Abstract 17200: Cystatin C Adds Prognostic Value Over Conventional Predictors of Cardiovascular Disease Outcomes: Results from the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Trial

Background Blood levels of the polypeptide, cystatin C, have been reported to be associated with increased cardiovascular mortality. However, cystatin C levels reflect renal dysfunction, and whether there is an association with cardiovascular outcomes independent of serum creatinine or eGFR is uncertain. This was examined in the LIPID study, a double-blind, randomised, placebo-controlled trial of pravastatin in patients with prior CHD. Of 9014 patients, 7863 had a baseline blood sample of sufficient volume for measurement of biomarker levels. Methods and Results Cystatin C levels were typically higher with higher levels of other risk factors. There was no difference in the median cystatin C level between pravastatin (median (IQR) 0.8 (0.7-0.9)) and placebo (0.8 (0.7-0.9)) groups ( P =0.38) at baseline. The risk of different CVD events was considered in multivariate time-to-event models adjusting for pravastatin treatment, conventional risk factors and other novel biomarkers. Baseline cystatin C was an independent predictor of a range of CVD events. The risk of a CHD event was 66% higher in the highest than the lowest quartile of cystatin C (Q4: >0.93 mg/dL) than the lowest (Q1: ≤0.72) (HR 1.66, 95% CI 1.37-2.00). The risk of a nonhemorrhagic stroke was 85% higher in Q4. The relative effects of pravastatin were similar across all quartiles of cystatin C with higher absolute reduction in Q4. While eGFR was a significant predictor (all P <0.008) of all outcomes except for stroke ( P =0.08) in a model with conventional risk factors, it was not a significant risk factor for any outcome when cystatin C was included in the model. Conclusion Cystatin C is an important predictor of future cardiovascular outcomes in patients with previous CHD events independent of eGFR.