Association of total white cell count with mortality and major adverse events in patients with peripheral arterial disease: a systematic review.
OBJECTIVE
Peripheral arterial disease (PAD) is principally caused by atherosclerosis, an established inflammatory disease. Total white cell count (TWCC) is a marker of inflammation and has been associated with outcomes for patients with inflammatory diseases. The aim of this systematic review was to assess the association of TWCC with mortality and major adverse events (MAEs) in PAD patients.


METHODS
Studies investigating the association of TWCC with outcome in patients with PAD were identified by a literature search using the Medline and Cochrane databases. To be eligible for inclusion, studies needed to investigate the association of TWCC with mortality or a composite endpoint that included mortality in patients with PAD. Studies were excluded when the primary focus was carotid artery disease, aortic aneurysmal disease, intracranial vascular disease, or rheumatoid arthritis and treatment with chemotherapy or transplantation of stem cells. Secondary searching of reference lists and relevant reviews was performed.


RESULTS
Ten studies including 8,490 patients with PAD met the inclusion criteria. All studies investigated more than 100 patients with four studies assessing more than 1,000 patients. Study quality varied with well-established risk factors of outcome such as age, smoking, diabetes, and the ankle brachial index being adjusted for inconsistently. The study populations were also disparate. Few studies reported relative risk and 95% confidence intervals for the association of TWCC with mortality or MAE. TWCC was positively and significantly associated with death alone in four of five studies investigating 3,387 patients. TWCC was positively and significantly associated with MAE in five of six studies investigating a total of 6,846 patients.


CONCLUSIONS
Current evidence suggests a positive association of TWCC with mortality and MAEs in patients with PAD. Further well-designed prospective studies are required with high-quality analysis and more complete reporting of outcomes.
Vascular Biology Unit, Queensland Research Centre for Peripheral Vascular Disease, School of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia; Clinical Skills Unit, School of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia; Department of Vascular and Endovascular Surgery, The Townsville Hospital, Queensland, Australia.
D
D
Martin
Clinical Skills Unit, School of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia.
D
D
Wallace
Institute of Sport and Exercise Science, James Cook University, Townsville, Queensland, Australia.
M
M
Crowe
Vascular Biology Unit, Queensland Research Centre for Peripheral Vascular Disease, School of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia; School of Veterinary and Biomedical Sciences, James Cook University, Townsville, Queensland, Australia.
C
C
Rush
Vascular Biology Unit, Queensland Research Centre for Peripheral Vascular Disease, School of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia; Department of Vascular and Endovascular Surgery, The Townsville Hospital, Queensland, Australia.
P
P
Tosenovsky
Vascular Biology Unit, Queensland Research Centre for Peripheral Vascular Disease, School of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia; Department of Vascular and Endovascular Surgery, The Townsville Hospital, Queensland, Australia. Electronic address: jonathan.golledge@jcu.edu.au.
J
J
Golledge
D055109:Ankle Brachial Index; D006801:Humans; D007249:Inflammation; D007958:Leukocyte Count; D058729:Peripheral Arterial Disease / Q000401:mortality*; D011379:Prognosis
Inflammation; Mortality; Peripheral arterial disease; Prognosis; White cell count