The present study prospectively investigated the predictive value of plasma HbA1c for the severity of CAD and mortality in patients with stable CAD. Consistent with previous small sample size studies [24–26], our data also demonstrated that elevated HbA1C levels significantly conferred to clinical discriminators not only for the presence of CAD, but also for the severity of coronary lesions in patients with CAD. However, both chi-squared for trend and multivariate Cox proportional regression analysis with adjustment for all potential confounders in our study showed the usefulness of HbA1c in predicting the early outcome of the enrolled population. Kaplan-Meier curve for cumulative event-free survival based on the tertiles of baseline plasma HbA1c levels apparently showed that the elevated HbA1c levels (>6.3%) were generally associated with increased early adverse outcome. More interestingly, subgroup analysis indicated that the predictive power of plasma HbA1c existed only in patients with DM who presented as stable CAD but not in populations without the history of DM. The results clearly suggested the important role of baseline plasma HbA1c in diabetic patients with CAD.
It has been demonstrated that DM is a risk for the development of CAD and individuals who had DM will suffer from more intensive atherosclerotic lesions and more cardiovascular events [29, 30]. Previous studies have already suggested an association of high-normal glucose and HbA1C level with the presence of CAD in a variety of individuals such as in patients with or without diabetes, in asymptomatic persons, even in general population with undiagnosed diabetes [3, 22, 24, 31–33]. However, to the best of our knowledge, there is no data available regarding the role of HbA1C in the prognostic predictor of patients with DM. In this study, we prospectively enrolled a large cohort of patients who presented as typical angina-like chest pain (stable angina) to evaluating the relationship between HbA1C and CAD. We found that HbA1C could significantly confer to clinical discriminators not only for the presence of CAD but also for the severity of coronary lesions in these patients. The results analyzed by univariate and multivariate logistic regression models indicated that plasma HbA1C levels was an independent predictors of the presence of CAD after adjusting for other risk factors of CAD and lipid parameters. AUC evaluation suggested a well discriminatory power of HbA1c for CAD in our population studied.
Indeed, HbA1C has been proposed as reliable tool for not only diagnosing DM but also identifying individuals at high risk of cardiovascular events with and without DM [1, 19]. Although accumulating evidence suggested that an elevated HbA1C level was clearly linked to a poor prognostic outcome in patients with AMI or ACS, even after cardiac surgery or coronary stent implantation, the prognostic value of baseline HbA1c in patients of stable angina has not been well established [11, 19, 20]. In the present study, we detected that the higher level of plasma HbA1c was relevant to adverse prognosis in patients with stable CAD during an average of 12 month follow-up. Among adverse cardiovascular events, the patients with higher HbA1c were more prone to receive the coronary intervention of revascularizations in agreement with previous studies. Therefore, the present study confirmed and extended previous studies regarding the role of HbA1c in predicting the severity and early outcome in stable CAD.
The underlying hypothesis of the current results might consisted in that the high levels of HbA1c were not only associated with the long-term disorder of glycolipid metabolism but also connected with low-grade systematic inflammation and atherosclerotic plaques progress . Our data might supported this hypothesis because we found that higher levels of HbA1c in the population studied were clearly associated with the adverse baseline characteristics such as higher cardiovascular risk profile and higher inflammatory biomarkers such as hs-CRP, leukocyte counts, fibrinogen, D-dimer, uric acid and so on. Our data were also in agreement with previous evidence that suggested a correlation between plasma HbA1c with above inflammatory biomarkers, chemical parameters, either alone or combined. These markers or risk factors had a direct role on the progression of atherosclerotic artery disease and adverse cardiovascular events [7, 31, 35–39]. Moreover, previous studies also suggested that the higher plasma HbA1c might indicate a potential impact of hyperglycemia on the vasculature before the establishments of formal diagnosis for clinically DM and/or overt atherosclerosis disease [7, 40]. Therefore, as a long half-life protein, HbA1c might be involved in both chronic inflammatory response and acute active phase of ACS, resulting in accelerating the progress and rupture of atherosclerotic lesions.
Summarily, in this prospective, a large cohort, short-term outcome study, the data clearly suggested that high level of plasma HbA1C (>6.3%) was an independent predictor for the presence and severity of CAD as well as the early outcome of patients with stable angina. Long-term follow-up may be needed for further revealing more information regarding the role of HbA1C in diabetic patients with stable CAD.