Atherosclerotic Plaque Characteristics and Coronary Lesions That Cause Ischemia

Posted On 2015-03-03 18:02:38

A study in the January 2015 issue of JACC Imaging describes the association between atherosclerotic plaque characteristics (APCs) assessed by coronary computed tomographic angiography (CTA) and lesion ischemia defined by fractional flow reserve (FFR). (1) The data is derived from the ‘Determination of Fractional Flow Reserve by Anatomic Computed Tomographic Angiography’ trial ( NCT01233518) (2). Although APCs by CTA-including aggregate plaque volume % (%APV), positive remodeling (PR), low attenuation plaque (LAP), and spotty calcification (SC)-are associated with future coronary syndromes (3), their relationship to lesion ischemia is incompletely understood.

Inthe reported multi-center data, 252 patients (mean age 63 years; 71% males)underwent coronary CTA, with FFR performed for 407 coronary lesions. CoronaryCTA was interpreted for <50% and ≥50% stenosis, with the latterconsidered obstructive. APCs by coronary CTA were defined as: 1) PR, lesiondiameter/reference diameter >1.10; 2) LAP, any voxel <30 Hounsfieldunits; and 3) SC, nodular calcified plaque <3 mm. Odds ratios (OR)and net reclassification improvement of APCs for lesion ischemia, definedby FFR ≤0.8, were analyzed.

By FFR, ischemia was present in 151 lesions (37%). %APV was associated with a 50% increased risk of ischemia per 5% additional APV. PR, LAP, and SC were associated with ischemia, with a 3 to 5 times higher prevalence than in non-ischemic lesions. In multivariable analyses, a stepwise increased risk of ischemia was observed for 1 (OR: 4.0, p < 0.001) and ≥2 (OR: 12.1, p < 0.001) APCs. These findings were APC dependent, with PR (OR: 5.3, p < 0.001) and LAP (OR: 2.1, p = 0.038) associated with ischemia, but not SC. When examined by stenosis severity, PR remained a predictor of ischemia for all lesions, whereas %APV and LAP were associated with ischemia for only ≥50%, but not for <50%, stenosis.

In summary, %APV and APCs identified by coronary CTA improved identification of coronary lesions that cause ischemia. PR is associated with all ischemia-causing lesions, whereas %APV and LAP are only associated with ischemia-causing lesions ≥50%.

Two editorials in JACC Imaging comment on this paper. (4,5)

In a previous paper, published in JACC in 2013, this group of authors examined the performance of percent aggregate plaque volume (%APV) by coronary computed tomography angiography (CTA) for identification of ischemic lesion of intermediate stenosis severity. (6)

In this study 58 patients with intermediate lesions (30% to 69% diameter stenosis) were identified, who underwent invasive angiography and fractional flow reserve. Coronary CTA measures included diameter stenosis, area stenosis, minimal lumen diameter (MLD), minimal lumen area (MLA) and %APV. %APV was defined as the sum of plaque volume divided by the sum of vessel volume from the ostium to the distal portion of the lesion. Fractional flow reserve ≤ 0.80 was considered diagnostic of lesion-specific ischemia. Area under the receiver operating characteristic curve and net reclassification improvement (NRI) were also evaluated.

Twenty-two of 58 lesions (38%) caused ischemia. Compared with nonischemic lesions, ischemic lesions had smaller MLD (1.3 vs. 1.7 mm, p = 0.01), smaller MLA (2.5 vs. 3.8 mm(2), p = 0.01), and greater %APV (48.9% vs. 39.3%, p < 0.0001). Area under the receiver operating characteristic curve was highest for %APV (0.85) compared with diameter stenosis (0.68), area stenosis (0.66), MLD (0.75), or MLA (0.78). Addition of %APV to other measures showed significant reclassification over diameter stenosis (NRI 0.77, p < 0.001), area stenosis (NRI 0.63, p = 0.002), MLD (NRI 0.62, p = 0.001), and MLA (NRI 0.43, p = 0.01).

Compared with diameter stenosis, area stenosis, MLD, and MLA, %APV by coronary CTA improved identification, discrimination, and reclassification of ischemic lesions of intermediate stenosis severity.

Two editorials in the February issue of CDT discusse this paper (7,8)

These paper add to our understanding of the relationship of coronary anatomy and physiology, which has been discussed for the last few decades. (9)


  1. Park HB, Heo R, Ó Hartaigh B, Cho I, Gransar H, Nakazato R, Leipsic J, Mancini GB, Koo BK, Otake H, Budoff MJ, Berman DS, Erglis A, Chang HJ, Min JK. Atherosclerotic Plaque Characteristics by CT Angiography Identify Coronary Lesions That Cause Ischemia: A Direct Comparison to Fractional Flow Reserve. JACC Cardiovasc Imaging. 2015;8:1-10. 
  2. Min JK, Leipsic J, Pencina MJ, Berman DS, Koo BK, van Mieghem C, Erglis A, Lin FY, Dunning AM, Apruzzese P, Budoff MJ, Cole JH, Jaffer FA, Leon MB, Malpeso J, Mancini GB, Park SJ, Schwartz RS, Shaw LJ, Mauri L. Diagnostic accuracy of fractional flow reserve from anatomic CT angiography. JAMA. 2012;308:1237-45.
  3. 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. Computed tomographic angiography characteristics of atherosclerotic plaques subsequently resulting in acute coronary syndrome. J Am Coll Cardiol. 2009 Jun 30;54(1):49-57.
  4. Colombo A, Panoulas VF. Diagnostic coronary angiography is getting old! JACC Cardiovasc Imaging. 2015;8:11-3.
  5. Ahmadi A, Kini A, Narula J Discordance Between Ischemia and Stenosis, or PINSS and NIPSS: Are We Ready for New Vocabulary?. JACC Cardiovasc Imaging. 2015;8:111-4.
  6. Nakazato R, Shalev A, Doh JH, Koo BK, Gransar H, Gomez MJ, Leipsic J, Park HB, Berman DS, Min JK Aggregate plaque volume by coronary computed tomography angiography is superior and incremental to luminal narrowing for diagnosis of ischemic lesions of intermediate stenosis severity. J Am Coll Cardiol. 2013;62:460-7. 
  7. Liu Y, Chow BJ, Dwivedi G. Computed tomography quantification of coronary plaque volume may provide further perspective on intermediate severity stenoses. Cardiovasc Diagn Ther 2015. doi: 10.3978/j.issn.2223-3652.2015.01.09
  8. Abd TT, George RT. Association of coronary plaque burden with fractional flow reserve: should we keep attempting to derive physiology from anatomy? Cardiovasc Diagn Ther 2014. doi: 10.3978/j.issn.2223-3652.2015.01.07
  9. Topol EJ, Nissen SE. Our preoccupation with coronary luminology. The dissociation between clinical and angiographic findings in ischemic heart disease. Circulation. 1995;92:2333-42