In this study, we investigated the type 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 the patients with discrepancies, the patients with increased FPG had a higher risk of in-hospital adverse cardiovascular outcomes than those with increased HbA1c.
Discrepancies between HbA1c and FPG have been reported by some studies. A study of 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 a discrepancy between HbA1c and FPG was present in approximately 30% of participants [21]. In our study, the discrepancy between HbA1c and FPG was also found in patients with ACS and diabetes. We found that the discrepancy group, composed of 77.5% patients with increased HbA1c but normal FPG and 22.5% patients with increased FPG but normal HbA1c, accounted for 29% of the 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 the increased FPG but normal HbA1c group were more likely to have lower eGFR and be treated with glucose-lowering agents. A higher proportion of glucose-lowering agent use may be related to 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 insufficiency may also reduce HbA1c values [22]. From our study, not only was a discrepancy between HbA1c and FPG be found in patients with chronic kidney disease but the proportion of the increased FPG group was found to be significantly higher than that of the increased HbA1c group.
There is a strong association between cardiovascular disease, diabetes and chronic kidney disease. People with diabetes and chronic kidney disease have a substantially increased risk of all-cause mortality, cardiovascular mortality, and kidney failure [23, 24]. Furthermore, we analyzed the relationship between the type of discrepancy and in-hospital outcomes. We know that HbA1c and FPG are both closely related to 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 that included 250 patients with ACS found that coronary atherosclerosis was more advanced in patients with HbA1c ≥ 5.7% than in 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, involving 30,536 subjects with diabetes history, and 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, HbA1c, and the discrepancy between FPG and HbA1c. Until now, the association of in-hospital outcomes with the discrepancy between HbA1c and FPG in patients with ACS and diabetes has not been clear. There are few studies focusing on this issue. From our study, we can conclude that patients in the increased FPG group, who were more likely to have a higher heart rate, poorer heart function, a higher incidence of STEMI and hypertension, had a 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 an adverse way [26]. From another study, we learned that the level of stress hyperglycemia often correlates with the severity of disease and can predict mortality [27]. In our study, we also found that patients with severe clinical conditions, such as a higher heart rate and poorer heart function, were more likely to have increased FPG. As a result, stress hyperglycemia may have a 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 a 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 in HbA1c in patients with renal insufficiency should be considered. However, in patients with ACS and diabetes, increased FPG may be associated with a higher risk of adverse in-hospital outcomes, even if HbA1c is well controlled. These patients, especially 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 of the discrepancies on the in-hospital outcomes of patients with ACS and diabetes, which has rarely been reported until now. Our study also has certain limitations. First, all-cause mortality was not included in the logistic regression analysis because of very limited events. Second, we could not collect all information related to glucose metabolism in this real-world study of ACS patients based on medical records, thus contributing to some residual confounding from unmeasured confounders. Last, fasting status, blood sample collection and testing methods were difficult to unify, as this was a real-world multicenter study.