Cystatin C Predicts Incident Cardiovascular Disease in Twins
2016 (English)In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 5, no 6, e003085Article in journal (Refereed) Published
Background - 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.
Methods and Results - 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 mu mol/L versus 79.4 +/- 20.3 mu mol/L).
Conclusions - 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.
Place, publisher, year, edition, pages
2016. Vol. 5, no 6, e003085
cardiovascular disease, co-twin-control study, cystatin C, genetic epidemiology, myocardial infarction, stroke
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-308954DOI: 10.1161/JAHA.115.003085ISI: 000386712700023OAI: oai:DiVA.org:uu-308954DiVA: diva2:1051295
FunderThe Karolinska Institutet's Research FoundationICT - The Next GenerationSwedish Society of Medicine