Association between plaque localization in proximal coronary segments and MACE outcomes in patients with mild CAC: Results from the EISNER study

Ramyashree Tummala, Donghee Han, John Friedman, Sean Hayes, Louise Thomson, Heidi Gransar, Piotr Slomka, Alan Rozanski, Damini Dey, Daniel Berman, Ramyashree Tummala, Donghee Han, John Friedman, Sean Hayes, Louise Thomson, Heidi Gransar, Piotr Slomka, Alan Rozanski, Damini Dey, Daniel Berman

Abstract

Objective: Coronary artery calcium score (CAC) is a validated tool to predict and reclassify cardiovascular risk. Additional metrics such as regional distribution and extent of CAC over Agatston CAC score may allow further risk stratification. In this study, we evaluate the prognostic significance of proximal CAC involvement in asymptomatic population from the prospective EISNER (Early-Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) registry, focusing on patients with mild CAC (score 1-99).

Methods: This study included a total of 2,047 adult asymptomatic subject who underwent baseline CAC scan and 14-year follow-up for MACE, defined as myocardial infarction, late revascularization, or cardiac death. Proximal involvement was defined as presence of CAC in the LM, proximal LAD, LCX or RCA. CAC was categorized as 0, 1-99, and ≥100.

Results: 1,090 (53.2%) subjects had no CAC, 576 (28.1%) had CAC 1-99, and 381 (18.7%) had CAC ≥100. Proximal involvement was seen in 67.2% of subjects with CAC 1-99 and 97.3% of subjects with CAC ≥100. In the CAC 1-99 category, the presence of proximal CAC was associated with increased MACE risk after adjustment for CAC score, CAC extent and conventional risk factors compared to those without proximal CAC (HR: 2.84 95% CI: 1.29-6.25, p=0.009).

Conclusion: In asymptomatic subjects with CAC scores of 1-99, the presence and extent of proximal CAC plaques provides strong independent prognostic information in predicting MACE.

Keywords: ASCVD, 10-year risk atherosclerotic cardiovascular disease score; BMI, body mass index; CAC, Coronary artery calcium; CAD, coronary artery disease; CVD, cardiovascular disease; Computed tomography; Coronary artery calcium; Coronary artery disease; EISNER, Early Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research; HDL, high-density lipoprotein; HR, hazard ratio; LAD, left anterior descending artery; LCX, left circumflex artery; LDL, low-density lipoprotein; LM, left main; MACE, major adverse cardiac events; NRI, net classification index; Plaque location; Prognosis; RCA, right coronary artery.

Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper

© 2022 Published by Elsevier B.V.

Figures

Fig. 1
Fig. 1
Study flow. Abbreviations: CAC, coronary artery calcium; N, number of subjects; LM, left main; LAD, left anterior descending artery; LCx, left circumflex artery; RCA, right coronary artery
Fig. 2
Fig. 2
(Central illustration), Kaplan–Meier curve for MACE according to CAC score and proximal involvement. Abbreviations: MACE, major adverse cardiac events; CAC, coronary artery calcium

References

    1. Budoff MJ, Shaw LJ, Liu ST, Weinstein SR, Mosler TP, Tseng PH, Flores FR, Callister TQ, Raggi P, Berman DS. Long-term prognosis associated with coronary calcification: observations from a registry of 25,253 patients. J Am Coll Cardiol. 2007;49:1860–1870.
    1. Narula J, Chandrashekhar Y, Ahmadi A, Abbara S, Berman DS, Blankstein R, Leipsic J, Newby D, Nicol ED, Nieman K, Shaw L, Villines TC, Williams M, Hecht HS. SCCT 2021 expert consensus document on coronary computed tomographic angiography: a report of the society of cardiovascular computed tomography. J Cardiovasc Comput Tomogr. 2021;15:192–217.
    1. Detrano R, Guerci AD, Carr JJ, Bild DE, Burke G, Folsom AR, Liu K, Shea S, Szklo M, Bluemke DA, O'Leary DH, Tracy R, Watson K, Wong ND, Kronmal RA. Coronary calcium as a predictor of coronary events in four racial or ethnic groups. N Engl J Med. 2008;358:1336–1345.
    1. Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, Braun LT, de-Ferranti S, Faiella-Tommasino J, Forman DE, Goldberg R, Heidenreich PA, Hlatky MA, Jones DW, Lloyd-Jones D, Lopez-Pajares N, Ndumele CE, Orringer CE, Peralta CA, Saseen JJ, Smith SC, Jr., Sperling L, Virani SS, Yeboah J. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the american college of cardiology/american heart association task force on clinical practice guidelines. Circulation. 2019;139:e1082–e1143.
    1. Criqui MH, Knox JB, Denenberg JO, Forbang NI, McClelland RL, Novotny TE, Sandfort V, Waalen J, Blaha MJ, MA Allison. Coronary artery calcium volume and density: potential interactions and overall predictive value: the multi-ethnic study of atherosclerosis. JACC Cardiovasc Imaging. 2017;10:845–854.
    1. Lo-Kioeng-Shioe MS, Vavere AL, Arbab-Zadeh A, Schuijf JD, Rochitte CE, Chen MY, Rief M, Kofoed KF, Clouse ME, Scholte AJ, Miller JM, Betoko A, Blaha MJ, Cox C, Deckers JW, Lima JAC. Coronary calcium characteristics as predictors of major adverse cardiac events in symptomatic patients: insights from the core 320 multinational study. J Am Heart Assoc. 2019;8
    1. Blaha MJ, Mortensen MB, Kianoush S, Tota-Maharaj R, Cainzos-Achirica M. Coronary artery calcium scoring: is it time for a change in methodology? JACC Cardiovasc Imaging. 2017;10:923–937.
    1. Williams M, Shaw LJ, Raggi P, Morris D, Vaccarino V, Liu ST, Weinstein SR, Mosler TP, Tseng PH, Flores FR, Nasir K, Budoff M. Prognostic value of number and site of calcified coronary lesions compared with the total score. JACC Cardiovasc Imaging. 2008;1:61–69.
    1. Ferencik M, Pencina KM, Liu T, Ghemigian K, Baltrusaitis K, Massaro JM, D'Agostino RB, Sr., O'Donnell CJ, Hoffmann U. Coronary artery calcium distribution is an independent predictor of incident major coronary heart disease events: results from the framingham heart study. Circ Cardiovasc Imaging. 2017;10
    1. Han D, Chen B, Gransar H, Achenbach S, Al-Mallah MH, Budoff MJ, Cademartiri F, Maffei E, Callister TQ, Chinnaiyan K, Chow BJW, DeLago A, Hadamitzky M, Hausleiter J, Kaufmann PA, Villines TC, Kim YJ, Leipsic J, Feuchtner G, Cury RC, Pontone G, Andreini D, Marques H, Rubinshtein R, Chang HJ, Lin FY, Shaw LJ, Min JK, Berman DS. Prognostic significance of plaque location in non-obstructive coronary artery disease: from the CONFIRM registry. Eur heart j Cardiov Imaging. 2022;23:1240–1247.
    1. Han D, Lin A, Kuronuma K, Tzolos E, Kwan AC, Klein E, Andreini D, Bax JJ, Cademartiri F, Chinnaiyan K, Chow BJW, Conte E, Cury RC, Feuchtner G, Hadamitzky M, Kim YJ, Leipsic JA, Maffei E, Marques H, Plank F, Pontone G, Villines TC, Al-Mallah MH, de Araújo Gonçalves P, Danad I, Gransar H, Lu Y, Lee JH, Lee SE, Baskaran L, Al'Aref SJ, Yoon YE, Van Rosendael A, Budoff MJ, Samady H, Stone PH, Virmani R, Achenbach S, Narula J, Chang HJ, Min JK, Lin FY, Shaw LJ, Slomka PJ, Dey D, Berman DS. Association of plaque location and vessel geometry determined by coronary computed tomographic angiography with future acute coronary syndrome-causing culprit lesions. JAMA Cardiol. 2022;7:309–319.
    1. Eisenberg E, McElhinney PA, Commandeur F, Chen X, Cadet S, Goeller M, Razipour A, Gransar H, Cantu S, Miller RJH, Slomka PJ, Wong ND, Rozanski A, Achenbach S, Tamarappoo BK, Berman DS, Dey D. Deep learning-based quantification of epicardial adipose tissue volume and attenuation predicts major adverse cardiovascular events in asymptomatic subjects. Circ Cardiovasc Imaging. 2020;13
    1. Cheng VY, Dey D, Tamarappoo B, Nakazato R, Gransar H, Miranda-Peats R, Ramesh A, Wong ND, Shaw LJ, Slomka PJ, Berman DS. Pericardial fat burden on ECG-gated noncontrast CT in asymptomatic patients who subsequently experience adverse cardiovascular events. JACC Cardiovascular imaging. 2010;3:352–360.
    1. Rozanski A, Gransar H, Shaw LJ, Kim J, Miranda-Peats L, Wong ND, Rana JS, Orakzai R, Hayes SW, Friedman JD, Thomson LE, Polk D, Min J, Budoff MJ, Berman DS. Impact of coronary artery calcium scanning on coronary risk factors and downstream testing the EISNER (early identification of subclinical atherosclerosis by noninvasive imaging research) prospective randomized trial. J Am College Cardiol. 2011;57:1622–1632.
    1. Commandeur F, Slomka PJ, Goeller M, Chen X, Cadet S, Razipour A, McElhinney P, Gransar H, Cantu S, Miller RJH, Rozanski A, Achenbach S, Tamarappoo BK, Berman DS, Dey D. Machine learning to predict the long-term risk of myocardial infarction and cardiac death based on clinical risk, coronary calcium, and epicardial adipose tissue: a prospective study. Cardiovasc Res. 2020;116:2216–2225.
    1. Khera R, Pandey A, Ayers CR, Carnethon MR, Greenland P, Ndumele CE, Nambi V, Seliger SL, Chaves PHM, Safford MM, Cushman M, Xanthakis V, Vasan RS, Mentz RJ, Correa A, Lloyd-Jones DM, Berry JD, de Lemos JA, IJ Neeland. Performance of the pooled cohort equations to estimate atherosclerotic cardiovascular disease risk by body mass index. JAMA Netw Open. 2020;3
    1. Lin A, Wong ND, Razipour A, McElhinney PA, Commandeur F, Cadet SJ, Gransar H, Chen X, Cantu S, Miller RJH, Nerlekar N, Wong DTL, Slomka PJ, Rozanski A, Tamarappoo BK, Berman DS, Dey D. Metabolic syndrome, fatty liver, and artificial intelligence-based epicardial adipose tissue measures predict long-term risk of cardiac events: a prospective study. Cardiovasc Diabetol. 2021;20:27.
    1. Leipsic J, Abbara S, Achenbach S, Cury R, Earls JP, Mancini GJ, Nieman K, Pontone G, Raff GL. SCCT guidelines for the interpretation and reporting of coronary ct angiography: a report of the society of cardiovascular computed tomography guidelines committee. J Cardiovasc Comput Tomogr. 2014;8:342–358.
    1. Blaha MJ, Budoff MJ, Tota-Maharaj R, Dardari ZA, Wong ND, Kronmal RA, Eng J, Post WS, Blumenthal RS, Nasir K. Improving the CAC score by addition of regional measures of calcium distribution: multi-ethnic study of atherosclerosis. JACC Cardiovascular imaging. 2016;9:1407–1416.
    1. Pencina MJ, D'Agostino RB, Sr., Steyerberg EW. Extensions of net reclassification improvement calculations to measure usefulness of new biomarkers. Stat Med. 2011;30:11–21.
    1. Adelhoefer S, Uddin SMI, Osei AD, Obisesan OH, Blaha MJ, Dzaye O. Coronary artery calcium scoring: new insights into clinical interpretation-lessons from the cac consortium. Radiol Cardiothorac Imaging. 2020;2
    1. Hoffmann U, Massaro JM, D'Agostino RB, Sr., Kathiresan S, Fox CS, O'Donnell CJ. Cardiovascular event prediction and risk reclassification by coronary, aortic, and valvular calcification in the framingham heart study. J Am Heart Assoc. 2016;5
    1. Arnson Y, Rozanski A, Gransar H, Friedman JD, Hayes SW, Thomson LE, Tamarappoo B, Slomka P, Wang F, Germano G, Dey D, Berman DS. Comparison of the coronary artery calcium score and number of calcified coronary plaques for predicting patient mortality risk. Am J Cardiol. 2017;120:2154–2159.
    1. Lahti SJ, Feldman DI, Dardari Z, Mirbolouk M, Orimoloye OA, Osei AD, Graham G, Rumberger J, Shaw L, Budoff MJ, Rozanski A, Miedema MD, Al-Mallah MH, Berman D, Nasir K, Blaha MJ. The association between left main coronary artery calcium and cardiovascular-specific and total mortality: the coronary artery calcium consortium. Atherosclerosis. 2019;286:172–178.
    1. Tota-Maharaj R, Joshi PH, Budoff MJ, Whelton S, Zeb I, Rumberger J, Al-Mallah M, Blumenthal RS, Nasir K, Blaha MJ. Usefulness of regional distribution of coronary artery calcium to improve the prediction of all-cause mortality. Am J Cardiol. 2015;115:1229–1234.
    1. Mushtaq S, De Araujo Goncalves P, Garcia-Garcia HM, Pontone G, Bartorelli AL, Bertella E, Campos CM, Pepi M, Serruys PW, Andreini D. Long-term prognostic effect of coronary atherosclerotic burden: validation of the computed tomography-Leaman score. Circ Cardiovasc Imaging. 2015;8
    1. Bax AM, Yoon YE, Gianni U, Ma X, Lu Y, Lee BC, Goebel B, Han D, Lee SE, Sung JM, Andreini D, Al-Mallah MH, Budoff MJ, Cademartiri F, Chinnaiyan K, Choi JH, Chun EJ, Conte E, Gottlieb I, Hadamitzky M, Kim YJ, Lee BK, Leipsic JA, Maffei E, Marques H, Goncalves PA, Pontone G, Shin S, Narula J, Lin FY, Shaw LJ, HJ Chang. Plaque character and progression according to the location of coronary atherosclerotic plaque. Am J Cardiol. 2021;158:15–22.

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