Polymorphism of the cystatin C gene in patients with acute coronary syndromes: Results from the PLATelet inhibition and patient Outcomes study

Purpose Elevated cystatin C concentration is an independent risk factor for cardiovascular (CV) events in patients with acute coronary syndromes. Genetic polymorphisms in CST3 influence cystatin C levels, but their relationship to outcomes is unclear. Methods We measured cystatin C concentrations in...

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Veröffentlicht in:The American heart journal 2014-07, Vol.168 (1), p.96-102.e2
Hauptverfasser: Åkerblom, Axel, MD, PhD, Eriksson, Niclas, PhD, Wallentin, Lars, MD, PhD, Siegbahn, Agneta, MD, PhD, Barratt, Bryan J., PhD, Becker, Richard C., MD, Budaj, Andrzej, MD, PhD, Himmelmann, Anders, MD, PhD, Husted, Steen, MD, DSc, Storey, Robert F., MD, DM, Johansson, Åsa, PhD, James, Stefan K., MD, PhD
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Sprache:eng
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Zusammenfassung:Purpose Elevated cystatin C concentration is an independent risk factor for cardiovascular (CV) events in patients with acute coronary syndromes. Genetic polymorphisms in CST3 influence cystatin C levels, but their relationship to outcomes is unclear. Methods We measured cystatin C concentrations in plasma, obtained within 24 hours of admission, in 16,279 acute coronary syndrome patients from the PLATO trial. In 9,978 patients, we performed a genome-wide association study with up to 2.5 million single nucleotide polymorphisms. Single nucleotide polymorphisms affecting cystatin C levels were evaluated in relation to the first occurrence of myocardial infarction (MI) or CV death within 1 year using Cox regression analysis. Results Several single nucleotide polymorphisms were associated with cystatin C levels, most significantly rs6048952 ( P = 7.82 × 10−16 ) adjacent to CST3 . Median cystatin C concentrations per genotype were 0.85 mg/L (A/A), 0.80 mg/L (A/G), and 0.73 mg/L (G/G). Modeled as additive, the allelic effect, multivariable adjusted, was −0.045 mg/L per G allele for rs6048952. The multivariable adjusted c -statistic regarding the combined end point (CV death or MI) was 0.6735. Adding cystatin C or genotype-adjusted cystatin C levels resulted in c -statistics of 0.6761 and 0.6758, respectively. The multivariable adjusted hazard ratios per G allele at rs6048952 in the entire population were 0.94 (95% CI 0.83–1.06) for CV death or MI and 0.88 (95% CI 0.71–1.08) for CV death. Conclusions Genetic polymorphisms affect cystatin C concentrations independently of kidney function. However, the polymorphisms were not observed to be associated with outcome, nor did they improve risk prediction or discriminative models.
ISSN:0002-8703
1097-6744
1097-6744
DOI:10.1016/j.ahj.2014.03.010