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Effect of ezetimibe–simvastatine over endothelial dysfunction in dyslipidemic patients: Assessment by 13N-ammonia positron emission tomography

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Journal of Nuclear Cardiology Aims and scope

Abstract

Background

Dyslipidemias constitute an independent risk factor for the development of atherogenesis and they also predispose to the development of endothelial dysfunction (ED). Using PET with 13N-ammonia, it is possible to quantify myocardial blood flow (MBF) in mL/min/g and to quantitatively evaluate ED. With the use of lipid lowering therapy it is possible to reduce ED and increase the MBF and the endothelial-dependent vasodilation index (ENDEVI). In this study, we aimed to evaluate with 13N-ammonia PET the benefic effects of the combined treatment ezetimibe/simvastatine on the endothelial function of dyslipidemic patients after 8 weeks of treatment.

Material and Methods

Fourteen consecutive patients with dyslipidemia diagnosis and 17 healthy volunteers were studied with a three phase [rest, Cold Pressor Test (CPT), and adenosine-induced hyperemia] 13N-ammonia PET for MBF quantification assessment. A second PET study was performed in the dyslipidemic group after 8 weeks of treatment with ezetimibe/simvastatine (10/40 mg). Myocardial flow reserve (MFR), ENDEVI, and %ΔMBF were calculated.

Results

Total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides concentrations were markedly altered in the dyslipidemic group and after 8 weeks of treatment these values improved. Dyslipidemic patients showed endothelial dysfunction when compared with the control group, (MFR 2.79 ± 0.94 vs 3.15 ± 0.48, P < 0.05 ; ENDEVI 1.28 ± 0.25 vs 1.53 ± 0.24, P < 0.05; and %ΔMBF 29.08 ± 24.62 vs 53 ± 24.60%, P < 0.05, respectively). After 8 weeks of treatment, we found a significant increase in all the endothelial function markers (MFR: 3.14 ± 0.86, P < 0.05, ENDEVI 1.65 ± 0.23, P < 0.05; %ΔMBF: 65.21 ± 23.43, P < 0.05).

Conclusions

Dyslipidemic patients show endothelial dysfunction measured with 13N-ammonia PET. Treatment with ezetimibe/simvastatine was effective improving the lipid profile as well as the endothelial function of these patients. PET may be a useful tool to monitor vascular reactivity and regression/progression of coronary atherosclerosis after pharmacologic interventions.

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References

  1. Goff DC, Bertoni AG, Kramer H, Bonds D, Blumenthal RS, Tsai MY, et al. Dyslipidemia prevalence, treatment, and control in the multi-ethnic study of atherosclerosis (MESA). Circulation 2006;113:647-56.

    Article  CAS  PubMed  Google Scholar 

  2. Kannel WB. The Framingham study: ITS 50-year legacy and future promise. J Atheroscler Thromb 2000;6(2):60-6.

    CAS  PubMed  Google Scholar 

  3. Wilson PWF, D’Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation 1998;97:1837.

    CAS  PubMed  Google Scholar 

  4. Stamler J, Wentworth D, Neaton JD, for the MRFIT Research Group. Is relationship between serum cholesterol and risk of premature death from coronary heart disease continuous and graded? Findings in 356 222 primary screeners of the Multiple Risk Factor Intervention Trial (MRFIT). JAMA 1986;256:2823-8.

    Article  CAS  PubMed  Google Scholar 

  5. Law MR, Wald NJ, Thompson SG. By how much and how quickly does reduction in serum cholesterol concentration lower risk of ischaemic heart disease? BMJ 1994;308:367-72.

    CAS  PubMed  Google Scholar 

  6. De Silva R, Camici PG. The role of positron emission tomography in the investigation of coronary circulatory function in man. Cardiovasc Res 1994;28:1595-612.

    Article  PubMed  Google Scholar 

  7. Nitzche EU, Choi Y, Czernin J, Hoh C, Huang SU, Schelbert H. Noninvasive quantification of myocardial blood flow in Humans. A direct comparison of the [13 N]ammonia and the [15O]water techniques. Circulation 1996;93:2000-6.

    Google Scholar 

  8. Zeiher AM, Drexler H, Wollschlager H, Just H. Endothelial dysfunction of the coronary microvasculature is associated with coronary blood flow regulation in patients with early atherosclerosis. Circulation 1991;84:1984-92.

    CAS  PubMed  Google Scholar 

  9. Alexanderson E, Romero J, Ricalde A, Alexanderson G, Meave A. Assessment of endothelial function by positron emission tomography. Curr Cardiol Rev 2006;2:2.

    Article  Google Scholar 

  10. Schelbert H, Wisenberg G, Phelps ME, Gould KL, Henze E, Hoffman EJ, Gomes A, Kuhl DE. Noninasive assessment of coronary stenoses by myocardial imaging during pharmacologic coronary vasodilation, VI: Detection of coronary artery disease in man with intravenous 13-NH3 and positron computed tomography. Am J Cardiol 1982;49:1197-207.

    Article  CAS  PubMed  Google Scholar 

  11. Kaufmann P, Gnecchi-Ruscone T, et al. Low density lipoprotein cholesterol and coronary microvascular dysfunction in hypercholesterolemia. J Am Coll Cardiol 2000;36:103-9.

    Article  CAS  PubMed  Google Scholar 

  12. Raitakari OT, Pitkanen O-P, Lehtimaki T, Lahdenpera S, Iida H, Yla-Herttuala S, Luoma J, Mattila K, Nikkari T, Taskinen M-L, Viikari JSA, Knuuti J. In vivo low density lipoprotein oxidation relates to coronary reactivity in young men. J Am Coll Cardiol 1997;30:97-102.

    Article  CAS  PubMed  Google Scholar 

  13. Baller D, Notohamiprodjo G, Gleichmann U, Holzinger J, Weise R, Lehmann J. Improvement in coronary flow reserve determined by positron emission tomography after 6 months of cholesterol-lowering therapy in patients with early stages of coronary atherosclerosis. Circulation 1999;99:2871-5.

    CAS  PubMed  Google Scholar 

  14. Pearson TA, Laurora I, Chu H, Kafonek S. The lipid treatment assessment project (L TAP): A multicenter survey to evaluate the percentages of dyslipidemic patients receiving lipid lowering therapy and achieving low density lipoprotein cholesterol goals. Arch Intern Med 2000;160:459M67.

    Article  Google Scholar 

  15. Knopp RH, Gitter H, Truitt T, for the Ezetimibe Study Group, et al. Effects of ezetimibe, a new cholesterol absorption inhibitor, on plasma lipids in patients with primary hypercholesterolemia. Eur Heart J 2003;24:729-41.

    Article  CAS  PubMed  Google Scholar 

  16. Davidson MH, McGarry T, Bettis R, et al. Ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia. J Am Coll Cardiol 2002;40:2125-34.

    Article  CAS  PubMed  Google Scholar 

  17. Gagne C, Bays HE, Weiss SR, for the Ezetimibe Study Group, et al. Efficacy and safety of ezetimibe added to ongoing stain therapy for treatment of patients with primary hypercholesterolemia. Am J Cardiol 2002;90:1084-91.

    Article  CAS  PubMed  Google Scholar 

  18. Third report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)

  19. Wienhard K, Dahlbom M, Eriksson L, Michel C, Bruckbauer T, Pietrzyk U, Heiss WD. The ECAT EXACT HR: Performance of a new high resolution positron scanner. J Comput Assist Tomogr 1994;18:110-8.

    Article  CAS  PubMed  Google Scholar 

  20. Kuhle WG, Porenta G, Huang SC, Buxton D, Gambhir SS, Hansen H, Phelps ME, Schelbert HR. Quantification of regional myocardial blood flow using [13N]ammonia and reoriented dynamic positron emission tomographic imaging. Circulation 1992;86:1004-17.

    CAS  PubMed  Google Scholar 

  21. Campisi R, Di Carli Marcelo. Assessment of coronary flow reserve and microcirculation: A clinical perspective. J Nucl Cardiol 2004;11:3-11.

    Article  PubMed  Google Scholar 

  22. Alexánderson E, Ricalde A, Estradas J, Alexánderson EG, Meave A. Evaluation of coronary blood flow by means of PET in the Mexican population without coronary artery disease. Arch Cardiol Mex 2005;75:35-41.

    PubMed  Google Scholar 

  23. Hein WH, Kuo L. LDLs impair vasomotor function of the coronary microcirculation: role of superoxide anions. Circ Res 1998;83:404-14.

    CAS  PubMed  Google Scholar 

  24. Anderson TJ, Meredith IT, Charbonneau F, et al. Endothelium-dependent coronary vasomotion relates to the susceptibility of LDL to oxidation in humans. Circulation 1996;93:1647-50.

    CAS  PubMed  Google Scholar 

  25. Yokoyama I, Ohtake T, Momamura S-I, et al. Reduced coronary flow reserve in hypercholesterolemic patients without overt coronary stenosis. Circulation 1996;94:3232-8.

    CAS  PubMed  Google Scholar 

  26. Dayanikli F, Grambow D, Muzik O, Mosca L, Rubenfire, Schwaiger M. Early detection of abnormal coronary flow reserve in asymptomatic men at high risk for coronary artery disease using positron emission tomography. Circulation 1994;90:808-17.

    CAS  PubMed  Google Scholar 

  27. Schindler TH, Nitzche EU, Schelbert HR, Olschewski M, Sayre J, Mix M, et al. Positron emission tomography-measured abnormal responses of myocardial blood flow to sympathetic stimulation are associated with the risk of developing cardiovascular events. J Am Coll Cardiol 2005;45:1505-12.

    Article  PubMed  Google Scholar 

  28. Alexanderson E, Garcia-Rojas L, Rodriguez M, et al. Endothelial function assessment by positron emission tomography in patients with hypercholesterolemia. Arch Cardiol Mex 2008;78(2):139-47.

    Google Scholar 

  29. Deanfield J, Donald A, Ferri C, Giannattasio C, Halcox J, Halligan S, et al. Endothelial function and dysfunction. Part I: Methodological issues for assessment in the different vascular beds: A statement by the working group on endothelin and endothelial factors of the European Society of Hypertension. J Hypertens 2005;23:7-17.

    Article  CAS  PubMed  Google Scholar 

  30. Schwartz GG, Olsson AG, Ezekowitz MD, Ganz P, Oliver MF, Waters D, Zeiher A, Chaitman BR, Leslie S, Stern T. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: The MIRACL study: A randomized controlled trial. JAMA 2001;285:1711-8.

    Article  CAS  PubMed  Google Scholar 

  31. Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, Joyal SV, Hill KA, Pfeffer MA, Skene AM. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004;350:1495-504.

    Article  CAS  PubMed  Google Scholar 

  32. Spencer FA, Allegrone J, Goldberg RJ, Gore JM, Fox KA, Granger CB, Mehta RH, Brieger D. Association of statin therapy with outcomes of acute coronary syndromes: the GRACE study. Ann Intern Med 2004;140:857-66.

    PubMed  Google Scholar 

  33. Gould KL, et al. Short-term cholesterol lowering decreases size and severity of perfusion abnormalities by positron emission tomography after dipyridamole in patients with coronary artery disease. A potential noninvasive marker of healing coronary endothelium. Circulation 1994;89(4):1530-8.

    CAS  PubMed  Google Scholar 

  34. Gould KL, Ornish D, Scherwitz L, Brown S, Edens RP, Hess MJ, Mullani N, Bolomey L, Dobbs F, Armstrong WT, Merritt T, Ports T, Sparler S, Billings J. Changes in myocardial perfusion abnormalities by positron emission tomography after long-term, intense risk factor modification. JAMA 1995;274(11):894-901.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgment

We thank the cyclotron staff at UNAM PET/CT UNIT for their assistance, particularly to N. M. T. Jorge Albarrán López and N. M. T. Andrés Sanabria Rodríguez for their help.

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Authors and Affiliations

  1. Unidad PET/CT Ciclotrón, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico

    Erick Alexanderson MD, Leonardo García-Rojas MD, Rodrigo Jácome MD, Rodrigo Calleja MD, Alfonso Martínez MD, Juan M. Ochoa MD & Aloha Meave MD

  2. Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico

    Erick Alexanderson MD, Moisés Jiménez MD & Aloha Meave MD

  3. Hospital General de México, Mexico City, Mexico

    Graciela Alexanderson MD

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  1. Erick Alexanderson MD
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  2. Leonardo García-Rojas MD
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Correspondence to Erick Alexanderson MD.

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Alexanderson, E., García-Rojas, L., Jiménez, M. et al. Effect of ezetimibe–simvastatine over endothelial dysfunction in dyslipidemic patients: Assessment by 13N-ammonia positron emission tomography. J. Nucl. Cardiol. 17, 1015–1022 (2010). https://doi.org/10.1007/s12350-010-9273-8

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  • DOI: https://doi.org/10.1007/s12350-010-9273-8

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