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Erschienen in: Heart and Vessels 4/2018

24.10.2017 | Original Article

Impact of malondialdehyde-modified low-density lipoprotein on coronary plaque vulnerability in patients not receiving lipid-lowering therapy: a whole coronary analysis with multislice-computed tomography

verfasst von: Tsuyoshi Ito, Taku Ichihashi, Hiroshi Fujita, Tomonori Sugiura, Nobuyuki Ohte

Erschienen in: Heart and Vessels | Ausgabe 4/2018

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Abstract

Vulnerable plaque disruption was suggested as a primary cause of acute coronary syndrome. This study investigated the impact of malondialdehyde-modified low-density lipoprotein (MDA-LDL) on whole coronary plaque vulnerability, based on multislice-computed tomography (MSCT). We included 197 patients that were not receiving lipid-lowering therapy. We retrospectively analyzed MSCT and MDA-LDL measurements. We defined a CT-derived vulnerable plaque as a plaque with a remodeling index > 1.10 and a mean CT density value < 30 HU. Vulnerable plaques were detected in 60 patients (30%). Patients with vulnerable plaques had significantly higher MDA-LDL levels than patients without vulnerable plaques (151.3 ± 42.3 vs. 118.5 ± 41.7 U/L, p < 0.01). A univariate regression analysis showed that vulnerable plaques were significantly related to MDA-LDL levels [10 U/L groups, odds ratio (OR): 1.19; p < 0.01] and in a multivariate model (10 U/L groups, OR: 1.18; p < 0.01). Patients with multivessel vulnerable plaques had significantly higher MDA-LDL levels than those with single-vessel involvement or no vulnerable plaque (172.4 ± 28.5 vs. 142.8 ± 44.2 vs. 118.5 ± 41.7 U/L, respectively; p < 0.01). MDA-LDL difference was observed for all LDL tertiles (bottom; 128.9 ± 41.1 vs. 97.3 ± 25.0 U/L, p < 0.01, middle; 142.6 ± 42.7 vs. 122.5 ± 35.1 U/L, p = 0.05, top; 166.0 ± 38.1 vs. 143.5 ± 51.6 U/L, p = 0.05). Increased MDA-LDL levels were associated with the presence and extent of vulnerable plaques, regardless of LDL levels.
Literatur
2.
Zurück zum Zitat Steinberg D, Lewis A (1997) Conner memorial lecture. oxidative modification of LDL and atherogenesis. Circulation 95:1062–1071CrossRefPubMed Steinberg D, Lewis A (1997) Conner memorial lecture. oxidative modification of LDL and atherogenesis. Circulation 95:1062–1071CrossRefPubMed
3.
Zurück zum Zitat Amaki T, Suzuki T, Nakamura F, Hayashi D, Imai Y, Morita H, Fukino K, Nojiri T, Kitano S, Hibi N, Yamazaki T, Nagai R (2004) Circulating malondialdehyde modified LDL is a biochemical risk marker for coronary artery disease. Heart 90:1211–1213CrossRefPubMedPubMedCentral Amaki T, Suzuki T, Nakamura F, Hayashi D, Imai Y, Morita H, Fukino K, Nojiri T, Kitano S, Hibi N, Yamazaki T, Nagai R (2004) Circulating malondialdehyde modified LDL is a biochemical risk marker for coronary artery disease. Heart 90:1211–1213CrossRefPubMedPubMedCentral
4.
Zurück zum Zitat Ito T, Fujita H, Tani T, Sugiura T, Ohte N (2015) Increased circulating malondialdehyde-modified low-density lipoprotein levels in patients with ergonovine-induced coronary artery spasm. Int J Cardiol 184:475–480CrossRefPubMed Ito T, Fujita H, Tani T, Sugiura T, Ohte N (2015) Increased circulating malondialdehyde-modified low-density lipoprotein levels in patients with ergonovine-induced coronary artery spasm. Int J Cardiol 184:475–480CrossRefPubMed
5.
Zurück zum Zitat Ito T, Fujita H, Tani T, Ohte N (2015) Malondialdehyde-modified low-density lipoprotein is a predictor of cardiac events in patients with stable angina on lipid-lowering therapy after percutaneous coronary intervention using drug-eluting stent. Atherosclerosis 239:311–317CrossRefPubMed Ito T, Fujita H, Tani T, Ohte N (2015) Malondialdehyde-modified low-density lipoprotein is a predictor of cardiac events in patients with stable angina on lipid-lowering therapy after percutaneous coronary intervention using drug-eluting stent. Atherosclerosis 239:311–317CrossRefPubMed
6.
Zurück zum Zitat Holvoet P, Collen D, Van de Werf F (1999) Malondialdehyde-modified LDL as a marker of acute coronary syndromes. JAMA 281:1718–1721CrossRefPubMed Holvoet P, Collen D, Van de Werf F (1999) Malondialdehyde-modified LDL as a marker of acute coronary syndromes. JAMA 281:1718–1721CrossRefPubMed
7.
Zurück zum Zitat Matsuo Y, Kubo T, Okumoto Y, Ishibashi K, Komukai K, Tanimoto T, Ino Y, Kitabata H, Hirata K, Imanishi T, Akagi H, Akasaka T (2013) Circulating malondialdehyde-modified low-density lipoprotein levels are associated with the presence of thin-cap fibroatheromas determined by optical coherence tomography in coronary artery disease. Eur Heart J Cardiovasc Imaging 14:43–50CrossRefPubMed Matsuo Y, Kubo T, Okumoto Y, Ishibashi K, Komukai K, Tanimoto T, Ino Y, Kitabata H, Hirata K, Imanishi T, Akagi H, Akasaka T (2013) Circulating malondialdehyde-modified low-density lipoprotein levels are associated with the presence of thin-cap fibroatheromas determined by optical coherence tomography in coronary artery disease. Eur Heart J Cardiovasc Imaging 14:43–50CrossRefPubMed
8.
Zurück zum Zitat Tajika K, Okamatsu K, Takano M, Inami S, Yamamoto M, Murakami D, Kobayashi N, Ohba T, Hata N, Seino Y, Mizuno K (2012) Malondialdehyde-modified low-density lipoprotein is a useful marker to identify patients with vulnerable plaque. Circ J 76:2211–2217CrossRefPubMed Tajika K, Okamatsu K, Takano M, Inami S, Yamamoto M, Murakami D, Kobayashi N, Ohba T, Hata N, Seino Y, Mizuno K (2012) Malondialdehyde-modified low-density lipoprotein is a useful marker to identify patients with vulnerable plaque. Circ J 76:2211–2217CrossRefPubMed
9.
Zurück zum Zitat Ikenaga H, Kurisu S, Kono S, Sumimoto Y, Watanabe N, Shimonaga T, Higaki T, Iwasaki T, Mitsuba N, Ishibashi K, Dohi Y, Fukuda Y, Kihara Y (2016) Impact of malondialdehyde-modified low-density lipoprotein on tissue characteristics in patients with stable coronary artery disease—integrated backscatter-intravascular ultrasound study. Circ J 80:2173–2182CrossRefPubMed Ikenaga H, Kurisu S, Kono S, Sumimoto Y, Watanabe N, Shimonaga T, Higaki T, Iwasaki T, Mitsuba N, Ishibashi K, Dohi Y, Fukuda Y, Kihara Y (2016) Impact of malondialdehyde-modified low-density lipoprotein on tissue characteristics in patients with stable coronary artery disease—integrated backscatter-intravascular ultrasound study. Circ J 80:2173–2182CrossRefPubMed
10.
Zurück zum Zitat Hoffmann U, Moselewski F, Cury RC, Ferencik M, Jang IK, Diaz LJ, Abbara S, Brady TJ, Achenbach S (2004) Predictive value of 16-slice multidetector spiral computed tomography to detect significant obstructive coronary artery disease in patients at high risk for coronary artery disease: patient-versus segment-based analysis. Circulation 110:2638–2643CrossRefPubMed Hoffmann U, Moselewski F, Cury RC, Ferencik M, Jang IK, Diaz LJ, Abbara S, Brady TJ, Achenbach S (2004) Predictive value of 16-slice multidetector spiral computed tomography to detect significant obstructive coronary artery disease in patients at high risk for coronary artery disease: patient-versus segment-based analysis. Circulation 110:2638–2643CrossRefPubMed
11.
Zurück zum Zitat Ito T, Terashima M, Kaneda H, Nasu K, Matsuo H, Ehara M, Kinoshita Y, Kimura M, Tanaka N, Habara M, Katoh O, Suzuki T (2011) Comparison of in vivo assessment of vulnerable plaque by 64-slice multislice computed tomography versus optical coherence tomography. Am J Cardiol 107:1270–1277CrossRefPubMed Ito T, Terashima M, Kaneda H, Nasu K, Matsuo H, Ehara M, Kinoshita Y, Kimura M, Tanaka N, Habara M, Katoh O, Suzuki T (2011) Comparison of in vivo assessment of vulnerable plaque by 64-slice multislice computed tomography versus optical coherence tomography. Am J Cardiol 107:1270–1277CrossRefPubMed
12.
Zurück zum Zitat Kotani K, Maekawa M, Kanno T, Kondo A, Toda N, Manabe M (1994) Distribution of immunoreactive malondialdehyde-modified low-density lipoprotein in human serum. Biochim Biophys Acta 1215:121–125CrossRefPubMed Kotani K, Maekawa M, Kanno T, Kondo A, Toda N, Manabe M (1994) Distribution of immunoreactive malondialdehyde-modified low-density lipoprotein in human serum. Biochim Biophys Acta 1215:121–125CrossRefPubMed
13.
Zurück zum Zitat Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M Jr, Detrano R (1990) Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 15:827–832CrossRefPubMed Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M Jr, Detrano R (1990) Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 15:827–832CrossRefPubMed
14.
Zurück zum Zitat Motoyama S, Sarai M, Harigaya H, Anno H, Inoue K, Hara T, Naruse H, Ishii J, Hishida H, Wong ND, Virmani R, Kondo T, Ozaki Y, Narula J (2009) Computed tomographic angiography characteristics of atherosclerotic plaques subsequently resulting in acute coronary syndrome. J Am Coll Cardiol 54:49–57CrossRefPubMed Motoyama S, Sarai M, Harigaya H, Anno H, Inoue K, Hara T, Naruse H, Ishii J, Hishida H, Wong ND, Virmani R, Kondo T, Ozaki Y, Narula J (2009) Computed tomographic angiography characteristics of atherosclerotic plaques subsequently resulting in acute coronary syndrome. J Am Coll Cardiol 54:49–57CrossRefPubMed
15.
Zurück zum Zitat Kubo T, Imanishi T, Takarada S, Kuroi A, Ueno S, Yamano T, Tanimoto T, Matsuo Y, Masho T, Kitabata H, Tsuda K, Tomobuchi Y, Akasaka T (2007) Assessment of culprit lesion morphology in acute myocardial infarction: ability of optical coherence tomography compared with intravascular ultrasound and coronary angioscopy. J Am Coll Cardiol 50:933–939CrossRefPubMed Kubo T, Imanishi T, Takarada S, Kuroi A, Ueno S, Yamano T, Tanimoto T, Matsuo Y, Masho T, Kitabata H, Tsuda K, Tomobuchi Y, Akasaka T (2007) Assessment of culprit lesion morphology in acute myocardial infarction: ability of optical coherence tomography compared with intravascular ultrasound and coronary angioscopy. J Am Coll Cardiol 50:933–939CrossRefPubMed
16.
Zurück zum Zitat Takahashi S, Kawasaki M, Miyata S, Suzuki K, Yamaura M, Ido T, Aoyama T, Fujiwara H, Minatoguchi S (2016) Feasibility of tissue characterization of coronary plaques using 320-detector row computed tomography: comparison with integrated backscatter intravascular ultrasound. Heart Vessels 31:29–37CrossRefPubMed Takahashi S, Kawasaki M, Miyata S, Suzuki K, Yamaura M, Ido T, Aoyama T, Fujiwara H, Minatoguchi S (2016) Feasibility of tissue characterization of coronary plaques using 320-detector row computed tomography: comparison with integrated backscatter intravascular ultrasound. Heart Vessels 31:29–37CrossRefPubMed
17.
Zurück zum Zitat Chu L, Hao H, Luo M, Huang Y, Chen Z, Lu T, Zhao X, Verfaillie CM, Zweier JL, Liu Z (2011) Ox-LDL modifies the behaviour of bone marrow stem cells and impairs their endothelial differentiation via inhibition of Akt phosphorylation. J Cell Mol Med 15:423–432CrossRefPubMed Chu L, Hao H, Luo M, Huang Y, Chen Z, Lu T, Zhao X, Verfaillie CM, Zweier JL, Liu Z (2011) Ox-LDL modifies the behaviour of bone marrow stem cells and impairs their endothelial differentiation via inhibition of Akt phosphorylation. J Cell Mol Med 15:423–432CrossRefPubMed
18.
Zurück zum Zitat Rauscher FM, Goldschmidt-Clermont PJ, Davis BH, Wang T, Gregg D, Ramaswami P, Pippen AM, Annex BH, Dong C, Taylor DA (2003) Aging, progenitor cell exhaustion, and atherosclerosis. Circulation 108:457–463CrossRefPubMed Rauscher FM, Goldschmidt-Clermont PJ, Davis BH, Wang T, Gregg D, Ramaswami P, Pippen AM, Annex BH, Dong C, Taylor DA (2003) Aging, progenitor cell exhaustion, and atherosclerosis. Circulation 108:457–463CrossRefPubMed
19.
Zurück zum Zitat Shah PK, Falk E, Badimon JJ, Fernandez-Ortiz A, Mailhac A, Villareal-Levy G, Fallon JT, Regnstrom J, Fuster V (1995) Human monocyte-derived macrophages induce collagen breakdown in fibrous caps of atherosclerotic plaques. Potential role of matrix-degrading metalloproteinases and implications for plaque rupture. Circulation 92:1565–1569PubMed Shah PK, Falk E, Badimon JJ, Fernandez-Ortiz A, Mailhac A, Villareal-Levy G, Fallon JT, Regnstrom J, Fuster V (1995) Human monocyte-derived macrophages induce collagen breakdown in fibrous caps of atherosclerotic plaques. Potential role of matrix-degrading metalloproteinases and implications for plaque rupture. Circulation 92:1565–1569PubMed
20.
Zurück zum Zitat Xu XP, Meisel SR, Ong JM, Kaul S, Cercek B, Rajavashisth TB, Sharifi B, Shah PK (1999) Oxidized low-density lipoprotein regulates matrix metalloproteinase-9 and its tissue inhibitor in human monocyte-derived macrophages. Circulation 99:993–998CrossRefPubMed Xu XP, Meisel SR, Ong JM, Kaul S, Cercek B, Rajavashisth TB, Sharifi B, Shah PK (1999) Oxidized low-density lipoprotein regulates matrix metalloproteinase-9 and its tissue inhibitor in human monocyte-derived macrophages. Circulation 99:993–998CrossRefPubMed
21.
Zurück zum Zitat Nishi K, Itabe H, Uno M, Kitazato KT, Horiguchi H, Shinno K, Nagahiro S (2002) Oxidized LDL in carotid plaques and plasma associates with plaque instability. Arterioscler Thromb Vasc Biol 22:1649–1654CrossRefPubMed Nishi K, Itabe H, Uno M, Kitazato KT, Horiguchi H, Shinno K, Nagahiro S (2002) Oxidized LDL in carotid plaques and plasma associates with plaque instability. Arterioscler Thromb Vasc Biol 22:1649–1654CrossRefPubMed
22.
Zurück zum Zitat Uno M, Kitazato KT, Suzue A, Itabe H, Hao L, Nagahiro S (2005) Contribution of an imbalance between oxidant-antioxidant systems to plaque vulnerability in patients with carotid artery stenosis. J Neurosurg 103:518–525CrossRefPubMed Uno M, Kitazato KT, Suzue A, Itabe H, Hao L, Nagahiro S (2005) Contribution of an imbalance between oxidant-antioxidant systems to plaque vulnerability in patients with carotid artery stenosis. J Neurosurg 103:518–525CrossRefPubMed
23.
Zurück zum Zitat Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith SC Jr, Watson K, Wilson PW, American College of Cardiology/American Heart Association Task Force on Practice Guidelines (2014) 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 63:2889–2934CrossRefPubMed Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith SC Jr, Watson K, Wilson PW, American College of Cardiology/American Heart Association Task Force on Practice Guidelines (2014) 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 63:2889–2934CrossRefPubMed
24.
Zurück zum Zitat Catapano AL, Graham I, De Backer G, Wiklund O, Chapman MJ, Drexel H, Hoes AW, Jennings CS, Landmesser U, Pedersen TR, Reiner Ž, Riccardi G, Taskinen MR, Tokgozoglu L, Verschuren WM, Vlachopoulos C, Wood DA, Zamorano JL, Authors/Task Force Members; Additional Contributor (2016) 2016 ESC/EAS guidelines for the management of dyslipidaemias. Eur Heart J 37:2999–3058CrossRefPubMed Catapano AL, Graham I, De Backer G, Wiklund O, Chapman MJ, Drexel H, Hoes AW, Jennings CS, Landmesser U, Pedersen TR, Reiner Ž, Riccardi G, Taskinen MR, Tokgozoglu L, Verschuren WM, Vlachopoulos C, Wood DA, Zamorano JL, Authors/Task Force Members; Additional Contributor (2016) 2016 ESC/EAS guidelines for the management of dyslipidaemias. Eur Heart J 37:2999–3058CrossRefPubMed
25.
Zurück zum Zitat Sachdeva A, Cannon CP, Deedwania PC, Labresh KA, Smith SC Jr, Dai D, Hernandez A, Fonarow GC (2009) Lipid levels in patients hospitalized with coronary artery disease: an analysis of 136,905 hospitalizations in Get With The Guidelines. Am Heart J 157:111–117CrossRefPubMed Sachdeva A, Cannon CP, Deedwania PC, Labresh KA, Smith SC Jr, Dai D, Hernandez A, Fonarow GC (2009) Lipid levels in patients hospitalized with coronary artery disease: an analysis of 136,905 hospitalizations in Get With The Guidelines. Am Heart J 157:111–117CrossRefPubMed
26.
Zurück zum Zitat Komukai K, Kubo T, Kitabata H, Matsuo Y, Ozaki Y, Takarada S, Okumoto Y, Shiono Y, Orii M, Shimamura K, Ueno S, Yamano T, Tanimoto T, Ino Y, Yamaguchi T, Kumiko H, Tanaka A, Imanishi T, Akagi H, Akasaka T (2014) Effect of atorvastatin therapy on fibrous cap thickness in coronary atherosclerotic plaque as assessed by optical coherence tomography: the EASY-FIT study. J Am Coll Cardiol 64:2207–2217CrossRefPubMed Komukai K, Kubo T, Kitabata H, Matsuo Y, Ozaki Y, Takarada S, Okumoto Y, Shiono Y, Orii M, Shimamura K, Ueno S, Yamano T, Tanimoto T, Ino Y, Yamaguchi T, Kumiko H, Tanaka A, Imanishi T, Akagi H, Akasaka T (2014) Effect of atorvastatin therapy on fibrous cap thickness in coronary atherosclerotic plaque as assessed by optical coherence tomography: the EASY-FIT study. J Am Coll Cardiol 64:2207–2217CrossRefPubMed
Metadaten
Titel
Impact of malondialdehyde-modified low-density lipoprotein on coronary plaque vulnerability in patients not receiving lipid-lowering therapy: a whole coronary analysis with multislice-computed tomography
verfasst von
Tsuyoshi Ito
Taku Ichihashi
Hiroshi Fujita
Tomonori Sugiura
Nobuyuki Ohte
Publikationsdatum
24.10.2017
Verlag
Springer Japan
Erschienen in
Heart and Vessels / Ausgabe 4/2018
Print ISSN: 0910-8327
Elektronische ISSN: 1615-2573
DOI
https://doi.org/10.1007/s00380-017-1074-4

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