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Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging 2/2009

01.02.2009 | Original Article

Structural alterations of the coronary arterial wall are associated with myocardial flow heterogeneity in type 2 diabetes mellitus

verfasst von: Thomas H. Schindler, Alvaro D. Facta, John O. Prior, Jerson Cadenas, Xiao-Li Zhang, Yanjie Li, James Sayre, Jonathan Goldin, Heinrich R. Schelbert

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 2/2009

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Abstract

Purpose

To determine the relationship between carotid intima–media thickness (IMT), coronary artery calcification (CAC), and myocardial blood flow (MBF) at rest and during vasomotor stress in type 2 diabetes mellitus (DM).

Methods

In 68 individuals, carotid IMT was measured using high-resolution vascular ultrasound, while the presence of CAC was determined with electron beam tomography (EBT). Global and regional MBF was determined in milliliters per gram per minute with 13N-ammonia and positron emission tomography (PET) at rest, during cold pressor testing (CPT), and during adenosine (ADO) stimulation.

Results

There was neither a relationship between carotid IMT and CAC (r = 0.10, p = 0.32) nor between carotid IMT and coronary circulatory function in response to CPT and during ADO (r = −0.18, p = 0.25 and r = 0.10, p = 0.54, respectively). In 33 individuals, EBT detected CAC with a mean Agatston-derived calcium score of 44 ± 18. There was a significant difference in regional MBFs between territories with and without CAC at rest and during ADO-stimulated hyperemia (0.69 ± 0.24 vs. 0.74 ± 0.23 and 1.82 ± 0.50 vs. 1.95 ± 0.51 ml/g/min; p ≤ 0.05, respectively) and also during CPT in DM but less pronounced (0.81 ± 0.24 vs. 0.83 ± 0.23 ml/g/min; p = ns). The increase in CAC was paralleled with a progressive regional decrease in resting as well as in CPT- and ADO-related MBFs (r = −0.36, p ≤ 0.014; r = −0.46, p ≤ 0.007; and r = −0.33, p ≤ 0.041, respectively).

Conclusions

The absence of any correlation between carotid IMT and coronary circulatory function in type 2 DM suggests different features and stages of early atherosclerosis in the peripheral and coronary circulation. PET-measured MBF heterogeneity at rest and during vasomotor stress may reflect downstream fluid dynamic effects of coronary artery disease (CAD)-related early structural alterations of the arterial wall.
Literatur
1.
Zurück zum Zitat Di Carli MF, Hachamovitch R. New technology for noninvasive evaluation of coronary artery disease. Circulation 2007;115:1464–80.PubMedCrossRef Di Carli MF, Hachamovitch R. New technology for noninvasive evaluation of coronary artery disease. Circulation 2007;115:1464–80.PubMedCrossRef
2.
Zurück zum Zitat Reddy KG, Nair RN, Sheehan HM, Hodgson JM. Evidence that selective endothelial dysfunction may occur in the absence of angiographic or ultrasound atherosclerosis in patients with risk factors for atherosclerosis. J Am Coll Cardiol 1994;23:833–43.PubMed Reddy KG, Nair RN, Sheehan HM, Hodgson JM. Evidence that selective endothelial dysfunction may occur in the absence of angiographic or ultrasound atherosclerosis in patients with risk factors for atherosclerosis. J Am Coll Cardiol 1994;23:833–43.PubMed
3.
Zurück zum Zitat Schindler TH, Cardenas J, Prior JO, Facta AD, Kreissl MC, Zhang XL, et al. Relationship between increasing body weight, insulin resistance, inflammation, adipocytokine leptin, and coronary circulatory function. J Am Coll Cardiol 2006;47:1188–95.PubMedCrossRef Schindler TH, Cardenas J, Prior JO, Facta AD, Kreissl MC, Zhang XL, et al. Relationship between increasing body weight, insulin resistance, inflammation, adipocytokine leptin, and coronary circulatory function. J Am Coll Cardiol 2006;47:1188–95.PubMedCrossRef
4.
Zurück zum Zitat Di Carli MF, Dorbala S, Hachamovitch R. Integrated cardiac PET-CT for the diagnosis and management of CAD. J Nucl Cardiol 2006;13:139–44.PubMedCrossRef Di Carli MF, Dorbala S, Hachamovitch R. Integrated cardiac PET-CT for the diagnosis and management of CAD. J Nucl Cardiol 2006;13:139–44.PubMedCrossRef
5.
Zurück zum Zitat Schindler TH, Zhang XL, Vincenti G, Mhiri L, Lerch R, Schelbert HR. Role of PET in the evaluation and understanding of coronary physiology. J Nucl Cardiol 2007;14:589–603.PubMedCrossRef Schindler TH, Zhang XL, Vincenti G, Mhiri L, Lerch R, Schelbert HR. Role of PET in the evaluation and understanding of coronary physiology. J Nucl Cardiol 2007;14:589–603.PubMedCrossRef
6.
Zurück zum Zitat Prior JO, Schindler TH, Facta AD, Hernandez-Pampaloni M, Campisi R, Dahlbom M, et al. Determinants of myocardial blood flow response to cold pressor testing and pharmacologic vasodilation in healthy humans. Eur J Nucl Med Mol Imaging 2007;34:20–7.PubMedCrossRef Prior JO, Schindler TH, Facta AD, Hernandez-Pampaloni M, Campisi R, Dahlbom M, et al. Determinants of myocardial blood flow response to cold pressor testing and pharmacologic vasodilation in healthy humans. Eur J Nucl Med Mol Imaging 2007;34:20–7.PubMedCrossRef
7.
Zurück zum Zitat Graner M, Varpula M, Kahri J, Salonen RM, Nyyssönen K, Nieminen MS, et al. Association of carotid intima–media thickness with angiographic severity and extent of coronary artery disease. Am J Cardiol 2006;97:624–9.PubMedCrossRef Graner M, Varpula M, Kahri J, Salonen RM, Nyyssönen K, Nieminen MS, et al. Association of carotid intima–media thickness with angiographic severity and extent of coronary artery disease. Am J Cardiol 2006;97:624–9.PubMedCrossRef
8.
Zurück zum Zitat Ogata T, Yasaka M, Yamagishi M, Seguchi O, Nagatsuka K, Minematsu K. Atherosclerosis found on carotid ultrasonography is associated with atherosclerosis on coronary intravascular ultrasonography. J Ultrasound Med 2005;24:469–74.PubMed Ogata T, Yasaka M, Yamagishi M, Seguchi O, Nagatsuka K, Minematsu K. Atherosclerosis found on carotid ultrasonography is associated with atherosclerosis on coronary intravascular ultrasonography. J Ultrasound Med 2005;24:469–74.PubMed
9.
Zurück zum Zitat Hoffmann U, Ferencik M, Cury RC, Pena AJ. Coronary CT angiography. J Nucl Med 2006;47:797–806.PubMed Hoffmann U, Ferencik M, Cury RC, Pena AJ. Coronary CT angiography. J Nucl Med 2006;47:797–806.PubMed
10.
Zurück zum Zitat Hoffmann U, Nagurney JT, Moselewski F, Pena A, Ferencik M, Chae CU, et al. Coronary multidetector computed tomography in the assessment of patients with acute chest pain. Circulation 2006;114:2251–60.PubMedCrossRef Hoffmann U, Nagurney JT, Moselewski F, Pena A, Ferencik M, Chae CU, et al. Coronary multidetector computed tomography in the assessment of patients with acute chest pain. Circulation 2006;114:2251–60.PubMedCrossRef
11.
Zurück zum Zitat Gould KL, Lipscomb K, Calvert C. Compensatory changes of the distal coronary vascular bed during progressive coronary constriction. Circulation 1975;51:1085–94.PubMed Gould KL, Lipscomb K, Calvert C. Compensatory changes of the distal coronary vascular bed during progressive coronary constriction. Circulation 1975;51:1085–94.PubMed
12.
Zurück zum Zitat Di Carli M, Czernin J, Hoh CK, Gerbaudo VH, Brunken RC, Huang SC, et al. Relation among stenosis severity, myocardial blood flow, and flow reserve in patients with coronary artery disease. Circulation 1995;91:1944–51.PubMed Di Carli M, Czernin J, Hoh CK, Gerbaudo VH, Brunken RC, Huang SC, et al. Relation among stenosis severity, myocardial blood flow, and flow reserve in patients with coronary artery disease. Circulation 1995;91:1944–51.PubMed
13.
Zurück zum Zitat Uren NG, Melin JA, De Bruyne B, Wijns W, Baudhuin T, Camici PG. Relation between myocardial blood flow and the severity of coronary-artery stenosis. N Engl J Med 1994;330:1782–8.PubMedCrossRef Uren NG, Melin JA, De Bruyne B, Wijns W, Baudhuin T, Camici PG. Relation between myocardial blood flow and the severity of coronary-artery stenosis. N Engl J Med 1994;330:1782–8.PubMedCrossRef
14.
Zurück zum Zitat Beanlands RS, Muzik O, Melon P, Sutor R, Sawada S, Muller D, et al. Noninvasive quantification of regional myocardial flow reserve in patients with coronary atherosclerosis using nitrogen-13 ammonia positron emission tomography. Determination of extent of altered vascular reactivity. J Am Coll Cardiol 1995;26:1465–75.PubMedCrossRef Beanlands RS, Muzik O, Melon P, Sutor R, Sawada S, Muller D, et al. Noninvasive quantification of regional myocardial flow reserve in patients with coronary atherosclerosis using nitrogen-13 ammonia positron emission tomography. Determination of extent of altered vascular reactivity. J Am Coll Cardiol 1995;26:1465–75.PubMedCrossRef
15.
Zurück zum Zitat Gould KL, Nakagawa Y, Nakagawa K, Sdringola S, Hess MJ, Haynie M, et al. Frequency and clinical implications of fluid dynamically significant diffuse coronary artery disease manifest as graded, longitudinal, base-to-apex myocardial perfusion abnormalities by noninvasive positron emission tomography. Circulation 2000;101:1931–9.PubMed Gould KL, Nakagawa Y, Nakagawa K, Sdringola S, Hess MJ, Haynie M, et al. Frequency and clinical implications of fluid dynamically significant diffuse coronary artery disease manifest as graded, longitudinal, base-to-apex myocardial perfusion abnormalities by noninvasive positron emission tomography. Circulation 2000;101:1931–9.PubMed
16.
Zurück zum Zitat Gould KL. Assessing progression or regression of CAD: the role of perfusion imaging. J Nucl Cardiol 2005;12:625–38.PubMedCrossRef Gould KL. Assessing progression or regression of CAD: the role of perfusion imaging. J Nucl Cardiol 2005;12:625–38.PubMedCrossRef
17.
Zurück zum Zitat Graf S, Khorsand A, Gwechenberger M, Novotny C, Kletter K, Sochor H, et al. Typical chest pain and normal coronary angiogram: cardiac risk factor analysis versus PET for detection of microvascular disease. J Nucl Med 2007;48:175–81.PubMed Graf S, Khorsand A, Gwechenberger M, Novotny C, Kletter K, Sochor H, et al. Typical chest pain and normal coronary angiogram: cardiac risk factor analysis versus PET for detection of microvascular disease. J Nucl Med 2007;48:175–81.PubMed
18.
Zurück zum Zitat Johnson NP, Gould KL. Clinical evaluation of a new concept: resting myocardial perfusion heterogeneity quantified by markovian analysis of PET identifies coronary microvascular dysfunction and early atherosclerosis in 1,034 subjects. J Nucl Med 2005;46:1427–37.PubMed Johnson NP, Gould KL. Clinical evaluation of a new concept: resting myocardial perfusion heterogeneity quantified by markovian analysis of PET identifies coronary microvascular dysfunction and early atherosclerosis in 1,034 subjects. J Nucl Med 2005;46:1427–37.PubMed
19.
Zurück zum Zitat Hernandez-Pampaloni M, Keng FY, Kudo T, Sayre JS, Schelbert HR. Abnormal longitudinal, base-to-apex myocardial perfusion gradient by quantitative blood flow measurements in patients with coronary risk factors. Circulation 2001;104:527–32.PubMedCrossRef Hernandez-Pampaloni M, Keng FY, Kudo T, Sayre JS, Schelbert HR. Abnormal longitudinal, base-to-apex myocardial perfusion gradient by quantitative blood flow measurements in patients with coronary risk factors. Circulation 2001;104:527–32.PubMedCrossRef
20.
Zurück zum Zitat Schindler TH, Facta AD, Prior JO, Campisi R, Inubushi M, Kreissl MC, et al. PET-measured heterogeneity in longitudinal myocardial blood flow in response to sympathetic and pharmacologic stress as a non-invasive probe of epicardial vasomotor dysfunction. Eur J Nucl Med Mol Imaging 2006;33:1140–9.PubMedCrossRef Schindler TH, Facta AD, Prior JO, Campisi R, Inubushi M, Kreissl MC, et al. PET-measured heterogeneity in longitudinal myocardial blood flow in response to sympathetic and pharmacologic stress as a non-invasive probe of epicardial vasomotor dysfunction. Eur J Nucl Med Mol Imaging 2006;33:1140–9.PubMedCrossRef
21.
Zurück zum Zitat Schindler TH, Zhang XL, Vincenti G, Mhiri L, Nkoulou R, Just H, et al. Diagnostic value of PET-measured heterogeneity in myocardial blood flows during cold pressor testing for the identification of coronary vasomotor dysfunction. J Nucl Cardiol 2007;14:688–97.PubMedCrossRef Schindler TH, Zhang XL, Vincenti G, Mhiri L, Nkoulou R, Just H, et al. Diagnostic value of PET-measured heterogeneity in myocardial blood flows during cold pressor testing for the identification of coronary vasomotor dysfunction. J Nucl Cardiol 2007;14:688–97.PubMedCrossRef
22.
Zurück zum Zitat Jarvisalo MJ, Jartti L, Nanto-Salonen K, Irjala K, Roennemaa T, Hartiala JJ, et al. Increased aortic intima–media thickness: a marker of preclinical atherosclerosis in high-risk children. Circulation 2001;104:2943–7.PubMedCrossRef Jarvisalo MJ, Jartti L, Nanto-Salonen K, Irjala K, Roennemaa T, Hartiala JJ, et al. Increased aortic intima–media thickness: a marker of preclinical atherosclerosis in high-risk children. Circulation 2001;104:2943–7.PubMedCrossRef
23.
Zurück zum Zitat Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M Jr., Detrano R. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 1990;15:827–32.PubMedCrossRef Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M Jr., Detrano R. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 1990;15:827–32.PubMedCrossRef
24.
Zurück zum Zitat Goldin JG, Yoon HC, Greaser LE 3rd, Heinze SB, McNitt-Gray MM, Brown MS, et al. Spiral versus electron-beam CT for coronary artery calcium scoring. Radiology 2001;221:213–21.PubMedCrossRef Goldin JG, Yoon HC, Greaser LE 3rd, Heinze SB, McNitt-Gray MM, Brown MS, et al. Spiral versus electron-beam CT for coronary artery calcium scoring. Radiology 2001;221:213–21.PubMedCrossRef
25.
Zurück zum Zitat Rumberger JA, Brundage BH, Rader DJ, Kondos G. Electron beam computed tomographic coronary calcium scanning: a review and guidelines for use in asymptomatic persons. Mayo Clin Proc 1999;74:243–52.PubMedCrossRef Rumberger JA, Brundage BH, Rader DJ, Kondos G. Electron beam computed tomographic coronary calcium scanning: a review and guidelines for use in asymptomatic persons. Mayo Clin Proc 1999;74:243–52.PubMedCrossRef
26.
Zurück zum Zitat Hodis HN, Mack WJ, Zheng L, Li Y, Torres M, Sevilla D, et al. Effect of peroxisome proliferator-activated receptor gamma agonist treatment on subclinical atherosclerosis in patients with insulin-requiring type 2 diabetes. Diabetes Care 2006;29:1545–53.PubMedCrossRef Hodis HN, Mack WJ, Zheng L, Li Y, Torres M, Sevilla D, et al. Effect of peroxisome proliferator-activated receptor gamma agonist treatment on subclinical atherosclerosis in patients with insulin-requiring type 2 diabetes. Diabetes Care 2006;29:1545–53.PubMedCrossRef
27.
Zurück zum Zitat Zeiher AM, Drexler H. Coronary hemodynamic determinants of epicardial artery vasomotor responses during sympathetic stimulation in humans. Basic Res Cardiol 1991;86(Suppl 2):203–13.PubMed Zeiher AM, Drexler H. Coronary hemodynamic determinants of epicardial artery vasomotor responses during sympathetic stimulation in humans. Basic Res Cardiol 1991;86(Suppl 2):203–13.PubMed
28.
Zurück zum Zitat De Bruyne B, Hersbach F, Pijls NH, Bartunek J, Bech JW, Heyndrickx GR, et al. Abnormal epicardial coronary resistance in patients with diffuse atherosclerosis but “normal” coronary angiography. Circulation 2001;104:2401–6.PubMedCrossRef De Bruyne B, Hersbach F, Pijls NH, Bartunek J, Bech JW, Heyndrickx GR, et al. Abnormal epicardial coronary resistance in patients with diffuse atherosclerosis but “normal” coronary angiography. Circulation 2001;104:2401–6.PubMedCrossRef
29.
Zurück zum Zitat Newman AB, Naydeck BL, Sutton-Tyrrell K, Edmundowicz D, O’Leary D, Kronmal R, et al. Relationship between coronary artery calcification and other measures of subclinical cardiovascular disease in older adults. Arterioscler Thromb Vasc Biol 2002;22:1674–9.PubMedCrossRef Newman AB, Naydeck BL, Sutton-Tyrrell K, Edmundowicz D, O’Leary D, Kronmal R, et al. Relationship between coronary artery calcification and other measures of subclinical cardiovascular disease in older adults. Arterioscler Thromb Vasc Biol 2002;22:1674–9.PubMedCrossRef
30.
Zurück zum Zitat Juonala M, Viikari JS, Laitinen T, Marniemi J, Helenius H, Roennemaa T, et al. Interrelations between brachial endothelial function and carotid intima–media thickness in young adults: the cardiovascular risk in young Finns study. Circulation 2004;110:2918–23.PubMedCrossRef Juonala M, Viikari JS, Laitinen T, Marniemi J, Helenius H, Roennemaa T, et al. Interrelations between brachial endothelial function and carotid intima–media thickness in young adults: the cardiovascular risk in young Finns study. Circulation 2004;110:2918–23.PubMedCrossRef
31.
Zurück zum Zitat Jarvisalo MJ, Raitakari M, Toikka JO, Putto-Laurila A, Rontu R, Laine S, et al. Endothelial dysfunction and increased arterial intima–media thickness in children with type 1 diabetes. Circulation 2004;109:1750–5.PubMedCrossRef Jarvisalo MJ, Raitakari M, Toikka JO, Putto-Laurila A, Rontu R, Laine S, et al. Endothelial dysfunction and increased arterial intima–media thickness in children with type 1 diabetes. Circulation 2004;109:1750–5.PubMedCrossRef
32.
Zurück zum Zitat Hashimoto M, Eto M, Akishita M, Kozaki K, Ako J, Iijima K, et al. Correlation between flow-mediated vasodilatation of the brachial artery and intima–media thickness in the carotid artery in men. Arterioscler Thromb Vasc Biol 1999;19:2795–800.PubMed Hashimoto M, Eto M, Akishita M, Kozaki K, Ako J, Iijima K, et al. Correlation between flow-mediated vasodilatation of the brachial artery and intima–media thickness in the carotid artery in men. Arterioscler Thromb Vasc Biol 1999;19:2795–800.PubMed
33.
Zurück zum Zitat Yan RT, Anderson TJ, Charbonneau F, Title L, Verma S, Lonn E. Relationship between carotid artery intima–media thickness and brachial artery flow-mediated dilation in middle-aged healthy men. J Am Coll Cardiol 2005;45:1980–6.PubMedCrossRef Yan RT, Anderson TJ, Charbonneau F, Title L, Verma S, Lonn E. Relationship between carotid artery intima–media thickness and brachial artery flow-mediated dilation in middle-aged healthy men. J Am Coll Cardiol 2005;45:1980–6.PubMedCrossRef
34.
Zurück zum Zitat Schachinger V, Zeiher AM. Quantitative assessment of coronary vasoreactivity in humans in vivo. Importance of baseline vasomotor tone in atherosclerosis. Circulation 1995;92:2087–94.PubMed Schachinger V, Zeiher AM. Quantitative assessment of coronary vasoreactivity in humans in vivo. Importance of baseline vasomotor tone in atherosclerosis. Circulation 1995;92:2087–94.PubMed
35.
Zurück zum Zitat Zeiher AM, Drexler H, Wollschlaeger H, Saurbier B, Just H. Coronary vasomotion in response to sympathetic stimulation in humans: importance of the functional integrity of the endothelium. J Am Coll Cardiol 1989;14:1181–90.PubMedCrossRef Zeiher AM, Drexler H, Wollschlaeger H, Saurbier B, Just H. Coronary vasomotion in response to sympathetic stimulation in humans: importance of the functional integrity of the endothelium. J Am Coll Cardiol 1989;14:1181–90.PubMedCrossRef
36.
Zurück zum Zitat Rumberger JA, Simons DB, Fitzpatrick LA, Sheedy PF, Schwartz RS. Coronary artery calcium area by electron-beam computed tomography and coronary atherosclerotic plaque area. A histopathologic correlative study. Circulation 1995;92:2157–62.PubMed Rumberger JA, Simons DB, Fitzpatrick LA, Sheedy PF, Schwartz RS. Coronary artery calcium area by electron-beam computed tomography and coronary atherosclerotic plaque area. A histopathologic correlative study. Circulation 1995;92:2157–62.PubMed
37.
Zurück zum Zitat Zeiher AM, Drexler H, Wollschlager H, Just H. Modulation of coronary vasomotor tone in humans. Progressive endothelial dysfunction with different early stages of coronary atherosclerosis. Circulation 1991;83:391–401.PubMed Zeiher AM, Drexler H, Wollschlager H, Just H. Modulation of coronary vasomotor tone in humans. Progressive endothelial dysfunction with different early stages of coronary atherosclerosis. Circulation 1991;83:391–401.PubMed
Metadaten
Titel
Structural alterations of the coronary arterial wall are associated with myocardial flow heterogeneity in type 2 diabetes mellitus
verfasst von
Thomas H. Schindler
Alvaro D. Facta
John O. Prior
Jerson Cadenas
Xiao-Li Zhang
Yanjie Li
James Sayre
Jonathan Goldin
Heinrich R. Schelbert
Publikationsdatum
01.02.2009
Verlag
Springer-Verlag
Erschienen in
European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 2/2009
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-008-0885-z

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