In this study, we investigated the types of discrepancy between HbA1c and FPG in patients with ACS and diabetes. We found that nearly one third of patients had a discrepancy between HbA1c and FPG. Of these patients with discrepancy, the patients with increased FPG had higher risk of in-hospital cardiovascular adverse outcomes than those with increased HbA1c.
Discrepancy between HbA1c and FPG was reported by some studies. A study about the risk of hypertension in patients with prediabetes demonstrated the discrepancy between HbA1c and FPG [20]. A study using data from residents of Yunnan Province, China, showed that the discrepancy between HbA1c and FPG occurred in about 30% of participants [21]. In our study, the discrepancy between HbA1c and FPG can be also found in patients with ACS and diabetes. We found that discrepancy group, which included 77.5% of patients in increased HbA1c but normal FPG group and 22.5% of patients in increased FPG but normal HbA1c group, accounted for 29% of total study population. Patients often experience hyperglycemia in the acute phase of many diseases, such as ACS, which is called stress hyperglycemia. HbA1c reflects average glycemia over approximately 3 months, so an increase in HbA1c usually indicates chronic hyperglycemia. We found that patients in increased FPG but normal HbA1c group were more likely to have lower eGFR and be treated with glucose-lowering agents. Higher proportion of glucose-lowering agents use may be related to the well-controlled blood glucose and lower HbA1c. Furthermore, changes in the metabolism of glucose-lowering drugs, insulin clearance, and the uremic environment in patients with renal function insufficient may also lower HbA1c value [22]. From our study, not only can the discrepancy between HbA1c and FPG be found in patients with chronic kidney disease (CKD), but also the proportion of increased FPG group was significantly higher than that of increased HbA1c group.
There is a strong association between cardiovascular disease, diabetes and CKD. People with diabetes and CKD have a greatly increased risk of all-cause mortality, cardiovascular mortality, and kidney failure [23,24]. Furthermore, we analyzed the relationship between the types of discrepancy and in-hospital outcomes. We have known that HbA1c and FPG were both closely related to the in-hospital outcomes. Most previous studies have shown that increased HbA1c or FPG was significantly associated with poor in-hospital outcomes in patients with ACS and diabetes. An observational study included 250 patients with ACS, which found that coronary atherosclerosis was more advanced in patients with HbA1c ≥ 5.7% than those with HbA1c < 5.7% [17]. Goyal, et al [25] conducted a post hoc analysis including two randomized controlled trials of acute myocardial infarction with ST-segment elevation, involved 30,536 subjects with diabetes history, which showed that patients with in-hospital glucose ≥ 144 mg/dL had a very high risk of death. However, in clinical practice, some conditions such as acute stress, renal dysfunction, and anemia can cause uncertainty in the measured values of FPG and HbA1c, such as discrepancy between FPG and HbA1c. Until now, it is not so clear about the association of in-hospital outcomes with the discrepancy between HbA1c and FPG in patients with ACS and diabetes. There are few studies focusing on this issue. From our study, we can draw a conclusion that patients in increased FPG group, who were more likely to have higher heart rate, poorer heart function, higher incidence of STEMI as well as hypertension, had higher risk of in-hospital cardiovascular adverse outcomes than those with increased HbA1c. Stress hyperglycemia, which is a reflection of high free fatty acids, insulin resistance, and steroid hormones, affects the course of the disease in the worst way [26]. From other study, we have learned that the level of stress hyperglycemia often correlates with the severity of disease and predict mortality [27]. In our study we also found that the patients with severe clinical condition, such as the higher heart rate and the poorer heart function, were more likely to have an increase in FPG. As a result, stress hyperglycemia may have greater adverse effect on patients with ACS and diabetes than chronic hyperglycemia.
The findings of this study may have some important implications for clinical practice. The HbA1c test is the major tool for assessing glycemic control and has strong predictive value for diabetes complications [28]. Chronic hyperglycemia is an important risk factor for cardiovascular disease and mortality [24], although the variability of HbA1c in patients with renal insufficiency should be concerned. However, in patients with ACS and diabetes, increased FPG may be associated with the higher risk of adverse in-hospital outcomes, even though the HbA1c is well controlled. These patients, especially including those with renal insufficiency, should be given more attention and closer monitoring in clinical practice.
The major strength of our study is that it is based on a nationally representative registry and aimed at investigating the discrepancy between HbA1c and FPG and the influence on the in-hospital outcomes of patients with ACS and diabetes, which was rarely reported till now. Our study also has certain limitations. Firstly, all-cause mortality was not included in the logistic regression analysis because of very limited events. Secondly, we cannot collect all information affected glucose metabolism from this real-world research for ACS patients based on medical records, thus contributing to some residual confounding from unmeasured confounders. Lastly, fasting statue, blood sample collection and testing methods were difficult to unify, as this was a real-world multicenter study.