Abstract 13713: Genetic Polymorphism and Relationship to Cystatin C Concentrations and Outcome - Results From the Platelet Inhibition and Patient Outcomes Study
Introduction: Plasma cystatin C is independently associated with cardiovascular (CV) risk in non-ST-elevation acute coronary syndromes (NSTE-ACS). The effect of genetic variability on cystatin C concentrations and outcome is unclear.
Methods: Plasma cystatin C concentrations were measured in blood, obtained within 24 hours of admission, in 16279 ACS patients from the PLATelet inhibition and patient Outcomes trial. 9978 patients were genome-wide genotyped with up to 2.5 million SNPs. The first occurrence of CV death or myocardial infarction (MI) within one year was evaluated by multivariable (clinical variables and biomarkers) Cox regression analysis and c-statistics both overall (all ACS) and in NSTE-ACS.
Results: We observed SNP association with cystatin C levels (up to p=7.82 x 10-16). The most significant SNP (rs6048952) was adjacent the CST3 gene with additive effect on cystatin C concentrations: 0.85mg/L, 0.80mg/L and 0.73mg/L for the A/A, A/G and G/G genotypes respectively. Multivariable c-statistics regarding the combined endpoint (CV death or MI) was 0.6619. Adding cystatin C concentrations or genetically adjusted cystatin C levels, exhibited c-statistics of 0.6705 and 0.6703, respectively.
The hazard ratio for rs6048952 was 0.93 (95%CI 0.82-1.04) regarding the combined endpoint, while 0.85 (95%CI 0.70-1.03) regarding CV death in all ACS patients. In the NSTE-ACS subgroup, the hazard ratio for rs6048952 was 0.72 (95%CI 0.54-0.95) (n=5583).
Conclusions: Genetic polymorphism, independently of kidney function, affects cystatin C concentrations, but does not appear to be associated with ischemic outcome in an overall ACS population. However, genetic variation may be associated with cardiovascular mortality in moderate-to-high risk NSTE-ACS patients.
- Renal function
- Acute coronary syndromes
- Genome-wide association studies (GWAS)
- Myocardial infarction
- © 2013 by American Heart Association, Inc.