Endothelial progenitor cells and major adverse cardiovascular events in patients receiving elective coronary angiography

Background and purpose: The association of circulating endothelial progenitor cells (EPCs) with different cardiovascular diseases and their related major adverse cardiovascular events (MACE) remained inconclusive. We aimed to clarify associations between the circulating EPC levels and the risk of MACE concerning different atherosclerosis-related diseases. Methods: This prospective cohort study was conducted from December 2009 to March 2015. Patients who underwent non-emergent coronary angiography (CAG) were included. The circulating EPC levels were measured using flow cytometry prior to the CAG procedure. The study evaluation of circulating EPC levels among patients with obstructive coronary artery disease (CAD) and other comorbidities. Patients were then assigned to tertiles by circulating EPC levels to evaluate the predictive values of the development of MACEs. Results: The study enrolled 1099 patients, of whom, 736 (67%) were men, with a mean age of 66.7 ± 12.5 years old. Overall, 637 (58%) patients were diagnosed with obstructive CAD according to CAG. MACE occurred in 268 (24.4%) patients. Circulating EPC levels were lower in patients with peripheral artery disease (PAD) but not associated with the presence of obstructive CAD, atrial fibrillation, chronic kidney disease (CKD), heart failure, and diabetes mellitus. Higher circulating EPC levels are linked with higher MACE among patients with suspected CAD, regardless of the presence or absence of obstructive CAD or CKD. The association did not present in patients with PAD. Conclusions: Higher circulating EPC levels are associated with a greater risk of MACE, regardless of the presence of obstructive CAD or CKD. This association was not apparent in the patients with PAD, suggesting impaired endothelial repair in these patients.

[1]  P. Yin,et al.  Mortality trend of heart diseases in China, 2013–2020 , 2022, Cardiology Plus.

[2]  J. Chan,et al.  Endothelial function and endothelial progenitor cells in systemic lupus erythematosus , 2022, Nature Reviews Rheumatology.

[3]  V. Salomaa,et al.  Metabolic Biomarker Discovery for Risk of Peripheral Artery Disease Compared With Coronary Artery Disease: Lipoprotein and Metabolite Profiling of 31 657 Individuals From 5 Prospective Cohorts , 2021, Journal of the American Heart Association.

[4]  T. Zeller,et al.  Biomarkers for Heart Failure Prognosis: Proteins, Genetic Scores and Non-coding RNAs , 2020, Frontiers in Cardiovascular Medicine.

[5]  L. Șorodoc,et al.  Biomarker Utility for Peripheral Artery Disease Diagnosis in Real Clinical Practice: A Prospective Study , 2020, Diagnostics.

[6]  D. Atar,et al.  The myth of ‘stable’ coronary artery disease , 2019, Nature Reviews Cardiology.

[7]  Chun-Chin Chang,et al.  Trimethylamine N-Oxide, Circulating Endothelial Progenitor Cells, and Endothelial Function in Patients with Stable Angina , 2019, Scientific Reports.

[8]  K. Ley,et al.  Immunity and Inflammation in Atherosclerosis , 2019, Circulation research.

[9]  D. Mark,et al.  Revascularization in stable coronary disease: evidence and uncertainties , 2018, Nature Reviews Cardiology.

[10]  A. Quyyumi,et al.  Progenitor Cells and Clinical Outcomes in Patients With Acute Coronary Syndromes , 2018, Circulation research.

[11]  J. Bosch,et al.  Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial. , 2018, Lancet.

[12]  Alan D. Lopez,et al.  Global, Regional, and National Burden of Cardiovascular Diseases for 10 Causes, 1990 to 2015 , 2017, Journal of the American College of Cardiology.

[13]  A. Avogaro,et al.  Levels of Circulating Progenitor Cells, Cardiovascular Outcomes and Death: A Meta-Analysis of Prospective Observational Studies. , 2016, Circulation research.

[14]  A. Oliveras,et al.  Endothelial Progenitor Cells Predict Cardiovascular Events after Atherothrombotic Stroke and Acute Myocardial Infarction. A PROCELL Substudy , 2015, PloS one.

[15]  Marc P. Bonaca,et al.  Long-term use of ticagrelor in patients with prior myocardial infarction. , 2015, The New England journal of medicine.

[16]  Jeroen J. Bax,et al.  2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. , 2013, European heart journal.

[17]  C. Gaudio,et al.  Endothelial progenitor cells predict long-term prognosis in patients with stable angina treated with percutaneous coronary intervention: five-year follow-up of the PROCREATION study. , 2013, Circulation journal : official journal of the Japanese Circulation Society.

[18]  Marc P. Bonaca,et al.  Vorapaxar in the secondary prevention of atherothrombotic events. , 2012, The New England journal of medicine.

[19]  G. Nickenig,et al.  Endothelial progenitor cells correlate with endothelial function in patients with coronary artery disease , 2007, Basic Research in Cardiology.

[20]  W. Shen,et al.  Circulating Endothelial Progenitor Cells, C-Reactive Protein and Severity of Coronary Stenosis in Chinese Patients with Coronary Artery Disease , 2007, Hypertension Research.

[21]  D. Link,et al.  The number of endothelial progenitor cell colonies in the blood is increased in patients with angiographically significant coronary artery disease. , 2006, Journal of the American College of Cardiology.

[22]  A. Avogaro,et al.  Number and Function of Endothelial Progenitor Cells as a Marker of Severity for Diabetic Vasculopathy , 2006, Arteriosclerosis, thrombosis, and vascular biology.

[23]  A. Avogaro,et al.  Endothelial progenitor cells and the diabetic paradox. , 2006, Diabetes care.

[24]  T. Imanishi,et al.  Endothelial progenitor cell senescence is accelerated in both experimental hypertensive rats and patients with essential hypertension , 2005, Journal of hypertension.

[25]  G. Nickenig,et al.  Circulating endothelial progenitor cells and cardiovascular outcomes. , 2005, The New England journal of medicine.

[26]  M. Gnecchi,et al.  Cytokine-Induced Mobilization of Circulating Endothelial Progenitor Cells Enhances Repair of Injured Arteries , 2004, Circulation.

[27]  R. Ferrari,et al.  CD34+ and Endothelial Progenitor Cells in Patients With Various Degrees of Congestive Heart Failure , 2004, Circulation.

[28]  S. Dimmeler,et al.  Endothelial Progenitor Cells: Characterization and Role in Vascular Biology , 2004, Circulation research.

[29]  G. Gurtner,et al.  Human Endothelial Progenitor Cells From Type II Diabetics Exhibit Impaired Proliferation, Adhesion, and Incorporation Into Vascular Structures , 2002, Circulation.

[30]  S. Fichtlscherer,et al.  Number and Migratory Activity of Circulating Endothelial Progenitor Cells Inversely Correlate With Risk Factors for Coronary Artery Disease , 2001, Circulation research.

[31]  K. Pantel,et al.  In vitro differentiation of endothelial cells from AC133-positive progenitor cells. , 1999, Blood.

[32]  R. Ross,et al.  Atherosclerosis is an inflammatory disease. , 1998, American heart journal.

[33]  Takayuki Asahara,et al.  Isolation of Putative Progenitor Endothelial Cells for Angiogenesis , 1997, Science.

[34]  M C Oz,et al.  Characterization of hematopoietic cells arising on the textured surface of left ventricular assist devices. , 1995, The Annals of thoracic surgery.

[35]  U. V. von Oppell,et al.  In vitro-lined endothelium: initial integrity and ultrastructural events. , 1994, Surgery.

[36]  G. Chisolm,et al.  Reendothelialization and maintenance of endothelial integrity in longitudinal denuded tracks in the thoracic aorta of rats. , 1983, Atherosclerosis.

[37]  M. Reidy,et al.  Distortion of endothelial repair. The effect of hypercholesterolaemia on regeneration of aortic endothelium following injury by endotoxin. A scanning electron microscope study. , 1978, Atherosclerosis.

[38]  S. Schwartz,et al.  Clustering of replicating cells in aortic endothelium. , 1976, Proceedings of the National Academy of Sciences of the United States of America.

[39]  S. Schwartz,et al.  The aortic intima. II. Repair of the aortic lining after mechanical denudation. , 1975, The American journal of pathology.

[40]  B. Gersh,et al.  ESC guidelines on the management of stable coronary artery disease — addenda The Task Force on the management of stable coronary artery disease of the European Society of Cardiology , 2013 .

[41]  T. Morishita,et al.  Number of endothelial progenitor cells in peripheral artery disease as a marker of severity and association with pentraxin-3, malondialdehyde-modified low-density lipoprotein and membrane type-1 matrix metalloproteinase. , 2012, Journal of atherosclerosis and thrombosis.

[42]  Frank J T Staal,et al.  Endothelial progenitor cell dysfunction: a novel concept in the pathogenesis of vascular complications of type 1 diabetes. , 2004, Diabetes.

[43]  G. Campbell,et al.  Venous Response to Endothelial Denudation , 1986, Pathology.