title: Neutrophil gelatinase-associated lipocalin as a biomarker of cardiovascular disease: a systematic review.
abstract: BACKGROUND
  Neutrophil gelatinase-associated lipocalin (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.
authors.affiliation: Department of Nephrology Dialysis and Transplantation, San Bortolo Hospital, Vicenza, Italy. dinnacruzmd@yahoo.com
authors.forename: Dinna N
authors.initials: DN
authors.lastname: Cruz
authors.forename: Sergio
authors.initials: S
authors.lastname: Gaiao
authors.forename: Alan
authors.initials: A
authors.lastname: Maisel
authors.forename: Claudio
authors.initials: C
authors.lastname: Ronco
authors.forename: Prasad
authors.initials: P
authors.lastname: Devarajan
mesh_terms: D000209:Acute-Phase Proteins / Q000032:analysis* / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002318:Cardiovascular Diseases / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D006333:Heart Failure / Q000378:metabolism / Q000473:pathology; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000032:analysis* / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D045265:Natriuretic Peptides / Q000097:blood / Q000652:urine; D011518:Proto-Oncogene Proteins / Q000032:analysis* / Q000378:metabolism; D012720:Severity of Illness Index
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D045265:Natriuretic Peptides; D011518:Proto-Oncogene Proteins; D020780:Matrix Metalloproteinase 9