In patients with acute myocardial infarction (MI), primary percutaneous coronary interventions are performed to minimize myocardial damage by restoring myocardial blood flow and oxygenation. However, despite opening the obstructed coronary artery, myocardial blood flow is not always completely restored, due to coronary microvascular obstruction and/or coronary microvascular dysfunction (CMD). Although infarct size is the most important predictor of ventricular function and prognosis, several studies have shown that both microvascular obstruction and CMD are associated with impaired left ventricular function and a worse prognosis.1However, when treating MI, still relatively little attention is paid to resolve CMD.2Multiple factors, including endothelial dysfunction, inflammation and oxidative stress as well as vasospasms are associated with increased vasoconstriction and contribute to CMD.
It is increasingly recognized that arginine vasopressin (AVP) may also play a role in CMD. AVP is a well-known regulator of the fluid balance in our body, but is also released in response to stress.2 The AVP- precursor pre-pro-vasopressin is produced in the hypothalamus and it is proteolytically cleaved into AVP neurophysin-II and copeptinduring transport to the pituitary gland, where they are stored, and released upon a decrease in blood pressure or an increase in osmolality, while an increase in left atrial pressure will decrease release of AVP. Furthermore, AVP is released in response to stress. Because AVP has a short half-life and is associated with platelets, which complicates its detection , while copeptin is more stable and simpler to measure. Its values correlates closely with AVP levels, and hence copeptin can be used as a surrogate marker for AVP release.3Indeed studies have shown that AVP and copeptin, together with troponin T, can be used as diagnostic and/or prognostic biomarkers in cardiovascular diseases, including MI, sepsis, heart failure and stroke (for a review see Mu et al 3).
However, in addition to being a biomarker, AVP has been shown to cause vasoconstriction in the coronary microvasculature, and its potency increases in the presence of diabetes 4as well asmyocardial ischemia.5In a recent paper in the Journal of the American Heart association, Al-Atta and colleagues therefore propose that AVP plays a role in microvascular dysfunction after MI.6 They performed serial measurements of AVP and copeptin in patients undergoing PPCI for MI, starting at the time of PPCI, until 24 hours later. AVP and copeptin levels were highest just prior revascularization, and increased rapidly over the next 90 minutes. Copeptin levels correlated inversely with diastolic blood pressure prior to revascularization, but surprisingly also with admission troponin and onset-to reperfusion time, suggesting that an increase in copeptin is an early marker of MI.
After revascularization, coronary flow reserve (CFR) and index of microvascular resistance (IMR) were tested invasively as indices of CMD in one cohort of 55 STEMI patients, while presence or absence of microvascular obstruction was diagnosed in a different cohort of 45 STEMI patients using late gadolinium enhancement during MRI 2-7 days post MI. When cohorts were divided based on the presence or absence of CMD (low CFR and high IMR) and coronary microvascular obstruction (MRI), it was found that copeptin levels at 24 hours of reperfusion, but not at admission, were significantly higher in patients with CMD but not in patients with coronary microvascular obstruction.6
These data indeed suggest that higher copeptin levels can serve as a biomarker for CMD. However, a direct correlation between CMD activation of the AVP system remains to be established prior to embarking on targeting the AVP system to reduce CMD in patients undergoing PPCI for MI.
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