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      Neutrophil Counts and Initial Presentation of 12 Cardiovascular Diseases : A CALIBER Cohort Study

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          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.

          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 × 10 9/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 × 10 9/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)

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          Neutrophil recruitment and function in health and inflammation.

          Elzbieta Kolaczkowska, Paul Kubes (2013)
          Neutrophils have traditionally been thought of as simple foot soldiers of the innate immune system with a restricted set of pro-inflammatory functions. More recently, it has become apparent that neutrophils are, in fact, complex cells capable of a vast array of specialized functions. Although neutrophils are undoubtedly major effectors of acute inflammation, several lines of evidence indicate that they also contribute to chronic inflammatory conditions and adaptive immune responses. Here, we discuss the key features of the life of a neutrophil, from its release from bone marrow to its death. We discuss the possible existence of different neutrophil subsets and their putative anti-inflammatory roles. We focus on how neutrophils are recruited to infected or injured tissues and describe differences in neutrophil recruitment between different tissues. Finally, we explain the mechanisms that are used by neutrophils to promote protective or pathological immune responses at different sites.
          Article 0 comments Cited 1052 times – based on 0 reviews     Review now
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            2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.

            David C. Goff, Donald M. Lloyd-Jones, Glen Bennett … (2014)
            Article 0 comments Cited 518 times – based on 0 reviews     Review now
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              Blood pressure and incidence of twelve cardiovascular diseases: lifetime risks, healthy life-years lost, and age-specific associations in 1·25 million people

              Eleni Rapsomaniki, Adam Timmis, Julie George … (2014)
              Summary Background The associations of blood pressure with the different manifestations of incident cardiovascular disease in a contemporary population have not been compared. In this study, we aimed to analyse the associations of blood pressure with 12 different presentations of cardiovascular disease. Methods We used linked electronic health records from 1997 to 2010 in the CALIBER (CArdiovascular research using LInked Bespoke studies and Electronic health Records) programme to assemble a cohort of 1·25 million patients, 30 years of age or older and initially free from cardiovascular disease, a fifth of whom received blood pressure-lowering treatments. We studied the heterogeneity in the age-specific associations of clinically measured blood pressure with 12 acute and chronic cardiovascular diseases, and estimated the lifetime risks (up to 95 years of age) and cardiovascular disease-free life-years lost adjusted for other risk factors at index ages 30, 60, and 80 years. This study is registered at ClinicalTrials.gov, number NCT01164371. Findings During 5·2 years median follow-up, we recorded 83 098 initial cardiovascular disease presentations. In each age group, the lowest risk for cardiovascular disease was in people with systolic blood pressure of 90–114 mm Hg and diastolic blood pressure of 60–74 mm Hg, with no evidence of a J-shaped increased risk at lower blood pressures. The effect of high blood pressure varied by cardiovascular disease endpoint, from strongly positive to no effect. Associations with high systolic blood pressure were strongest for intracerebral haemorrhage (hazard ratio 1·44 [95% CI 1·32–1·58]), subarachnoid haemorrhage (1·43 [1·25–1·63]), and stable angina (1·41 [1·36–1·46]), and weakest for abdominal aortic aneurysm (1·08 [1·00–1·17]). Compared with diastolic blood pressure, raised systolic blood pressure had a greater effect on angina, myocardial infarction, and peripheral arterial disease, whereas raised diastolic blood pressure had a greater effect on abdominal aortic aneurysm than did raised systolic pressure. Pulse pressure associations were inverse for abdominal aortic aneurysm (HR per 10 mm Hg 0·91 [95% CI 0·86–0·98]) and strongest for peripheral arterial disease (1·23 [1·20–1·27]). People with hypertension (blood pressure ≥140/90 mm Hg or those receiving blood pressure-lowering drugs) had a lifetime risk of overall cardiovascular disease at 30 years of age of 63·3% (95% CI 62·9–63·8) compared with 46·1% (45·5–46·8) for those with normal blood pressure, and developed cardiovascular disease 5·0 years earlier (95% CI 4·8–5·2). Stable and unstable angina accounted for most (43%) of the cardiovascular disease-free years of life lost associated with hypertension from index age 30 years, whereas heart failure and stable angina accounted for the largest proportion (19% each) of years of life lost from index age 80 years. Interpretation The widely held assumptions that blood pressure has strong associations with the occurrence of all cardiovascular diseases across a wide age range, and that diastolic and systolic associations are concordant, are not supported by the findings of this high-resolution study. Despite modern treatments, the lifetime burden of hypertension is substantial. These findings emphasise the need for new blood pressure-lowering strategies, and will help to inform the design of randomised trials to assess them. Funding Medical Research Council, National Institute for Health Research, and Wellcome Trust.
              Article 0 comments Cited 352 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Anoop Dinesh Shah
                Journal
                Journal ID (nlm-ta): J Am Coll Cardiol
                Journal ID (iso-abbrev): J. Am. Coll. Cardiol
                Title: Journal of the American College of Cardiology
                Publisher: Elsevier Biomedical
                ISSN (Print): 0735-1097
                ISSN (Electronic): 1558-3597
                Publication date PMC-release: 07 March 2017
                Publication date (Print): 07 March 2017
                Volume: 69
                Issue: 9
                Pages: 1160-1169
                Affiliations
                [a ]Farr Institute of Health Informatics Research, UCL Institute of Health Informatics, University College London, London, United Kingdom
                [b ]University College London Hospitals NHS Foundation Trust, London, United Kingdom
                [c ]National Institute for Cardiovascular Outcomes Research, UCL Institute of Cardiovascular Science, University College London, London, United Kingdom
                Author notes
                [∗ ] 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.Farr Institute of Health Informatics Research, UCL Institute of Health Informatics222 Euston Road, University College LondonLondon NW1 2DAUnited Kingdom anoop@ 123456doctors.org.uk
                Article
                Publisher ID: S0735-1097(17)30109-2
                DOI: 10.1016/j.jacc.2016.12.022
                PMC ID: 5332591
                PubMed ID: 28254179
                SO-VID: 9d470394-8fd2-491c-919d-e6ae14e64a2a
                Copyright © © 2017 The Authors
                License:

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 15 June 2016
                Date revision received : 13 December 2016
                Date accepted : 19 December 2016
                Categories
                Subject: Original Investigation

                ScienceOpen disciplines: Cardiovascular Medicine
                Keywords: disease mechanisms,electronic health records,epidemiology,incidence,inflammation,ci, confidence interval,cvd, cardiovascular disease,hf, heart failure,hr, hazard ratio,iqr, interquartile range,mi, myocardial infarction,pad, peripheral arterial disease
                Data availability:
                ScienceOpen disciplines: Cardiovascular Medicine
                Keywords: disease mechanisms, electronic health records, epidemiology, incidence, inflammation, ci, confidence interval, cvd, cardiovascular disease, hf, heart failure, hr, hazard ratio, iqr, interquartile range, mi, myocardial infarction, pad, peripheral arterial disease

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