Author + information
- Received June 15, 2016
- Revision received December 13, 2016
- Accepted December 19, 2016
- Published online February 27, 2017.
- Anoop Dinesh Shah, MBBS, PhDa,b,∗ (, )
- Spiros Denaxas, PhDa,
- Owen Nicholas, PhDc,
- Aroon D. Hingorani, MBBS, PhDa,b and
- Harry Hemingway, MB BChira
- aFarr Institute of Health Informatics Research, UCL Institute of Health Informatics, University College London, London, United Kingdom
- bUniversity College London Hospitals NHS Foundation Trust, London, United Kingdom
- cNational Institute for Cardiovascular Outcomes Research, UCL Institute of Cardiovascular Science, University College London, London, United Kingdom
- ↵∗Address for correspondence:
Dr. Anoop Dinesh Shah, Farr Institute of Health Informatics Research, UCL Institute of Health Informatics, 222 Euston Road, University College London, London NW1 2DA, United Kingdom.
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.
Objectives 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)
This study was supported by the National Institute for Health Research (RP-PG-0407-10314, PI HH); Wellcome Trust (WT 086091/Z/08/Z, PI HH); the Medical Research Prognosis Research Strategy Partnership (G0902393/99558, PI HH) and the Farr Institute of Health Informatics Research, funded by the Medical Research Council (K006584/1, PI HH), in partnership with Arthritis Research UK, the British Heart Foundation, Cancer Research UK, the Economic and Social Research Council, the Engineering and Physical Sciences Research Council, the National Institute of Health Research, the National Institute for Social Care and Health Research (Welsh Assembly Government), the Chief Scientist Office (Scottish Government Health Directorates) and the Wellcome Trust. ADS was supported by a Wellcome Trust clinical research training fellowship (0938/30/Z/10/Z). Dr. Denaxas was supported by a UCL Provost's Strategic Development Fund fellowship. The funding organizations had no involvement in the design of the study; the collection, analysis, and interpretation of the data; or the decision to approve publication of the finished manuscript.
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received June 15, 2016.
- Revision received December 13, 2016.
- Accepted December 19, 2016.
- 2017 The Authors