Coronary calcification identifies the vulnerable patient rather than the vulnerable Plaque
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%) (
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