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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.

Hypotension is a common complication during coronary angiography. Multiple factors can lead to hypotension in cath lab including bleeding and vasovagal reaction. Vagal induced hypotension is commonly associated with severe pain and anxiety. However, other causes of hypotension in cath lab should be considered. Here we present a case of 76-year-old male was brought for coronary angiography and the procedure was complicated by hypotension from an overlooked bladder distention.

Despite advances in diagnostic and therapeutic interventions, coronary heart disease remains as one of the leading causes of death in developed countries. ST-segment elevation myocardial infarction is associated with the highest mortality and is an indication for emergent reperfusion therapy. Current guidelines for emergent reperfusion not only include ST segment elevations but also consider evidence of a new onset Left Bundle Branch Block (LBBB). However, accumulating evidence indicates that RBBB is also associated with poor outcome in coronary artery disease. To-date, guidelines do not comment on the urgency of reperfusion therapy with sole evidence of a new onset Right Bundle Branch Block (RBBB). Particularly we question whether clinicians should focus on new-onset RBBB as a ST-segment elevation equivalent. If so, appropriate management of patients with the new onset RBBB during cardiac ischemia can have a significant impact on cardiac function and outcomes. In this series, we present four cases of new-onset acute RBBB associated with chest pain in the setting of acute myocardial infarction with critical lesions of the left anterior descending artery. We also highlight the need to consider new RBBB as an additional indication for acute reperfusion therapy in acute myocardial infarction. This will call for revision in the current guidelines by American Heart Association following the initiative recently implemented by the European Society of Cardiology 2018.

Background: Studies have suggested that nitrated apolipoprotein A1 (NT-apoA1) levels may be associated with coronary artery disease (CAD). We therefore hypothesized that NT-apoA1 might be associated with the prediction of all-cause mortality in CAD patients. Methods: Using an ELISA, we measured plasma NT-apoA1 levels in 236 patients with known or suspected coronary artery disease (CAD) undergoing coronary angiography. The patients were then followed prospectively for the development of all-cause mortality for up to 7 years. Results: Lower NT-apoA1 levels were associated with worse renal function, lower HDL levels, higher triglyceride levels and lower ejection fraction. There was positive correlation between NT-apoA1 and HDL cholesterol levels (correlation coefficient 0.366; p Conclusions: Higher NT-apoA1 levels are significantly associated with lower all-cause mortality in CAD patients, which may relate to HDL cholesterol function. Further studies are warranted to investigate this paradoxical finding.

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.

Introduction: The blunting of the expected improvement in cardiovascular health over the past decade has been attributed in part to the substantial increase in the prevalence of obesity. Atrial fibrillation and heart failure are among the cardiovascular diseases with increasing incidence in the US. We sought to evaluate the effect of obesity on the predicted 6-month mortality in our patients with atrial fibrillation [AF] and acute coronary syndrome [ACS] utilizing the GRACE score [GS], a validated risk assessment model for predicting death within 6-months of hospital discharge. Methods: Eighty patients, 88% black, 54% female, mean age 68, +/-12, h/o AF admitted with ACS were included. Results: An extraordinarily high prevalence of DM and HTN [46% and 95% respectively] and obesity [46%] were noted. The mean weight: 87 Kg, +/- 23. The mean BMI was 31 kgm 2 , +/-10; median BMI 29 kgm 2 and 25% had a BMI of 35 kgm 2 or greater, (Chart). Seventy-five percent of the cohort had clinical or radiographic evidence of congestion. Ejection fraction: mean 45%, +/-17. B-type natriuretic peptide [BNP] level: mean 765 pg/ml. BNP was significantly and negatively related to obesity [BMI p= 0.0001; r= - 0.422; weight p= 0.001; r= - .359]. This inverse relationship of BNP and obesity was most apparent when comparing the level of BNP in patients who were at or above the median BMI (29.3 kgm 2 ), p= 0.001, (Fig). Although we found a significant direct association of the GS with age [p Conclusions: In a traditionally high risk cohort with AF and ACS a high prevalence of obesity was recorded. Clinical or radiographic evidence of congestion was present in the majority. We found no significant link between obesity in this population and the GS—predictor of 6-month mortality. Can this be another cardiovascular paradox? Lengthier outcome studies of larger cohorts are warranted.

Objectives To investigate the long-term prognostic significance of baseline plasma PLTP levels in a group of well-characterized male patients with diabetes mellitus and known or suspected coronary artery disease referred for coronary angiography. Background PLTP is a plasma protein that mediates the net transfer and exchange of phospholipids between lipoproteins. It has been implicated in the pathogenesis of atherosclerosis and elevated plasma levels have been reported in patients with diabetes mellitus. Methods Baseline plasma PLTP levels were measured in 154 male patients with diabetes mellitus who were referred for coronary angiography and followed prospectively for 5 years for the development of all-cause mortality. Results After adjustment for a variety of baseline clinical, angiographic and laboratory parameters, plasma PLTP levels (analyzed as a continuous variable) were an independent predictor of all-cause mortality at 5 years (HR, 1.55; 95% CI, 1.22–2.00; P = 0.0009). Furthermore, in 3 additional multivariate models that also included a wide variety of contemporary biomarkers with established prognostic efficacy (i.e., ST2, GDF-15, Cystatin C, Fibrinogen, and NT-proBNP), PLTP remained an independent predictor of all-cause mortality at 5 years. Conclusions Elevated baseline plasma levels of PLTP are associated with an increased risk of long-term all-cause mortality in patients with diabetes and known or suspected coronary disease. Furthermore, this association is independent of a variety of clinical, angiographic, and laboratory variables, including a whole host of contemporary biomarkers with established prognostic efficacy.

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.

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.

Background Patients with diabetes mellitus (DM) have been shown to have higher levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of endothelial nitric oxide (NO) synthase. Higher plasma levels of ADMA have been implicated in the pathogenesis of endothelial dysfunction and atherosclerosis by lowering NO levels. High baseline plasma levels of ADMA in patients with DM have been shown to predict diabetes related complications. However, there are limited data on the prognostic significance of baseline ADMA levels in patients with established DM. Methods The present study investigated the long-term prognostic significance of baseline plasma ADMA levels in a well-characterized cohort of 170 high-risk diabetic men with known or suspected coronary artery disease who were referred for coronary angiography. All patients were followed prospectively for the development of vascular outcomes, including all-cause mortality. Results After controlling for a variety of baseline variables (including established biomarkers such as hs-CRP and fibrinogen), plasma ADMA levels (analyzed as the upper tertile of baseline values compared with the lower two tertiles) were a strong and independent predictor of all-cause mortality (HR 2.63, 95% CI 1.13–6.11, p =0.0247) when using a Cox proportional hazards model. In addition, baseline ADMA values were also an independent predictor of the composite outcome of all-cause mortality or MI (fatal or non-fatal) (HR 2.44, 95% CI 1.26–4.72, p =0.0079), as well as the composite outcome of all-cause mortality, MI (fatal or nonfatal), or stroke (HR 2.00, 95% CI 1.10–3.62, p =0.0232). Conclusion These data demonstrate that elevated baseline levels of ADMA are a strong and independent predictor of cardiovascular outcomes (including all-cause mortality) in patients with DM.

Growth Differentiation Factor-15 (GDF-15) is elevated and prognostic in CAD. Sparse data is available on potential mechanism or its activity in minority populations. Methods: Cohort: 80 patients with AF and ACS. Standard labs, EKG, and echo were performed along with coronary angiography and

Background Neutrophil to lymphocyte ratio (N/L ratio) has been shown to predict long-term mortality in patients undergoing percutaneous coronary intervention (PCI). African Americans have been shown to have lower mean neutrophil counts compared to whites. The usefulness of the N/L ratio in predicting long-term mortality in African Americans undergoing PCI is unknown. Methods We evaluated a total of 372 African American patients (327 patients with lower N/L ratio [

Phospholipid transfer protein (PLTP) is an important modulator of phospholipid transfer and exchange among proteins. It also plays a role in inflammation and oxidative stress. Accordingly, PLTP has been implicated in the development of atherosclerosis. Left ventricular (LV) systolic dysfunction is common in patients with atherosclerosis, and both inflammation and oxidative stress have also been implicated in its development and progression. The goal of the present study was to examine the relation between plasma PLTP activity and LV systolic function. Baseline plasma PLTP activity was measured in 389 male patients referred for coronary angiography for a variety of indications. Detailed clinical, angiographic and laboratory characteristics were available for the patients. Compared to those patients with normal LV function (defined as an ejection fraction of ≥55% on ventriculography), patients with any degree of LV dysfunction had elevated PLTP activity (median PLTP 17.8 pmol/μl/h versus 15.9 pmol/μl/h, p = 0.0038). Using multivariate analysis, and adjusting for a variety of confounding variables known to affect both LV function and PLTP activity, PLTP activity was an independent predictor of the presence of any left ventricular systolic dysfunction in the entire population (OR 1.47, 95% CI 1.12–1.93, p = 0.0052). Furthermore, PLTP activity was an independent predictor of the presence of LV dysfunction in both patients with and without myocardial infarction on presentation (OR 2.39, 95% CI 1.18–4.86, p = 0.0161 and OR 1.41, 95% CI 1.05–1.89, p = 0.0206, respectively). In conclusion, PLTP activity may represent a novel marker of LV systolic dysfunction in patients with known or suspected coronary artery disease.

BACKGROUND In experimental animal studies, potassium has been demonstrated to protect against the development of atherosclerosis through a variety of mechanisms. Data regarding the role of potassium in the development of human atherosclerosis are sparse. The objective of this study was to determine the association between plasma potassium levels and angiographically defined coronary artery disease (CAD). METHODS In a cohort of 389 male patients undergoing coronary angiography for a variety of clinical indications, the association between baseline serum potassium levels and the extent of angiographically defined atherosclerosis was analyzed. Adjustments were made for clinical and laboratory variables (including inflammatory markers) known to be associated with atherosclerosis. RESULTS By multivariate logistic regression analysis, baseline serum potassium levels were an independent predictor of the presence of multivessel disease (odds ratio (OR) 1.31, 95% confidence interval (CI) 1.01-1.69; P < 0.05). In addition, in the non-myocardial infarction subpopulation of patients, serum potassium was also an independent predictor of the presence of multivessel disease by multivariate logistic regression analysis (OR 1.34, 95% CI, 1.02-1.76; P < 0.05). In the myocardial infarction (MI) subpopulation, serum potassium was not a predictor of multivessel disease, possibly due to the confounding effect of hypokalemia known to be present during MI. CONCLUSIONS These data demonstrate that a simple baseline serum potassium level is independently associated with the presence of multivessel disease, even in the context of clinical CAD risk factors and other established inflammatory markers.

BACKGROUND Nitric oxide (NO) is produced from L-arginine by NO synthase and is an important molecule with antiatherogenic properties. Asymmetric dimethylarginine (ADMA) acts as an endogenous inhibitor of endothelial NO synthase. As such, it has been associated with endothelial dysfunction and elevated circulating levels of ADMA have been found in patients with cardiovascular risk factors. In addition, high baseline plasma levels of ADMA have been shown to be an independent predictor of adverse outcomes in a variety of patient populations. However, there are very limited data in patients with acute coronary syndromes (ACS). METHODS This study investigated the long-term prognostic significance of baseline plasma ADMA levels in a well-characterized cohort of 193 men with ACS who were referred for coronary angiography. All patients were followed up prospectively for the development of vascular outcomes. RESULTS After controlling for a variety of baseline variables (including established biomarkers such as high-sensitivity C-reactive protein and fibrinogen), plasma ADMA levels (analyzed as the upper tertile of baseline values compared with the lower two tertiles) were a strong and independent predictor of each of the individual endpoints of all-cause mortality [hazard ratio (HR): 2.45, 95% confidence interval (CI): 1.08-5.57; P=0.0325] and myocardial infarction (HR: 2.28, 95% CI: 1.14-4.57; P=0.0204) when using a Cox proportional hazards model. In addition, baseline ADMA values were also an independent predictor of the composite outcome of all-cause mortality, fatal or nonfatal myocardial infarction, or stroke (HR: 1.81, 95% CI: 1.01-3.25; P=0.0482). CONCLUSION These data show that elevated baseline levels of ADMA are a strong and independent predictor of cardiovascular outcomes (including mortality) in patients with ACS.

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. © 2009 Wiley-Liss, Inc.

SummaryRed 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 10.4, high RDW was a strong and independent predictor of mortality. For patients with Hgb ≥10.4 to

Objectives The purpose of this study was to determine the association of the F11 receptor (F11R) with human vascular disease. Background A molecule identified as critical for platelet adhesion to a cytokine-inflamed endothelial surface in vitro is F11R. The F11R is known to be expressed in platelets and endothelium and reported recently to be overexpressed in atherosclerotic plaques. Methods A novel enzyme-linked immunosorbent assay was developed for the measurement of soluble F11R in human plasma. The F11R levels, along with a number of other biomarkers, were measured in 389 male patients with known or suspected coronary artery disease (CAD) undergoing coronary angiography at a Veterans Administration Medical Center. Results Patients with normal or nonobstructive disease (CAD angiographic score of 0), mild-to-moderate disease (score of 1 to 3), and severe disease (score of 4 to 6) had median F11R plasma levels of 38.6 pg/ml (mean 260 ± 509.6 pg/ml), 45.2 pg/ml (mean 395.3 ± 752.7 pg/ml), and 105.8 pg/ml (mean 629 ± 831.7 pg/ml), respectively (p = 0.03). By multivariate analysis, the variables independently associated with CAD score were age, hyperlipidemia, chronic renal insufficiency, left ventricular function, and plasma F11R levels. The F11R was the only biomarker that was independently associated with CAD score. Consistent with the previously reported effects of tumor necrosis factor (TNF)-alpha on F11R expression in cultured endothelial cells, F11R levels correlated strongly with plasma TNF-alpha levels (r = 0.84; p Conclusions Plasma F11R is independently associated with the presence and severity of angiographically defined CAD. By virtue of its strong correlation to plasma TNF-alpha, F11R may be an important mediator of the effects of inflammation on the vessel wall. Strategies that block F11R may represent a novel approach to the treatment of human atherosclerosis.

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.

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.

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.

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.

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.

Aims To determine the prognostic value of baseline plasma adiponectin levels in patients with known or suspected coronary artery disease referred for coronary angiography. Methods and results Adiponectin was measured in 325 male patients with stable angina, troponin-negative unstable angina, and non-ST-segment elevation myocardial infarction (MI) 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 MI. Follow-up data at 24 months were available for 97% of the patients. Adiponectin was the only biomarker to independently predict the individual endpoints of all-cause mortality, cardiac mortality, and MI. The 24-month survival rates for patients in the lower (≤4.431 mg/L), middle (>4.431 and ≤8.008 mg/L), and upper (>8.008 mg/L) tertiles of plasma adiponectin values were 95.0, 90.4, and 83.5%, respectively ( P = 0.0232 by log-rank test). Furthermore, when patients with chest pain were risk-stratified into those with and without a non-ST-segment elevation acute coronary syndrome (NSTEACS), adiponectin remained an independent predictor of both all-cause mortality and cardiac mortality in the NSTEACS subgroup. Conclusion In a cohort of male patients undergoing coronary angiography, a single baseline determination of plasma adiponectin is independently predictive of the subsequent risk of death and MI.

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 level13 g/dl compared with 81% in the group with a hemoglobin levelor = 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.

Background: Factor XI deficiency has been associated with bleeding diathesis mostly secondary to trauma and post-operatively depending on the severity of deficiency. Cases with factor XI deficiency having undergone cardiac surgery and coronary intervention after appropriate replacement therapy have been reported in the past. The presence of inhibitor in factor XI deficiency poses a hematological challenge and literature regarding coronary intervention in such patients is limited. Immunosuppressive therapy, plasma exchange and factor VII product transfusions have been used prior to cardiac interventions in few such reported cases. Method: We report our approach in such a case of Percutaneous Transluminal Coronary Angioplasty in a 72-year-old male of Jewish origin who has congenital factor XI deficiency complicated with acquired inhibitor. Results: In some cases, the acuity of the coronary syndrome may mandate immediate coronary intervention. However, patient’s history of factor XI deficiency and acquired inhibitor pose a major dilemma of further course of action. We performed percutaneous balloon angioplasty in this case with no anti-coagulant and with favorable outcome. Conclusion: Under these circumstances of significant coagulation disorder and based on the case report, we recommend that balloon angioplasty be undertaken with no additional anti-coagulation other than Aspirin.

Defecatory complications are common after spinal cord injury (SCI) and have been attributed, in part, to an imbalance of the autonomic nervous system between parasympathetic and sympathetic effects on the colon. Because parasympathetic (i.e., cholinergic) input to the bowel may be downregulated after SCI, it was hypothesized that neostigmine, a medication that increases cholinergic tone by blocking the metabolism of acetylcholine, might promote bowel evacuation in these persons. Since neostigmine is known to cause bradycardia and bronchoconstriction, we also assessed whether these side-effects could be prevented by coadministration of neostigmine with glycopyrrolate, an anticholinergic agent that has limited activity on the muscarinic receptors of the colon. The hypothesis was tested in 13 persons with SCI in whom videofluoroscopy was carried out after instillation of a barium oatmeal paste into the rectum and descending colon. On separate days, subjects received, in a randomized, blinded design, one of three intravenous infusates (normal saline, 2 mg neostigmine, or 2 mg neostigmine + 0.4 mg glycopyrrolate). The effect of these infusates on bowel evacuation of the barium paste, heart rate, and airway resistance was determined. Both neostigmine and neostigmine + glycopyrrolate resulted in prompt bowel evacuation. The nadir heart rate was lower after neostigmine alone than with the combination. Neostigmine administration increased both total and central airway resistance, an effect that was not observed with the coadministration of glycopyrrolate. Other side-effects of neostigmine and the combination of drugs included muscle fasciculations and dry mouth, both of which were mild and short-lived. Abdominal cramping was noted in subjects with spinal cord lesions below thoracic level 10. These results indicated that neostigmine/glycopyrrolate administration is safe and well tolerated in persons with chronic SCI.

Direct thrombin inhibitors (DTI) are emerging as alternative anticoagulants to unfractionated heparin and indirect thrombin inhibitors in patients undergoing percutaneous coronary intervention (PCI). We review the pharmacological properties of these newer antithrombotic agents and evaluate the clinical data demonstrating their use in patients undergoing PCI].

SummaryRecent data suggests that CD40L is involved in the pathogenesis of atherothrombotic disease. This review will focus on the history of CD40L, its role in platelet-mediated pathogenesis of atherothrombotic disease, its association to clinical syndromes and procedures, and its role in determining plaque rupture.

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.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.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.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.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.

Contrast-associated nephropathy (CaN) has become a major cause of iatrogenic acute renal failure, especially with the increasing use of radiographic contrast media in both diagnostic and interventional procedures. CaN is the third most common cause of iatrogenic acute renal failure, and is associated with increased morbidity and in-hospital mortality. CaN typically presents as an acute rise in serum creatinine levels, usually within 48 hours after exposure to contrast media. Renal medullary ischemia secondary to contrast-induced vasoconstriction is now believed to be the most likely cause of CaN, although direct renal tubular cytotoxicity does appear to play a role. The occurrence of CaN is directly related to the number of coexisting clinical risk factors. Among the many risk factors, preexisting renal impairment, the presence of diabetes mellitus and the volume of the contrast agent administered are the most important. The most effective means of reducing the incidence of CaN is through prevention, by first identifying the risk factors and then attempting to correct for them before the administration of contrast material. Although the earliest and most well-tested preventive measure, namely intravenous hydration, continues to be the most effective way to prevent CaN, recent studies have provided many new preventive modalities. The growing use of these new agents, such as acetylcysteine, endothelin blockers, and most recently fenoldopam, has increased the options available for the prevention of CaN.

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.

Unstable angina pectoris and non-Q-wave myocardial infarction are clinical syndromes that share many pathophysiologic and clinical features. In the spectrum of coronary artery disease, these syndromes lie between chronic stable angina and Q-wave myocardial infarction. Although both conditions are associated with significant morbidity and mortality, patients presenting with these syndromes can be further risk stratified into higher and lower risk based on a number of readily available clinical features and biochemical parameters. Such risk stratification can allow for more tailored treatment and better resource allocation. Although routine early coronary angiography and revascularization has not been shown to be superior to conservative management, certain high-risk patients may benefit from a more aggressive strategy. Medical therapy with the use of antiplatelet, anticoagulant, and antiischemic agents remains the cornerstone of emergent treatment for patients presenting with these syndromes. The recent demonstration of a reduction in both morbidity and mortality with the glycoprotein IIb/IIIa antagonists has further expanded the armamentarium of available agents. Following initial stabilization, risk stratification with stress testing can help identify patients with a large residual ischemic burden who may benefit from coronary angiography with revascularization if feasible.

The underlying concept in the pathophysiologic characteristics of angina pectoris and myocardial ischemia in patients with coronary artery obstructive disease is a mismatch between myocardial oxygen demands and coronary blood flow. 1, 2 Myocardial oxygen consumption increases in response to physical or emotional stresses or both, and in certain pathophysiologic states such as sepsis. In obstructive coronary disease, the vasculature may not be able to meet the myocardial oxygen demands, and ischemia develops. 1 Therapy in angina pectoris and myocardial ischemia involves the restoration of a more favorable balance between myocardial oxygen supply and demand, which includes interventions to increase coronary supply (bypass surgery, atherectomy, balloon angioplasty, coronary vasodilators) and drugs to decrease demand (~-adrenergic blockers)J, 3 Many investigators have concluded that heart race (HR) is the most important determinant of myocardial oxygen demand, overshadowing myocardial contractility and left ventricular wall tension. 46 We review the experience with a new class of drugs, the sinus node inhibitors, in the t reatment of angina pectoris. This experience has shed light on the role of HR reduction alone in relieving myocardial ischemia and has raised new questions regarding the mechanisms by which certain antianginal drugs provide their clinical benefits.

Vesnarinone is a new and novel inotropic drug that has unique and complex mechanisms of action. It inhibits phosphodiesterase, thereby leading to increased intracellular calcium, and also affects numerous myocardial ion channels, resulting in the prolongation of the opening time of sodium channels and the decrease in the delayed outward and inward rectifying potassium current. In vitro, it has also demonstrated significant effects on cytokine production, which may account for some of its observed clinical benefits. Hemodynamic studies in humans with congestive heart failure reveal that vesnarinone can improve ventricular function. Placebo-controlled studies in large numbers of patients with heart failure have suggested a morbidity and mortality benefit with a 60 mg daily dose. There is increased mortality with vesnarinone at the 120 mg daily dose, however, suggesting a narrow therapeutic window for the drug. Its predominant toxic side effect is a 2% incidence of reversible neutropenia.

Rationale and objective Our previous studies have determined that the F11 receptor (F11R; aka JAM-A) exerts a critical force in the adhesion of human platelets to inflamed endothelial cells (ECs), and thus can play a significant role in the initiation of atherosclerotic plaque formation. In the present study, we focus on a subsequent event in plaque development – the migration of smooth muscle cells (SMCs) from the media to the intima of inflamed vessels. Here we report our investigation of the expression of F11R in atherosclerotic arteries of coronary artery disease (CAD) patients, and of the role of F11R in the migration of SMCs involved in atherogenesis. Methods and results Histological staining and specific-antibody immunofluorescence of excised, human atherosclerotic coronary arteries revealed the expression of F11R in the SMCs of the intima. RT-PCR and SDS-PAGE followed by immunoblotting procedures demonstrated that F11R mRNA and the F11R protein levels were enhanced by the stimulation of cultured human aortic SMCs with a combined treatment of proinflammatory cytokines (TNFα + INFγ + IL-β1). Neither the F11R message nor protein was expressed in non-stimulated SMCs. The functional role of F11R in SMCs’ migration was studied in cytokine-stimulated SMCs by interference of F11R expression with siRNA. Silencing of the F11R gene of cytokines-treated SMCs inhibited the expression of both F11R mRNA and F11R protein. Functionally, silencing of the F11R gene blocked the proliferation and migration of these inflamed SMCs, both critical events in atherogenesis. Conclusions The new findings of this study are that F11R mRNA and F11R protein are expressed in SMCs of the intima (but not in the media) of atherosclerotic arteries of CAD patients, and that F11R is required for the proliferation and migration of inflamed SMCs. Based on these findings, we conclude that in addition to the previously reported role of F11R in the initiation of plaque formation, F11R plays also an important role in the subsequent growth of atherosclerotic plaques. Identification of drugs that interfere with these pathophysiologic actions of F11R thus represents an effective new approach for the prevention and treatment of atherosclerosis, heart attacks and stroke.

Low-molecular-weight heparin (LMWH) has been a mainstay for the management of acute coronary syndromes (ACS) for almost a decade. However, several recent developments have seriously threatened the prominence of this drug class: (i) the adoption of an early invasive strategy, frequently leading to percutaneous coronary intervention (PCI) where the dosing and monitoring of LMWH is unfamiliar to most operators, (ii) the results of the SYNERGY trial, which not only failed to establish the superiority of enoxaparin over unfractionated heparin with respect to efficacy, but also demonstrated more bleeding with LMWH, and (iii) the results of the REPLACE-2 and ACUITY trials, which have demonstrated the advantages of an ACS and PCI treatment strategy based on direct thrombin inhibition with bivalirudin. To confront these challenges, cardiologists committed to the continued use of LMWH must develop safe and user-friendly approaches to transition patients from the noninvasive to invasive settings. This review summarizes an approach that takes advantage of the fact that LMWH can be readily monitored with the point-of-care activated clotting time (ACT) assay. This assay is inexpensive, available in virtually every catheterization laboratory, and familiar to most operators who monitor unfractionated heparin (UFH). A key concept that is presented is that the ACT is a more accurate measure of LMWH-induced anticoagulation than of UFH-induced anticoagulation. Our preliminary work suggests that during PCI operators should target an ACT of 175 seconds in the presence, and 200 seconds in the absence, of adjunctive glycoprotein IIb/IIIa inhibition. Sheath removal is recommended at an ACT160. These guidelines may facilitate continued use of LMWH, which has the potential to reduce cost (less expensive than bivalirudin), diminish the need for intravenous medication (can be administered subcutaneously in the noninvasive setting with minimal to no monitoring), and provide an ideal anticoagulant during PCI (easy to monitor with the ACT, at least partially reversible with protamine in the event of coronary perforation, effective antithrombin with no platelet activation, thereby potentially reducing the need for routine adjunctive IIb/IIIa inhibition).

Studies on body mass index (BMI) and post-percutaneous coronary intervention (PCI) outcomes have suggested an "obesity paradox" (lower post-PCI mortality rates in obese patients compared to patients of normal weight). Hypothesis. We assessed the hypothesis that BMI is an independent predictor of post-PCI long-term mortality in African-Americans.We evaluated 777 patients (146 with normal BMI [BMI18.5 to25 kg/m2], 261 overweight patients [BMIor = 25 to30 kg/m2], and 370 obese patients [BMIor = 30 kg/m2]) who underwent PCI during January 2003 to August 2006.After a median follow up of 4 +/- 1 years, the overall mortality rate was 10.5% (82 deaths). The survival rate was 84%, 90% and 92% in the normal BMI, overweight and obese groups, respectively (p = 0.014 by log-rank test; hazard ratio relative to the obese group was 2.2 for the normal weight and 1.2 for the overweight groups). After adjustment for baseline clinical and procedural characteristics (age, smoking history, chronic renal insufficiency, end-stage renal disease, left main coronary artery intervention, preprocedure hemoglobin, left ventricular ejection fraction and successful PCI) using a Cox proportional hazards model, there was no significant difference in the long-term all-cause mortality rate among the three groups (p = 0.93).BMI does not appear to be an independent predictor of long-term mortality after PCI in African-Americans.

BACKGROUND Recent studies have questioned the safety of drug-eluting stents because of a higher incidence of late stent thrombosis, raising the possibility that drug-eluting stents may be associated with an increased mortality. The effect of drug-eluting stents on mortality in African-Americans is unknown. METHODS We evaluated 628 African-American patients (354 patients treated with drug-eluting stents and 274 patients treated with bare metal stents) between January 2003 and August 2005, using data from our bolus-only platelet glycoprotein IIb/IIIa inhibitor database. The primary end point was all-cause mortality obtained using social security death index. RESULTS After a mean follow-up of 3+/-0.9 years, the mortality rate in the bare metal stents group was 12.8% compared with 7.1% in the drug-eluting stents group [adjusted P value=0.19; hazard ratio (HR) for bare metal stents group compared with drug-eluting stents group for death=1.4; 95% confidence interval (CI): 0.8-2.4]. In a subgroup analysis, patients presenting with acute coronary syndrome had a higher mortality when treated with bare metal stents compared with drug-eluting stents (17.1 vs. 6.3%, P=0.022; HR=2.2; 95% CI: 1.1-4.4). Patients with chronic kidney disease (all patients with creatinine >1.5 mg/dl) also had a higher mortality with bare metal stents compared with drug-eluting stents (36.7 vs. 20.4%, P=0.044; HR=2.3; 95% CI: 1.02-5.2). CONCLUSION Drug-eluting stents seem to be safe in African-Americans and may improve survival in certain subgroups such as patients with acute coronary syndromes and chronic kidney disease.

Recent studies have called into question the benefit of perioperative beta blockade, especially in patients at low to moderate risk of cardiac events. Once considered standard of care, the role of beta-blocker therapy now lies mired in conflicting data that are difficult to apply to the at-risk patient. We provide an overview of the evolution of perioperative beta blockade, beginning with the physiology of the adrenergic system, with emphasis on the biologic rationale for the perioperative implementation of beta-blockers. Although initial studies were small in size and statistically limited, early data showed cardiac benefit with the use of perioperative beta-blockers. However, larger, more recent studies now suggest a lack of benefit and potential harm from this practice. This paradigm holds true especially in those at low-to-moderate cardiovascular risk profiles. Potential explanations for these paradoxical results are discussed, stressing the key differences between earlier and current studies that may explain these divergent outcomes. We conclude by commenting on performance measures as they relate to perioperative beta-blockers and make recommendations for the continued safe implementation of this practice.

Anemia has been shown to be an independent predictor of long-term mortality after percutaneous coronary intervention (PCI). African-Americans are known to have lower hemoglobin (Hgb) levels compared with Caucasians. The impact of anemia on long-term mortality in African-Americans undergoing PCI is unknown. We evaluated a total of 715 African-American patients (313 patients with anemia and 402 patients without anemia as defined by the World Health Organization [Hgb13 g/dl for men and12 g/dl for women]) using data from our bolus-only glycoprotein IIb/IIIa database. After a median follow-up of 3.2 years (interquartile range 2.4 to 3.8), there were a total of 72 (10%) deaths. Survival rate was 84% in the anemic group compared with 94% in the control group (hazard ratio [HR] 2.8, unadjusted p0.001 by log-rank test). After adjustment for baseline clinical and procedural characteristics using a Cox proportional hazards model, Hgb as a dichotomous variable was a strong and independent predictor of all-cause mortality during the follow-up period (HR for death 2.0, 95% confidence interval 1.2 to 3.4, adjusted p = 0.012). Also, when Hgb was analyzed as a categorical variable having 3 groups with empirically determined cutoffs at11.1,or =11.1 to12.7, andor =12.7 g/dl, the effect remained significant (adjusted p = 0.008), with a HR of 2.3 for the group with lowest Hgb compared with the group with highest value (HR 2.6 for group with Hgbor =11.1 to12.7 compared with the group with the highest Hgb value). In conclusion, baseline Hgb is a strong and independent predictor of all-cause long-term mortality in African-Americans undergoing PCI.

We designed a study to compare the novel point-of-care assay Hemonox clotting time (Hemonox-CT) with the activated clotting time (ACT) and anti-Xa activity to monitor the anticoagulation effects of enoxaparin and dalteparin during percutaneous coronary intervention (PCI).A total of 90 patients undergoing cardiac catheterization were assigned to intravenous (IV) enoxaparin 0.5 mg/kg, dalteparin 50 international units/kg or unfractionated heparin (UFH) 50 units/kg. We measured Hemonox-CT, ACT and plasma anti-Xa levels after serial sampling.Baseline Hemonox-CT was similar in the enoxaparin (68 +/- 9 sec) and dalteparin (68 +/- 7 sec) groups with no detectable anti-Xa activity at baseline. Minutes after IV administration of enoxaparin and dalteparin, the mean Hemonox-CT increased to 171 +/- 60 sec and 214 +/- 70 sec for both groups, respectively. UFH induced a higher Hemonox-CT response (800 +/- 243 sec). At all time points, Hemonox-CT was higher than the ACT. Peak Hemonox-CT was associated with a therapeutic anti-Xa activity ranging from 0.50 to 1.35 U/ml (mean 0.89 U/ml) for the enoxaparin group and 0.69 to 1.48 U/ml (mean 0.91 U/ml) for the dalteparin group. After reaching peak levels, there was a gradual and parallel decline in Hemonox-CT and anti-Xa activity. The enoxaparin and dalteparin-treated patients successfully underwent PCI without major hemorrhagic complications.The Hemonox-CT has better sensitivity to both enoxaparin and dalteparin than does the ACT. Also, Hemonox-CT correlates with anti-Xa activity after IV administration. Hemonox-CT may become an important tool to monitor the anticoagulation effects of low-molecular weight heparin during PCI. Additional studies are needed to determine the target Hemonox-CT.

Background Red blood cell distribution width (RDW), a numerical measure of the variability in size of circulating erythrocytes, has recently been shown to be a strong predictor of adverse outcomes in patients with heart failure and in patients with prior myocardial infarction but no symptomatic heart failure at baseline, even after adjustment for hematocrit. However, there are no data in other cardiac populations, including patients with acute coronary syndromes (ACS). Methods The present study investigated the long-term prognostic significance of baseline RDW in a well-characterized cohort of 389 male patients who were referred to coronary angiography for a variety of indications. All patients were followed prospectively for all-cause mortality, and data regarding this endpoint was available for 97% of the population at 24 months. Results After controlling for a variety of baseline variables (including hemoglobin and the presence of heart failure), RDW (analyzed as a categorical variable comparing the upper tertile of baseline values to the lower two levels combined) was a strong and independent predictor of all-cause mortality using a Cox proportional hazards model [hazard ratio (HR) 2.69, 95% confidence interval (CI) 1.50–4.84, p =0.0008]. In addition, baseline RDW was also an independent predictor of all-cause mortality in the non-anemic (HR 4.73, 95% CI 2.06–10.86, p =0.0003) and ACS (HR 2.90, 95% CI 1.32–6.38, p =0.0082) subpopulations of patients. Conclusions These data demonstrate that elevated RDW is a strong and independent predictor of all-cause mortality in an unselected population of male patients across a broad spectrum of risk (including ACS) referred for coronary angiography.

The activated clotting time (ACT) has been reported to be sensitive to the anticoagulant activity of the low-molecular weight heparin dalteparin following intravenous (IV) administration.To evaluate the feasibility of an ACT-guided dalteparin dose adjustment strategy during percutaneous coronary intervention (PCI).This was a retrospective study of 104 consecutive patients who underwent PCI using an ACT-guided strategy of IV dalteparin. All patients received an initial IV bolus of 50 IU/kg of dalteparin. The minimum target ACT was 175 seconds for patients who received glycoprotein IIb/IIIa inhibitors and 200 seconds for patients who did not. Patients who did not achieve the target ACT after the initial 50 IU/kg were given supplemental boluses of dalteparin based on the assumption that for every additional 10 IU/kg of dalteparin, the ACT will rise by approximately 10 seconds.After the initial bolus of dalteparin, the mean baseline ACT rose from 138 +/- 41 seconds to 235 +/- 78 seconds. In the 36 patients (35% of the study population) who required a mean supplemental dose of 14 +/- 6 IU/kg/kg, the mean ACT after the supplemental dose was 239 +/- 79 seconds. The composite endpoint of in-hospital death, target vessel revascularization (TVR) and myocardial infarction (MI) was 5.8%. Major and minor bleeding rates were 1% each. The composite incidence of death/MI/TVR was comparable to, and the bleeding complications were lower than, those achieved in the SYNERGY and STEEPLE trials.ACT-guided dose adjustment of intravenously administered dalteparin during PCI appears to constitute a feasible strategy.

Tirofiban administered at a bolus dose of 25 mcg/kg is associated with a higher level of platelet inhibition compared to that associated with the standard 10 mcg/kg tirofiban bolus dose. In our previous study on bolus-only glycoprotein IIb/IIIa receptor inhibition during percutaneous coronary intervention (PCI), the eptifibatide bolus-only group demonstrated similar efficacy, but significantly fewer bleeding complications compared to the abciximab bolus-only group.To compare the in-hospital outcomes of high-dose (25 mcg/kg) tirofiban bolusonly vs. eptifibatide double bolus-only during PCI. In addition, the degree of platelet inhibition achieved by this novel tirofiban dosing strategy was assessed.We retrospectively analyzed 876 consecutive patients who underwent PCI using a single high-dose bolus of tirofiban (25 mcg/kg) or eptifibatide (180 mcg/kg x 2, 10 minutes apart) from January 2003 to August 2005 in a single institution. Patients with ST-segment elevation myocardial infarction were excluded.The percentage of platelet inhibition was 94% between 3-15 minutes post bolus of 25 mcg/kg of tirofiban. The platelet inhibition dropped to 92% at the end of the procedure (between 20-40 minutes) and to 74% at the time of sheath removal between 2-3 hours. After adjustment for the baseline and procedural characteristics, there was no difference in the composite endpoint of death, myocardial infarction, revascularization and bleeding complications (5.5% in tirofiban group vs. 5.3% in eptifibatide group; p = 0.79).A single high-dose bolus of tirofiban rapidly achieves profound platelet inhibition and a significant antiplatelet effect is maintained until sheath removal. This dosing during PCI appears safe and compares favorably with eptifibatide bolus-only during PCI.

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 fractionor =45%) versus those with moderate to severe systolic dysfunction (ejection fraction45%). 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.

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.

The management of the hypercholesterolemic patient has evolved tremendously with the introduction of the HMG-CoA Reductase inhibitors, a class of drugs better known as the statins. Statins modify cholesterol metabolism by inhibiting the rate-limiting enzyme of cholesterol biosynthesis, producing greater decreases in plasma cholesterol levels than previously realized with hypolipidemic therapy. With the advent of the classic statin-megatrials such as the Scandinavian Simvastatin Survival Study (4S), WOSCOPS, CARE, and the more recent Heart Protection Study (HPS), the role of statins in both the primary and secondary prevention and ultimate risk reduction of patients with coronary disease has been firmly established.With an increase in use and popularity, a number of beneficial actions of the statins unrelated to their cholesterol-lowering ability have been reported. These effects have generated greater interest in the possible additional roles and indications for the use of these drugs. Of central focus in this paper is the cholesterol-independent benefit of this group of agents on the cardiovascular system, particularly on the lowering of systemic blood pressure. A number of hypotheses have been proposed for this action and these shall be reviewed within this paper.We explore recent data that suggests that statins may provide substantial reduction of blood pressure in the hypertensive, hypercholesterolemic patient independent of their lipid-lowering effect. In addition, we review several notable publications that postulate unique mechanisms for this action and benefit. We also present plausible explanations as to why some of the larger statin trials did not report similar such findings.