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Frequency of Cholesterol Crystals in Culprit Coronary Artery Aspirate During Acute Myocardial Infarction and Their Relation to Inflammation and Myocardial Injury

      Cholesterol crystals (CCs) have been associated with plaque rupture through mechanical injury and inflammation. This study evaluated the presence of CCs during acute myocardial infarction (AMI) and associated myocardial injury, inflammation, and arterial blood flow before and after percutaneous coronary intervention. Patients presenting with AMI (n = 286) had aspiration of culprit coronary artery obstruction. Aspirates were evaluated for crystal content, size, composition, and morphology by scanning electron microscopy, crystallography, and infrared spectroscopy. These were correlated with inflammatory biomarkers, cardiac enzymes, % coronary stenosis, and Thrombolysis in Myocardial Infarction (TIMI) blush and flow grades. Crystals were detected in 254 patients (89%) and confirmed to be cholesterol by spectroscopy. Of 286 patients 240 (84%) had CCs compacted into clusters that were large enough to be measured and analyzed. Moderate to extensive CC content was present in 172 cases (60%). Totally occluded arteries had significantly larger CC clusters than partially occluded arteries (p <0.05). Patients with CC cluster area >12,000 µm2 had significantly elevated interleukin-1 beta (IL-1β) levels (p <0.01), were less likely to have TIMI blush grade of 3 (p <0.01), and more likely to have TIMI flow grade of 1 (p <0.01). Patients with recurrent AMI had smaller CC cluster area (p <0.04), lower troponin (p <0.02), and IL-1β levels (p <0.04). Women had smaller CC clusters (p <0.04). Macrophages in the aspirates were found to be attached to CCs. Coronary artery aspirates had extensive deposits of CCs during AMI. In conclusion, presence of large CC clusters was associated with increased inflammation (IL-1β), increased arterial narrowing, and diminished reflow following percutaneous coronary intervention.
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      References

        • Martinon F.
        • Pétrilli V.
        • Mayor A.
        • Tardivel A.
        • Tschopp J.
        Gout-associated uric acid crystals activate the NALP3 inflammasome.
        Nature. 2006; 440: 237-241
        • Rege R.V.
        • Prystowsky J.B.
        Inflammation and a thickened mucus layer in mice with cholesterol gallstones.
        J Surg Res. 1998; 74: 81-85
        • Okada A.
        • Yasui T.
        • Fujii Y.
        • Niimi K.
        • Hamamoto S.
        • Hirose M.
        • Kojima Y.
        • Itoh Y.
        • Tozawa K.
        • Hayashi Y.
        • Kohri K.
        Renal macrophage migration and crystal phagocytosis via inflammatory-related gene expression during kidney stone formation and elimination in mice: detection by association analysis of stone-related gene expression and microstructural observation.
        J Bone Miner Res. 2010; 25: 2701-2711
        • Düwell P.
        • Kono H.
        • Rayner K.J.
        • Sirois C.M.
        • Vladimer G.
        • Bauernfeind F.
        • Abela G.S.
        • Franchi L.
        • Nunez G.
        • Schnurr M.
        • Espevik T.
        • Lien G.
        • Fitzgerald K.A.
        • Rock K.L.
        • Moore K.J.
        • Wright S.D.
        • Hornung V.
        • Latz E.
        NLRP3 Inflammasomes are required for atherogenesis and activated by cholesterol crystals that form early in disease.
        Nature. 2010; 464: 1357-1362
        • Abela G.S.
        • Aziz K.
        Cholesterol crystals rupture biological membranes and human plaques during acute cardiovascular events: a novel insight into plaque rupture by scanning electron microscopy.
        Scanning. 2006; 28: 1-10
        • Abela G.S.
        • Aziz K.
        • Vedre A.
        • Pathak D.
        • Talbott J.D.
        • DeJong J.
        Effect of cholesterol crystals on plaques and intima in arteries of patients with acute coronary and cerebrovascular syndromes.
        Am J Cardiol. 2009; 103: 959-968
        • Dai J.
        • Tian J.
        • Hou J.
        • Xing L.
        • Liu S.
        • Ma L.
        • Yu H.
        • Ren X.
        • Dong N.
        • Yu B.
        Association between cholesterol crystals and culprit lesion vulnerability in patients with acute coronary syndrome: an optical coherence tomography study.
        Atherosclerosis. 2016; 247: 111-117
        • Kleinbongard P.
        • Konorza T.
        • Böse D.
        • Baars T.
        • Haude M.
        • Erbel R.
        • Heusch G.
        Lessons from human coronary aspirate.
        J Mol Cell Cardiol. 2012; 52: 890-896
        • Thygesen K.
        • Alpert J.S.
        • Jaffe A.S.
        • Simoons M.L.
        • Chaitman B.R.
        • White H.D.
        The Writing Group on behalf of the Joint ESC/ACCF/AHA/WHF Task Force for the Universal Definition of Myocardial Infarction Third Universal Definition of Myocardial Infarction.
        Circulation. 2012; 126: 2020-2035
        • Gadeela N.
        • Rubinstein J.
        • Tamhane U.
        • Huang R.
        • Pathak D.R.
        • Hosein H.A.
        • Rich M.
        • Dhar G.
        • Abela G.S.
        The impact of circulating cholesterol crystals on vasomotor function: implications for no-reflow phenomenon.
        JACC Cardiovasc Interv. 2011; 4: 521-529
        • Gibson C.M.
        • Cannon C.P.
        • Murphy S.A.
        • Marble S.J.
        • Barron H.V.
        • Braunwald E.
        • TIMI Study Group
        Relationship of the TIMI myocardial perfusion grades, flow grades, frame count, and percutaneous coronary intervention to long-term outcomes after thrombolytic administration in acute myocardial infarction.
        Circulation. 2002; 105: 1909-1913
        • Everitt B.S.
        Isolating sources of association in r x c tables.
        in: The Analysis of Contingency Tables. 2nd ed. Chapman and Hall, New York, NY1992: 41-48
        • Colafrancesco S.
        • Priori R.
        • Alessandri C.
        • Perricone C.
        • Pendolino M.
        • Picarelli G.
        • Valesini G.
        IL-18 serum level in adult onset Still's disease: a marker of disease activity.
        Int J Inflam. 2012; 2012: 156890https://doi.org/10.1155/2012/156890
        • Hollenshorst R.W.
        Vascular status of patients who have cholesterol emboli in the retina.
        Am J Ophthalmol. 1966; 61: 1159-1165
        • Falanga V.
        • Fine M.J.
        • Kapoor W.N.
        The cutaneous manifestations of cholesterol crystal embolization.
        Arch Dermatol. 1986; 122: 1194-1198
        • Edwards M.S.
        • Corriere M.A.
        • Craven T.E.
        • Pan X.M.
        • Rapp J.H.
        • Pearce J.D.
        • Mertaugh N.B.
        • Hansen K.J.
        Atheroembolism during percutaneous renal artery revascularization.
        J Vasc Surg. 2007; 46: 55-61
        • Laloux P.
        • Brucher J.M.
        Lacunar infarctions due to cholesterol emboli.
        Stroke. 1991; 22: 1440-1444
        • Niccoli G.
        • Scalone G.
        • Lerman A.
        • Crea F.
        Coronary microvascular obstruction in acute myocardial infarction.
        Eur Heart J. 2016; 37: 1024-1033
        • Pervaiz M.H.
        • Durga S.
        • Janoudi A.
        • Berger K.
        • Abela G.S.
        PET/CTA detection of muscle inflammation related to cholesterol crystal emboli without arterial obstruction.
        J Nucl Cardiol. 2017; https://doi.org/10.1007/s12350-017-0826-y
        • Ørn S.
        • Ueland T.
        • Manhenke C.
        • Sandanger Ø.
        • Godang K.
        • Yndestad A.
        • Mollnes T.E.
        • Dickstein K.
        • Aukrust P.
        Increased interleukin-1β levels are associated with left ventricular hypertrophy and remodeling following acute ST segment elevation myocardial infarction treated by primary percutaneous coronary intervention.
        J Intern Med. 2012; 272: 267-276
        • Ridker P.M.
        • Thuren T.
        • Zalewski A.
        • Libby P.
        Interleukin-1β inhibition and the prevention of recurrent cardiovascular events: rationale and design of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS).
        Am Heart J. 2011; 162: 597-605
        • Ridker P.M.
        • Everett B.M.
        • Thuren T.
        • MacFadyen J.G.
        • Chang W.H.
        • Ballantyne C.
        • Fonseca F.
        • Nicolau J.
        • Koenig W.
        • Anker S.D.
        • Kastelein J.J.P.
        • Cornel J.H.
        • Pais P.
        • Pella D.
        • Genest J.
        • Cifkova R.
        • Lorenzatti A.
        • Forster T.
        • Kobalava Z.
        • Vida-Simiti L.
        • Flather M.
        • Shimokawa H.
        • Ogawa H.
        • Dellborg M.
        • Rossi P.R.F.
        • Troquay R.P.T.
        • Libby P.
        • Glynn R.J.
        • CANTOS Trial Group
        Antiinflammatory therapy with Canakinumab for atherosclerotic disease.
        N Engl J Med. 2017; https://doi.org/10.1056/NEJMoa1707914
        • Everett B.M.
        • Pradhan A.D.
        • Solomon D.H.
        • Paynter N.
        • Macfadyen J.
        • Zaharris E.
        • Gupta M.
        • Clearfield M.
        • Libby P.
        • Hasan A.A.
        • Glynn R.J.
        • Ridker P.M.
        Rationale and design of the Cardiovascular Inflammation Reduction Trial: a test of the inflammatory hypothesis of atherothrombosis.
        Am Heart J. 2013; 166: 199-207
        • Nidorf S.M.
        • Eikelboom J.W.
        • Thompson P.L.
        Targeting cholesterol crystal-induced inflammation for the secondary prevention of cardiovascular disease.
        J Cardiovasc Pharmacol Ther. 2014; 19: 45-52
        • Patel R.
        • Janoudi A.
        • Vedre A.
        • Aziz K.
        • Tamhane U.
        • Rubinstein J.
        • Abela O.
        • Berger K.
        • Abela G.S.
        Plaque rupture and thrombosis are reduced by lowering cholesterol levels and crystallization with ezetimibe and are correlated with fluorodeoxyglucose positron emission tomography.
        Arterioscler Thromb Vasc Biol. 2011; 31: 2007-2014
        • Loomis C.R.
        • Shipley G.G.
        • Small D.M.
        The phase behavior of hydrated cholesterol.
        J Lipid Res. 1979; 20: 525-535
        • Nasiri M.
        • Janoudi A.
        • Vanderberg A.
        • Frame M.
        • Flegler C.
        • Flegler S.
        • Abela G.S.
        Role of cholesterol crystals in atherosclerosis is unmasked by altering tissue preparation methods.
        Microsc Res Tech. 2015; 78: 969-974
        • Patetsios P.
        • Song M.
        • Shutze W.P.
        • Pappas C.
        • Rodino W.
        • Ramirez J.A.
        • Panetta T.F.
        Identification of uric acid and xanthine oxidase in atherosclerotic plaque.
        Am J Cardiol. 2001; 88: 188-191
        • Berge K.E.
        • Tian H.
        • Graf G.A.
        • Yu L.
        • Grishin N.V.
        • Schultz J.
        • Kwiterovich P.
        • Shan B.
        • Barnes R.
        • Hobbs H.H.
        Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters.
        Science. 2000; 290: 1771-1775
        • Keeley E.C.
        • Grines C.L.
        Scraping of aortic debris by coronary guiding catheters: a prospective evaluation of 1,000 cases.
        J Am Coll Cardiol. 1998; 32: 1861-1865