Neutrophil gelatinase-associated lipocalin as a biomarker of cardiovascular disease: a systematic review

Background: Neutrophil gelatinase-associated lipo calin (NGAL) is a biomarker of acute kidney injury (AKI). Recently, elevated NGAL levels have also been reported in heart failure, coronary heart disease, and stroke. Other studies demonstrate that NGAL is upregulated in failing myocardium and in atherosclerotic plaque. Our aim was to synthesize the current evidence on NGAL and cardiovascular disease (CVD), and to clarify the prognostic significance of systemic NGAL levels in CVD. Methods: We performed a systematic review to identify experimental and human studies on NGAL and CVD. We excluded articles which specifically dealt with AKI or renal endpoints. Results: We identified 22 studies, including both animal and human data. NGAL is highly expressed in the heart, both in failing myocardium and myocarditis, and is also expressed in atherosclerotic plaques. Areas of co-localization of NGAL and matrix metalloproteinase (MMP)-9 exhibited increased MMP-9 proteolytic activity. Systemic NGAL levels correlated with renal function and severity of CVD in several, but not all, studies. An association between elevated systemic NGAL levels and clinical outcomes (e.g., death, hospital readmissions) were reported in six CVD studies, but these had limited adjustment for potential confounders. Conclusions: There is ample literature to support a putative role of NGAL in the pathophysiology of CVD, but at present there is insufficient data regarding the clinical utility of systemic NGAL levels in the management of CVD. Available evidence regarding NGAL as a predictor of outcomes in CVD is very limited.