title: Cystatin C identifies cardiovascular risk better than creatinine-based estimates of glomerular filtration in middle-aged individuals without a history of cardiovascular disease.
abstract: OBJECTIVE
  Creatinine- and cystatin C-based estimates of renal function are considered to be cardiovascular disease (CVD) risk factors, but the clinical utility in middle-aged subjects without a history of CVD is controversial.
  
  
  METHODS
  We related plasma cystatin C and creatinine-based glomerular filtration rate (GFR) [MDRD, CKD-EPI-2009, and CKD-EPI-comb (a combination of creatinine and cystatin C)] to incident CVD, CVD mortality, all-cause mortality, and heart failure in 4650 middle-aged subjects without CVD.
  
  
  RESULTS
  The hazard ratio (HR) per standard deviation increment (95% CI) of cystatin C predicted incident CVD (1.22, 1.11-1.33; P < 0.0001), CVD mortality (1.44, 1.24-1.66; P < 0.0001), all-cause mortality (1.15, 1.05-1.26; P = 0.002), and heart failure (1.27, 1.05-1.55; P = 0.02), whereas MDRD and CKD-EPI-2009 only predicted CVD mortality (0.79, 0.66-0.93; P = 0.006 and 0.78, 0.66-0.92; P = 0.003, respectively). Cystatin C led to a significant increase in the net reclassification improvement for all endpoints, except heart failure. Only within the quartile with the worst renal function were all measures related to all-cause and CVD mortality. The top 25% of cystatin C in the population significantly predicted risk of incident CVD and CVD mortality, whereas MDRD and CKD-EPI-2009 were predictors of CVD mortality only at a GFR < 60 mL/min/1.73 m(2) (11-13% of the population) and of incident CVD only at a GFR < 45 mL/min/1.73 m(2) (<1% of the population).
  
  
  CONCLUSIONS
  Cystatin C is a better risk marker for CVD morbidity and mortality than creatinine-based GFR. Whether this is explained by cystatin C being a better marker for true GFR or through other effects of cystatin C remains to be shown.
authors.affiliation: Department of Internal Medicine, Trelleborg Hospital, Trelleborg, Sweden; Institution of Clinical Sciences, Lund University, Malmö, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Svensson-Färbom
authors.forename: M
authors.initials: M
authors.lastname: Ohlson Andersson
authors.forename: P
authors.initials: P
authors.lastname: Almgren
authors.forename: B
authors.initials: B
authors.lastname: Hedblad
authors.forename: G
authors.initials: G
authors.lastname: Engström
authors.forename: M
authors.initials: M
authors.lastname: Persson
authors.forename: A
authors.initials: A
authors.lastname: Christensson
authors.forename: O
authors.initials: O
authors.lastname: Melander
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000175:diagnosis* / Q000401:mortality; D002423:Cause of Death; D003404:Creatinine / Q000378:metabolism; D055316:Cystatin C / Q000378:metabolism*; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology*; D006333:Heart Failure / Q000175:diagnosis / Q000401:mortality; D006801:Humans; D007676:Kidney Failure, Chronic / Q000401:mortality / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D015415:Biomarkers; D055316:Cystatin C; D003404:Creatinine
keywords: MDRD; cardiovascular disease; chronic kidney disease; cystatin C; estimated glomerular filtration rate