The above consideration may be extended to other atherosclerotic-related diseases: for example, a progressive and significant increase occurs in serum NGAL following acute cerebrovascular events (ischaemic stroke, TIA), and persists for up to 1 year [16,17]. Moreover, in their prospective study conducted on 144 subjects with acute cerebrovascular disease, Falke et al. found that NGAL levels, if measured 1–3 days after the event, were a useful tool for stratifying the patients according to their mortality risk during a 4-year follow-up period . As NGAL is one of the proteins with marked hyper-expression following myocardial infarction, in both the necrotic area and the healthy surrounding tissue [10,19], it may be considered an active mediator in post-ischaemic inflammation and remodelling responses. In fact, circulating NGAL levels are markedly higher in patients with acute myocardial infarction (AMI) than in healthy subjects. Moreover, markedly high NGAL levels occurring immediately after AMI were found to be predictive of an unfavourable medium-term outcome. In patients with underlying chronic heart failure (CHF), NGAL levels changed in relation to variations found in clinical and neuro-hormonal markers of cardiac injury. Findings made in murine models confirm that NGAL hyper-expression occurs, both in vivo (damaged myocardium), and in vitro after IL-1 beta (a potent inflammatory cytokine) stimulation in cardiomyocyte cultures . In a recent study  conducted on 46 patients with CHF of different severity, Bolignano et al. reported NGAL levels that were markedly increased with respect to levels in an age-matched healthy control population. These values, moreover, presented a clear correlation with the clinical severity expressed according to the NYHA classification (R = 0·714, P = 0·0001), and with the levels of systolic pressure (R = 0·19, P = 0·05), cholesterolemia (R = 0·19, P = 0·04), albuminemia (R = −0·18, P = 0·05) and ejection fraction (R = −0·19, P = 0·05). The patients were therefore given a 2-year follow-up in order to evaluate the mortality related to cardiovascular events and, on completion of follow-up, the authors observed that the basal levels of NGAL >783 ng mL−1 (optimal cut-off by ROC analysis) were associated with a significantly higher mortality, thus confirming the potential utility of NGAL measurement in staging patients according to cardiovascular risk.
Although it appears reasonable to assume that the damaged myocardium represents the main source of the increase in NGAL levels, other organs may also significantly contribute to NGAL production, consequent to local (ischaemic?) damage following the heart injury itself. An example of this is given in a recent paper : urinary NGAL (uNGAL) excretion, significantly higher in CHF patients than in control subjects, was correlated with levels of creatininemia, GFR, albuminuria and also NT-proBNP, an important biomarker of severity of cardiac impairment.
Likewise, it was found that although patients with CHF secondary to CAD had normal renal function, they presented serum NGAL levels that were markedly higher than those in controls, the increase being independently correlated with the NYHA class and the estimated GFR value .
It is therefore of importance to establish whether an increase in systemic NGAL levels is, albeit partially, a further expression of renal injury occurring during the course of CHF.