Affiliation:
1. Center for Cardiovascular Disease Prevention, Divisions of Preventive Medicine and Cardiovascular Diseases, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, 900 Commonwealth Avenue, Boston, MA 02215, USA
2. Division of Intramural Research, Cardiovascular Branch, Lab of Inflammation and Cardiometabolic Diseases, National Heart Lung and Blood Institute, Bethesda, MD, USA
3. Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA
Abstract
Abstract
Aims
The neutrophil–lymphocyte ratio (NLR) is a readily available inflammatory biomarker that may associate with atherosclerosis and predict cardiovascular (CV) events. The aims of this study are to determine whether the NLR predicts incident major adverse cardiovascular events (MACE) and is modified by anti-inflammatory therapy.
Methods and results
Baseline and on-treatment NLRs were calculated from complete blood counts among 60 087 participants randomized in the CANTOS, JUPITER, SPIRE-1, SPIRE-2, and CIRT trials to receive placebo or canakinumab, rosuvastatin, bococizumab, or methotrexate, respectively, and followed up for MACE. All analyses were performed first in CANTOS, and then externally validated in the other four trials. For the five trials, hazard ratios for major CV events and mortality comparing NLR quartiles were computed using Cox proportional hazards models, and the effect of each randomized intervention on the NLR was evaluated in comparison to placebo. The NLR modestly correlated with interleukin-6, C-reactive protein, and fibrinogen levels but minimally with lipids. In all five randomized trials, baseline NLR predicted incident CV events and death; the per-quartile increase in risk of MACE was 20% in CANTOS [95% confidence interval (CI) 14–25%, P < 0.0001], 31% in SPIRE-1 (95% CI 14–49%, P = 0.00007), 27% in SPIRE-2 (95% CI 12–43%, P = 0.0002), 9% in CIRT (95% CI 0.2–20%, P = 0.045), and 11% in JUPITER (95% CI 1–22%, P = 0.03). While lipid-lowering agents had no significant impact on the NLR, anti-inflammatory therapy with canakinumab lowered the NLR (P < 0.0001).
Conclusion
The NLR, an easily obtained inflammatory biomarker, independently predicts CV risk and all-cause mortality, and is reduced by interleukin-1β blockade with canakinumab.
Funder
AstraZeneca
National Heart, Lung, and Blood Institute
American Heart Association
Publisher
Oxford University Press (OUP)
Subject
Cardiology and Cardiovascular Medicine