Association of platelet count with all-cause mortality and risk of cardiovascular and respiratory morbidity in stable COPD

Abstract

Background: Platelet count is a prognostic indicator in the general population and elderly. Thrombocytosis during acute exacerbation of COPD (AECOPD) has been associated with mortality; however, the relationship between platelet count and mortality in stable COPD is unknown.

Methods: We performed post hoc secondary analysis on a subsample of 1797 patients in the Study to Understand Mortality and Morbidity in COPD (SUMMIT) who had blood samples drawn at baseline. Participants were current or former smokers, 40-80 years old with moderate COPD and history or increased risk of cardiovascular (CV) disease. The primary outcome was on and post-treatment all-cause mortality. Secondary outcomes included first-on-treatment moderate/severe AECOPD and on-treatment CV composite event (CV death, myocardial infarction, stroke, unstable angina and transient ischemic attack). Multivariable Cox proportional hazards models were used to investigate study endpoint associations with platelet count quintile grouping, continuous platelet count utilizing two-term fractional polynomials, and categories of low, normal and high platelet count (< 150, ≥150 to < 300, ≥300 × 109/L).

Results: Patients were followed for 2.3 ± 0.9 years for vital status and 1.6 ± 1.1 years for morbidity endpoints during which 105 (5.8%) died, 651 (36.2%) experienced AECOPD (159 with severe AECOPD) and 86 (4.8%) experienced a CV event. A U-shaped association between platelet count and all-cause mortality was observed. Compared to the third quintile group (Q3) of platelet count, risk of death was increased in the lowest quintile group (Q1; hazard ratio [HR]: 1.73; 95% confidence interval [CI]: 0.93-3.23) and highest quintile group (Q5; HR: 1.66; 95%CI: 0.89-3.10), though point estimates were imprecise. Using clinical cutoffs, compared with normal platelet counts (≥150 to < 300 × 109/L), risk of all-cause mortality was nominally increased among patients with thrombocytopenia (HR: 1.46; 95%CI: 0.81-2.64) and high platelet count (HR: 1.66; 95%CI: 0.96-2.86). Compared with Q3, CV events were nominally increased for Q5 (HR: 1.71; 95%CI: 0.83-3.49) and Q1 (HR: 1.41; 95%CI: 0.70, 2.85). There was no association between platelet count and AECOPD.

Conclusions: In stable COPD platelet count demonstrated a U-shaped association with increased risk of 3-year all-cause mortality, though a platelet count level above or below which risk of mortality was increased could not be definitively identified.

Trial registration: ClinicalTrials.gov NCT01313676 .

Keywords: Cardiovascular disease; Chronic obstructive pulmonary disease; Exacerbations; Mortality; Platelet count.

Conflict of interest statement

Ethics approval and consent to participate

The study was approved by local ethics committees and was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines.

Consent for publication

Not applicable.

Competing interests

AF declares no conflict of interest. JAA, CC and JCY are employees of, and own shares in, GlaxoSmithKline plc. NJC is employed by Veramed Ltd., a Contract Research Organisation undertaking contracted statistical analyses of respiratory studies funded by GlaxoSmithKline plc. RW served as the Chair of the Summit Clinical Endpoint Committee and has received grant support and received consulting fees from GlaxoSmithKline plc during the conduct of the study. He has received grants and consulting fees from AstraZeneca and Boehringer Ingelheim. He has received consulting fees from Contrafect, Pulmonx, Roche, Spiration, Sunovion, Merck, Circassia, Verona, Mylan, Theravance, and Propeller Health unrelated to the submitted work. NNH has participated on advisory boards for GlaxoSmithKline plc, Mylan and AstraZeneca, and has received Research Grants from GlaxoSmithKline plc, AstraZeneca and Boehringer Ingelheim.

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Figures

Fig. 1

Association of platelet count with death from any cause. Open circles and 95% confidence intervals represent hazard ratio in each quintile in reference to middle quintile, shown as a filled circle. Curve and shaded region show hazard ratio and 95% confidence region of platelet count as a continuous variable in reference to the median platelet count

Fig. 2

Association of platelet count with first on-treatment (a) moderate/severe COPD exacerbations, b severe COPD exacerbations, and (c) cardiovascular composite event (cardiovascular death, myocardial infarction, stroke, unstable angina, and transient ischemic attack) Open circles and 95% confidence intervals represent hazard ratio in each quintile in reference to middle quintile, shown as a filled circle. Curve and shaded region show hazard ratio and 95% confidence region of platelet count as a continuous variable in reference to the median platelet count