title: Cystatin C Predicts Incident Cardiovascular Disease in Twins.
abstract: Cystatin C is associated with both renal function and atherosclerotic cardiovascular disease (ASCVD). We have previously shown a genetic correlation between cystatin C and prevalent ASCVD. The objective of this article is to study whether variation in cystatin C or creatinine predicts incident ASCVD when controlled for genetic factors.
  
  
  
  The predictive value of cystatin C and creatinine for incident ASCVD was studied in 11 402 Swedish twins, free of CVD at baseline, in an adjusted Cox-regression model during a median follow-up of 71 months. Twin pairs discordant for incident stroke, myocardial infarction and ASCVD during follow-up were identified and within-pair comparisons regarding cystatin C and creatinine levels were performed. We also investigated whether contact frequency and degree of shared environment influences were associated with similarity in cystatin C levels. In univariate analysis, cystatin C predicted incident ASCVD hazard ratio 1.57, 95% CI 1.47-1.67. When adjusted for traditional Framingham risk factors as covariates, cystatin C remained a predictor of incident stroke hazard ratio 1.45, 95% CI (1.25-1.70), ASCVD hazard ratio 1.26, 95% CI (1.13-1.41), and myocardial infarction hazard ratio 1.16, 95% CI (1.01-1.33). In twins discordant for incident stroke, cystatin C at baseline was higher in the twin who experienced a stroke compared to the healthy co-twin (1.11±0.3 mg/L versus 1.06±0.3 mg/L), whereas creatinine was lower in the twin who developed CVD compared to their healthy co-twins (76.1±16.9 μmol/L versus 79.4±20.3 μmol/L).
  
  
  
  Variation in cystatin C relates to incident ASCVD and to stroke when adjusted for genetic confounding. In identical twins, cystatin C may be a sensitive marker of early hypertensive end-organ damage and small-vessel disease, whereas creatinine level may reflect nutritional status. The findings in disease-discordant monozygotic twins indicate that unique, possibly preventable, environmental factors are important.
authors.affiliation: Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden Department of Emergency Medicine, Karolinska University Hospital Solna, Stockholm, Sweden johannes.arpegard@ki.se.
authors.forename: Johannes
authors.initials: J
authors.lastname: Arpegård
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Patrik K E
authors.initials: PK
authors.lastname: Magnusson
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Xu
authors.initials: X
authors.lastname: Chen
authors.affiliation: Division of Clinical Chemistry, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Ridefelt
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Pedersen
authors.affiliation: Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: De Faire
authors.affiliation: Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden Department of Emergency Medicine, Karolinska University Hospital Solna, Stockholm, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Svensson
mesh_terms: D000789:Angina, Unstable / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology; D050197:Atherosclerosis / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology; D055316:Cystatin C / Q000378:metabolism*; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology; D020521:Stroke / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology; D013548:Sweden / Q000453:epidemiology; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic
chemical_list: D055316:Cystatin C
keywords: cardiovascular disease; co‐twin‐control study; cystatin C; genetic epidemiology; myocardial infarction; stroke