Neutrophil gelatinase-associated lipocalin (NGAL) and cardiovascular events in patients with stable coronary artery disease

Abstract

Inflammation is an important mediator in the pathogenesis of atherosclerosis. Neutrophil gelatinase-associated lipocalin (NGAL) is a small glycoprotein secreted by neutrophils. NGAL regulates the activity of matrix metalloproteinase-9, which plays a role in plaque instability. It has therefore been hypothesised that NGAL may modulate inflammation and promote the development and progression of atherosclerosis. Our aim was to assess the predictive value of plasma NGAL in a prospective cohort study of 876 high-risk patients with stable coronary artery disease (CAD). NGAL levels were measured using the NGAL Test^TM from BioPorto Diagnostics. Clinical follow-up was performed after a median of 3.1 years. The endpoint was a combination of non-fatal acute myocardial infarction (MI), cardiovascular death (CVD), or ischaemic stroke. The NGAL concentration was (median [25;75%]: 64.3 µg/L [51.3;81.4]). The area under the receiver operating characteristic curve (AUC) was 0.56 (95% confidence interval (CI): 0.49;0.64) for the diagnosis of the composite endpoint and 0.66 (95% CI: 0.56;0.75) after adding NGAL to high-sensitive C-reactive protein (hs-CRP), leucocyte count, interleukin-6 (IL-6), calprotectin, age, sex, body mass index (BMI), diabetes mellitus, smoking and creatinine. However, the AUC for hs-CRP, leucocyte count, IL-6, calprotectin, age, sex, BMI, diabetes mellitus, smoking and creatinine without NGAL was similar at 0.66 (95% CI: 0.56;0.76). NGAL alone had no predictive value with respect to the composite endpoint of non-fatal AMI, ischaemic stroke, or CVD in stable CAD patients. NGAL did not add any predictive value to the endpoint compared with existing inflammatory biomarkers and cardiovascular risk factors.

Keywords:

• Atherosclerosis
• biomarkers
• coronary artery disease
• inflammation
• neutrophil gelatinase-associated lipocalin

Acknowledgements

We gratefully acknowledge the help from technicians Vivi Bo Mogensen, Mai Stenulm Veirup, and Tine Vasegaard for laboratory assistance and Morten Würtz, Søs Neergaard-Petersen, and Lise Nielsen Wulff for collecting data and blood samples.

Disclosure statement

ZS has no conflict of interest to declare. NEM has no conflict of interest to declare. ELG has received speaker honoraria or consultancy fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, MSD, Pfizer and Roche. AMH has received speaker’s fees from CSL Behring, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb and Leo Pharma and unrestricted research support from Octapharma, CSL Behring and Leo Pharma. SDK has received speakers fee from AstraZeneca, Bayer, and BMS/Pfizer. SBL has no conflict of interest to declare.

Additional information

Funding

This work was supported by the Danish Agency for Science Technology and Innovation (grant no. 2101‐05‐0052 to Kristensen); Novo‐Nordic Foundation (grant no. NNF14OC0008817 to Kristensen); Faculty of Health Sciences, Aarhus University; Denmark, The Danish Heart Foundation; A.P. Møller Foundation; Department of Clinical Medicine, Aarhus University; The Eva and Henry Fraenkel Foundation; The Aase and Ejnar Danielsen Foundation; The Korning Foundation; The Physician's assurance association anno 1891, and The Sophus Jacobsen and Spouse Astrid Jacobsen Foundation. The funding sources had no influence on the study design, collection, analysis or interpretation of the data, writing of the article, or the decision to submit the article for publication