title: Cystatin C is independently associated with total and cardiovascular mortality in individuals undergoing coronary angiography. The Ludwigshafen Risk and Cardiovascular Health (LURIC) study.
abstract: OBJECTIVE
  Cystatin C is a well established marker of kidney function. There is evidence that cystatin C concentrations are also associated with mortality. The present analysis prospectively evaluated the associations of cystatin C with all-cause and cardiovascular (CV) mortality in a well-characterized cohort of persons undergoing angiography, but without overt renal insufficiency.
  
  
  METHODS
  Cystatin C was available in 2998 persons (mean age: 62.7 ± 10.5 years; 30.3% women). Of those 2346 suffered from coronary artery disease (CAD) and 652 (controls) did not. Creatinine (mean ± SD: 83.1 ± 47.8 vs. 74.1 ± 24.7 μmol/L, p = 0.036) but not Cystatin C (mean ± SD: 1.02 ± 0.44 vs. 0.92 ± 0.26 mg/L, p = 0.065) was significantly higher in patients with CAD. After a median follow-up of 9.9 years, in total 898 (30%) deaths occurred, 554 (18.5%) due to CV disease and 326 (10.9%) due to non-CV causes. Multivariable-adjusted Cox analysis (adjusting for eGFR and established cardiovascular risk factors, lipid lowering therapy, angiographic coronary artery disease, and C-reactive protein) revealed that patients in the highest cystatin C quartile were at an increased risk for all-cause (hazard ratio (HR) 1.93, 95% CI 1.50-2.48) and CV mortality (HR 2.05 95% CI 1.48-2.84) compared to those in the lowest quartile. The addition of cystatin C to a model consisting of established cardiovascular risk factors increased the area under the receiver-operating characteristic curve for CV and all-cause mortality, but the difference was statistically not significant. However, reclassification analysis revealed significant improvement by addition of cystatin C for CV and all-cause mortality (p < 0.001), respectively.
  
  
  CONCLUSIONS
  The concentration of cystatin C is strongly associated with long-term all-cause and cardiovascular mortality in patients referred to coronary angiography, irrespective of creatinine-based renal function.
authors.affiliation: Division of Nephrology, Department of Medicine I, University of Bonn, Germany. woitas@uni-bonn.de
authors.forename: Rainer P
authors.initials: RP
authors.lastname: Woitas
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Kleber
authors.forename: Andreas
authors.initials: A
authors.lastname: Meinitzer
authors.forename: Tanja B
authors.initials: TB
authors.lastname: Grammer
authors.forename: Günther
authors.initials: G
authors.lastname: Silbernagel
authors.forename: Stefan
authors.initials: S
authors.lastname: Pilz
authors.forename: Andreas
authors.initials: A
authors.lastname: Tomaschitz
authors.forename: Gisela
authors.initials: G
authors.lastname: Weihrauch
authors.forename: Harald
authors.initials: H
authors.lastname: Dobnig
authors.forename: Winfried
authors.initials: W
authors.lastname: März
authors.forename: Hubert
authors.initials: H
authors.lastname: Scharnagl
mesh_terms: D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D017023:Coronary Angiography / Q000401:mortality*; D003324:Coronary Artery Disease / Q000097:blood* / Q000000981:diagnostic imaging / Q000401:mortality*; D003404:Creatinine / Q000097:blood; D055316:Cystatin C / Q000097:blood*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: C525030:CST3 protein, human; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D055316:Cystatin C; D002097:C-Reactive Protein; D003404:Creatinine
keywords: Coronary artery disease; Cystatin C; Mortality; Renal function; eGFR