In this study, we found that AMI patients with elevated admission blood glucose had higher risks of 30-day MACEs, compared with patients who had normal admission blood glucose. There was a positive linear association between admission blood glucose and the risk of 30-day MACEs in AMI patients. This association was more significant in STEMI patients or patients below 65 years old. In clinical management of patients with AMI, more attention should be paid to the admission blood glucose.
Elevated admission blood glucose was frequently reported to be an important factor of poor prognosis for patients with AMI, including increased risk of heart failure,21 hospital mortality,9 and left ventricular dysfunction.14 A single-center prospective study showed that elevated admission blood glucose was an independent prognostic factor for all-cause mortality in AMI patients.15 The Cooperative Cardiovascular Project analyzed data on 141,680 patients aged 65 years or older with AMI and reported a positive linear association between the admission blood glucose and the 30-day and 1-year mortality rates.13 With the cut-off value of 110 mg/dL (6.0 mmol/L), this study reported a higher risk of 30-day and 1-year mortality for patients with higher blood glucose.13 A prospective study on AMI patients found that compared to those with blood glucose lower than 140 mg/dL (7.8 mmol/L), patients whose blood glucose higher than 157 mg/dL (8.7 mmol/L) had a significant higher risk of 30-day mortality.9 Among ACS patients undergoing primary PCI, patients with admission blood glucose ≥ 11.1 mmol/L, but not between 6.0 and 11.1 mmol/L, had a higher risk of MACEs at 30 days [adjusted HR (95%CI): 5.21 (2.47, 10.98), P < 0.001], as compared to those < 6.0 mmol/L.22 Consistent with previous studies, in this study, we found that among AMI patients, the risk of 30-day MACEs was linearly increased as admission blood glucose increased. Compared to those with admission blood glucose of 5.4 mmol/L to 6.3 mmol/L, patients with admission blood glucose higher than 10.7 mmol/L had a significant higher risk of 30-day MACEs.
Several hypotheses have been suggested to explain the relation between elevated admission blood glucose and high risk of adverse cardiovascular outcomes in AMI patients. Elevated admission blood glucose might reflect a surge in stress hormones, such as catecholamines and cortisol, which produced an insulin-resistant state. It reduced glucose uptake by ischemic myocardium, increased circulating free fatty acids, and inhibited glucose oxidation, leading to increased membrane damage, arrhythmias, and reduced contractility.23–26 In addition, acute elevated blood glucose was reported to have an association with increased thrombin formation, platelet activation, and fibrin clot resistance to lysis, which might increase the risk of thrombotic complications among AMI patients.27, 28 Finally, previous clinical studies reported that acute elevated blood glucose was associated with left ventricular dysfunction, larger myocardial infarction size and higher risk of cardiogenic shock,14, 22, 29 which may directly explain the association between elevated blood glucose and the increased risk of MACEs among AMI patients.
In addition, our analyses first reported a significant interaction between admission blood glucose and myocardial infarction type on the risk of 30-day MACEs (P for interaction = 0.016). In STEMI patients, there was a significant linear relationship between admission blood glucose and the risk of 30-day MACEs [OR (95%CI): 1.07 (1.04, 1.10), P < 0.001]. However, in NSTEMI patients, the association was not significant [OR (95%CI): 1.02 (0.98, 1.05), P = 0.393]. Interestingly, there was also a significant interaction between admission blood glucose and age on the risk of 30-day MACEs (P for interaction = 0.025). The relationship between admission blood glucose and the risk of 30-day MACEs was more significant in patients below 65 years [OR (95%CI): 1.08 (1.05, 1.11), P < 0.001] than in patients 65 years or older [OR (95%CI): 1.03 (1.00, 1.06), P = 0.066]. Among patients ≥ 65 years or NSTEMI, the nonsignificant association between admission blood glucose and the risk of 30-day MACEs might be explained by following reasons. NSTEMI patients were older and more likely to have diabetes (Table S1). Therefore, the elevated admission blood glucose in NSTEMI patients may not be the stress-induced after acute myocardial infarction, but the result of chronic poor blood glucose control.22, 30 The degree of oxidative stress was closely related to acute rather than chronic fluctuations in blood glucose.31 Besides, previous studies reported that NSTEMI had a lower risk of in-hospital cardiovascular death and mortality at 2 months.32, 33 Consistent with these findings, STEMI patients in this study had a higher risk of 30-day MACEs after adjusting for potential covariates [OR (95%CI): 1.41 (1.11, 1.80), P = 0.005] compared with NSTEMI patients. However, NSTEMI patients tended to have a higher risk profile. Compared with STEMI patients, NSTEMI patients preferred to be older and have multivessel artery diseases or prior myocardial infarction.12, 33–35 And NSTEMI patients in this study underwent less PCI and had a longer time from symptom onset to arrival (Table S1). Those abovementioned high-risk characteristics might attenuate the relationship between admission blood glucose and the risk of 30-day MACEs.
The findings from this study had several clinical applications. First, we expanded current knowledge in the relationship between admission blood glucose and risk of 30-day MACEs in AMI patients. The prognostic value of elevated admission blood glucose may have substantial benefits for risk stratification and management of AMI patients. Second, by demonstrating the difference of this association between STEMI patients and NSTEMI patients, this study suggested that when managing AMI patients with high admission blood glucose, more attention should be paid to STEMI patients. Finally, to our knowledge, this was the largest retrospective study of Indian population on this subject using ACS-QUIK data.
This research still had some limitations. First, given the nature of post-analysis study, there may be some residual confounding that was not measured. In addition, this study was limited to admission blood glucose. Since data on blood glucose during hospitalization and follow-up information was not available, we were not able to assess the whether the blood glucose were persistent during hospitalization. Further studies were needed on the appropriate management of high admission blood glucose in patients with AMI.
In conclusion, this study supported that elevated admission blood glucose was a significant independent predictor of 30-day MACEs for AMI patients, and this relationship was found only in STEMI patients, not in NSTEMI patients. In clinical work, more attention should be paid to STEMI patients with elevated admission blood glucose to prevent the occurrence of MACEs.