Proteomic Discovery and Validation of the Confounding Effect of Heparin Administration on the Analysis of Candidate Cardiovascular Biomarkers
Hans Christian Beck (1), Lisette O. Jensen (1) Charlotte Gils (1), Albertine M. M. Ilondo (1), Martin Frydland (2), Christian Hassager (2), Ole K. Møller-Helgestad (2), Jacob E. Møller (1) and Lars M. Rasmussen (1) (1) Odense University Hospital, Odense, DK (2) Rigshospitalet, Copenhagen, DK
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Hans Christian Beck (Presenter) Odense universitetshospital
Relevant Financial Disclosures
(within past 24 months)
No relevant financial relationship(s) to disclose.
Abstract
BACKGROUND: Several plasma proteins have been suggested
as markers for a variety of cardiovascular conditions
but fail to qualify in independent patient cohorts.
This may relate to interference of medication on plasma
protein concentrations. We used proteomics to identify
plasma proteins that changed in concentration with heparin
administration and therefore potentially may confound
their evaluation as biomarkers in situations in
which heparin is used.
METHODS: We used a proteomic approach based on
isobaric tagging and nano-LC-MS/MS analysis to
quantify several hundred proteins in a discovery study
in which individual plasma samples from 9 patients at
intravascular ultrasound follow-up 12 months after an
acute myocardial infarction before heparin administration
and 2, 15, and 60 min after heparin administration;
we validated our findings in 500 individual
plasma samples obtained at admission from patients
with suspected ST segment elevation myocardial infarction
(STEMI), of whom 363 were treated with
heparin before admission.
RESULTS: In the discovery study, 25 of 653 identified
plasma proteins displayed a changed concentration after
heparin administration (Bonferroni-corrected P
value at P < 7.66 x 10-5). Fourteen of the proteins
changed significantly among heparin-treated patients in the
validation study (nominal significance level of P < 6.92 x
10-5). Among heparin-affected proteins in both the discovery
study and the validation study were midkine, spondin 1,
secreted frizzled-like protein 1, lipoprotein lipase, and follistatin,all previously associated with STEMI.
CONCLUSIONS: Medications such as heparin administration
given before blood sampling may confound biomarker
discovery and should be carefully considered in
such studies.
= Discovery stage.
= Translation stage.
= Clinically available.
