Elsevier

Atherosclerosis

Volume 229, Issue 1, July 2013, Pages 124-129
Atherosclerosis

Coronary calcification identifies the vulnerable patient rather than the vulnerable Plaque

https://doi.org/10.1016/j.atherosclerosis.2013.03.010Get rights and content

Highlights

  • Unstable coronary plaques showed a significantly lower degree of calcification compared to stable plaques.

  • An inverse correlation was present between extension of calcification and degree of cap inflammation.

  • CAC score identifies the vulnerable patient rather than the vulnerable plaque.

Abstract

Objective

Presence of coronary artery calcium (CAC) is associated with a high risk of adverse cardiovascular outcomes. Nevertheless, although CAC is a marker of atherosclerosis it is still uncertain whether CAC is a marker of plaque vulnerability. Therefore, the aim of this study was to verify if calcification identifies a vulnerable patient rather than the vulnerable plaque.

Methods

A morphologic and morphometric study on 960 coronary segments (CS) of 2 groups of patients was performed: (i) 17 patients who died from AMI (510 CS); (ii) 15 age-matched control patients without cardiac history (CTRL, 450 CS).

Results

Calcification was found in 47% CS of AMI and in 24.5% CS of CTRL. The area of calcification was significantly higher in AMI compared to CTRL (p = 0.001). An inverse correlation was found between the extension of calcification and cap inflammation (r2 = 0.017; p = 0.003). Multivariate regression analysis demonstrated that the calcification was not correlated with the presence of unstable plaques (p = 0.65). Similarly, the distance of calcification from the lumen did not represent an instability factor (p = 0.68).

Conclusion

The present study suggests that CAC score evaluation represents a valid method to define the generic risk of acute coronary events in a population, but it is not useful to identify the vulnerable plaque that need to be treated in order to prevent an acute event.

Introduction

It has been widely demonstrated that acute coronary syndromes (ACS) are related to rupture and acute thrombosis over a mildly stenotic plaque, rather than to a slow growth with final occlusion of a plaque encroaching the lumen [1], [2], [3]. Several studies highlighted the role of inflammatory cells (macrophages and T lymphocytes), metalloproteases and cytokines in the transformation of a stable plaque into a vulnerable one [4], [5], [6]. It has been suggested that calcific content of a plaque is another key factor for plaque destabilization, potentially modifying mechanical plaque's characteristics and predisposing it to rupture [7] (Fig. 1).

Indeed, calcification is the most frequent complication of atherosclerotic lesions [8]. There is a strong relationship between mortality and total coronary artery calcium (CAC) score evaluated by cardiac computed tomography (CT) [7], [9], [10]. Presence of CAC is a well-established marker of coronary plaque burden and is associated with a high risk of adverse cardiovascular outcomes [11], [12]. Although coronary calcification is a marker of atherosclerosis, its effect on plaque instability seems to be less evident. It is still uncertain whether coronary calcification is a marker for plaque vulnerability.

The recent introduction of intravascular ultrasound (IVUS) provided conflicting results compared to CT-based studies [13], [14], showing minor calcification in culprit lesions of ACS in respect to patients with stable angina [15].

Moreover, it is worth noting that in the modified AHA classification of coronary plaques the frequent fibrocalcific plaques are considered as stable lesions [16]. These findings are difficult to reconcile with those derived by CT.

In order to better define the role of calcification in coronary plaques destabilization we perform a detailed morphologic, morphometric and topographic study evaluating serial sections of the whole coronary tree of patients died from acute myocardial infarction (AMI) and non-cardiac causes.

Section snippets

Patient population

We studied 960 coronary segments (CS) of 32 consecutive autopsies of 2 group of patients who have died at the Policlinico of the University of Rome Tor Vergata: 17 patients died from AMI (AMI group, 10 males/7 females, mean age 68.8 ± 9.5 years) and 15 age-matched control patients without positive cardiac history (CTRL group, 8 males/7 females, mean age 75.4 ± 12.6 years) who died from non-cardiac causes and in whom at least one coronary showed a cross-sectional luminal stenosis >50%. In the

General findings

No differences were observed between AMI and CTRL groups for age, gender, distribution of major risk factors (hypertension, hyperlipidemia, smoking, diabetes) and renal pathology (Table 1).

Myocardial histopathologic examination confirmed an acute transmural infarct as cause of death in all patients who died from AMI. Myocardium from CTRL group of patients showed neither infarct nor small necrosis in all cases. The cause of death in the CTRL group was bronchopneumonia in 8, bowel infarction in

Discussion

The results of our morphologic study confirm that the severity of coronary calcification is closely related to atherosclerotic plaque burden, luminal stenosis and fatal ischemic cardiac events, as previously reported [7], [10], [11]. A possible explanation that calcification was more prevalent in patients with AMI than in controls could be that in the AMI group the stable or unstable plaques, as compared to pre-atherosclerotic lesions, are more common than in the CTRL group (90.8% vs. 65.8%) (

References (24)

  • N. Alexopoulos et al.

    Calcification in atherosclerosis

    Nat Rev Cardiol

    (2009)
  • H.C. Stary et al.

    A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association

    Arterioscler Thromb Vasc Biol

    (1995)
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