Plasma Osteopontin Levels and Adverse Cardiovascular Outcomes in the PEACE Trial

Osteopontin (OPN) is a secreted glycophosphoprotein that has a role in inflammation, immune response and calcification. We hypothesized that plasma OPN levels are associated with adverse cardiovascular outcomes in patients with stable coronary artery disease (CAD) and preserved ejection fraction (EF...

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Bibliographic Details
Published in:PloS one Vol. 11; no. 6; p. e0156965
Main Authors: Abdalrhim, Ahmed D., Marroush, Tariq S., Austin, Erin E., Gersh, Bernard J., Solak, Nusret, Rizvi, Syed A., Bailey, Kent R., Kullo, Iftikhar J.
Format: Journal Article
Language:English
Published: United States Public Library of Science 10.06.2016
Public Library of Science (PLoS)
Subjects:
Age
Aged
Analysis
Angioplasty
Antihypertensive Agents - therapeutic use
Atherosclerosis
Biocompatibility
Biology and Life Sciences
Biomarkers
Calcification
Cardiovascular disease
Cardiovascular System - physiopathology
Chemiluminescence
Coefficient of variation
Complications and side effects
Coronary artery
Coronary artery disease
Coronary Artery Disease - blood
Coronary Artery Disease - diagnosis
Coronary Artery Disease - drug therapy
Coronary Artery Disease - mortality
Coronary vessels
Diagnosis
Female
Follow-Up Studies
Genetic aspects
Glycoproteins
Hazards
Health risk assessment
Heart
Heart attacks
Heart diseases
Heart failure
Humans
Hypertension
Hypothesis testing
Immune response
Immune system
Indoles - therapeutic use
Inflammation
Male
Measurement
Medical imaging
Medical treatment
Medicine and Health Sciences
Middle Aged
Myocardial infarction
Osteopontin
Osteopontin - blood
Patient outcomes
Patients
Physiological aspects
Prognosis
Regression analysis
Research and Analysis Methods
Risk Factors
Secondary analysis
Sex
Statistical analysis
Stroke Volume - physiology
United States
United States > US
Minnesota
ISSN:1932-6203, 1932-6203
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Description
Summary:Osteopontin (OPN) is a secreted glycophosphoprotein that has a role in inflammation, immune response and calcification. We hypothesized that plasma OPN levels are associated with adverse cardiovascular outcomes in patients with stable coronary artery disease (CAD) and preserved ejection fraction (EF) enrolled in the PEACE trial. We measured plasma OPN levels at baseline in 3567 CAD patients (mean age 64.5 ± 8.1 years, 81% men) by a sandwich chemiluminescent assay (coefficient of variation = 4.1%). OPN levels were natural log (Ln) transformed prior to analyses. We assessed whether Ln OPN levels were associated with the composite primary endpoint of cardiovascular death, non-fatal myocardial infarction and hospitalization for heart failure using multiple event multivariable Cox proportional hazards regression. Adjustment was performed for: (a) age and sex; (b) additional potential confounders; and (c) a parsimonious set of statistically significant 10 variates. During a median follow-up of 4.8 years, 416 adverse cardiovascular outcomes occurred in 366 patients. Ln OPN was significantly associated with the primary endpoint; HR (95% CI) = 1.56 (1.27, 1.92); P <0.001, and remained significant after adjustment for age and sex [1.31 (1.06, 1.61); P = 0.01] and after adjustment for relevant covariates [1.24 (1.01, 1.52); P = 0.04]. In a secondary analysis of the individual event types, Ln OPN was significantly associated with incident hospitalization for heart failure: HR (95% CI) = 2.04 (1.44, 2.89); P <0.001, even after adjustment for age, sex and additional relevant covariates. In conclusion, in patients with stable CAD and preserved EF on optimal medical therapy, plasma OPN levels were independently associated with the composite incident endpoint of adverse cardiovascular outcomes as well as incident hospitalization for heart failure.
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Competing Interests: The authors have declared that no competing interests exist.
Conceived and designed the experiments: IJK KRB AA. Performed the experiments: AA TM NS. Analyzed the data: EA KRB. Contributed reagents/materials/analysis tools: IJK SR. Wrote the paper: AA EA NS BG SR TM KRB IJK.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0156965