Improving the relationship between coronary artery calcium score and coronary plaque burden: Addition of regional measures of coronary artery calcium distribution
Introduction
Coronary artery calcium (CAC) scoring has established utility in refining cardiovascular risk stratification among intermediate-risk patients [1] and in those in whom treatment decisions are uncertain [2]. This is thought to be the result of the strong association between the presence of CAC and the overall burden of coronary atherosclerosis [3], inclusive of non-calcified, mixed calcified and fully calcified coronary plaque.
Agatston et al. [4] developed the most commonly used method for calculating the burden of CAC in the late 1980s. The Agatston score involves multiplying the area of each individual calcified plaque by a factor derived from the maximal plaque density (CT attenuation) in Hounsfield Units, and then adding the values obtained for all coronary plaques identified. The Agatston CAC score is thus an aggregate score and does not account for the regional distribution of CAC. In addition, this method disproportionally weights increased coronary plaque density, meaning that heavily calcified plaque contributes more to the score than less calcified “mixed” plaque. Recent research has demonstrated that cardiovascular events may in fact be inversely related to plaque density, and probably more closely linked to total coronary plaque volume [5].
Characterizing the regional distribution of CAC may be important for two reasons. First, patients with more diffuse coronary artery disease (CAD) have worse cardiovascular outcomes when compared to patients with more focal CAD [6]. The PROSPECT study [7] demonstrated the importance of total plaque burden in predicting cardiovascular events, while a sub-study of the COURAGE trial noted the superiority of coronary plaque burden over ischemic burden in predicting the risk of myocardial infarction [8]. Furthermore, while highly dense local plaque may correlate with local coronary artery stenosis severity, focusing on coronary stenosis has the inherent potential to underestimate coronary plaque burden [9], due to the outward remodeling of coronary plaque, as originally described by Glagov et al. [10].
Whether accounting for regional CAC distribution improves the association of the Agatston CAC score with overall coronary atherosclerotic plaque burden has not been rigorously evaluated. We studied whether the addition of measures of increasingly diffuse CAC distribution improves the association of CAC scoring with overall coronary atherosclerotic plaque burden on concomitant coronary CT angiography (CCTA).
Section snippets
Study population
A total of 920 consecutive patients (93% symptomatic) who underwent multi-detector CT coronary angiography (CCTA) between January 2006 and December 2009 were included in this study. This is a cross-sectional study, the details of which have been previously published [11]. The institutional review board at the study institution approved the study, and patients' informed consent requirement was waived. Exclusion criteria were known CAD, iodine allergy, and chronic kidney disease (creatinine
Results
The mean age of the study population was 57 ± 12 years old, and 53% were female. The ethnic composition was 58% White, and 34% African American. A total of 93% were symptomatic, with 80% presenting with chest pain and 36% identifying dyspnea. There was a high prevalence of cardiovascular risk factors (Table 1, hypertension: 73%, diabetes mellitus 20%, hyperlipidemia 66%, smoking 17%, positive family history of premature CAD 33%). Of those who had prior stress testing performed (n = 421), 69%
Discussion
In this analysis of the regional distribution of CAC in relation to total atherosclerosis burden on CCTA, we demonstrated that while the Agatston CAC score is associated with total coronary plaque burden, measures of increasingly diffuse CAC distribution further stratify patients with an increased SIS, increasing the correlation of the Agatston CAC score with SIS on CCTA. The ability to improve the Agatston CAC score by adding measures of regional CAC distribution is inherent in the way the
Limitations
Our dataset did not allow a definition of total coronary plaque burden on CCTA defined by the volumetric analysis of plaque burden. While highly correlated with SIS, assessment of total plaque volume has been demonstrated to be a superior method of determining coronary atherosclerotic burden, and has a higher predictive value for acute coronary syndrome compared to luminal stenosis and Agatston CAC scoring [21]. Data on cardiovascular outcomes for this dataset is also not available to
Conclusion
Addition of regional measures of CAC, including the number of coronary arteries with CAC and a measure of concentrated versus diffuse CAC, provide a more accurate description of overall plaque burden than the absolute Agatston CAC score alone. Within the intermediate CAC score groups (1–100, 101–400), the number of CAC-positive coronary arteries improves the association with the overall coronary plaque burden on CCTA. Future studies are needed focusing on the prognostic importance of new
Author disclosures
None.
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2017, JACC: Cardiovascular ImagingCitation Excerpt :Additionally, the density score used here is only the average density for each participant, and range of density scores may also be important to consider. Another limitation is that traditional CAC scoring does not account for the location (proximal vs. distal, focal vs. diffuse) or dispersion of the density, which may also affect the risk for cardiovascular events (18–20). The inverse association of CAC density with incident CHD and CVD events is consistent across all levels of CAC volume, and across multiple strata of other risk variables.