In this study, we investigated the relationship between pDM and CAC in patients with stable chest pain who underwent a cardiac CT. The main findings are: 1) A CAC score ≥ 100 AU was significantly associated with pDM, and was independent of conventional cardiovascular risk factors and statin consumption. 2) Female sex was associated with less CAC burden.
To the best of our knowledge, this is the first study to investigate the relationship between pDM and the presence of CAC in patients with stable chest pain. These findings are likely to be relevant, as there are currently no established guidelines for the primary prevention of CV events in patients with pDM. This association is in line with current evidence. It has been shown that CV and renal diseases are more prevalent in pDM patients. In fact, a recent meta-analysis found that pDM at baseline was associated with increased risk of all cause mortality and CV disease (6). Moreover, in pDM patients who suffered an acute coronary syndrome, coronary aterosclerosis burden appeared to be more significant than in euglycemia (7). Therefore, pDM patients may represent an opportunity to reduce CV related morbidity, as pDM confers higher CV risk (8). Early intervention to reduce HbA1c might be of interest for the prevention of CV events. There is already evidence that primary prevention can effectively delay and prevent conversion from pDM to T2DM (9).
Several studies have established that inflammatory and immunologic processes that play a role in early atherosclerosis in patients with DM are also found in those who have pDM (10). Sarwar et al. showed that the CV risk begins in the pre-diabetes range, below the type II DM cut-off, and increases with increasing glucose exposure (11).
Hyperglycaemia is associated with increased reactive oxidative species (ROS), which contribute to the pathogenesis of CV disease (12). Although traditional CV risk calculators fail to capture the risk conferred by HbA1c, recently, the ADVANCE risk tool was developed including the HbA1c to predict the CV risk in subjects with type II DM (13). However, ADVANCE risk tool is not validated in pDM patients.
Although women have less CAC compared to men of similar age and burden of risk factors, CAC has the same prognostic value in women than in men. A meta-analysis of 5 population-based studies that included 6739 women, showed that women with CAC > 0 (36% in total) had twice as many events at 7–12 years as those who had CAC = 0 (14). The prognostic value of the CAC score has been demonstrated in large prospective and retrospective cohorts. MESA (Multi-Ethnic Study of Atherosclerosis) established that patients with a CAC score between 101–300 AU had a risk of coronary events 7.7 times higher than those with a score of 0 UA, being the risk 9.7 times higher in those with a Score > 300 AU (4). The detection of subclinical atherosclerosis at a early stage is crucial to improve CV prevention and outcomes by allowing early implementation of primary prevention strategies (15).
This study has several limitations. First, this was a cross-sectional observational study that could not definitively establish causality. Thus, the causal relationship between pDM and CAC remains controversial. Second, our study cohort was relatively small. Third, HbA1c values reflect mean endogenous exposure to glucose over the preceding 2 to 3 months. However, HbA1c values show low intraindividual variability, particularly in people without diabetes.