Presenter of 1 Presentation
HIGH BLOOD NEUTROPHIL COUNTS AND ISCHEMIC VASCULAR DISEASE: OBSERVATIONAL AND GENETIC STUDIES
Abstract
Background and Aims
Background: High total leukocyte and neutrophil counts and the ratio between them have been associated with high risk of cardiovascular disease. Specific ischemic vascular endpoints have however not been investigated and the causal potential of such associations remains unexplored. Our aim was to examine the associations between blood leukocyte subpopulation counts and risk of specific ischemic vascular endpoints using observational and genetic studies.
Methods
Methods: Observationally, we included 101,730 participants from the prospective Copenhagen General Population Study. Ischemic vascular endpoints were coronary artery disease (CAD), myocardial infarction (MI), ischemic cerebrovascular disease (ICVD), ischemic stroke (IS), non-Alzheimer’s dementia (non-AD), and vascular dementia (VD). Genetically, we applied a two-sample Mendelian Randomization (MR) design including 438,847 individuals.
Results
Results: Multivariable adjusted hazard ratios (HR) (95% confidence interval) for individuals in the 95-100th versus the 25-75th percentile group of neutrophil counts were 1.22 (1.10-1.36) for CAD, 1.22 (1.02-1.45) for MI, and 1.29 (1.05-1.59) for non-AD. Odds ratios (95% confidence interval) per one-SD increase in genetically determined neutrophil counts were 1.14 (1.05-1.23) for CAD and 1.22 (1.06-1.41) for MI. A series of sensitivity analyses accounting for pleiotropy, invalid genetic instruments, and outliers were applied and showed similar results. No genetic estimates could be generated for ICVD, non-AD and VD, due to lack of available genomic consortia.
Conclusions
Conclusion: High blood neutrophil counts were observationally and genetically associated with risk of CAD and MI. The present novel findings support a direct role for neutrophils in atherosclerosis development and highlight these pathways as potential drug targets.