Clinical InvestigationGeneticsPolymorphisms associated with in vitro aspirin resistance are not associated with clinical outcomes in patients with coronary artery disease who report regular aspirin use
Section snippets
Patient population
Using the DDCD, an ongoing longitudinal clinical registry of patients undergoing cardiac procedures at Duke University Medical Center (DUMC) since 1969 and its associated CATHGEN biorepository (http://cathgen.duhs.duke.edu), which has collected and stored blood samples (for DNA, RNA, and plasma) from consenting patients at the time of cardiac catheterization since 2001, we studied potential clinical and genetic factors associated with death, MI, or stroke during regular aspirin use in patients
Patient population
We identified 11,754 eligible patients in the DDCD who were not enrolled in CATHGEN and who had available follow-up for the development of the clinical model and 3,449 who had DNA samples available in CATHGEN. Baseline characteristics, concomitant medication use, and outcomes of these cohorts are displayed in Table I. Median (interquartile range) follow-up was 3.5 years (1.4-5.0 years) in the nongenetic cohort and 4.0 years (1.7-5.0 years) in the CATHGEN cohort. Baseline characteristics were
Discussion
Numerous genetic associations with in vitro aspirin resistance have been reported, although their ability to predict future events in patients reporting aspirin use is not known. We examined the association of SNPs that have been associated with aspirin resistance in the laboratory with clinical events during follow-up while using aspirin in 3,449 patients with CAD. Despite adequate statistical power, we found no evidence for significantly increased risk for clinical events associated with any
Limitations
Despite methodological strengths, there are limitations that require consideration. First, we did not measure laboratory aspirin response in our study. Second, although we selected variants of interest from the literature, because of differences in population admixture and linkage disequilibrium, we may not have captured the causal variant, thus diminishing any potential association of the SNP of interest with clinical outcome. Therefore, we cannot know with confidence whether the selected
Conclusions
The present study failed to find an association between genetic variants associated with heightened in vitro platelet function during aspirin exposure and death, MI, or stroke during aspirin treatment in long-term follow-up in patients with significant CAD. The use of these genetic variants for risk stratifying patients with CAD or for guiding more aggressive antiplatelet therapy in this population is not justified.
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2016, International Journal of CardiologyCitation Excerpt :The surface of platelets contains lots of transmembrane Glucose Protein (GP) receptors, which are highly polymorphic and are encoded by two or more allelic isoforms. Single nucleotide polymorphisms (SNPs), which occur within a gene or in the regulatory regions near a gene, are the important contributors to residual platelet reactivity in patients with aspirin resistance [15]. The difference in amino acid sequences resulted from these SNPs might affect the secondary or tertiary structure of the GP receptors, and ultimately lead to corresponding changes in their biological function.
Philip F. Binkley, MD, MPH served as guest editor for this article.