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Cystatin C and cardiovascular disease: A mendelian randomization study
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Number of Authors: 72
2016 (English)In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 68, no 9, 934-945 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. It is unclear whether this relationship is causal, arises from residual confounding, and/or is a consequence of reverse causation.

OBJECTIVES: The aim of this study was to use Mendelian randomization to investigate whether cystatin C is causally related to CVD in the general population. METHODS We incorporated participant data from 16 prospective cohorts (n ¼ 76,481) with 37,126 measures of cystatin C and added genetic data from 43 studies (n ¼ 252,216) with 63,292 CVD events. We used the common variant rs911119 in CST3 as an instrumental variable to investigate the causal role of cystatin C in CVD, including coronary heart disease, ischemic stroke, and heart failure.

RESULTS: Cystatin C concentrations were associated with CVD risk after adjusting for age, sex, and traditional risk factors (relative risk: 1.82 per doubling of cystatin C; 95% confidence interval [CI]: 1.56 to 2.13; p ¼ 2.12 1014). The minor allele of rs911119 was associated with decreased serum cystatin C (6.13% per allele; 95% CI: 5.75 to 6.50; p ¼ 5.95 10211), explaining 2.8% of the observed variation in cystatin C. Mendelian randomization analysis did not provide evidence for a causal role of cystatin C, with a causal relative risk for CVD of 1.00 per doubling cystatin C (95% CI: 0.82 to 1.22; p ¼ 0.994), which was statistically different from the observational estimate (p ¼ 1.6 105 ). A causal effect of cystatin C was not detected for any individual component of CVD.

CONCLUSIONS: Mendelian randomization analyses did not support a causal role of cystatin C in the etiology of CVD. As such, therapeutics targeted at lowering circulating cystatin C are unlikely to be effective in preventing CVD. 

Place, publisher, year, edition, pages
2016. Vol. 68, no 9, 934-945 p.
National Category
Clinical Medicine
Research subject
Health and Welfare
Identifiers
URN: urn:nbn:se:du-23629DOI: 10.1016/j.jacc.2016.05.092PubMedID: 27561768OAI: oai:DiVA.org:du-23629DiVA: diva2:1058062
Available from: 2016-12-20 Created: 2016-12-20 Last updated: 2016-12-20Bibliographically approved

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CiteExportLink to record
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Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
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More styles
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  • Other locale
More languages
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  • asciidoc
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