Coronary calcium in patients with and without diabetes: first manifestation of acute or chronic coronary events is characterized by different calcification patterns

The mean period of follow-up was 6.3 ±3.4 year. During this period 628 subjects (94%) were free from any cardiac events (Group I). Throughout follow up 39 (6%) of patients experienced a cardiac event: 18 of them suffered acute events (13 acute MI and 5 unstable angina pectoris – Group II) and in 21 of them chronic events were documented (Group III). Eight patients died without having any known prior cardiac event (non-cardiac death).

The baseline characteristics of the participants are given in Table 1. Patients with events were older than those without and those with chronic events were older than those with acute. The frequency of hypertension was twice higher among those with chronic than in those with acute event and no events. All the other clinical and laboratory parameters were not statistically different between study groups. There were 67 patients with and 600 patients without diabetes in our study. It should be pointed out that 78% of the patients with DM had CAC (TCS above zero) vs. 50% of patients without DM (p < 0.001).

The CAC characteristics of patients are given in Table 2. Among subjects without events half had CAC (TCS > 0) while all those with chronic and three quarter of the acute events group had CAC. Equally, the mean CAC score was 10 times higher in the chronic events group than in those without events (914 vs. 93 AU) and 17 times higher than the mean TCS of the acute group (914 vs. 55 AU). Ninety five percent of the patients with chronic events had more than one calcified vessel compared to 67% of the patients with acute events and only 30% of those without events (p < 0.001).

The incidence of acute and chronic events by TCS categories is given in Table 3 and Figure 1. During follow-up incidence of the CAD events (all types pooled together) rose consequently from 2% in subjects without CAC to 34% in subjects with the highest CAC category TCS > 600 AU (p < 0.001). However, different pattern in the development of the first acute and chronic coronary events in accordance with the CAC category was observed. Among the 32 subjects with TCS > 600 AU, 11 (34%) developed chronic event while none of them had acute event. In contrast, none of subjects with TCS = 0 or TCS 1–100 AU had chronic events. Subjects with TCS 101–600 AU presented 10 (9%) chronic and 5 (4.5%) acute events (p < 0.001).

The main finding of our study is that asymptomatic subjects with ECAC, both with and without DM did not developed first acute CAD-related events during up to 10 years of follow-up. Our data support the suggestion that ECAC is associated with a stable form of atherosclerosis which is mainly manifested by a chronic rather than acute course of CAD [7‐9].

Previous studies have shown a dramatically increased incidence rate of CAD events (when all types of events pooled together) among those with the highest levels of CAC compared to those with CAC = zero [3‐6]. However, as we demonstrate in the current analysis, a different pattern in development of acute and chronic coronary events in accordance with CAC category can be distinguished. The acute events in our study occurred mostly in subjects with mild and moderate CAC and even in absence of CAC. This might have an important clinical relevance, since minimal or mild CAC should not be categorized into a lower risk category (as suggested by the SHAPE investigators) [17]. These findings are also supported by histopathological studies, intravascular ultrasound and CT observations that consistently demonstrated that acute events rise mainly from soft non-calcified or mildly calcified plaques [18‐27]. In a series of cases of sudden coronary death, more than 50% of thin-cap fibroatheromas showed a lack of calcification or only speckled calcification on postmortem radiographs of coronary arteries [18]. Several studies demonstrated the destabilizing effect of the lipid core, whereas presence of calcium was a stabilizing force and calcified lesions were more resistant to rupture (similar to fibrous plaque) [19, 20].

Thus, it seems that ECAC represents a long standing chronic stage of slowly growing coronary atherosclerosis and can be regarded as a healing process leading to stabilization and decrease vulnerability of the plaques [28]. On the other hand, ECAC causes negative vessels remodeling resulting in flow restriction and leading to clinical manifestations such as chronic angina or silent ischemia upon a routine stress test [18‐28].

The prevalence of CAC in our patients with DM was significantly higher than in patients without DM. The clinical value of CAC score in diabetic patients has been recently demonstrated in several studies: CAC score can further stratify diabetic patients according to the presence and extent of CAC into patients with very low or high CV risk [10‐13, 29].

It should be stated that our population was predominantly masculine, and this may represent a potential limitation since the epicardial adipose tissue volume shows gender disparities, being strongly associated with coronary atherosclerosis in men [30]. Therefore, despite of the strong theoretical background and biological plausibility, caution should be used in interpreting our findings because it was not a randomized controlled trial and we cannot rule out other factors that could have influenced the observed clinical outcomes.

Asymptomatic subjects with ECAC did not develop first acute events, but presented a high level of chronic CAD-related events during a long term follow-up. In contrast, most of the acute CAD-related events firstly occurred in subjects with mild and moderate CAC.