical and procedural characteristics using a Cox proportional hazards model, the abciximab group had a significantly higher mortality compared to the eptifibatide group (P = 0.003; Hazard ratio (HR) for eptifibatide compared to abciximab was 0.49 (95% confidence intervals [CI]: 0.30-0.78). The long-term mortality was not significantly different in the tirofiban group compared to the abciximab group (P = 0.33) or the eptifibatide group (P = 0.20), perhaps because of shorter follow-up period and fewer patients in the tirofiban group. CONCLUSION: When given as bolus-only during PCI, eptifibatide may improve long-term survival compared to abciximab.

Baseline plasma adiponectin levels as a predictor of left ventricular systolic dysfunction in patients referred for coronary angiography.

The objective of the present study was to determine the association between plasma adiponectin and left ventricular (LV) systolic function. Baseline plasma adiponectin was measured in 389 patients undergoing coronary angiography for a variety of indications at a Veterans Affairs Medical Center. Detailed demographic, clinical, laboratory, and angiographic data were available for patients. LV systolic function was assessed using ventriculography, and patients were grouped into those with normal or mild dysfunction (ejection fraction > or =45%) versus those with moderate to severe systolic dysfunction (ejection fraction <45%). After adjusting for a variety of clinically relevant covariates known to affect LV systolic function, adiponectin was independently associated with LV systolic function in the entire cohort of patients (p = 0.0002) using multivariate linear regression analysis. In addition, using multivariate logistic regression analysis, adiponectin was an independent predictor of the presence of moderate to severe LV dysfunction (odds ratio 1.54, 95% confidence interval 1.21 to 1.97, p = 0.0005). Moreover, baseline adiponectin was also independently associated with LV function in both the myocardial infarction (MI) and non-MI subpopulations of patients (p = 0.0401 and p= 0.0023, respectively). Finally, in the non-MI subpopulation, baseline adiponectin was an independent predictor of moderate to severe LV systolic dysfunction (odds ratio 1.52, 95% confidence interval 1.15 to 2.02, p = 0.0034). In conclusion, baseline plasma adiponectin was an independent predictor of LV systolic dysfunction in a population of patients referred for coronary angiography.

Low plasma RANTES levels are an independent predictor of cardiac mortality in patients referred for coronary angiography.

OBJECTIVE: Our objective was to evaluate the prognostic value of baseline plasma RANTES levels in patients with known or suspected coronary artery disease. RANTES is a chemokine produced by a variety of cell types including platelets that has been implicated in atherosclerosis. METHODS AND RESULTS: Baseline plasma RANTES levels were measured in 389 male patients undergoing coronary angiography at a Veterans Affairs Medical Center. The patients were followed-up prospectively for the occurrence of cardiac mortality and myocardial infarction. Follow-up data at 24 months were available for 97% of patients. In the entire cohort of patients, low baseline RANTES levels were an independent predictor of cardiac mortality. For cardiac death at 24 months, the survival rate was 87.3% in the lowest tertile of RANTES values, compared with 94% in the upper 2 tertiles combined (P=0.0298 by log rank test). Furthermore, when patients were risk-stratified into those with and without an acute coronary syndrome, RANTES was an independent predictor of both cardiac mortality and myocardial infarction in those without an acute coronary syndrome. Finally, RANTES was also an independent predictor of cardiac mortality in the diabetic subset. CONCLUSIONS: In a cohort of male patients undergoing coronary angiography, low baseline plasma RANTES levels are an independent predictor of cardiac mortality.

Usefulness of Complement C1q to Predict 10-Year Mortality in Men With Diabetes Mellitus Referred for Coronary Angiography.

The complement system consists of a family of proteins that play a critical role in the innate immune system. Complement activation has been implicated in many chronic inflammatory diseases, including atherosclerosis. However, a number of experimental studies have highlighted a beneficial role of component C1q in early atherosclerosis and in diabetes mellitus (DM). Despite these data, there have been no studies that have specifically examined the utility of plasma complement C1q as a clinical biomarker in patients with known or suspected coronary artery disease. In this study, baseline plasma complement C1q levels were measured in 159 men with DM who were referred for coronary angiography and who were followed up prospectively for the development of all-cause mortality for 10 years. After adjustment for baseline clinical, angiographic, and laboratory parameters, reduced plasma complement C1q levels were an independent predictor of all-cause mortality at 10 years (hazard ratio 0.66, 95% confidence interval 0.52 to 0.84, p = 0.0006). In additional multivariate models that adjusted for a variety of biomarkers with established prognostic efficacy, complement C1q remained an independent predictor of all-cause mortality at 10 years. In conclusion, reduced levels of complement C1q are associated with an increased risk of all-cause mortality at 10 years in patients with DM referred for coronary angiography. Furthermore, this association is independent of a variety of clinical, angiographic, laboratory variables, including biomarkers with established prognostic efficacy in the prediction of adverse cardiovascular outcomes.

Usefulness of the serum complement component C4 as a predictor of stroke in patients with known or suspected coronary artery disease referred for coronary angiography.

The complement system has been implicated in the pathogenesis of atherosclerosis. In addition, complement activation and complement-mediated brain injury have been found in a variety of central nervous system diseases, including stroke. However, there are limited data about the value of complement components for prediction of stroke. Complement C3 and C4 levels, in addition to a variety of established biomarkers, were measured in 389 men with known or suspected coronary artery disease referred for coronary angiography for a variety of indications at a Veterans Affairs Medical Center. Patients were followed prospectively for the development of stroke, which was defined and classified according to criteria of the Trial of Org 10172 in Acute Stroke Treatment (TOAST). All strokes were confirmed with magnetic resonance imaging or computed tomography. For the 97% of patients in whom 24-month follow-up data were available, there were 23 strokes (5.9%). By multivariate Cox proportional hazard analysis, complement C4 was an independent predictor of stroke, with a hazard ratio of 1.57 (95% confidence interval 1.03 to 2.39, p = 0.0358). The 24-month stroke-free survival rate for the patients whose complement C4 levels were equal to or below the median value for the entire cohort was 96.1% compared with 90.1% for patients whose complement C4 levels were above the median value, p = 0.0127 by log rank test). In conclusion, in a cohort of men across a spectrum of risk referred for coronary angiography, a single baseline determination of serum complement C4 level is an independent predictor of the future development of stroke.

Usefulness of baseline plasma myeloperoxidase levels as an independent predictor of myocardial infarction at two years in patients presenting with acute coronary syndrome.

Baseline plasma myeloperoxidase (MPO) levels have been shown to independently predict the early risk of myocardial infarction (MI) in patients presenting with chest pain. In addition, baseline MPO levels have been demonstrated to predict the development of adverse cardiac events up to 6 months after an acute coronary syndrome (ACS). However, in contrast to other biomarkers, there are no data about the long-term independent predictive value of baseline MPO values in patients with ACS. The present study investigated the long-term prognostic significance of baseline MPO levels in a well-characterized cohort of 193 men with ACS who were referred for coronary angiography at a Veterans Administration Medical Center. All patients were followed prospectively for the development of death and MI, and follow-up data were available for all patients at 24 months. After controlling for different baseline clinical, laboratory, and angiographic variables, baseline plasma MPO values were a strong and independent predictor of MI at 24 months by multivariate analysis. Using the median MPO value of the entire cohort of patients (i.e., 20.34 ng/ml) as a prespecified cutoff, the MI-free survival at 24 months for the group whose baseline MPO values were < or =20.34 ng/ml was 88% compared with 74% in those whose values were >20.34 ng/ml (p = 0.0249 by log-rank test). In conclusion, these data demonstrate that baseline MPO levels independently predict MI at 2 years in patients with ACS.

Relation of baseline plasma phospholipid levels to cardiovascular outcomes at two years in men with acute coronary syndrome referred for coronary angiography.

In addition to cholesterol and triglycerides, plasma also contains phospholipids. The choline-containing phospholipids constitute >90% of total plasma phospholipids. To date, no studies have looked specifically at the prognostic significance of total phospholipids in patients with known or suspected coronary artery disease. The present study investigated the long-term prognostic significance of total choline-containing phospholipid levels in a well-characterized cohort of 193 men with acute coronary syndromes who were referred for coronary angiography at a Department of Veterans Affairs Medical Center. All patients were followed prospectively for the development of vascular outcomes. After controlling for a variety of baseline variables (including established biomarkers such high-sensitivity C-reactive protein and fibrinogen), plasma phospholipid values (analyzed as a continuous variable) were a strong and independent predictor of each of the individual end points of all-cause mortality (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.41 to 0.90, p = 0.0126), cardiac mortality (HR 0.49, 95% CI 0.29 to 0.81, p = 0.0057), and myocardial infarction (HR 0.71, 95% CI 0.52 to 0.98, p = 0.0342) when using a Cox proportional-hazards model. In addition, baseline phospholipid values were also an independent predictor of the composite outcome of all-cause mortality, fatal or nonfatal myocardial infarction, or stroke (HR 0.66, 95% CI 0.49 to 0.90, p = 0.0075). In conclusion, these data demonstrate that low baseline levels of total choline-containing phospholipid are a strong and independent predictor of cardiovascular outcomes (including mortality) in patients with acute coronary syndromes.

Comparison of platelet function and morphology in patients undergoing percutaneous coronary intervention receiving bivalirudin versus unfractionated heparin versus clopidogrel pretreatment and bivalirudin.

We hypothesized that direct thrombin inhibition could attenuate platelet activation and release of soluble CD40 ligand (sCD40L), a marker of inflammation, during percutaneous coronary intervention (PCI). To assess platelet function under flow conditions with bivalirudin versus unfractionated heparin (UFH), we employed the cone and plate(let) analyzer (CPA) assay in drug-spiked blood samples from volunteers (n = 3) in vitro, and then in PCI patients who received bivalirudin alone (n = 20), UFH alone (n = 15), and clopidogrel pretreatment plus bivalirudin (n = 15). Scanning electron microscopy was employed to image bivalirudin or UFH-treated platelets to determine whether platelet function observations had a morphologic explanation. Enzyme immunoassay was used to measure sCD40L levels in PCI patients. In vitro, bivalirudin decreased platelet surface coverage; UFH increased platelet surface coverage. In PCI patients, bivalirudin alone decreased platelet surface coverage, UFH alone increased platelet surface coverage, and clopidogrel pretreatment plus bivalirudin additively reduced platelet surface coverage. Unlike UFH, bivalirudin did not activate platelets in SEM studies. Bivalirudin alone or coupled with clopidogrel significantly reduced plasma sCD40L in PCI patients. In conclusion, our findings suggest that under flow conditions, bivalirudin alone or coupled with clopidogrel may have an antiplatelet effect versus UFH alone during PCI. These data suggest that bivalirudin and UFH may confer an anti-inflammatory effect by reducing sCD40L during PCI.

Usefulness of Plasma Tissue Inhibitor of Matrix Metalloproteinase-4 to Predict Death and Myocardial Infarction in Patients With Diabetes Mellitus Referred for Coronary Angiography.

TIMP-4 is the newest member of a family of secreted proteins known as the tissue inhibitors of metalloproteases that selectively inhibit matrix metalloproteases. TIMP-4 is abundantly expressed in human cardiovascular structures and has been implicated in cardiovascular disease. Furthermore, it has also been shown to be a novel target of peroxisome proliferator-activated receptor gamma in rat smooth muscle cells, suggesting a potential role in diabetes mellitus as well. However, there have been no studies that have specifically examined the utility of baseline plasma TIMP-4 levels for the prediction of long-term adverse cardiovascular outcomes. In this study, baseline plasma TIMP-4 levels were measured in 162 male patients with diabetes mellitus who were referred for coronary angiography and followed prospectively for the development of all-cause mortality and enzymatically confirmed myocardial infarction (MI) out to 5 years. After adjustment for a variety of baseline clinical, angiographic and laboratory parameters, plasma TIMP-4 levels were an independent predictor of all-cause mortality (hazard ratio 1.60, 95% CI 1.13 to 2.26; p = 0.0082) and MI (hazard ratio 1.61, 95% CI 1.19 to 2.18; p = 0.0021) at 5 years. Furthermore, in additional multivariate models that adjusted for a variety of biomarkers with established prognostic efficacy, TIMP-4 remained an independent predictor of adverse outcomes. In conclusion, elevated levels of TIMP-4 are associated with an increased risk of long-term all-cause mortality and MI in patients with diabetes mellitus referred for coronary angiography. Moreover, this association is independent of a variety of clinical, angiographic, and laboratory variables, including biomarkers with established prognostic efficacy in the prediction of adverse cardiovascular outcomes.

Benefit of bolus-only platelet glycoprotein IIb/IIIa inhibition during percutaneous coronary intervention: insights from the very early outcomes in the Evaluation of 7E3 for the Prevention of Ischemic Complications (EPIC) trial.

BACKGROUND: Platelet glycoprotein IIb/IIIa inhibitors are administered during percutaneous coronary intervention as a bolus followed by infusion. The need for an infusion was established by the Evaluation of 7E3 for the Prevention of Ischemic Complications (EPIC) trial conducted during the percutaneous transluminal coronary balloon angioplasty (PTCA) era, when the threat of acute thrombotic complications prevailed over concerns regarding bleeding, and stenting was considered an adverse event. METHODS: The EPIC trial randomized high-risk PTCA patients to 3 arms: placebo, abciximab bolus only, and abciximab bolus plus infusion. The present analysis of the EPIC outcomes was done at 6-hour intervals during the first 24 hours after PTCA to identify any early benefit derived from the abciximab bolus-only arm. RESULTS: At 6 hours after randomization, the primary composite end point of death, myocardial infarction, or urgent intervention was significantly reduced by 46% with abciximab bolus-only compared with placebo (2.9% vs 5.3%; P = .022), which is mainly due to a reduced rate of urgent intervention. There was also a numerical but not statistically significant reduction in myocardial infarction rate using abciximab bolus-only compared with placebo. A lower bleeding rate in the bolus-only arm compared with bolus plus infusion has been reported. CONCLUSIONS: As stenting and thienopyridine use have become routine, there has been a decrease in the incidence of acute closure and an increasing concern for bleeding complications after percutaneous coronary intervention, which potentially may be addressed by adopting a bolus-only glycoprotein IIb/IIIa inhibitor strategy. The early protective ischemic effect of abciximab bolus-only observed in the EPIC trial may be relevant in this regard.

Tissue inhibitor of metalloproteinase-1 (TIMP-1) is an independent predictor of all-cause mortality, cardiac mortality, and myocardial infarction.

BACKGROUND: Matrix metalloproteinases and their inhibitors have been implicated in both vascular and ventricular remodeling, and in atherosclerotic plaque rupture. The prognostic value of plasma tissue inhibitor of metalloproteinase-1 (TIMP-1) levels in patients with established or suspected coronary artery disease is unknown. METHODS: Tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-9 (MMP-9) levels, along with a number of other established biomarkers, were measured in 389 male patients undergoing coronary angiography at a Veterans Administration Medical Center. The patients were then followed prospectively for the occurrence of all-cause mortality, cardiac mortality, and myocardial infarction (MI). RESULTS: Follow-up data at 24 months were available for 97% of the patients. For the entire cohort of patients, TIMP-1 was the only biomarker to independently predict all-cause mortality and MI. In addition, the ratio of TIMP-1 to matrix metalloproteinase-9 was independently predictive of cardiac mortality at 24 months. The 24-month survival rates for patients in the lower quartile (< 66.5 ng/mL), interquartile (66.5-100 ng/mL), and upper quartile (> 100 ng/mL) of plasma TIMP-1 values were 95.3%, 89.3%, and 72.2%, respectively (P < .001). Furthermore, when patients with chest pain were risk stratified into those with and without an acute coronary syndrome, TIMP-1 remained an independent predictor of all-cause mortality in both subgroups. CONCLUSIONS: In a cohort of male patients undergoing coronary angiography, a single baseline determination of plasma TIMP-1 is independently predictive of the subsequent risk of death and MI.

Usefulness of anemia in men as an independent predictor of two-year cardiovascular outcome in patients presenting with acute coronary syndrome.

Anemia has been shown to be an independent risk factor for the development of adverse cardiovascular outcomes in a variety of patient populations. In the case of patients presenting with acute coronary syndrome (ACS), anemia has been demonstrated to be a powerful and independent predictor of 30-day outcomes. However, there are limited and conflicting data about the long-term independent predictive value of anemia in patients with ACS. This is in contrast to non-ACS populations in which anemia has been shown to be an independent predictor of long-term outcomes. The present study investigated the long-term prognostic significance of anemia in a well-characterized cohort of 193 men with ACS who were referred for coronary angiography at a Veterans Affairs Medical Center. All patients were followed prospectively for the development of death or acute myocardial infarction (AMI), and follow-up data were available for all patients at 24 months. After controlling for a variety of baseline clinical, laboratory, and angiographic variables, hemoglobin (analyzed as a continuous variable and as a categorical variable using the World Health Organization cutoff of 13 g/dl for men) was a strong and independent predictor of the composite end point of death or AMI at 24 months when using a Cox proportional hazards model. At 24 months, the event-free survival was 64% in the group with a hemoglobin level < 13 g/dl compared with 81% in the group with a hemoglobin level > or = 13 g/dl (p = 0.0065 by log-rank test). In conclusion, these data demonstrate that baseline anemia is a strong and independent predictor of death or AMI at 2 years in patients with ACS.

Usefulness of the white blood cell count as a predictor of angiographic findings in an unselected population referred for coronary angiography.

There are limited data about the relative importance of the many different but inter-related inflammatory markers with respect to their ability to independently predict the presence and extent of coronary artery disease (CAD). In addition, studies demonstrating such associations have often been conducted in well-defined populations and have excluded patients with or not adjusted for co-morbidities associated with CAD. In a cohort of 389 men who underwent coronary angiography for a variety of clinical indications and across a spectrum of risk, the following inflammatory markers were measured at baseline to determine their relative abilities to predict angiographic outcomes: C-reactive protein, myeloperoxidase, tissue inhibitor of metalloproteinase-1, erythrocyte sedimentation rate, and white blood cell (WBC) count. This analysis was done in the context of traditional CAD risk factors and other co-morbidities associated with CAD (such as morbid obesity, renal dysfunction, heart failure, and so forth). WBC count was the only marker that was independently associated with angiographically documented CAD (p = 0.0184). Further, WBC count (odds ratio 1.31, 95% confidence interval 1.05 to 1.64, p = 0.0157) and plasma myeloperoxidase (odds ratio 1.35, 95% confidence interval 1.08 to 1.69, p = 0.0090) were the only inflammatory markers that were independently predictive of the presence of multivessel disease on coronary angiography. In conclusion, these data demonstrate that a simple baseline WBC count is independently associated with angiographic CAD, and that it can predict the presence of multivessel disease, even in the context of clinical CAD risk factors and other established inflammatory markers.

Usefulness of Plasma Matrix Metalloproteinase-3 Levels to Predict Myocardial Infarction in Men With and Without Acute Coronary Syndrome.

Matrix metalloproteinase-3 (MMP-3), or stromelysin-1, is a matrix metalloproteinase which is expressed in atherosclerotic plaques and which has been implicated in the pathogenesis of acute coronary syndrome (ACS). Functional polymorphisms in the promoter region of the human MMP-3 gene resulting in an increased expression of MMP-3 have been shown to predict the risk of incident myocardial infarction (MI). However, there have been no studies that have specifically examined the utility of baseline plasma MMP-3 levels for the prediction of long-term MI. In this study, baseline plasma MMP-3 levels were measured in 355 male patients who were referred for coronary angiography and followed prospectively for the development of enzymatically confirmed MI out to 5 years. After adjustment for a variety of baseline clinical, angiographic, and laboratory parameters, plasma MMP-3 levels were an independent predictor of MI at 5 years (hazards ratio 1.42, 95% CI 1.13 to 1.79; p = 0.0023). Furthermore, in 5 additional multivariate models that included a variety of contemporary biomarkers associated with adverse outcomes and MI, MMP-3 remained an independent predictor of MI at 5 years. Similar results were obtained when the analyses were restricted to the subpopulation of patients presenting with ACS. In conclusion, elevated levels of MMP-3 are associated with an increased risk of long-term MI in patients with and without ACS referred for coronary angiography. Furthermore, this association is independent of a variety of clinical, angiographic, laboratory variables, including biomarkers with established prognostic efficacy for the prediction of MI.

Inhibition of tissue factor gene induction and activity using a hairpin ribozyme.

BACKGROUND: Tissue factor (TF) is a membrane-bound glycoprotein that initiates the clotting cascade. Inhibition of the TF pathway has been shown to prevent thrombosis and restenosis after arterial injury in a variety of animal models. METHODS AND RESULTS: We describe a novel approach to inhibiting the expression of the TF protein that involves the targeted destruction of cellular TF mRNA with the use of a tetraloop hairpin ribozyme. After construction of the ribozyme and determination of its optimal length and kinetic parameters, a ribozyme expression vector that used the retroviral vector pMV12 was constructed. The ability of this expression vector to generate anti-TF ribozyme was further augmented by positioning of the anti-TF ribozyme downstream of a rat tRNA val (RNA polymerase II) promoter. The resultant construct containing the anti-TF ribozyme was then used to transfect vascular smooth muscle cells and generate a variety of clonal cell lines. Northern blot analyses performed on 3 transfected and 3 untransfected clones demonstrated markedly reduced TF mRNA levels in the transfected clones both during quiescence and after serum stimulation. Cell lysates analyzed for total TF activity by monitoring factor Xa generation similarly demonstrated a statistically significant and concordant reduction in TF activity in smooth muscle cells transfected with the ribozyme expression vector compared with both untransfected clones and clones transfected with the empty vector. CONCLUSIONS: These results demonstrate the feasibility of an antithrombotic strategy based on ribozyme technology.

The activated clotting time (ACT) can be used to monitor enoxaparin and dalteparin after intravenous administration.

BACKGROUND: The use of low-molecular weight heparin (LMWH) during percutaneous coronary intervention (PCI) has been limited by the presumed inability to monitor its anticoagulant effect using bedside assays. OBJECTIVES: This study was designed to compare the dose-response of enoxaparin, dalteparin and unfractionated heparin (UFH) on the activated clotting time (ACT), and to determine whether the ACT or aPTT can be used to monitor intravenous (IV) low molecular weight heparin (LMWH). METHODS: A total of 130 patients undergoing cardiac catheterization were assigned to intravenous enoxaparin 0.5 mg/kg, dalteparin 50 international units/kg or UFH 50 units/kg. Of the 130 patients, 46 (35%) underwent PCI, all of whom received a glycoprotein (GP) IIb/IIIa inhibitor. We measured ACT, activated partial thromboplastin time (aPTT) and plasma anti-Xa levels after serial sampling. RESULTS: Both enoxaparin and dalteparin induced a significant rise in the ACT and aPTT, with an ACT dose-response approximately one-half the magnitude of that obtained using UFH. The time course of changes in the ACT and aPTT after administration of enoxaparin and dalteparin was virtually identical, with a return to baseline at approximately 2 hours. The enoxaparin and dalteparin-treated patients successfully underwent PCI with no major hemorrhagic complications. CONCLUSIONS: The ACT is equally sensitive to IV enoxaparin and dalteparin. These data support an ACT-guided strategy for intravenously administered LMWH during PCI. Additional studies with larger patient populations may be indicated to determine the ideal target ACT for LMWH in PCI.

Elevated baseline plasma IL-8 levels are an independent predictor of long-term all-cause mortality in patients with acute coronary syndrome.

OBJECTIVES: To investigate the long-term prognostic significance of baseline plasma IL-8 levels in a group of well-characterized male patients presenting with acute coronary syndrome. BACKGROUND: IL-8 is a cytokine that has been implicated in the pathogenesis of atherosclerosis and acute coronary syndrome. Elevated plasma levels have been reported in patients with acute coronary syndrome. METHODS: Baseline plasma IL-8 levels were measured in 180 male patients with acute coronary syndrome who were referred for coronary angiography and followed prospectively for the development of all-cause mortality for 5 years. RESULTS: In a multivariate model that included a wide variety of baseline clinical, laboratory and angiographic parameters in the selection process, baseline plasma IL-8 levels (analyzed as a continuous variable) emerged as a significant predictor of all-cause mortality at 5 years (HR, 1.43; 95% CI, 1.08-1.88; p = 0.0123). Furthermore, in 3 additional multivariate models that also included in the selection process a number of contemporary biomarkers with established prognostic efficacy in ACS (i.e., NT-proBNP, hs-CRP, hemoglobin and RDW), IL-8 remained an independent predictor of all-cause mortality at 5 years. CONCLUSION: Elevated baseline plasma levels of IL-8 are associated with an increased risk of long-term all-cause mortality in patients with acute coronary syndrome. Furthermore, this association is independent of a variety of clinical, laboratory and angiographic variables, including contemporary biomarkers with established prognostic efficacy in acute coronary syndrome.

Relation of baseline plasma MMP-1 levels to long-term all-cause mortality in patients with known or suspected coronary artery disease referred for coronary angiography.

OBJECTIVES: To investigate the long-term prognostic significance of baseline plasma MMP-1 levels in a group of well-characterized male patients with known or suspected coronary artery disease, including those presenting with acute coronary syndrome. BACKGROUND: MMP-1 is an interstitial collagenase that is considered the primary enzyme responsible for collagen degradation. In addition, MMP-1 can lead to platelet activation through the PAR1 pathway that is independent of thrombin. METHODS: Baseline plasma MMP-1 levels were measured in 364 male patients who were referred for coronary angiography and followed prospectively for five years for the development of all-cause mortality. RESULTS: After adjustment for a variety of baseline clinical, angiographic and laboratory parameters, baseline plasma MMP-1 levels (analyzed as a continuous variable) were an independent predictor of all-cause mortality at 5 years (HR, 1.49; 95% CI, 1.23-1.80; P < 0.0001). Furthermore, in 3 additional multivariate models that included a wide variety of contemporary biomarkers with established prognostic efficacy (i.e., ST2, GDF-15, Cystatin C, hs-CRP, Myeloperoxidase, NT-proBNP, TIMP-1, Adiponectin, RDW, hemoglobin, and Erythropoietin), MMP-1 remained an independent predictor of all-cause mortality at 5 years. Similar results were obtained when the analyses were restricted to the subpopulation of patients presenting with acute coronary syndrome. CONCLUSIONS: Elevated levels of MMP-1 are associated with an increased risk of long-term all-cause mortality in patients with known or suspected coronary disease that is independent of a variety of clinical, angiographic, and laboratory variables, including a whole host of contemporary biomarkers with established prognostic efficacy representing multiple different pathophysiologic processes.