Increased IMA indicates a reduced albumin-metal binding capacity associated with ischemia and the production of oxygen-free radical species [9, 14]. Albumin can act as a “sacrificial” antioxidant to reduce damage during reperfusion. IMA is caused by the damage to the N-terminus of albumin. Also, endothelial damage is caused by extracellular hypoxia, acidosis, Na-K pump malfunction, and free radical damage. The albumin-metal binding ability of copper, nickel, and cobalt decreases during acute ischemia, leading to metabolic protein variation (IMA) [15]. This study identified the significant increase in plasma IMA, a potential early novel biomarker for AAD diagnosis within 24 hours after symptom onset. Additionally, IMA was highly effective in distinguishing AAD from AMI, PE, and NCCP compared with D-dimer.
Similarly, previous reports have also shown that the IMA level is significantly high and could be a sensitive biochemical marker for the diagnosis of myocardial ischemia [10, 16]. Studies have shown that the IMA level in acute coronary syndromes increases within 10 minutes, then further increases for the next 6–12 hours, before decreasing to a normal level within 12–24 hours [17], consistent with this study [18, 19]. The FDA has approved IMA as a marker for myocardial infarction prognosis. However, the diagnostic accuracy of IMA for AMI diagnosis is unknown [20]. IMA, as a marker, has been investigated in the diagnosis of severe sepsis, bacterial infections and is associated with oxidative stress parameters [20]. However, no study has assessed the IMA value in cardiovascular disease diagnosis.
The study indicated that IMA could be a marker for AAD. The classical hypothesis shows that the albumin effect could be due to expansion of circulating plasma volume, which ensures adequate organ perfusion. This study indicated that the additional benefit could be due to the enhancement of the transport function of albumin, improving the outcome in AAD. Moreover, IMA can be generated in any regional ischemia. The disruption of aortic media changes aorta hemodynamics when aortic dissection occurs. Furthermore, intramural hemorrhage can cause diffusion, especially when the intimal layer is destroyed, thus the blood flow in the media. Endothelial damage is caused by blood flow and shear stress. Furthermore, aorta hemodynamics significantly changes in the large areas of the aorta. It can cause higher IMA circulation than in small or medium vessels of PE and acute coronary syndrome.
IMA is a nonspecific marker for tissue ischemia. It has been previously studied in patients with PE, acute mesenteric ischemia, cerebral hemorrhage, deep venous thrombosis, acute coronary syndrome, ischemic stroke, and stroke [21–25]. Herein, IMA levels were significantly high in AAD since aortic dissection can involve coronary artery, subclavian artery, and internal carotid artery. IMA also increases in patients with aortic cross-clamping, cross-clamping during arterial reconstruction, and chronic claudication [21].
This research suggests that IMA could be related to various circulation ischemia, such as AAD, PE, AMI, and NCCP. Although the IMA level was elevated in AMI and PE, it was lower than in AAD. In addition, the best threshold of IMA, specificity, and sensitivity were 59.35 u/L, 85.71%, and 66.67%, respectively. However, this best threshold excludes aortic dissection with a negative predictive value of 85.72%, similar to D-dimer (negative predictive value, 87.23%). Furthermore, a higher threshold of IMA was associated with higher positive predictive values. Therefore, IMA could be a promising biomarker for the early diagnosis of AAD.
This research could provide a novel biomarker for the early diagnosis of AAD. The diagnostic performance of IMA was also assessed. IMA showed a better diagnostic performance than D-dimer. However, this study has some limitations. This was a single-center study, and large-sample studies in multiple centers are required to validate the findings. Second, this study did not include all patients with nonspecific chest pains, thus selection bias. Finally, this study included only Chinese participants. Therefore, other participants from other regions should be used to validate the results. In summary, IMA can be used as a marker for AAD.