Abstract
Background/Objectives: Inflammation represents a cornerstone in the development of atherosclerosis and early detection is essential to avoid cardiovascular events. Biomarkers like interleukin-1 beta, interleukin-6, or high sensitivity CRP (hs-CRP) have been investigated intensively in this field. Since they have several limitations, additional biomarkers are needed for cardiovascular risk stratification. The acute phase protein, neutrophil gelatinase-associated lipocalin (NGAL), modulates inflammation and is elevated in cardiovascular disease (CVD). Moreover, it contributes to plaque destabilization. Methods: In this prospective, single-center study, we included 323 asymptomatic patients with at least one cardiovascular risk factor or established CVD. NGAL levels were measured in plasma samples using a commercially available ELISA. Carotid, femoral, and total atherosclerotic plaque volumes (PV) were measured using a 3D ultrasound system (Philips iU22). Patients were separated into a low (n = 243) and high (n = 80) total PV group. Results: NGAL was significantly higher in patients with high total PV versus patients with low total PV. The NGAL amplitude for the prediction of high total PV was significantly higher when compared with hs-CRP. A high predictive value could also be observed for patients without established CVD. Conclusion: NGAL seems to be a promising biomarker for the identification of asymptomatic patients with atherosclerotic disease.
Highlights
Cardiovascular disorders represent the major cause of death in the industrialized world
Single-center study, we investigated the role of the acute phase protein neutrophil gelatinase-associated lipocalin (NGAL) on atherosclerosis in outpatients with at least one established CVRF or a manifestation of cardiovascular disease (CVD)
The clinical proof of concept of this hypothesis was recently published by Ridker et al, showing positive effects of the interleukin 1-ß-antibody canakinumab in patients with previous myocardial infarction in the CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcome) study [3]
Summary
Cardiovascular disorders represent the major cause of death in the industrialized world. Recent clinical trials reported elevated NGAL plasma levels in coronary artery disease, myocardial infarction, and heart failure [6]. These findings are derived from animal experimental data but have been confirmed in clinical studies [7,8]. NGAL seems to be a predictor of all-cause mortality in ST segment elevation myocardial infarction (STEMI) patients and positively correlates with the severity of coronary heart disease [10,11]. Experimental data revealed that NGAL forms a complex with matrix metalloproteinase-9 (MMP-9), thereby prolonging the proteolytic activity of MMP-9 and contributing to plaque vulnerability This could lead to plaque rupture and subsequently, to a cardiovascular event. According to the abovementioned characteristics of NGAL, we hypothesized that this biomarker may be altered in patients with peripheral atherosclerotic disease and may be a valuable biomarker to guide patient management in preventive medicine
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