Background
Cardiovascular disease is the leading cause of both death and premature death in China and is the cause of 40% of deaths in the Chinese population [
1]. Acute coronary syndrome (ACS) is an acute manifestation of cardiovascular disease with a high risk of mortality that can lead to critical conditions such as cardiogenic shock and cardiac arrest. Patients with ACS and diabetes usually have worse clinical outcomes than those with normal blood glucose [
2‐
8], regardless of in-hospital or long-term outcomes. Indicators commonly used for evaluating blood glucose include intravenous blood glucose, glycosylated hemoglobin (HbA
1c), and glycosylated serum albumin. Glucose was first used in the diagnosis of diabetes, including fasting plasma glucose (FPG), oral glucose tolerance tests and random blood glucose. In 2013, the American Diabetes Association approved the use of HbA
1c to diagnose diabetes [
9]. In addition to their diagnostic value, FPG and HbA
1c are also associated with clinical outcomes. Several studies have shown that abnormal blood glucose is an important factor associated with clinical outcomes in patients with ACS and diabetes [
10‐
17].
However, the discrepancy between HbA1c and FPG can be observed in clinical practice, which has not been fully investigated until now. This condition may be related to factors such as acute stress, renal dysfunction, and anemia, which may affect FPG and HbA1c. The discrepancy can be an increased FPG with a normal HbA1c or an increased HbA1c with a normal FPG. We decided to explore which discrepancy indicates worse in-hospital outcomes. There are few studies focusing on this issue.
The Improving Care for Cardiovascular Disease in China - Acute Coronary Syndrome (CCC-ACS) project is a national, hospital-based quality improvement project with an ongoing database, aiming to increase adherence to ACS guidelines in China and to improve patient outcomes. We conducted this study based on the CCC-ACS project to investigate the types of discrepancies between HbA1c and FPG and their relationships to in-hospital outcomes.
Discussion
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 HbA
1c and FPG have been reported by some studies. A study of the risk of hypertension in patients with prediabetes demonstrated the discrepancy between HbA
1c and FPG [
20]. A study using data from residents of Yunnan Province, China, showed that a discrepancy between HbA
1c and FPG was present in approximately 30% of participants [
21]. In our study, the discrepancy between HbA
1c and FPG was also found in patients with ACS and diabetes. We found that the discrepancy group, composed of 77.5% patients with increased HbA
1c but normal FPG and 22.5% patients with increased FPG but normal HbA
1c, 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. HbA
1c reflects average glycemia over approximately 3 months, so an increase in HbA
1c usually indicates chronic hyperglycemia. We found that patients in the increased FPG but normal HbA
1c group were more likely to have lower eGFR and to be treated with glucose-lowering agents. A higher proportion of glucose-lowering agent use may be related to well-controlled blood glucose and lower HbA
1c. Furthermore, changes in the metabolism of glucose-lowering drugs, insulin clearance, and the uremic environment in patients with renal function insufficiency may also reduce HbA
1c values [
22]. From our study, not only was a discrepancy between HbA
1c 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 HbA
1c 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 HbA
1c and FPG are both closely related to in-hospital outcomes. Most previous studies have shown that increased HbA
1c 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 HbA
1c ≥ 5.7% than in those with HbA
1c < 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. A retrospective cohort study of 768 patients with post-myocardial infarction was conducted, and the results showed that presence of impaired glucose tolerance and newly diagnosed diabetes mellitus is associated with increased incidence of adverse outcomes [
26]. Kiviniemi et al. conducted a prospective cohort study that included patients with coronary artery disease, and the results showed that the adverse outcomes in patients with impaired glucose tolerance or impaired fasting glucose does not differ from those values in patients with normal glycemic status, while patients with type 2 diabetes had a higher risk of adverse outcomes [
27]. Contradictory results between this and previous studies may not be fully explained, but the differences in research population and medical treatment may play a role. However, in clinical practice, some conditions, such as acute stress, renal dysfunction, and anemia, can cause uncertainty in the measured values of FPG and HbA
1c and the discrepancy between them. Until now, the association of in-hospital outcomes with the discrepancy between HbA
1c 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, and higher incidence rates of STEMI and hypertension, had a higher risk of in-hospital cardiovascular adverse outcomes than those with increased HbA
1c. 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 [
28]. From another study, we learned that the level of stress hyperglycemia often correlates with the severity of disease and can predict mortality [
29]. 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 HbA
1c test is a major tool for assessing glycemic control and has strong predictive value for diabetes complications [
30]. Chronic hyperglycemia is an important risk factor for cardiovascular disease and mortality [
24], although the variability in HbA
1c 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 HbA
1c 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 is 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.
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