Marijuana Use and In-Hospital Outcomes After Percutaneous Coronary Intervention in Michigan, United States.

OBJECTIVES: The aim of this study was to evaluate the association between reported marijuana use and post-percutaneous coronary intervention (PCI) in-hospital outcomes. BACKGROUND: Marijuana use is increasing as more states in the United States legalize its use for recreational and medicinal purposes. Little is known about the frequency of use and relative safety of marijuana among patients presenting for PCI. METHODS: The authors analyzed Blue Cross Blue Shield of Michigan Cardiovascular Consortium PCI registry data between January 1, 2013, and September 30, 2016. One-to-one propensity matching and multivariable logistic regression were used to adjust for differences between patients with or without reported marijuana use, and rates of post-PCI complications were compared. RESULTS: Among 113,477 patients, 3,970 reported marijuana use. Compared with those without reported marijuana use, patients with reported marijuana use were likely to be younger (53.9 years vs 65.8 years), to use tobacco (73.0% vs 26.8%), to present with ST-segment elevation myocardial infarction (27.3% vs 15.9%), and to have fewer cardiovascular comorbidities. After matching, compared with patients without reported marijuana use, those with reported marijuana use experienced significantly higher risks for bleeding (adjusted odds ratio [aOR]: 1.54; 95% confidence interval [CI]: 1.20-1.97; P < 0.001) and cerebrovascular accident (aOR: 11.01; 95% CI: 1.32-91.67; P = 0.026) and a lower risk for acute kidney injury (aOR: 0.61; 95% CI: 0.42-0.87; P = 0.007). There were no significant differences in risks for transfusion and death. CONCLUSIONS: A modest fraction of patients undergoing PCI used marijuana. Reported marijuana use was associated with higher risks for cerebrovascular accident and bleeding and a lower risk for acute kidney injury after PCI. Clinicians and patients should be aware of the higher risk for post-PCI complications in these patients.

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.

Stent size selection using 64-detector coronary computed tomography angiography: a comparison to invasive coronary angiography.

RATIONALE AND OBJECTIVES: Compare stent size selection using coronary computed tomography angiography (CCTA) to invasive coronary angiography (ICA). CCTA is increasingly performed before cardiac catheterization; however, the utility of incorporating these data into coronary interventions is unknown. METHODS: Retrospective study of 18 consecutive patients with 24 coronary artery lesions evaluated with 64-detector CCTA followed by ICA and resulting stent placement. Two blinded interventional cardiologists independently reviewed designated arterial segments on both CCTA and ICA during different reading sessions and determined anticipated stent length and nominal diameter, maximum stenosis, the need for postdilation of either stent margin, and final proximal and distal stent diameters. RESULTS: There was strong correlation between CCTA and ICA in the anticipated stent length (r = 0.85, P < .001) and final stent diameter (proximal end r = 0.74, P < .001; distal end r = 0.63, P = .001). Anticipated stent length was longer with CCTA compared to ICA (27.0 +/- 16.0 vs. 21.8 +/- 13.3 mm; P = .006). The final stent diameters were larger with CCTA compared to ICA, both at the proximal end (3.6 +/- 0.5 vs. 3.1 +/- 0.5 mm; P < .001) and distal end (3.2 +/- 0.6 vs. 2.9 +/- 0.4 mm; P = .004). CONCLUSIONS: Using 64-detector CCTA, interventional cardiologists select longer stents with larger final stent diameters than with ICA. Further studies are needed to determine the clinical utility of incorporating CCTA, when available, in defining interventional strategy.

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.

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.

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 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.

Outcomes of Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Atrial fibrillation (AF) is increasing in prevalence, and patients with a history of AF commonly undergo percutaneous coronary intervention (PCI). There is a paucity of contemporary data on the association between AF and clinical outcomes after PCI. OBJECTIVES: The study sought to evaluate the association between AF and in-hospital adverse outcomes using a large, prospective multicenter registry. METHODS: Data for consecutive PCI cases from 47 hospitals performed between April 2011 and December 2014 were utilized for the analysis. Propensity-matched multivariate analysis was used to adjust for differences in baseline characteristics between patients with and without a history of AF. RESULTS: Of 113,283 PCI cases during the study period, a history of AF was present in 13,912 patients (12%), which varied by institution (range 2.5% to 18.4%). At baseline, patients with a history of AF were older and were more likely to have comorbid congestive heart failure, cardiomyopathy, cerebrovascular disease, and chronic lung disease. Patients with a history of AF were more likely to have in-hospital complications, including in-hospital mortality (3% vs. 1%). In propensity-matched analysis, patients with a history of AF were more likely to be treated with a bare-metal stent (27% vs. 18%). In the propensity-matched model, AF remained independently associated with an increased risk of developing post-procedural bleeding (odds ratio [OR]: 1.32; 95% confidence interval [CI]: 1.15 to 1.52), heart failure (OR: 1.33; 95% CI: 1.17 to 1.52), cardiogenic shock (OR: 1.26; 95% CI: 1.08 to 1.48), and in-hospital mortality (OR: 1.41; 95% CI: 1.18 to 1.68). CONCLUSIONS: AF is common among patients undergoing PCI. AF is associated with older age, the presence of other comorbidities, and independently associated with in-hospital post-procedural heart failure, cardiogenic shock, and mortality.

Plasma interleukin-10 levels and adverse outcomes in acute coronary syndrome.

UNLABELLED: PURPOSE OR BACKGROUND: Interleukin (IL)-10 is an immunoregulatory cytokine that is produced by a variety of cell types, such as macrophages and activated monocytes. IL-10 possesses numerous anti-inflammatory, anti-thrombotic and anti-atherosclerotic properties. Furthermore, patients with acute coronary syndrome have been demonstrated to have reduced levels of IL-10 compared to their stable counterparts. For these reasons, it has been proposed that IL-10 plays a protective role in both atherogenesis and plaque vulnerability. However, 2 short-term studies on the prognostic utility of IL-10 in patients with acute coronary syndrome have provided conflicting results, with one study showing that reduced levels of IL-10 were predictors of adverse outcomes and another showing that elevated levels predicted poor outcomes. The objective of the present study was to investigate the long-term prognostic significance of baseline IL-10 levels in patients with acute coronary syndrome. METHODS: Baseline plasma IL-10 levels were measured in 193 well-characterized male patients with acute coronary syndrome who were referred for coronary angiography and followed prospectively for 5 years for the development of major adverse cardiovascular events. RESULTS: After controlling for a variety of baseline variables (including established biomarkers such as high-sensitivity C-reactive protein and N-terminal-pro-B-type natriuretic peptide), plasma IL-10 levels (whether analyzed as a continuous variable or as a categorical variable using receiver operating characteristic-derived cut point) were a strong and independent predictor of the composite outcome of death or non-fatal myocardial infarction when using a Cox proportional hazards model. CONCLUSIONS: These data demonstrate that, despite biologic plausibility for IL-10 as being a cardioprotective cytokine, elevated baseline plasma levels of IL-10 are a strong and independent predictor of long-term adverse cardiovascular outcomes in patients with acute coronary syndrome.

Relation of baseline plasma ADMA levels to cardiovascular morbidity and mortality at two years in men with diabetes mellitus referred for coronary angiography.

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.

Relationship of baseline plasma ADMA levels to cardiovascular outcomes at 2 years in men with acute coronary syndrome referred for coronary angiography.

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.

Relation of baseline serum potassium levels to angiographic findings 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.

Association of plasma levels of F11 receptor/junctional adhesion molecule-A (F11R/JAM-A) with human atherosclerosis.

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 < 0.0001). 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.

Adiponectin is an independent predictor of all-cause mortality, cardiac mortality, and myocardial infarction in patients presenting with chest pain.

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 (< or =4.431 mg/L), middle (>4.431 and < or =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.

Association of a polymorphism in the P2X7 gene with tuberculosis in a Gambian population.

Adenosine triphosphate (ATP) ligation of P2X(7) receptors expressed on human macrophages that are infected with mycobacteria induces cell death and subsequent loss of intracellular bacterial viability. Marked heterogeneity observed in cell donor ATP responsiveness suggests that this antimycobacterial mechanism may be genetically regulated. Five single-nucleotide polymorphisms (SNPs) previously identified in a putative 1.8-kb promoter region upstream of P2RX7 exon 1 were screened for associations with clinical tuberculosis. The frequencies of these promoter SNPs and a polymorphism in P2RX7 exon 13 at position 1513 were compared among >300 Gambian patients with tuberculosis and >160 ethnically matched control subjects by sequence-specific oligonucleotide hybridization and ligation detection reaction analysis. A significant protective association against tuberculosis was found for 1 promoter SNP, at nucleotide position -762 (odds ratio [OR] for variant C allele, 0.70; 95% confidence interval [CI], 0.54-0.89; P=.003; OR for CC genotype, 0.545; 95% CI, 0.318-0.934; P=.027). This association supports a role for ATP/P2X(7)-mediated host regulation of Mycobacterium tuberculosis infection.