title: Neutrophil Counts and Initial Presentation of 12 Cardiovascular Diseases: A CALIBER Cohort Study.
abstract: BACKGROUND
  Neutrophil counts are a ubiquitous measure of inflammation, but previous studies on their association with cardiovascular disease (CVD) were limited by small numbers of patients or a narrow range of endpoints.
  
  
  OBJECTIVE
  This study investigated associations of clinically recorded neutrophil counts with initial presentation for a range of CVDs.
  
  
  METHODS
  We used linked primary care, hospitalization, disease registry, and mortality data in England. We included people 30 years or older with complete blood counts performed in usual clinical care and no history of CVD. We used Cox models to estimate cause-specific hazard ratios (HRs) for 12 CVDs, adjusted for cardiovascular risk factors and acute conditions affecting neutrophil counts (such as infections and cancer).
  
  
  RESULTS
  Among 775,231 individuals in the cohort, 154,179 had complete blood counts performed under acute conditions and 621,052 when they were stable. Over a median 3.8 years of follow-up, 55,004 individuals developed CVD. Adjusted HRs comparing neutrophil counts 6 to 7 versus 2 to 3 × 109/l (both within the 'normal' range) showed strong associations with heart failure (HR: 2.04; 95% confidence interval [CI]: 1.82 to 2.29), peripheral arterial disease (HR: 1.95; 95% CI: 1.72 to 2.21), unheralded coronary death (HR: 1.78; 95% CI: 1.51 to 2.10), abdominal aortic aneurysm (HR: 1.72; 95% CI: 1.34 to 2.21), and nonfatal myocardial infarction (HR: 1.58; 95% CI: 1.42 to 1.76). These associations were linear, with greater risk even among individuals with neutrophil counts of 3 to 4 versus 2 to 3 × 109/l. There was a weak association with ischemic stroke (HR: 1.36; 95% CI: 1.17 to 1.57), but no association with stable angina or intracerebral hemorrhage.
  
  
  CONCLUSIONS
  Neutrophil counts were strongly associated with the incidence of some CVDs, but not others, even within the normal range, consistent with underlying disease mechanisms differing across CVDs. (White Blood Cell Counts and Onset of Cardiovascular Diseases: a CALIBER Study [CALIBER]; NCT02014610).
authors.affiliation: Farr Institute of Health Informatics Research, UCL Institute of Health Informatics, University College London, London, United Kingdom; University College London Hospitals NHS Foundation Trust, London, United Kingdom. Electronic address: anoop@doctors.org.uk.
authors.forename: Anoop Dinesh
authors.initials: AD
authors.lastname: Shah
authors.affiliation: Farr Institute of Health Informatics Research, UCL Institute of Health Informatics, University College London, London, United Kingdom.
authors.forename: Spiros
authors.initials: S
authors.lastname: Denaxas
authors.affiliation: National Institute for Cardiovascular Outcomes Research, UCL Institute of Cardiovascular Science, University College London, London, United Kingdom.
authors.forename: Owen
authors.initials: O
authors.lastname: Nicholas
authors.affiliation: Farr Institute of Health Informatics Research, UCL Institute of Health Informatics, University College London, London, United Kingdom; University College London Hospitals NHS Foundation Trust, London, United Kingdom.
authors.forename: Aroon D
authors.initials: AD
authors.lastname: Hingorani
authors.affiliation: Farr Institute of Health Informatics Research, UCL Institute of Health Informatics, University College London, London, United Kingdom.
authors.forename: Harry
authors.initials: H
authors.lastname: Hemingway
mesh_terms: D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000097:blood* / Q000453:epidemiology*; D015331:Cohort Studies; D004739:England / Q000453:epidemiology; D005260:Female; D006801:Humans; D015994:Incidence; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009504:Neutrophils; D016016:Proportional Hazards Models
keywords: disease mechanisms; electronic health records; epidemiology; incidence; inflammation