Progression of coronary artery calcification at the crossroads: sign of progression or stabilization of coronary atherosclerosis?

Abstract

Coronary artery calcification (CAC) has been strongly established as an independent predictor of adverse events, with a significant incremental prognostic value over traditional risk stratification algorithms. CAC progression has been associated with a higher rate of events. In parallel, several randomized studies and meta-analysis have shown the effectiveness of statins to slow progression and even promote plaque regression. However, evidence regarding the effect of routine medical therapy on CAC has yielded conflicting results, with initial studies showing significant CAC regression, and contemporaneous data showing rather the opposite. Accordingly, there is currently a great controversy on whether progression of CAC is a sign of progression or stabilization of coronary artery disease (CAD). The finding of inexorable CAC progression despite the implementation of intensive contemporaneous medical therapy suggests that further understanding of this phenomenon should be undertaken before the implementation of CAC as a surrogate endpoint for longitudinal studies, or for prospective follow-up of patients under routine medical treatment.

Keywords: Prognostic value; atherothrombosis; imaging; longitudinal studies; statin.

Figure 1

Hypothetical case-scenario of a 55-year-old asymptomatic male with hypercholesterolemia. At baseline, he had a CAC score of 120 (82^th percentile). After three years, the patient remained asymptomatic, with normal lipid profile since lipid-lowering therapy with statins was implemented. At follow-up, a significant progression of CAC was observed (CAC 190, annual increase 19%). Paradoxically, the same CAC at follow-up can both be related to a significant plaque progression, or to plaque mineralization as an expression of stabilization. Likewise, although CAC at any time point is a robust independent predictor of events, it can reflect conflicting interpretations (i.e., in two patients with the same CAC and CAC percentile; one can indicate extensive plaque burden with multiple spotty and focal calcifications, and the other can represent stable fibrocalcific plaques). This example represents the limitations of CAC for longitudinal assessments, particularly if plaque stabilization systemic therapies are initiated. CAC, coronary artery calcium.