van der Laan, Sander W, Fall, Tove, Soumare, Aicha, Teumer, Alexander, Sedaghat, Sanaz, Baumert, Jens, Zabaneh, Delilah, van Setten, Jessica, Isgum, Ivana, Galesloot, Tessel E et al (show 62 more authors)
(2016)
Cystatin C and Cardiovascular Disease A Mendelian Randomization Study.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 68 (9).
pp. 934-945.
Abstract
<h4>Background</h4>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.<h4>Objectives</h4>The aim of this study was to use Mendelian randomization to investigate whether cystatin C is causally related to CVD in the general population.<h4>Methods</h4>We incorporated participant data from 16 prospective cohorts (n = 76,481) with 37,126 measures of cystatin C and added genetic data from 43 studies (n = 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.<h4>Results</h4>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 = 2.12 × 10(-14)). The minor allele of rs911119 was associated with decreased serum cystatin C (6.13% per allele; 95% CI: 5.75 to 6.50; p = 5.95 × 10(-211)), 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 = 0.994), which was statistically different from the observational estimate (p = 1.6 × 10(-5)). A causal effect of cystatin C was not detected for any individual component of CVD.<h4>Conclusions</h4>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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | coronary heart disease, genetics, heart failure, ischemic stroke |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 04 Oct 2016 13:43 |
| Last Modified: | 19 Jan 2023 07:29 |
| DOI: | 10.1016/j.jacc.2016.05.092 |
| Open Access URL: | http://www.sciencedirect.com/science/article/pii/S... |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3003600 |
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