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Coronary Artery Disease: HELP
Articles by Laurence S. Sperling
Based on 20 articles published since 2008
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Between 2008 and 2019, Laurence Sperling wrote the following 20 articles about Coronary Artery Disease.
 
+ Citations + Abstracts
1 Editorial Exercise Is Medicine: Proof . . . and Possibilities? 2017

Sperling, Laurence S / Sandesara, Pratik B / Kim, Jonathan H. ·Division of Cardiology, Emory University, Emory Clinical Cardiovascular Research Institute, Atlanta, Georgia. Electronic address: lsperli@emory.edu. · Division of Cardiology, Emory University, Emory Clinical Cardiovascular Research Institute, Atlanta, Georgia. ·JACC Cardiovasc Imaging · Pubmed #28528159.

ABSTRACT: -- No abstract --

2 Editorial Reducing the burden of disease and death from familial hypercholesterolemia: a call to action. 2014

Knowles, Joshua W / O'Brien, Emily C / Greendale, Karen / Wilemon, Katherine / Genest, Jacques / Sperling, Laurence S / Neal, William A / Rader, Daniel J / Khoury, Muin J. ·Stanford University School of Medicine and Cardiovascular Institute, Stanford, CA; The FH Foundation, South Pasadena, CA. · Duke Clinical Research Institute, Durham, NC. Electronic address: emily.obrien@duke.edu. · The FH Foundation, South Pasadena, CA. · McGill University, Montreal, Canada. · Emory University School of Medicine, Atlanta, GA. · West Virginia University, Morgantown, WV. · University of Pennsylvania, Philadelphia, PA. · Office of Public Health Genomics, Centers for Disease Control & Prevention, Atlanta, GA. ·Am Heart J · Pubmed #25458642.

ABSTRACT: Familial hypercholesterolemia (FH) is a genetic disease characterized by substantial elevations of low-density lipoprotein cholesterol, unrelated to diet or lifestyle. Untreated FH patients have 20 times the risk of developing coronary artery disease, compared with the general population. Estimates indicate that as many as 1 in 500 people of all ethnicities and 1 in 250 people of Northern European descent may have FH; nevertheless, the condition remains largely undiagnosed. In the United States alone, perhaps as little as 1% of FH patients have been diagnosed. Consequently, there are potentially millions of children and adults worldwide who are unaware that they have a life-threatening condition. In countries like the Netherlands, the United Kingdom, and Spain, cascade screening programs have led to dramatic improvements in FH case identification. Given that there are currently no systematic approaches in the United States to identify FH patients or affected relatives, the patient-centric nonprofit FH Foundation convened a national FH Summit in 2013, where participants issued a "call to action" to health care providers, professional organizations, public health programs, patient advocacy groups, and FH experts, in order to bring greater attention to this potentially deadly, but (with proper diagnosis) eminently treatable, condition.

3 Editorial Waiting for the National Cholesterol Education Program Adult Treatment Panel IV Guidelines, and in the meantime, some challenges and recommendations. 2012

Martin, Seth S / Metkus, Thomas S / Horne, Aaron / Blaha, Michael J / Hasan, Rani / Campbell, Catherine Y / Yousuf, Omair / Joshi, Parag / Kaul, Sanjay / Miller, Michael / Michos, Erin D / Jones, Steven R / Gluckman, Ty J / Cannon, Christopher P / Sperling, Laurence S / Blumenthal, Roger S. · ·Am J Cardiol · Pubmed #22497674.

ABSTRACT: The National Cholesterol Education Program Adult Treatment Panel (ATP) has provided education and guidance for decades on the management of hypercholesterolemia. Its third report (ATP III) was published 10 years ago, with a white paper update in 2004. There is a need for translation of more recent evidence into a revised guideline. To help address the significant challenges facing the ATP IV writing group, this statement aims to provide balanced recommendations that build on ATP III. The authors aim for simplicity to increase the likelihood of implementation in clinical practice. To move from ATP III to ATP IV, the authors recommend the following: (1) assess risk more accurately, (2) simplify the starting algorithm, (3) prioritize statin therapy, (4) relax the follow-up interval for repeat lipid testing, (5) designate <70 mg/dl as an "ideal" low-density lipoprotein cholesterol target, (6) endorse targets beyond low-density lipoprotein cholesterol, (7) refine therapeutic target levels to the equivalent population percentile, (8) remove misleading descriptors such as "borderline high," and (9) make lifestyle messages simpler. In conclusion, the solutions offered in this statement represent ways to translate the totality of published reports into enhanced hyperlipidemia guidelines to better combat the devastating impact of hyperlipidemia on cardiovascular health.

4 Review Cardiac rehabilitation and risk reduction: time to "rebrand and reinvigorate". 2015

Sandesara, Pratik B / Lambert, Cameron T / Gordon, Neil F / Fletcher, Gerald F / Franklin, Barry A / Wenger, Nanette K / Sperling, Laurence. ·Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia. · Intervent International, Savannah, Georgia. · Mayo Clinic, Rochester, Minnesota. · Department of Cardiovascular Medicine, William Beaumont Hospital, Royal Oak, Michigan. · Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia. Electronic address: lsperli@emory.edu. ·J Am Coll Cardiol · Pubmed #25634839.

ABSTRACT: Atherosclerotic cardiovascular disease (ASCVD) continues to increase annually in the United States along with its associated enormous costs. A multidisciplinary cardiac rehabilitation (CR) and risk reduction program is an essential component of ASCVD prevention and management. Despite the strong evidence for CR in the secondary prevention of ASCVD, it remains vastly underutilized due to significant barriers. The current model of CR delivery is unsustainable and needs significant improvement to provide cost-effective, patient-centered, comprehensive secondary ASCVD prevention.

5 Review Non-high-density lipoprotein cholesterol versus apolipoprotein B in cardiovascular risk stratification: do the math. 2011

Ramjee, Vimal / Sperling, Laurence S / Jacobson, Terry A. ·J. Willis Hurst Internal Medicine Residency, Emory University School of Medicine, Atlanta, GA 30303, USA. ·J Am Coll Cardiol · Pubmed #21777740.

ABSTRACT: With the emergence of new lipid risk markers and a growing cardiometabolic risk burden in the United States, there is a need to better integrate residual risk into cardiovascular disease (CVD) risk stratification. In anticipation of the Adult Treatment Panel IV (ATP IV) guidelines from the National Cholesterol Education Program (NCEP), there exists controversy regarding the comparative performance of the 2 foremost markers, apolipoprotein B (apoB) and non-high-density lipoprotein cholesterol (non-HDL-C), as they relate to the current standard of risk assessment and treatment: low-density lipoprotein cholesterol (LDL-C). Although some emerging markers may demonstrate better performance compared with LDL-C, certain fundamental characteristics intrinsic to a beneficial biomarker must be met prior to routine use. Collectively, studies have found that non-HDL-C and apoB perform better than LDL-C in CVD risk prediction, both on- and off-treatment, as well as in subclinical CVD risk prediction. The performance of non-HDL-C compared with apoB, however, has been a point of ongoing debate. Although both offer the practical benefits of accuracy independent of triglyceride level and prandial state, non-HDL-C proves to be the better marker of choice at this time, given established cutpoints with safe and achievable goals, no additional cost, and quick time to result with an easy mathematical calculation. The purpose of this review is to assess the performance of these parameters in this context and to discuss the considerations of implementation into clinical practice.

6 Review The role of C-reactive protein as a risk predictor of coronary atherosclerosis: implications from the JUPITER trial. 2011

Abd, Thura T / Eapen, Danny J / Bajpai, Ambareesh / Goyal, Abhinav / Dollar, Allen / Sperling, Laurence. ·Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA. Tabd@emory.edu ·Curr Atheroscler Rep · Pubmed #21274757.

ABSTRACT: Much controversy surrounds the use of high-sensitivity C-reactive protein (hs-CRP) as a marker of cardiovascular (CV) risk. Although data regarding the association of hs-CRP with CV disease is extensive and consistent, its role in clinical practice remains unclear. The American Heart Association (AHA) recently published a scientific statement regarding criteria for evaluation of novel markers of CV risk. This article provides a comprehensive review of data regarding hs-CRP as a risk marker for CV disease in the context of these AHA criteria. The impact of the JUPITER trial on the utility of hs-CRP as a risk marker is emphasized. The review concludes with an evidence-based statement regarding the current role of hs-CRP in CV risk prediction.

7 Clinical Trial Elevated Levels of Serum Fibrin and Fibrinogen Degradation Products Are Independent Predictors of Larger Coronary Plaques and Greater Plaque Necrotic Core. 2016

Corban, Michel T / Hung, Olivia Y / Mekonnen, Girum / Eshtehardi, Parham / Eapen, Danny J / Rasoul-Arzrumly, Emad / Al Kassem, Hatem / Manocha, Pankaj / Ko, Yi-An / Sperling, Laurence S / Quyyumi, Arshed A / Samady, Habib. ·Division of Cardiology, Department of Medicine, Emory University School of Medicine. ·Circ J · Pubmed #26911453.

ABSTRACT: BACKGROUND: Co-existence of vulnerable plaque and pro-thrombotic state may provoke acute coronary events. It was hypothesized that elevated serum levels of fibrin and fibrinogen degradation products (FDP) are associated with larger total plaque and necrotic core (NC) areas. METHODS AND RESULTS: Seventy-five patients presenting with stable anginal symptoms (69%) or stabilized acute coronary syndrome (ACS; 31%), and found to have non-obstructive coronary artery disease (CAD) with a fractional flow reserve >0.8, were studied. Invasive virtual histology intravascular ultrasound (VH-IVUS) was performed in 68 LAD arteries, 6 circumflex arteries, and 1 right coronary artery. Serum FDP levels were measured using ELISA technique. Plaque volumetrics and composition were assessed in each VH-IVUS frame and averaged. The median age of patients was 56 (47-63) years; 52% were men and 23% had diabetes. The average length of coronary artery studied was 62 mm. After adjustment for systemic risk factors, medications, CRP levels and ACS, male gender (P<0.001) and serum FDP levels (P=0.02) were independent predictors of a larger NC area. Older age (P<0.001), male gender (P<0.0001) and increased serum FDP level (P=0.03) were associated with a larger plaque area. CONCLUSIONS: In patients with CAD, a higher serum level of FDP is independently associated with larger plaques and greater plaque NC.

8 Article Comparison of the Association Between High-Sensitivity Troponin I and Adverse Cardiovascular Outcomes in Patients With Versus Without Chronic Kidney Disease. 2018

Sandesara, Pratik B / O'Neal, Wesley T / Tahhan, Ayman Samman / Hayek, Salim S / Lee, Suegene K / Khambhati, Jay / Topel, Matthew L / Hammadah, Muhammad / Alkhoder, Ayman / Ko, Yi-An / Gafeer, Mohamad Mazen / Beshiri, Agim / Murtagh, Gillian / Kim, Jonathan H / Wilson, Peter / Shaw, Leslee / Epstein, Stephen E / Sperling, Laurence S / Quyyumi, Arshed A. ·Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia. Electronic address: psandes@emory.edu. · Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia. · Department of Internal Medicine, Emory University School of Medicine, Atlanta, Georgia. · Department of Biostatistics and Bioinformatics, Emory University, Atlanta, Georgia. · Diagnostics Division, Abbott Laboratories, North Chicago, Illinois. · MedStar Washington Hospital Center, MedStar Heart and Vascular Institute, Washington, District of Columbia. ·Am J Cardiol · Pubmed #29628129.

ABSTRACT: It is unknown whether the association of high-sensitivity troponin I (hs-TnI) with adverse cardiovascular outcomes varies by the presence of chronic kidney disease (CKD). We examined the association of hs-TnI with adverse cardiovascular outcomes in those with and without CKD in 4,107 (mean age, 64 years; 63% men; 20% black) patients from the Emory Cardiovascular Biobank who underwent coronary angiography. CKD (n = 1,073) was defined as estimated glomerular filtration rate <60 ml/min/1.73 m

9 Article Circulating soluble urokinase plasminogen activator receptor levels and peripheral arterial disease outcomes. 2017

Samman Tahhan, Ayman / Hayek, Salim S / Sandesara, Pratik / Hajjari, Jamal / Hammadah, Muhammad / O'Neal, Wesley T / Kelli, Heval M / Alkhoder, Ayman / Ghasemzadeh, Nima / Ko, Yi-An / Aida, Hiroshi / Gafeer, Mohamad Mazen / Abdelhadi, Naser / Mohammed, Kareem Hosny / Patel, Keyur / Arya, Shipra / Reiser, Jochen / Vaccarino, Viola / Sperling, Laurence / Quyyumi, Arshed. ·Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, United States. · Department of Biostatistics and Bioinformatics, Emory University, United States. · Department of Surgery, Emory University School of Medicine, United States. · Department of Medicine, Rush University Medical Center, United States. · Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, United States; Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, United States. · Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, United States. Electronic address: aquyyum@emory.edu. ·Atherosclerosis · Pubmed #28728756.

ABSTRACT: BACKGROUND AND AIMS: Circulating soluble urokinase plasminogen activator receptor (suPAR) is a marker of immune activation associated with atherosclerosis. Whether suPAR levels are associated with prevalent peripheral arterial disease (PAD) and its adverse outcomes remains unknown and is the aim of the study. METHODS: SuPAR levels were measured in 5810 patients (mean age 63 years, 63% male, 77% with obstructive coronary artery disease [CAD]) undergoing cardiac catheterization. The presence of PAD (n = 967, 17%) was classified as carotid (36%), lower/upper extremities (30%), aortic (15%) and multisite disease (19%). Multivariable logistic and Cox regression models were used to determine independent predictors of prevalent PAD and outcomes including all-cause death, cardiovascular death and PAD-related events after adjustment for age, gender, race, body mass index, smoking, diabetes, hypertension, hyperlipidemia, renal function, heart failure history, and obstructive CAD. RESULTS: Plasma suPAR levels were 22.5% (p < 0.001) higher in patients with PAD compared to those without PAD. Plasma suPAR was higher in patients with more extensive PAD (≥2 compared to single site) p < 0.001. After multivariable adjustment, suPAR was associated with prevalent PAD; odds ratio (OR) for highest compared to lowest tertile of 2.0, 95% CI (1.6-2.5) p < 0.001. In Cox survival analyses adjusted for clinical characteristics and medication regimen, suPAR (in the highest vs. lowest tertile) remained an independent predictor of all-cause death [HR 3.1, 95% CI (1.9-5.3)], cardiovascular death [HR 3.5, 95% CI (1.8-7.0)] and PAD-related events [HR = 1.8, 95% CI (1.3-2.6) p < 0.001 for all]. CONCLUSIONS: Plasma suPAR level is predictive of prevalent PAD and of incident cardiovascular and PAD-related events. Whether SuPAR measurement can help screen, risk stratify, or monitor therapeutic responses in PAD requires further investigation.

10 Article An Aggregate Biomarker Risk Score Predicts High Risk of Near-Term Myocardial Infarction and Death: Findings From BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes). 2017

Ghasemzadeh, Nima / Brooks, Maria M / Vlachos, Helen / Hardison, Regina / Sikora, Sergey / Sperling, Laurence / Quyyumi, Arshed A / Epstein, Stephen E. ·Emory University School of Medicine, Atlanta, GA. · Graduate School of Public Health, University of Pittsburgh, PA. · CardioCell, San Diego, CA. · Emory University School of Medicine, Atlanta, GA aquyyum@emory.edu. · MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, DC. ·J Am Heart Assoc · Pubmed #28673897.

ABSTRACT: BACKGROUND: In a previous study, we found that a biomarker risk score (BRS) comprised of C-reactive protein, fibrin-degradation products, and heat shock protein-70 predicts risk of myocardial infarction and death in coronary artery disease patients. We sought to: (1) validate the BRS in the independent BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) cohort, (2) investigate whether 1 year of intensive medical therapy is associated with improved BRS, and (3) elucidate whether an altered BRS parallels altered risk. METHODS AND RESULTS: Two thousand thirty-two subjects with coronary artery disease were followed for 5.3±1.1 years for cardiovascular events. Biomarkers were measured at baseline and retested in 1304 subjects at 1 year. BRS was determined as the biomarker number above previously defined cut-off values (C-reactive protein >3 mg/L, heat shock protein-70 >0.313 ng/mL, and fibrin-degradation products >1 μg/mL). After adjustment for covariates, those with a BRS of 3 had a 4-fold increased risk of all-cause death and a 6.8-fold increased risk of cardiac death compared with those with a BRS of 0 (95% CI, 2.9-16.0; CONCLUSIONS: Our results validate the ability of the BRS to identify coronary artery disease patients at very high near-term risk of myocardial infarction/death. After 1 year of intensive medical therapy, the BRS decreased significantly, and the reclassified BRS continued to track with risk. Our results suggest that repeated BRS measurements might be used to assess risk and recalibrate therapy.

11 Article Pathway-Specific Aggregate Biomarker Risk Score Is Associated With Burden of Coronary Artery Disease and Predicts Near-Term Risk of Myocardial Infarction and Death. 2017

Ghasemzedah, Nima / Hayek, Salim S / Ko, Yi-An / Eapen, Danny J / Patel, Riyaz S / Manocha, Pankaj / Al Kassem, Hatem / Khayata, Mohamed / Veledar, Emir / Kremastinos, Dimitrios / Thorball, Christian W / Pielak, Tomasz / Sikora, Sergey / Zafari, A Maziar / Lerakis, Stamatios / Sperling, Laurence / Vaccarino, Viola / Epstein, Stephen E / Quyyumi, Arshed A. ·From the Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA (N.G., S.S.H., D.J.E., R.S.P., P.M., H.A.K., M.K., E.V., A.M.Z., S.L., L.S., V.V., A.A.Q.) · Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA (Y.-A.K.) · Institute of Cardiovascular Science, University College London, United Kingdom (R.S.P.) · Division of Cardiology, Atlanta VA Medical Center, GA (A.M.Z.) · Department of Biostatistics, Florida International University, Miami (E.V.) · Department of Cardiology, University of Athens School of Medicine, Greece (D.K.) · Clinical Research Centre, Copenhagen University Hospital, Denmark (C.W.T., T.P.) · Stemedica Cell Technologies, Inc., San Diego, CA (S.S.) · Department of Epidemiology, Emory University, Atlanta, GA (V.V.) · and MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, DC (S.E.E.). ·Circ Cardiovasc Qual Outcomes · Pubmed #28280039.

ABSTRACT: BACKGROUND: Inflammation, coagulation, and cell stress contribute to atherosclerosis and its adverse events. A biomarker risk score (BRS) based on the circulating levels of biomarkers C-reactive protein, fibrin degradation products, and heat shock protein-70 representing these 3 pathways was a strong predictor of future outcomes. We investigated whether soluble urokinase plasminogen activator receptor (suPAR), a marker of immune activation, is predictive of outcomes independent of the aforementioned markers and whether its addition to a 3-BRS improves risk reclassification. METHODS AND RESULTS: C-reactive protein, fibrin degradation product, heat shock protein-70, and suPAR were measured in 3278 patients undergoing coronary angiography. The BRS was calculated by counting the number of biomarkers above a cutoff determined using the Youden's index. Survival analyses were performed using models adjusted for traditional risk factors. A high suPAR level ≥3.5 ng/mL was associated with all-cause death and myocardial infarction (hazard ratio, 1.83; 95% confidence interval, 1.43-2.35) after adjustment for risk factors, C-reactive protein, fibrin degradation product, and heat shock protein-70. Addition of suPAR to the 3-BRS significantly improved the C statistic, integrated discrimination improvement, and net reclassification index for the primary outcome. A BRS of 1, 2, 3, or 4 was associated with a 1.81-, 2.59-, 6.17-, and 8.80-fold increase, respectively, in the risk of death and myocardial infarction. The 4-BRS was also associated with severity of coronary artery disease and composite end points. CONCLUSIONS: SuPAR is independently predictive of adverse outcomes, and its addition to a 3-BRS comprising C-reactive protein, fibrin degradation product, and heat shock protein-70 improved risk reclassification. The clinical utility of using a 4-BRS for risk prediction and management of patients with coronary artery disease warrants further study.

12 Article Depression and chest pain in patients with coronary artery disease. 2017

Hayek, Salim S / Ko, Yi-An / Awad, Mosaab / Del Mar Soto, Andrea / Ahmed, Hina / Patel, Keyur / Yuan, Michael / Maddox, Spencer / Gray, Brandon / Hajjari, Jamal / Sperling, Laurence / Shah, Amit / Vaccarino, Viola / Quyyumi, Arshed A. ·Division of Cardiology, Emory University School of Medicine, Atlanta, GA, United States. · Division of Cardiology, Emory University School of Medicine, Atlanta, GA, United States; Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, United States. · Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, United States. · Department of Medicine, Emory University School of Medicine, Atlanta, GA, United States. · Division of Cardiology, Emory University School of Medicine, Atlanta, GA, United States; Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, United States. · Division of Cardiology, Emory University School of Medicine, Atlanta, GA, United States. Electronic address: aquyyum@emory.edu. ·Int J Cardiol · Pubmed #28041701.

ABSTRACT: BACKGROUND: Depression is common in patients with coronary artery disease (CAD) and is associated with more frequent chest pain. It is however unclear whether this is due to differences in underlying CAD severity. We sought to determine [1] whether depressive symptoms are associated with chest pain independently of CAD severity, [2] whether improvement in depressive symptoms over time is associated with improvement in chest pain and [3] whether the impact of revascularization on chest pain differs between patients with and without depression. METHODS AND RESULTS: 5158 patients (mean age 63±12years, 65% male, 20% African American) undergoing cardiac catheterization completed the Seattle Angina Questionnaire (SAQ) and Patient Health Questionnaire-8 (PHQ-8) to assess angina severity and screen for depression, respectively, both at baseline and between 6 and 24months of follow-up. We found significant correlations between PHQ-8 scores and angina frequency (SAQ-AF, r=-0.28), physical limitation (SAQ-PL, r=-0.32) and disease perception (SAQ-DS r=-0.37, all P<0.001), which remained significant after adjustment for clinical characteristics, CAD severity, and anti-depressant use. Improvement in depressive symptoms at follow-up was associated with improvement in angina subscales (SAQ-AF β 1.34, P<0.001), SAQ-PL β 1.85, P<0.001), and SAQ-DS (β 2.12, P<0.001), independently of CAD severity or revascularization. Patients with depression who underwent revascularization had less improvement in chest pain frequency than those without depressive symptoms. CONCLUSIONS: Depression is associated with angina, independently of CAD severity. Patients with depression may not derive as adequate symptomatic benefit from revascularization as those without. Whether treatment of underlying depression improves chest pain needs to be further studied.

13 Article Abnormal heart-rate response during cardiopulmonary exercise testing identifies cardiac dysfunction in symptomatic patients with non-obstructive coronary artery disease. 2017

Chaudhry, Sundeep / Kumar, Naresh / Behbahani, Hushyar / Bagai, Akshay / Singh, Binoy K / Menasco, Nick / Lewis, Gregory D / Sperling, Laurence / Myers, Jonathan. ·Research and Development, MET-TEST, Inc., Atlanta, GA, United States. Electronic address: schaudhry@mettest.net. · Research Division, Whitby Cardiovascular Institute, Whitby, Canada. · Division of Cardiology, St. Michael's Hospital, University of Toronto, Canada. · Division of Cardiovascular Medicine, Hofstra Northwell School of Medicine, Hofstra University, New York, NY, United States. · Research and Development, MET-TEST, Inc., Atlanta, GA, United States. · Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston, MA, United States. · Division of Preventive Cardiology, Emory University, Atlanta, GA, United States. · Division of Cardiovascular Medicine, Stanford University and Veterans Affairs, Palo Alto Health Care System, Palo Alto, CA, United States. ·Int J Cardiol · Pubmed #27863351.

ABSTRACT: BACKGROUND: Symptomatic non-obstructive coronary artery disease is a growing clinical dilemma for which contemporary testing is proving to be of limited clinical utility. New methods are needed to identify cardiac dysfunction. METHODS AND RESULTS: This is a prospective observational cohort study conducted from December 2013 to August 2015 in two outpatient cardiology clinics (symptomatic cohort) and 24 outpatient practices throughout the US (healthy cohort) with centralized methodology and monitoring to compare heart-rate responses during cardiopulmonary exercise testing (CPET). Participants were 208 consecutive patients (median age, 61; range, 32-86years) with exercise intolerance and without prior heart or lung disease in whom coronary anatomy was defined and 116 healthy subjects (median age, 45; range, 26-66years). Compared to stress ECG, the novel change in heart-rate as a function of work-rate parameter (ΔHR-WR Slope) demonstrated significantly higher sensitivity to detect under-treated atherosclerosis with similar specificity. In men, area under the ROC curve increased from 60% to 94% for non-obstructive CAD and from 64% to 80% for obstructive CAD. In women, AUC increased from 64% to 85% for non-obstructive CAD and from 66% to 90% for obstructive CAD. ΔHR-WR Slope correctly reclassified abnormal studies in the non-obstructive CAD group from 22% to 81%; in the obstructive CAD group from 18% to 84% and in the revascularization group from 35% to 78%. CONCLUSION: Abnormal heart-rate response during CPET is more effective than stress ECG for identifying under-treated atherosclerosis and may be of utility to identify cardiac dysfunction in symptomatic patients with normal routine cardiac testing.

14 Article Novel Biomarker of Oxidative Stress Is Associated With Risk of Death in Patients With Coronary Artery Disease. 2016

Patel, Riyaz S / Ghasemzadeh, Nima / Eapen, Danny J / Sher, Salman / Arshad, Shawn / Ko, Yi-an / Veledar, Emir / Samady, Habib / Zafari, A Maziar / Sperling, Laurence / Vaccarino, Viola / Jones, Dean P / Quyyumi, Arshed A. ·From Department of Medicine, Emory University School of Medicine, Atlanta, GA (R.S.P., N.G., D.J.E., S.S., S.A., H.S., A.M.Z., L.S., V.V., D.P.J., A.A.Q.) · Institute of Cardiovascular Science, University College London, United Kingdom (R.S.P.) · Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Atlanta, GA (Y.K.) · Department of Medicine, Baptist Health South Florida, Miami, FL (E.V.) · Department of Epidemiology, Rollins School of Public Health, Atlanta, GA (E.V., V.V.) · and Department of Medicine, Atlanta Veterans Affairs Medical Center, Decatur, GA (A.M.Z.). ·Circulation · Pubmed #26673559.

ABSTRACT: BACKGROUND: Free radical scavengers have failed to improve patient outcomes, promoting the concept that clinically important oxidative stress may be mediated by alternative mechanisms. We sought to examine the association of emerging aminothiol markers of nonfree radical mediated oxidative stress with clinical outcomes. METHODS AND RESULTS: Plasma levels of reduced (cysteine and glutathione) and oxidized (cystine and glutathione disulphide) aminothiols were quantified by high performance liquid chromatography in 1411 patients undergoing coronary angiography (mean age 63 years, male 66%). All patients were followed for a mean of 4.7 ± 2.1 years for the primary outcome of all-cause death (n=247). Levels of cystine (oxidized) and glutathione (reduced) were associated with risk of death (P<0.001 both) before and after adjustment for covariates. High cystine and low glutathione levels (>+1 SD and <-1 SD, respectively) were associated with higher mortality (adjusted hazard ratio [HR], 1.63; 95% confidence interval [CI], 1.19-2.21; HR, 2.19; 95% CI, 1.50-3.19; respectively) compared with those outside these thresholds. Furthermore, the ratio of cystine/glutathione was also significantly associated with mortality (adjusted HR, 1.92; 95% CI, 1.39-2.64) and was independent of and additive to high-sensitivity C-reactive protein level. Similar associations were found for other outcomes of cardiovascular death and combined death and myocardial infarction. CONCLUSIONS: A high burden of oxidative stress, quantified by the plasma aminothiols, cystine, glutathione, and their ratio, is associated with mortality in patients with coronary artery disease, a finding that is independent of and additive to the inflammatory burden. Importantly, these data support the emerging role of nonfree radical biology in driving clinically important oxidative stress.

15 Article Plasma soluble urokinase-type plasminogen activator receptor level is independently associated with coronary microvascular function in patients with non-obstructive coronary artery disease. 2015

Mekonnen, Girum / Corban, Michel T / Hung, Olivia Y / Eshtehardi, Parham / Eapen, Danny J / Al-Kassem, Hatem / Rasoul-Arzrumly, Emad / Gogas, Bill D / McDaniel, Michael C / Pielak, Tomasz / Thorball, Christian W / Sperling, Laurence / Quyyumi, Arshed A / Samady, Habib. ·Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA. · Clinical Research Center, Copenhagen University Hospital, Hvidovre, Denmark. · Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA. Electronic address: hsamady@emory.edu. ·Atherosclerosis · Pubmed #25574858.

ABSTRACT: BACKGROUND: Soluble urokinase-type plasminogen activator receptor (suPAR) is a novel biomarker released from leukocytes and endothelial cells that has been associated with atherosclerotic cardiovascular disease. We hypothesized that plasma suPAR level is an independent predictor of coronary microvascular function. METHODS: Coronary blood flow velocity and plasma suPAR levels were evaluated in patients with non-obstructive coronary artery disease. Coronary flow reserve (CFR) was calculated as the ratio of hyperemic to basal average peak blood flow velocity and coronary microvascular dysfunction was defined as CFR ≤ 2.0 in the setting of a fractional flow reserve value of ≥0.75. Plasma suPAR levels were measured using ELISA technique. The association between suPAR and CFR was investigated using univariate and multivariate regression analyses. RESULTS: In 66 patients, 47% were men, 26% had diabetes, 68% had hypertension and 76% had dyslipidemia. Mean age was 55 ± 12 years and median suPAR level 2.82 (2.08-3.40) ng/mL. Plasma suPAR levels correlated with age (r = 0.31, p = 0.01), body mass index (r = 0.25, p = 0.04) and high-sensitivity C-reactive protein (hs-CRP) (r = 0.33, p = 0.009). While median suPAR level was not significantly different in patients with different cardiovascular risk factors, patients on statin therapy had significantly higher suPAR level (p = 0.03). SuPAR correlated negatively with CFR and, after multivariate adjustment for established cardiovascular risk factors, medications profiles and hs-CRP, suPAR remained an independent predictor of CFR (B = -0.30, p = 0.04), indicating an independent association between suPAR level and coronary microvascular function. CONCLUSIONS: In this cross-sectional study, plasma suPAR level was an independent predictor of coronary microvascular function. Larger prospective clinical trials are warranted to investigate the prognostic value of this novel biomarker and the role of immune dysregulation in coronary microvascular disease.

16 Article Plasma stromal cell-derived factor 1α/CXCL12 level predicts long-term adverse cardiovascular outcomes in patients with coronary artery disease. 2015

Ghasemzadeh, Nima / Hritani, Abdul Wahab / De Staercke, Christine / Eapen, Danny J / Veledar, Emir / Al Kassem, Hatem / Khayata, Mohamed / Zafari, A Maziar / Sperling, Laurence / Hooper, Craig / Vaccarino, Viola / Mavromatis, Kreton / Quyyumi, Arshed A. ·Emory University School of Medicine, Atlanta, GA, USA. · Center for Disease Control and Prevention, Atlanta, GA, USA. · Department of Biostatistics, Florida International University, Miami, FL, USA; Department of Epidemiology, Rollins School of Public Health, Atlanta, GA, USA. · Emory University School of Medicine, Atlanta, GA, USA; Atlanta Veterans Affairs Medical Center, Decatur, GA, USA. · Emory University School of Medicine, Atlanta, GA, USA; Department of Epidemiology, Rollins School of Public Health, Atlanta, GA, USA. · Emory University School of Medicine, Atlanta, GA, USA. Electronic address: aquyyum@emory.edu. ·Atherosclerosis · Pubmed #25461737.

ABSTRACT: OBJECTIVE: Stromal derived factor-1α/CXCL12 is a chemoattractant responsible for homing of progenitor cells to ischemic tissues. We aimed to investigate the association of plasma CXCL12 with long-term cardiovascular outcomes in patients with coronary artery disease (CAD). METHODS: 785 patients aged: 63 ± 12 undergoing coronary angiography were independently enrolled into discovery (N = 186) and replication (N = 599) cohorts. Baseline levels of plasma CXCL12 were measured using Quantikine CXCL12 ELISA assay (R&D systems). Patients were followed for cardiovascular death and/or myocardial infarction (MI) for a mean of 2.6 yrs. Cox proportional hazard was used to determine independent predictors of cardiovascular death/MI. RESULTS: The incidence of cardiovascular death/MI was 13% (N = 99). High CXCL12 level based on best discriminatory threshold derived from the ROC analysis predicted risk of cardiovascular death/MI (HR = 4.81, p = 1 × 10(-6)) independent of traditional risk factors in the pooled cohort. Addition of CXCL12 to a baseline model was associated with a significant improvement in c-statistic (AUC: 0.67-0.73, p = 0.03). Addition of CXCL12 was associated with correct risk reclassification of 40% of events and 10.5% of non-events. Similarly for the outcome of cardiovascular death, the addition of the CXCL12 to the baseline model was associated with correct reclassification of 20.7% of events and 9% of non-events. These results were replicated in two independent cohorts. CONCLUSION: Plasma CXCL12 level is a strong independent predictor of adverse cardiovascular outcomes in patients with CAD and improves risk reclassification.

17 Article Circulating CD34+ progenitor cells and risk of mortality in a population with coronary artery disease. 2015

Patel, Riyaz S / Li, Qunna / Ghasemzadeh, Nima / Eapen, Danny J / Moss, Lauren D / Janjua, A Umair / Manocha, Pankaj / Kassem, Hatem Al / Veledar, Emir / Samady, Habib / Taylor, W Robert / Zafari, A Maziar / Sperling, Laurence / Vaccarino, Viola / Waller, Edmund K / Quyyumi, Arshed A. ·Dept. of Medicine, Emory University School of Medicine, Atlanta, GA, USA. · Institute of Cardiovascular Sciences, University College London, London, UK. · Dept of Medicine, Baptist Health South Florida, Florida, USA. · Dept. of Medicine, Atlanta Veterans Affairs Medical Center, Decatur, GA, USA. ·Circ Res · Pubmed #25323857.

ABSTRACT: RATIONALE: Low circulating progenitor cell numbers and activity may reflect impaired intrinsic regenerative/reparative potential, but it remains uncertain whether this translates into a worse prognosis. OBJECTIVES: To investigate whether low numbers of progenitor cells associate with a greater risk of mortality in a population at high cardiovascular risk. METHODS AND RESULTS: Patients undergoing coronary angiography were recruited into 2 cohorts (1, n=502 and 2, n=403) over separate time periods. Progenitor cells were enumerated by flow cytometry as CD45(med+) blood mononuclear cells expressing CD34, with additional quantification of subsets coexpressing CD133, vascular endothelial growth factor receptor 2, and chemokine (C-X-C motif) receptor 4. Coefficient of variation for CD34 cells was 2.9% and 4.8%, 21.6% and 6.5% for the respective subsets. Each cohort was followed for a mean of 2.7 and 1.2 years, respectively, for the primary end point of all-cause death. There was an inverse association between CD34(+) and CD34(+)/CD133(+) cell counts and risk of death in cohort 1 (β=-0.92, P=0.043 and β=-1.64, P=0.019, respectively) that was confirmed in cohort 2 (β=-1.25, P=0.020 and β=-1.81, P=0.015, respectively). Covariate-adjusted hazard ratios in the pooled cohort (n=905) were 3.54 (1.67-7.50) and 2.46 (1.18-5.13), respectively. CD34(+)/CD133(+) cell counts improved risk prediction metrics beyond standard risk factors. CONCLUSIONS: Reduced circulating progenitor cell counts, identified primarily as CD34(+) mononuclear cells or its subset expressing CD133, are associated with risk of death in individuals with coronary artery disease, suggesting that impaired endogenous regenerative capacity is associated with increased mortality. These findings have implications for biological understanding, risk prediction, and cell selection for cell-based therapies.

18 Article Soluble urokinase plasminogen activator receptor level is an independent predictor of the presence and severity of coronary artery disease and of future adverse events. 2014

Eapen, Danny J / Manocha, Pankaj / Ghasemzadeh, Nima / Patel, Riyaz S / Al Kassem, Hatem / Hammadah, Muhammad / Veledar, Emir / Le, Ngoc-Anh / Pielak, Tomasz / Thorball, Christian W / Velegraki, Aristea / Kremastinos, Dimitrios T / Lerakis, Stamatios / Sperling, Laurence / Quyyumi, Arshed A. ·Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA (D.J.E., P.M., N.G., R.S.P., H.A.K., M.H., E.V., N.A.L., S.L., L.S., A.A.Q.). · Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA (D.J.E., P.M., N.G., R.S.P., H.A.K., M.H., E.V., N.A.L., S.L., L.S., A.A.Q.) Department of Medicine, Cardiff University, Cardiff, UK (R.S.P.). · Clinical Research Center, Copenhagen University Hospital Copenhagen, Denmark (T.P., C.W.T.). · Medical School of Athens, Athens, Greece (A.V., D.T.K., S.L.). · Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA (D.J.E., P.M., N.G., R.S.P., H.A.K., M.H., E.V., N.A.L., S.L., L.S., A.A.Q.) Medical School of Athens, Athens, Greece (A.V., D.T.K., S.L.). ·J Am Heart Assoc · Pubmed #25341887.

ABSTRACT: INTRODUCTION: Soluble urokinase plasminogen activator receptor (suPAR) is an emerging inflammatory and immune biomarker. Whether suPAR level predicts the presence and the severity of coronary artery disease (CAD), and of incident death and myocardial infarction (MI) in subjects with suspected CAD, is unknown. METHODS AND RESULTS: We measured plasma suPAR levels in 3367 subjects (67% with CAD) recruited in the Emory Cardiovascular Biobank and followed them for adverse cardiovascular (CV) outcomes of death and MI over a mean 2.1±1.1 years. Presence of angiographic CAD (≥50% stenosis in ≥1 coronary artery) and its severity were quantitated using the Gensini score. Cox's proportional hazard survival and discrimination analyses were performed with models adjusted for established CV risk factors and C-reactive protein levels. Elevated suPAR levels were independently associated with the presence of CAD (P<0.0001) and its severity (P<0.0001). A plasma suPAR level ≥3.5 ng/mL (cutoff by Youden's index) predicted future risk of MI (hazard ratio [HR]=3.2; P<0.0001), cardiac death (HR=2.62; P<0.0001), and the combined endpoint of death and MI (HR=1.9; P<0.0001), even after adjustment of covariates. The C-statistic for a model based on traditional risk factors was improved from 0.72 to 0.74 (P=0.008) with the addition of suPAR. CONCLUSION: Elevated levels of plasma suPAR are associated with the presence and severity of CAD and are independent predictors of death and MI in patients with suspected or known CAD.

19 Article Aggregate risk score based on markers of inflammation, cell stress, and coagulation is an independent predictor of adverse cardiovascular outcomes. 2013

Eapen, Danny J / Manocha, Pankaj / Patel, Riyaz S / Hammadah, Muhammad / Veledar, Emir / Wassel, Christina / Nanjundappa, Ravi A / Sikora, Sergey / Malayter, Dylan / Wilson, Peter W F / Sperling, Laurence / Quyyumi, Arshed A / Epstein, Stephen E. ·Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA 30322, USA. ·J Am Coll Cardiol · Pubmed #23665099.

ABSTRACT: OBJECTIVES: This study sought to determine an aggregate, pathway-specific risk score for enhanced prediction of death and myocardial infarction (MI). BACKGROUND: Activation of inflammatory, coagulation, and cellular stress pathways contribute to atherosclerotic plaque rupture. We hypothesized that an aggregate risk score comprised of biomarkers involved in these different pathways-high-sensitivity C-reactive protein (CRP), fibrin degradation products (FDP), and heat shock protein 70 (HSP70) levels-would be a powerful predictor of death and MI. METHODS: Serum levels of CRP, FDP, and HSP70 were measured in 3,415 consecutive patients with suspected or confirmed coronary artery disease (CAD) undergoing cardiac catheterization. Survival analyses were performed with models adjusted for established risk factors. RESULTS: Median follow-up was 2.3 years. Hazard ratios (HRs) for all-cause death and MI based on cutpoints were as follows: CRP ≥3.0 mg/l, HR: 1.61; HSP70 >0.625 ng/ml, HR; 2.26; and FDP ≥1.0 μg/ml, HR: 1.62 (p < 0.0001 for all). An aggregate biomarker score between 0 and 3 was calculated based on these cutpoints. Compared with the group with a 0 score, HRs for all-cause death and MI were 1.83, 3.46, and 4.99 for those with scores of 1, 2, and 3, respectively (p for each: <0.001). Annual event rates were 16.3% for the 4.2% of patients with a score of 3 compared with 2.4% in 36.4% of patients with a score of 0. The C statistic and net reclassification improved (p < 0.0001) with the addition of the biomarker score. CONCLUSIONS: An aggregate score based on serum levels of CRP, FDP, and HSP70 is a predictor of future risk of death and MI in patients with suspected or known CAD.

20 Minor Response to Letter Regarding Article "Novel Biomarker of Oxidative Stress Is Associated With Risk of Death in Patients With Coronary Artery Disease". 2016

Patel, Riyaz S / Ghasemzadeh, Nima / Eapen, Danny J / Sher, Salman / Arshad, Shawn / Ko, Yi-An / Veledar, Emir / Samady, Habib / Zafari, A Maziar / Sperling, Laurence / Vaccarino, Viola / Jones, Dean P / Quyyumi, Arshed A. ·Department of Medicine Emory University School of Medicine Atlanta, GA. · Department of Biostatistics and Bioinformatics Rollins School of Public Health Atlanta, GA. · Department of Medicine Baptist Health South Florida Miami, FL. ·Circulation · Pubmed #27245653.

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