Skip to main content
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging 7/2012

01.07.2012 | Original Article

Effects of type 2 diabetes mellitus on coronary microvascular function and myocardial perfusion in patients without obstructive coronary artery disease

verfasst von: Caterina Marciano, Maurizio Galderisi, Paola Gargiulo, Wanda Acampa, Carmen D’Amore, Roberta Esposito, Enza Capasso, Gianluigi Savarese, Laura Casaretti, Francesco Lo Iudice, Giovanni Esposito, Giuseppe Rengo, Dario Leosco, Alberto Cuocolo, Pasquale Perrone-Filardi

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 7/2012

Einloggen, um Zugang zu erhalten

Abstract

Purpose

We assessed the impact of type 2 diabetes, in the presence of other major cardiovascular risk factors, on coronary microvascular function and myocardial perfusion in patients without obstructive coronary artery disease (CAD).

Methods

In this prospective study, 23 patients with type 2 diabetes and 26 nondiabetic patients matched for age, sex and other cardiovascular risk factors underwent a cold pressure test (CPT) and dipyridamole transthoracic echocardiography to determine their coronary flow (CF) ratio. Within 2 weeks, all diabetic patients also underwent dipyridamole-rest myocardial perfusion single-photon emission (MPS) CT. None of the patients with or without diabetes had significant CAD on invasive coronary angiography.

Results

The CPT-CF ratio was significantly lower in diabetic patients than in nondiabetic patients (1.46 ± 0.26 vs. 1.71 ± 0.32, p = 0.006) and was correlated significantly with fasting glycaemia (r = −0.35, p = 0.01), but not with glycated haemoglobin. The dipyridamole-CF ratio was also lower in diabetic patients than in nondiabetic patients (2.38 ± 0.74 vs. 2.75 ± 0.49, p = 0.04). On MPS imaging, 5 diabetic patients (22%) had stress-induced ischaemia and the remaining 18 (78%) had normal myocardial perfusion. The dipyridamole-CF ratio was not different in patients with and without reversible defects (2.3 ± 1.1 vs. 2.4 ± 0.6, p = 0.97).

Conclusion

Coronary microvascular function is impaired in type 2 diabetic patients without significant CAD, compared to nondiabetic patients with similar other cardiovascular risk factors. In the majority of diabetic patients, microvascular dysfunction is associated with normal myocardial perfusion.
Literatur
1.
Zurück zum Zitat Schramm TK, Gislason GH, Køber L, Rausmussen S, Rausmussen JN, Abildstrøm SZ, et al. Diabetes patients requiring glucose-lowering therapy and nondiabetics with a prior myocardial infarction carry the same cardiovascular risk: a population study of 3.3 million people. Circulation. 2008;117:1945–54.PubMedCrossRef Schramm TK, Gislason GH, Køber L, Rausmussen S, Rausmussen JN, Abildstrøm SZ, et al. Diabetes patients requiring glucose-lowering therapy and nondiabetics with a prior myocardial infarction carry the same cardiovascular risk: a population study of 3.3 million people. Circulation. 2008;117:1945–54.PubMedCrossRef
2.
Zurück zum Zitat Pitkanen OP, Nuutila P, Raitakari OT, Ronnemaa T, Koskinen PJ, Iida H, et al. Coronary flow reserve is reduced in young men with IDDM. Diabetes. 1998;47:248–54.PubMedCrossRef Pitkanen OP, Nuutila P, Raitakari OT, Ronnemaa T, Koskinen PJ, Iida H, et al. Coronary flow reserve is reduced in young men with IDDM. Diabetes. 1998;47:248–54.PubMedCrossRef
3.
4.
Zurück zum Zitat Di Carli MF, Janisse J, Grunberger G, Ager J. Role of chronic hyperglycemia in the pathogenesis of coronary microvascular dysfunction in diabetes. J Am Coll Cardiol. 2003;41:1387–93.PubMedCrossRef Di Carli MF, Janisse J, Grunberger G, Ager J. Role of chronic hyperglycemia in the pathogenesis of coronary microvascular dysfunction in diabetes. J Am Coll Cardiol. 2003;41:1387–93.PubMedCrossRef
5.
Zurück zum Zitat Galderisi M, Capaldo B, Sidiropulos M, D’Errico A, Ferrara L, Turco A, et al. Determinants of reduction of coronary flow reserve in patients with type 2 diabetes mellitus or arterial hypertension without angiographically determined epicardial coronary stenosis. Am J Hypertens. 2007;20:1283–90.PubMedCrossRef Galderisi M, Capaldo B, Sidiropulos M, D’Errico A, Ferrara L, Turco A, et al. Determinants of reduction of coronary flow reserve in patients with type 2 diabetes mellitus or arterial hypertension without angiographically determined epicardial coronary stenosis. Am J Hypertens. 2007;20:1283–90.PubMedCrossRef
6.
Zurück zum Zitat Lang RM, Bieriq M, Devereux RB, Devereux RB, Flachskampf FA, Foster E, et al. Recommendations for chamber quantification. Eur J Echocardiogr. 2006;7:79–108.PubMedCrossRef Lang RM, Bieriq M, Devereux RB, Devereux RB, Flachskampf FA, Foster E, et al. Recommendations for chamber quantification. Eur J Echocardiogr. 2006;7:79–108.PubMedCrossRef
7.
Zurück zum Zitat Fox K, Garcia MA, Ardissino D, Buszman P, Camici PG, Crea F, et al. ESC guidelines on the management of stable angina pectoris. Eur Heart J. 2006;27:1341–81.PubMedCrossRef Fox K, Garcia MA, Ardissino D, Buszman P, Camici PG, Crea F, et al. ESC guidelines on the management of stable angina pectoris. Eur Heart J. 2006;27:1341–81.PubMedCrossRef
8.
Zurück zum Zitat Rodbard HW, Blonde L, Braithwaite SS, Brett EM, Cobin RH, Handelsman Y, et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus. Endocr Pract. 2007;13:1–68.PubMed Rodbard HW, Blonde L, Braithwaite SS, Brett EM, Cobin RH, Handelsman Y, et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus. Endocr Pract. 2007;13:1–68.PubMed
9.
Zurück zum Zitat Wirch JL, Wolfe LA, Weissgerber TL, Davies GA. Cold pressor test protocol to evaluate cardiac autonomic function. Appl Physiol Nutr Metab. 2006;31:235–43.PubMedCrossRef Wirch JL, Wolfe LA, Weissgerber TL, Davies GA. Cold pressor test protocol to evaluate cardiac autonomic function. Appl Physiol Nutr Metab. 2006;31:235–43.PubMedCrossRef
10.
Zurück zum Zitat Sicari R, Nihoyannopoulos P, Evangelista A, Kasprzak J, Lancellotti P, Poldermans D, et al. Stress echocardiography expert consensus statement: European Association of Echocardiography (EAE). Eur J Echocardiogr. 2008;9:415–37.PubMedCrossRef Sicari R, Nihoyannopoulos P, Evangelista A, Kasprzak J, Lancellotti P, Poldermans D, et al. Stress echocardiography expert consensus statement: European Association of Echocardiography (EAE). Eur J Echocardiogr. 2008;9:415–37.PubMedCrossRef
11.
Zurück zum Zitat Campisi R, Czernin J, Schöder H, Sayre JW, Marengo FD, Phelps ME, et al. Effects of long-term smoking on myocardial blood flow, coronary vasomotion, and vasodilator capacity. Circulation. 1998;98:119–25.PubMed Campisi R, Czernin J, Schöder H, Sayre JW, Marengo FD, Phelps ME, et al. Effects of long-term smoking on myocardial blood flow, coronary vasomotion, and vasodilator capacity. Circulation. 1998;98:119–25.PubMed
12.
Zurück zum Zitat Campisi R, Nathan L, Pampaloni MH, Schöder H, Sayre JW, Chaudhuri G, et al. Noninvasive assessment of coronary microcirculatory function in postmenopausal women and effects of short-term and long-term estrogen administration. Circulation. 2002;105:425–30.PubMedCrossRef Campisi R, Nathan L, Pampaloni MH, Schöder H, Sayre JW, Chaudhuri G, et al. Noninvasive assessment of coronary microcirculatory function in postmenopausal women and effects of short-term and long-term estrogen administration. Circulation. 2002;105:425–30.PubMedCrossRef
13.
Zurück zum Zitat Siegrist PT, Gaemperli O, Koepfli P, Schepis T, Namdar M, Valenta I, et al. Repeatability of cold pressor test-induced flow increase assessed with H(2)(15)O and PET. J Nucl Med. 2006;47:1420–6.PubMed Siegrist PT, Gaemperli O, Koepfli P, Schepis T, Namdar M, Valenta I, et al. Repeatability of cold pressor test-induced flow increase assessed with H(2)(15)O and PET. J Nucl Med. 2006;47:1420–6.PubMed
14.
Zurück zum Zitat Biondi B, Galderisi M, Pagano L, Sidiropulos M, Pulcrano M, D’Errico A, et al. Endothelial mediated coronary flow reserve in patients with mild thyroid hormone deficiency. Eur J Endocrinol. 2009;161:323–9.PubMedCrossRef Biondi B, Galderisi M, Pagano L, Sidiropulos M, Pulcrano M, D’Errico A, et al. Endothelial mediated coronary flow reserve in patients with mild thyroid hormone deficiency. Eur J Endocrinol. 2009;161:323–9.PubMedCrossRef
15.
Zurück zum Zitat Galderisi M, Cicala S, Caso P, De Simone L, D’Errico A, Petrocelli A, et al. Coronary flow reserve and myocardial diastolic dysfunction in arterial hypertension. Am J Cardiol. 2002;90:860–4.PubMedCrossRef Galderisi M, Cicala S, Caso P, De Simone L, D’Errico A, Petrocelli A, et al. Coronary flow reserve and myocardial diastolic dysfunction in arterial hypertension. Am J Cardiol. 2002;90:860–4.PubMedCrossRef
16.
Zurück zum Zitat Hesse B, Tägil K, Cuocolo A, Anagnostopoulos C, Bardiés M, Bax J, et al. EANM/ESC procedural guidelines for myocardial perfusion imaging in nuclear cardiology. Eur J Nucl Med Mol Imaging. 2005;32:855–97.PubMedCrossRef Hesse B, Tägil K, Cuocolo A, Anagnostopoulos C, Bardiés M, Bax J, et al. EANM/ESC procedural guidelines for myocardial perfusion imaging in nuclear cardiology. Eur J Nucl Med Mol Imaging. 2005;32:855–97.PubMedCrossRef
17.
Zurück zum Zitat Petretta M, Acampa W, Evangelista L, Daniele S, Ferro A, Cuocolo A. Impact of inducible ischemia by stress SPECT in cardiac risk assessment in diabetic patients: rationale and design of a prospective, multicenter trial. J Nucl Cardiol. 2008;15:100–4.PubMedCrossRef Petretta M, Acampa W, Evangelista L, Daniele S, Ferro A, Cuocolo A. Impact of inducible ischemia by stress SPECT in cardiac risk assessment in diabetic patients: rationale and design of a prospective, multicenter trial. J Nucl Cardiol. 2008;15:100–4.PubMedCrossRef
18.
Zurück zum Zitat Hachamovitch R, Berman DS, Kiat H, Cohen I, Cabico A, Friedman J, et al. Exercise myocardial perfusion SPECT in patients without known coronary artery disease. Circulation. 1996;93:905–14.PubMed Hachamovitch R, Berman DS, Kiat H, Cohen I, Cabico A, Friedman J, et al. Exercise myocardial perfusion SPECT in patients without known coronary artery disease. Circulation. 1996;93:905–14.PubMed
19.
Zurück zum Zitat Nitenberg A, Pham I, Antony I, Valensi P. Cardiovascular outcome of patients with abnormal coronary vasomotion and normal coronary arteriography is worse in type 2 diabetes mellitus than in arterial hypertension: A 10 year follow-up study. Atherosclerosis. 2005;183:113–20.PubMedCrossRef Nitenberg A, Pham I, Antony I, Valensi P. Cardiovascular outcome of patients with abnormal coronary vasomotion and normal coronary arteriography is worse in type 2 diabetes mellitus than in arterial hypertension: A 10 year follow-up study. Atherosclerosis. 2005;183:113–20.PubMedCrossRef
20.
Zurück zum Zitat Schindler TH, Nitzasche EU, Schelbert HR, Olschewski M, Saayre 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.PubMedCrossRef Schindler TH, Nitzasche EU, Schelbert HR, Olschewski M, Saayre 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.PubMedCrossRef
21.
Zurück zum Zitat Herzog BA, Husmann L, Valenta I, Gaemperli O, Siegrist PT, Tay FM, et al. Long-term prognostic value of 13N-ammonia myocardial perfusion positron emission tomography added value of coronary flow reserve. J Am Coll Cardiol. 2009;54:150–6.PubMedCrossRef Herzog BA, Husmann L, Valenta I, Gaemperli O, Siegrist PT, Tay FM, et al. Long-term prognostic value of 13N-ammonia myocardial perfusion positron emission tomography added value of coronary flow reserve. J Am Coll Cardiol. 2009;54:150–6.PubMedCrossRef
22.
Zurück zum Zitat Mahfouz RA, Dwidar AE, El Tahlawi MA. Endothelial-mediated coronary flow reserve and its relation to mitral annular tissue Doppler velocities in offspring of hypertensive parents. Echocardiography. 2011;28:1113–8.PubMedCrossRef Mahfouz RA, Dwidar AE, El Tahlawi MA. Endothelial-mediated coronary flow reserve and its relation to mitral annular tissue Doppler velocities in offspring of hypertensive parents. Echocardiography. 2011;28:1113–8.PubMedCrossRef
23.
Zurück zum Zitat Moro PJ, Flavian A, Jacquier A, Kober F, Quilici J, Gaborit B, et al. Gender differences in response to cold pressor test assessed with velocity-encoded cardiovascular magnetic resonance of the coronary sinus. J Cardiovasc Magn Reson. 2011;13:54–62.PubMedCrossRef Moro PJ, Flavian A, Jacquier A, Kober F, Quilici J, Gaborit B, et al. Gender differences in response to cold pressor test assessed with velocity-encoded cardiovascular magnetic resonance of the coronary sinus. J Cardiovasc Magn Reson. 2011;13:54–62.PubMedCrossRef
24.
Zurück zum Zitat Williams SB, Goldfine AB, Timimi FK, Ting HH, Roddy MA, Simonson DC, et al. Acute hyperglycemia attenuates endothelium-dependent vasodilation in humans in vivo. Circulation. 1998;97:1695–701.PubMed Williams SB, Goldfine AB, Timimi FK, Ting HH, Roddy MA, Simonson DC, et al. Acute hyperglycemia attenuates endothelium-dependent vasodilation in humans in vivo. Circulation. 1998;97:1695–701.PubMed
25.
Zurück zum Zitat Sobrevia L, Mann GE. Dysfunction of the endothelial nitric oxide signaling pathway in diabetes and hyperglycemia. Exp Physiol. 1997;82:423–52.PubMed Sobrevia L, Mann GE. Dysfunction of the endothelial nitric oxide signaling pathway in diabetes and hyperglycemia. Exp Physiol. 1997;82:423–52.PubMed
26.
Zurück zum Zitat Di Carli F, Bianco-Batlles D, Landa ME, Kazmrs A, Groehn H, Muzik O, et al. Effects of autonomic neuropathy on coronary blood flow in patients with diabetes mellitus. Circulation. 1999;100:813–9.PubMed Di Carli F, Bianco-Batlles D, Landa ME, Kazmrs A, Groehn H, Muzik O, et al. Effects of autonomic neuropathy on coronary blood flow in patients with diabetes mellitus. Circulation. 1999;100:813–9.PubMed
27.
Zurück zum Zitat Marini C, Bezante GP, Gandolfo P, Modonesi E, Morbelli SD, Depascale A, et al. Optimization of flow reserve measurement using SPECT technology to evaluate the determinants of coronary microvascular dysfunction in diabetes. Eur J Nucl Med Mol Imaging. 2010;37:357–67.PubMedCrossRef Marini C, Bezante GP, Gandolfo P, Modonesi E, Morbelli SD, Depascale A, et al. Optimization of flow reserve measurement using SPECT technology to evaluate the determinants of coronary microvascular dysfunction in diabetes. Eur J Nucl Med Mol Imaging. 2010;37:357–67.PubMedCrossRef
28.
Zurück zum Zitat Djaberi R, Roodt J, Schuijf JD, Rabelink TJ, de Koning EJ, Pereira AM, et al. Endothelial dysfunction in diabetic patients with abnormal myocardial perfusion in the absence of epicardial obstructive coronary artery disease. J Nucl Med. 2009;50:1980–6.PubMedCrossRef Djaberi R, Roodt J, Schuijf JD, Rabelink TJ, de Koning EJ, Pereira AM, et al. Endothelial dysfunction in diabetic patients with abnormal myocardial perfusion in the absence of epicardial obstructive coronary artery disease. J Nucl Med. 2009;50:1980–6.PubMedCrossRef
29.
Zurück zum Zitat Perrone-Filardi P, Cuocolo A, Brevetti G, Silvestro A, Storto G, Dellegrottaglie S, et al. Relation of artery flow-mediated vasodilation to significant coronary artery disease in patients with peripheral arterial disease. Am J Cardiol. 2005;96:1337–41.PubMedCrossRef Perrone-Filardi P, Cuocolo A, Brevetti G, Silvestro A, Storto G, Dellegrottaglie S, et al. Relation of artery flow-mediated vasodilation to significant coronary artery disease in patients with peripheral arterial disease. Am J Cardiol. 2005;96:1337–41.PubMedCrossRef
30.
Zurück zum Zitat Storto G, Pellegrino T, Sorrentino AR, Luongo L, Petretta M, Cuocolo A. Estimation of coronary flow reserve by sestamibi imaging in type 2 diabetic patients with normal coronary arteries. J Nucl Cardiol. 2007;14:194–9.PubMedCrossRef Storto G, Pellegrino T, Sorrentino AR, Luongo L, Petretta M, Cuocolo A. Estimation of coronary flow reserve by sestamibi imaging in type 2 diabetic patients with normal coronary arteries. J Nucl Cardiol. 2007;14:194–9.PubMedCrossRef
31.
Zurück zum Zitat Pellegrino T, Storto G, Perrone-Filardi P, Sorrentino AR, Silvestro A, Petretta M, et al. Relationship between brachial artery flow-mediated dilation and coronary flow reserve in patients with peripheral artery disease. J Nucl Med. 2005;46:1997–2002.PubMed Pellegrino T, Storto G, Perrone-Filardi P, Sorrentino AR, Silvestro A, Petretta M, et al. Relationship between brachial artery flow-mediated dilation and coronary flow reserve in patients with peripheral artery disease. J Nucl Med. 2005;46:1997–2002.PubMed
32.
Zurück zum Zitat Nabel EG, Ganz P, Gordon JB, Alexander RW, Selwyn AP. Dilation of normal and constriction of atherosclerotic coronary arteries caused by the cold pressure test. Circulation. 1988;77:43–52.PubMedCrossRef Nabel EG, Ganz P, Gordon JB, Alexander RW, Selwyn AP. Dilation of normal and constriction of atherosclerotic coronary arteries caused by the cold pressure test. Circulation. 1988;77:43–52.PubMedCrossRef
33.
Zurück zum Zitat Jeserich M, Schindler TH, Olschewski M, Unmussing M, Just H, Solzbach U. Vitamin C improves endothelial function of epicardial coronary arteries in patients with hypercholesterolemia or essential hypertension – assessed by cold pressure testing. Eur Heart J. 1999;20:1676–80.PubMedCrossRef Jeserich M, Schindler TH, Olschewski M, Unmussing M, Just H, Solzbach U. Vitamin C improves endothelial function of epicardial coronary arteries in patients with hypercholesterolemia or essential hypertension – assessed by cold pressure testing. Eur Heart J. 1999;20:1676–80.PubMedCrossRef
34.
Zurück zum Zitat Schindler TH, Magosaki N, Jeserich M, Olschewski M, Nitzsche E, Holubarsch C, et al. Effect of ascorbic acid on endothelial dysfunction in chronic smokers assessed by cold pressure testing. Cardiology. 2000;94:239–46.PubMedCrossRef Schindler TH, Magosaki N, Jeserich M, Olschewski M, Nitzsche E, Holubarsch C, et al. Effect of ascorbic acid on endothelial dysfunction in chronic smokers assessed by cold pressure testing. Cardiology. 2000;94:239–46.PubMedCrossRef
35.
Zurück zum Zitat Kiviniemi TO, Toikka JO, Koskenvuo JW, Sabaste A, Saraste M, Parkka JP, et al. Vasodilation of epicardial coronary artery can be measured with transthoracic echocardiography. Ultrasound Med Biol. 2007;33:362–70.PubMedCrossRef Kiviniemi TO, Toikka JO, Koskenvuo JW, Sabaste A, Saraste M, Parkka JP, et al. Vasodilation of epicardial coronary artery can be measured with transthoracic echocardiography. Ultrasound Med Biol. 2007;33:362–70.PubMedCrossRef
36.
Zurück zum Zitat Sudhir K, MacGregor JS, Barbant SD, Foster E, Fitzgerald PJ, Chatterjee K, et al. Assessment of coronary conductance and resistance vessel reactivity in response to nitroglycerin, ergonovine and adenosine: in vivo studies with simultaneous intravascular two-dimensional and Doppler ultrasound. J Am Coll Cardiol. 1993;21:1261–8.PubMedCrossRef Sudhir K, MacGregor JS, Barbant SD, Foster E, Fitzgerald PJ, Chatterjee K, et al. Assessment of coronary conductance and resistance vessel reactivity in response to nitroglycerin, ergonovine and adenosine: in vivo studies with simultaneous intravascular two-dimensional and Doppler ultrasound. J Am Coll Cardiol. 1993;21:1261–8.PubMedCrossRef
37.
Zurück zum Zitat Perrone-Filardi P, Achenbach S, Möhlenkamp S, Reiner Z, Sambuceti G, Schuijf JD, et al. Cardiac computed tomography and myocardial perfusion scintigraphy for risk stratification in asymptomatic individuals without known cardiovascular disease: a position statement of the Working Group on Nuclear Cardiology and Cardiac CT of the European Society of Cardiology. Eur Heart J. 2011;32:1986–93.PubMedCrossRef Perrone-Filardi P, Achenbach S, Möhlenkamp S, Reiner Z, Sambuceti G, Schuijf JD, et al. Cardiac computed tomography and myocardial perfusion scintigraphy for risk stratification in asymptomatic individuals without known cardiovascular disease: a position statement of the Working Group on Nuclear Cardiology and Cardiac CT of the European Society of Cardiology. Eur Heart J. 2011;32:1986–93.PubMedCrossRef
Metadaten
Titel
Effects of type 2 diabetes mellitus on coronary microvascular function and myocardial perfusion in patients without obstructive coronary artery disease
verfasst von
Caterina Marciano
Maurizio Galderisi
Paola Gargiulo
Wanda Acampa
Carmen D’Amore
Roberta Esposito
Enza Capasso
Gianluigi Savarese
Laura Casaretti
Francesco Lo Iudice
Giovanni Esposito
Giuseppe Rengo
Dario Leosco
Alberto Cuocolo
Pasquale Perrone-Filardi
Publikationsdatum
01.07.2012
Verlag
Springer-Verlag
Erschienen in
European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 7/2012
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-012-2117-9

Weitere Artikel der Ausgabe 7/2012

European Journal of Nuclear Medicine and Molecular Imaging 7/2012 Zur Ausgabe

Society communications

The Toast of Vienna