Coronary plaque characteristics and CAC score in relation to CHD risk in CAD patients
Coronary Artery Plaque Characteristics Associated With Adverse Outcomes in the SCOT-HEART Study
Introduction and methods
Non-invasive imaging with coronary computed tomography angiography (CTA) can provide structural information of the coronary artery wall. Presence and constituents of atherosclerotic plaque can be assessed, even in the absence of flow-limiting disease. Positive remodeling, low attenuation plaque, spotty calcification, and the “napkin ring” sign can be determined on coronary CTA, which have been described to serve as correlates for adverse plaque characteristics, such as a large necrotic core, microcalcification and a thin fibrous cap. These plaque characteristics are associated with an increased risk of subsequent acute coronary syndromes (ACS) [1-3].
Use of coronary CTA on top of routine care has been shown to improve diagnostic certainty and patient care in patients with stable chest pain in the COmputed Tomography of the HEART (SCOT-HEART). This lead to a reduced rate of coronary heart disease (CHD) death or non-fatal myocardial infarction (MI) [4-6]. However, it remains unknown whether further risk stratification and targeted intensification of therapy can result in additional benefits in patients with adverse plaque characteristics.
This secondary post-hoc analysis (n=1.769) of the SCOT-HEART trial determined the extent of adverse coronary artery plaque characteristics on coronary CTA and their association with subsequent clinical outcomes. The SCOT-HEART trial was a multicenter controlled trial of coronary CTA in outpatients (n=2.073) with suspected angina pectoris due to CAD. Participants were randomized to standard care or coronary CTA on top of standard care and followed for five years . CV risk was assessed using the ASSIGN score, a score validated for the Scottish population . Coronary artery calcium (CAC) score was assessed on non-contrast computed tomography (CT) using the Agatston scoring method. Coronary arteries were characterized based on stenosis severity: normal, non-obstructive, or obstructive. For each of 15 coronary segments the presence or absence of the following characteristics was assessed: positive remodeling, low attenuation plaque, spotty calcification, and the “napkin ring” sign. An individual adverse plaque was defined as one with positive remodeling or low-attenuation plaque. The primary clinical endpoint was the occurrence of CHD death or non-fatal MI.
- Out of 26.535 analyzed segments of 1.769 patients, positive remodeling was seen in 1.163 segments (4.4%), low attenuation plaque in 213 (0.8%), spotty calcification in 472 (1.8%) and the napkin ring sign in 78 segments (0.3%).
- 608 (34%) patients had adverse plaques. These patients had a higher CV risk score and higher calcium score. CHD death or non-fatal MI was observed three times more often in patients with ≥1 adverse plaque, compared to those without adverse plaques (4.1% vs. 1.4%, P<0.001; HR: 3.01, 95%CI: 1.61-5.63, P=0.001).
- Presence of spotty calcification or the napkin ring sign was not associated with outcomes.
- Most events were seen in those with adverse plaques in the proximal segments rather than the mid and distal segments (4.7% vs. 1.7%, P=0.197).
Coronary artery stenosis
- Patients with obstructive CAD had a two-fold higher risk to experience CHD death or non-fatal MI (4.9% vs. 2.4%, P=0.024; HR: 1.99, 95%CI: 1.05-3.79, P=0.036), compared to those with non-obstructive CAD.
- Adverse plaques were seen in 40% (268/671) of patients with non-obstructive CAD and in 75% (340/452) of patients with obstructive CAD.
- At year 5, similar outcomes were seen for patients with non-obstructive CAD and obstructive CAD without adverse plaque (HR: 4.95, 95%CI: 1.34-18.29, P=0.016 and HR: 7.73, 95%CI: 1.73-34.54, P=0.007), compared to those with normal coronary arteries.
- Compared with patients with normal coronary arteries, patients with obstructive CAD and
adverse plaque had a >10-fold increased rate of CHD death or nonfatal MI at 5 years (HR: 11.50, 95%CI: 3.39-39.04, P<0.001).
Coronary artery calcium score
- In patients with a CAC score ≥1.000 Agatston units (AU), risk for CHD death or non-fatal MI was 13-fold higher, compared with those without coronary artery calcification. Overall, calcification was positively associated with increasing risk for CHD death or non-fatal MI.
- In patients with obstructive CAD, an 8-fold higher CAC score was found, compared to those with non-obstructive CAD (435 AU [IQR: 138-1.127 AU] vs. 54 AU [IQR: 12-190 AU], P<0.001).
- In multivariable analysis, CAC score was the only statistically significant predictor of CHD death or non-fatal MI (HR: 1.17, 95%CI: 1.04-1.33).
- The risk for events did not differ in those with vs. without adverse plaque who had a CAC score >100 AU.
- In those with a CAC score <100 AU, an increased risk of CHD death or non-fatal MI was observed in those with adverse plaque, compared to those without adverse plaque (HR: 3.38, 95%CI: 1.13-10.08, P=0.03).
This post-hoc analysis of the SCOT-HEART trial demonstrated that adverse coronary plaque characteristics on coronary CTA provide prognostic information on adverse events up to five years in outpatients with suspected angina pectoris due to CAD. Although these findings suggest that plaque composition and its hemodynamic consequences are associated with future MI, the main factor governing patient outcomes appears to be the burden of coronary atherosclerosis. Patients with obstructive CAD and adverse plaques showed the highest rates of CHD death and non-fatal MI during follow-up, suggesting the identification of a subgroup of patients who would benefit from more intensive medical therapy.
In their editorial comment , Shaw et al. discuss several interesting lessons that emerged from the secondary analysis conducted by Williams et al..
The observation that the presence of adverse plaque characteristics was associated with risk of CHD death or nonfatal MI in univariable analysis, but that this was no longer a significant relation in a multivariable model, remind us that plaque vulnerability does not equal patient vulnerability. Multiple factors influence plaque burden, and the dynamic interplay of all these factors and their effect on CV event risk is difficult to assess. The data showed that adverse plaque was predictive at 2 years, but not at 5 years of follow-up, in line with the previously described concept of a temporal nature of risk. Disease progression and intervening therapeutic intervention can attenuate the prognostic relationship between a factor and outcomes.
A notable finding of the SCOT-HEART trial was that CAC was predictive of CHD outcomes in models in which the presence of obstructive CAD and markers of adverse plaque were not. The authors note that that CAC score reflects the overall burden of atherosclerosis and is thus a major determinant of risk. The data obtained in those with minimal CAC showed an ˜3-fold increased risk of CAD events. Thus, the data support the role of CAC scanning alone as a means for selective use of CTA, especially in those categorized with a low pre-test risk score.
The authors conclude that with the ability to perform whole-heart atherosclerosis quantification and characterization by non-invasive imaging, we can learn to understand CAD risk better based on diverse atherosclerotic-disease markers in large clinical populations. It is important to pay attention to the dynamicity rather than the cross-sectional characteristics of the plaques. “We have so much more to learn about atherosclerosis and patient vulnerability.”