ASSA14-03-39 Identification of Aspirin response related gene profiles in the elderly population with coronary artery disease

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Abstract

Aims

Aspirin is widely used in the primary and secondary prevention of cardiovascular diseases. Nevertheless, the responses to aspirin administration vary from one patient to another. A small proportion of patients experience thrombo-embolic events during their daily aspirin therapy, defined as clinical aspirin resistance (AR).

Aims

Recent studies showed that aspirin exposure might have an influence on the expression of various genes, thus responsible for the variability in aspirin effects. The aim of our studywas to identify aspirin responses related gene profiles, and investigate the correlation between target genes expression and clinical outcomes in the elderly population with coronary artery disease (CAD).

Methods

A total of 152 aged patients with CAD treated with low-dose aspirin (100 mg/d) were enrolled in this study. All enrolled patients were distributed according to quartile of 0.5 mmol/l AA-induced platelet aggregation, and AR was defined as the upper quartile of AA-induced platelet aggregation. Total blood RNA were extracted within 4 h and reversely transcribed immediately. Expression of fourteen genes (CLU, CMTM5, CTTN, MPL, TMEM64, SELP, HLA-DQA1, HLA-DRB4, ITGA2B, ITGB3, THBS1, CXCL5, PPBP, and SPARC) was measuredusing real-time quantitative PCR method. Clinical outcomes were defined as the occurrence of cardiovascular events and death during regular aspirin administration.

Results

The quartile cut points of AA-induced platelet aggregation for the 25th, 50th, and 75th percentiles of the enrolled population were 9.7%, 12.0%, and 14.3%, respectively. AR was defined as AA-induced platelet aggregation ≥14.3%. Expressions of six genes (CTTN CXCL5 HLA-DQA1 HLA-DRB4 THBS1 SPARC)were significantly higher in AR group than no-AR group (p < 0.01). What’s more, with a mean follow-up of 6 months, clinical outcomesoccurred more frequently in AR group as compared tono-AR group (p < 0.05).

Conclusion

Six genes (CTTN CXCL5 HLA-DQA1 HLA-DRB4 THBS1 SPARC) were up-regulated in AR group than no-AR group (p < 0.01). What’s more, AR patients have higher risks for cardiovascular events and death than non-AR group (p < 0.05)

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