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Vol. 30. Núm. 10.
Páginas 753-760 (outubro 2011)
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Vol. 30. Núm. 10.
Páginas 753-760 (outubro 2011)
Original article
Open Access
Predictors of circulating endothelial progenitor cell levels in patients without known coronary artery disease referred for multidetector computed tomography coronary angiography
Preditores de níveis de células progenitoras endoteliais em pacientes sem doença coronária conhecida referenciados para coronariografia por tomografia computorizada multidetectores
Visitas
8247
Nuno Bettencourta,b,
Autor para correspondência
bettencourt.n@gmail.com

Corresponding author.
, Susana Oliveirac, Andre Michael Toschked, João Rochaa, Daniel Leitea, Mónica Carvalhoa, Sónia Xaráa, Andreas Schusterb, Amedeo Chiribirib, Adelino Leite-Moreirae, Eike Nagelb, Helena Alvesc, Vasco Gamaa
a Cardiology Department, Centro Hospitalar de Gaia/Espinho, Vila Nova de Gaia, Portugal
b Division of Imaging Sciences, Kings College London, London, United Kingdom
c Centro de Histocompatibilidade do Norte, Porto, Portugal
d Department of Medical Informatics, Biometry and Epidemiology (IBE), Ludwig-Maximilians University of Munich, Munich, Germany
e Department of Physiology, Faculty of Medicine, University of Porto, Porto, Portugal
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Abstract
Introduction

Endothelial progenitor cells (EPCs) have an important role in vascular repair. Levels in peripheral circulation are thought to be related to overall cardiovascular risk and may represent potential therapeutic targets. The aim of this work is to identify predictors of circulating EPC concentrations in patients without known coronary artery disease (CAD).

Methods

The study population consisted of 215 patients without known CAD referred for multidetector computed tomography (MDCT) coronary angiography (CTA) during a 6-month period. All patients underwent: 1) short anamnesis; 2) anthropometric measurements; 3) blood pressure and heart rate assessment; 4) blood tests; and 5) MDCT (including quantification of visceral fat, quantification of coronary artery calcification [CAC] and CTA).

Results

The patients’ mean age was 58±11 years (26–84) and 61% were male. Dyslipidemia (59%) and hypertension (57%) were the most prevalent risk factors. Twenty-seven percent met the ATP III criteria for metabolic syndrome. Mean Framingham risk score was 12±9%. Sixty-seven percent had no significant CAD but 64% had some degree of coronary calcification. The mean CAC (Agatston) was 186±433.

Mean EPC concentration, expressed as a percentage of total white blood cells, was 0.05±0.08% (0.0–0.58%). EPCs were inversely related to the presence of diabetes mellitus and smoking, and positively related to C-reactive protein. No significant correlations were found between EPCs and other risk factors, measurements of adiposity, atherosclerotic burden or severity of CAD.

Conclusion

In patients without known CAD referred for MDCT, EPC levels in peripheral blood cannot be significantly estimated or predicted from knowledge of patient anamnesis, risk factors, visceral fat, CAC or CTA.

Keywords:
Endothelial progenitor cells
Cardiovascular risk factors
Multidetector CT
Coronary artery disease
Resumo
Introdução

As células progenitoras endoteliais (EPC) desempenham um papel primordial no processo de reparação vascular. Os seus níveis circulantes no sangue periférico parecem estar relacionados com o risco cardiovascular global e podem representar potenciais alvos terapêuticos. O objectivo deste estudo foi identificar eventuais preditores da concentração de EPC em pacientes sem doença coronária (CAD) conhecida.

População e métodos

Foram incluídos 215 doentes sem CAD conhecida, referenciados para coronariografia por tomografia computadorizada multidetectores (MDCT), durante um período de 6 meses. Todos os doentes foram submetidos a: 1) anamnese, 2) medidas antropométricas, 3) avaliação da pressão arterial e frequência cardíaca, 4) estudo analítico e 5) MDCT (incluindo a quantificação da gordura visceral, quantificação da calcificação coronária (CAC) e angiografia coronária).

Resultados

A média de idades era de 58±11 anos (26–84), 61% do sexo masculino. Os factores de risco vascular mais frequentes foram dislipidemia (59%) e hipertensão (57%). Vinte e sete por cento dos doentes cumpriam os critérios ATP III para a síndrome metabólica. O Framingham Risk Score médio foi de 12±9%. Sessenta e sete por cento não tinham CAD significativa, mas 64% apresentavam algum grau de calcificação coronária. A CAC média (Agatston) foi de 186±433. A concentração média de EPC, expressa em percentagem do total de leucócitos, foi de 0,05±0,08% (0,0–0,58%). A concentração de EPC correlacionou-se inversamente com a presença de diabetes mellitus e tabagismo e positivamente com a Proteína C Reactiva. Não houve correlações significativas entre os níveis de EPC e outros factores de risco, medidas de adiposidade, carga aterosclerótica total ou gravidade da CAD.

Conclusão

Em pacientes sem CAD conhecida referenciados para MDCT, os níveis de EPC no sangue periférico não podem ser estimados a partir do conhecimento do contexto clínico, factores de risco, gordura visceral, CAC ou coronariografia.

Palavras-chave:
Células progenitoras endoteliais
Factores de risco cardiovascular
Tomografia computorizada multidetectores
Doença coronária
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References
[1.]
G.P. Fadini, S. Sartore, M. Albiero, et al.
Number and function of endothelial progenitor cells as a marker of severity for diabetic vasculopathy.
Arterioscler Thromb Vasc Biol, 26 (2006), pp. 2140-2146
[2.]
T. Asahara, T. Murohara, A. Sullivan, et al.
Isolation of putative progenitor endothelial cells for angiogenesis.
Science, 275 (1997), pp. 964-967
[3.]
M. Vasa, S. Fichtlscherer, A. Aicher, et al.
Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease.
Circ Res, 89 (2001), pp. E1-E7
[4.]
O.M. Tepper, R.D. Galiano, J.M. Capla, et al.
Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures.
Circulation, 106 (2002), pp. 2781-2786
[5.]
C.J. Loomans, E.J. De Koning, F.J. Staal, et al.
Endothelial progenitor cell dysfunction: a novel concept in the pathogenesis of vascular complications of type 1 diabetes.
Diabetes, 53 (2004), pp. 195-199
[6.]
H.Y. Wang, P.J. Gao, K.D. Ji, et al.
Circulating endothelial progenitor cells. C-reactive protein and severity of coronary stenosis in Chinese patients with coronary artery disease.
Hypertens Res, 30 (2007), pp. 133-141
[7.]
N. Werner, S. Kosiol, T. Schiegl, et al.
Circulating endothelial progenitor cells and cardiovascular outcomes.
N Engl J Med, 353 (2005), pp. 999-1007
[8.]
M. Hristov, C. Fach, C. Becker, et al.
Reduced numbers of circulating endothelial progenitor cells in patients with coronary artery disease associated with long-term statin treatment.
Atherosclerosis, 192 (2007), pp. 413-420
[9.]
A.D. Hughes, E. Coady, S. Raynor, et al.
Reduced endothelial progenitor cells in European and South Asian men with atherosclerosis.
Eur J Clin Invest, 37 (2007), pp. 35-41
[10.]
C. Schmidt-Lucke, L. Rössig, S. Fichtlscherer, et al.
Reduced number of circulating endothelial progenitor cells predicts future cardiovascular events: proof of concept for the clinical importance of endogenous vascular repair.
Circulation, 111 (2005), pp. 2981-2987
[11.]
J. Chen, M. Chopp.
Neurorestorative treatment of stroke: cell and pharmacological approaches.
NeuroRx: the journal of the American Society for Experimental NeuroTherapeutics, 3 (2006), pp. 466-473
[12.]
Third Report of the National Cholesterol Education Program (NCEP).
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report.
Circulation, 106 (2002), pp. 3143-3421
[13.]
Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: executive summary.
Expert Panel on the Identification, Evaluation, and Treatment of Overweight in Adults.
Am J Clin Nutr, 68 (1998), pp. 899-917
[14.]
G.A. Borkan, S.G. Gerzof, A.H. Robbins, et al.
Assessment of abdominal fat content by computed tomography.
Am J Clin Nutr, 36 (1982), pp. 172-177
[15.]
N. Bettencourt, J. Rocha, M. Carvalho, et al.
Multidetector computed tomography in the exclusion of coronary artery disease in patients with presurgical valve disease.
Circ Cardiovasc Imaging, 2 (2009), pp. 306-313
[16.]
W.G. Austen, J.E. Edwards, R.L. Frye, et al.
A reporting system on patients evaluated for coronary artery disease. Report of the Ad Hoc Committee for Grading of Coronary Artery Disease, Council on Cardiovascular Surgery, American Heart Association.
Circulation, 51 (1975), pp. 5-40
[17.]
G.P. Fadini, C. Agostini, A. Avogaro.
Characterization of endothelial progenitor cells.
Biochem Biophys Res Commun, 336 (2005), pp. 1-2
[18.]
Bongartz G, Golding SJ, Jurik AG, et al. European Guidelines for Multidetector Computed Tomography. Funded by the European Commission. Contract number FIGM-CT2000-20078-CT-TIP. March 2004.
[19.]
European Commission.
European Guidelines on quality criteria for computed tomography.
Report EUR 16262 EN. Luxembourg: Office for Official Publication of the European Communities,
[20.]
P.W. Wilson, R.B. D’Agostino, D. Levy, et al.
Prediction of coronary heart disease using risk factor categories.
Circulation, 97 (1998), pp. 1837-1847
[21.]
J.M. Hill, G. Zalos, J.P. Halcox, et al.
Circulating endothelial progenitor cells, vascular function, and cardiovascular risk.
N Engl J Med, 348 (2003), pp. 593-600
[22.]
Q. Xiao, S. Kiechl, S. Patel, et al.
Endothelial progenitor cells, cardiovascular risk factors, cytokine levels and atherosclerosis — results from a large population-based study.
[23.]
A. Oliveras, M.J. Soler, O.M. Martínez-Estrada, et al.
Endothelial progenitor cells are reduced in refractory hypertension.
J Hum Hypertens, 22 (2008), pp. 183-190
[24.]
M. Pirro, F. Bagaglia, L. Paoletti, et al.
Hypercholesterolemia-associated endothelial progenitor cell dysfunction. Therapeutic advances in cardiovascular disease.
Ther Adv Cardiovasc Dis, 2 (2008), pp. 329-339
[25.]
M. Vasa, S. Fichtlscherer, K. Adler, et al.
Increase in circulating endothelial progenitor cells by statin therapy in patients with stable coronary artery disease.
Circulation, 103 (2001), pp. 2885-2890
[26.]
J. Llevadot, S. Murasawa, Y. Kureishi, et al.
HMG-CoA reductase inhibitor mobilizes bone marrow-derived endothelial progenitor cells.
J Clin Invest, 108 (2001), pp. 399-405
[27.]
A.O. Spiel, F.B. Mayr, J.M. Leitner, et al.
Simvastatin and rosuvastatin mobilize endothelial progenitor cells but do not prevent their acute decrease during systemic inflammation.
Thromb Res, 123 (2008), pp. 108-113
[28.]
A.M. Leone, S. Rutella, M.B. Giannico, et al.
Effect of intensive vs standard statin therapy on endothelial progenitor cells and left ventricular function in patients with acute myocardial infarction: Statins for regeneration after acute myocardial infarction and PCI (STRAP) trial.
Int J Cardiol, 130 (2008), pp. 457-462
[29.]
T. Takahashi, C. Kalka, H. Masuda, et al.
Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization.
Nat Med, 5 (1999), pp. 434-438
[30.]
S. Shintani, T. Murohara, H. Ikeda, et al.
Mobilization of endothelial progenitor cells in patients with acute myocardial infarction.
Circulation, 103 (2001), pp. 2776-2779
[31.]
M. Gill, S. Dias, K. Hattori, et al.
Vascular trauma induces rapid but transient mobilization of VEGFR2(+)AC133(+) endothelial precursor cells.
Circ Res, 88 (2001), pp. 167-174
[32.]
J. George, E. Goldstein, S. Abashidze, et al.
Circulating endothelial progenitor cells in patients with unstable angina: association with systemic inflammation.
European Heart Journal, 25 (2004), pp. 1003-1008
[33.]
J. Aoki, P.W. Serruys, H. Van Beusekom, et al.
Endothelial progenitor cell capture by stents coated with antibody against CD34: the HEALING-FIM (Healthy Endothelial Accelerated Lining Inhibits Neointimal Growth-First In Man) Registry.
J Am Coll Cardiol, 45 (2005), pp. 1574-1579
[34.]
M. Miglionico, G. Patti, A. D’Ambrosio, et al.
Percutaneous coronary intervention utilizing a new endothelial progenitor cells antibody-coated stent: a prospective single-center registry in high-risk patients.
Catheter Cardiovasc Interv, 71 (2008), pp. 600-604
[35.]
M. Co, E. Tay, C.H. Lee, et al.
Use of endothelial progenitor cell capture stent (Genous Bio-Engineered R Stent) during primary percutaneous coronary intervention in acute myocardial infarction: intermediate- to long-term clinical follow-up.
Am Heart J, 155 (2008), pp. 128-132
[36.]
C. Jung, N. Fischer, M. Fritzenwanger, et al.
Endothelial progenitor cells in adolescents: impact of overweight, age, smoking, sport and cytokines in younger age.
Clin Res Cardiol, 98 (2009), pp. 179-188
[37.]
J. Müller-Ehmsen, D. Braun, T. Schneider, et al.
Decreased number of circulating progenitor cells in obesity: beneficial effects of weight reduction.
Eur Heart J, 29 (2008), pp. 1560-1568
[38.]
G.P. Fadini, A. Coracina, I. Baesso, et al.
Peripheral blood CD34+KDR+ endothelial progenitor cells are determinants of subclinical atherosclerosis in a middle-aged general population.
[39.]
G. Chironi, L. Walch, M. Pernollet, et al.
Decreased number of circulating CD34+KDR+ cells in asymptomatic subjects with preclinical atherosclerosis.
Atherosclerosis, 191 (2007), pp. 115-120
[40.]
H. Güven, R.M. Shepherd, R.G. Bach, et al.
The number of endothelial progenitor cell colonies in the blood is increased in patients with angiographically significant coronary artery disease.
J Am Coll Cardiol, 48 (2006), pp. 1579-1587
[41.]
J. Leor, M. Marber.
Endothelial progenitors: a new Tower of Babel?.
J Am Coll Cardiol, 48 (2006), pp. 1588-1590
[42.]
M. Prokopi, G. Pula, U. Mayr, et al.
Proteomic analysis reveals presence of platelet microparticles in endothelial progenitor cell cultures.
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