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Cystatin C and Cardiovascular Disease: A Mendelian Randomization Study

Journal of the American College of Cardiology, 2016-08, Vol.68 (9), p.934-945 [Peer Reviewed Journal]

Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved. ;Copyright Elsevier Limited Aug 30, 2016 ;info:eu-repo/semantics/openAccess ;ISSN: 0735-1097 ;ISSN: 1558-3597 ;EISSN: 1558-3597 ;DOI: 10.1016/j.jacc.2016.05.092 ;PMID: 27561768

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Title:
Cystatin C and Cardiovascular Disease: A Mendelian Randomization Study
Author: van der Laan, Sander W ; Fall, Tove ; Soumaré, Aicha ; Teumer, Alexander ; Sedaghat, Sanaz ; Baumert, Jens ; Zabaneh, Delilah ; van Setten, Jessica ; Isgum, Ivana ; Galesloot, Tessel E ; Arpegård, Johannes ; Amouyel, Philippe ; Trompet, Stella ; Waldenberger, Melanie ; Dörr, Marcus ; Magnusson, Patrik K ; Giedraitis, Vilmantas ; Larsson, Anders ; Morris, Andrew P ; Felix, Janine F ; Morrison, Alanna C ; Franceschini, Nora ; Bis, Joshua C ; Kavousi, Maryam ; O'Donnell, Christopher ; Drenos, Fotios ; Tragante, Vinicius ; Munroe, Patricia B ; Malik, Rainer ; Dichgans, Martin ; Worrall, Bradford B ; Erdmann, Jeanette ; Nelson, Christopher P ; Samani, Nilesh J ; Schunkert, Heribert ; Marchini, Jonathan ; Patel, Riyaz S ; Hingorani, Aroon D ; Lind, Lars ; Pedersen, Nancy L ; de Graaf, Jacqueline ; Kiemeney, Lambertus A L M ; Baumeister, Sebastian E ; Franco, Oscar H ; Hofman, Albert ; Uitterlinden, André G ; Koenig, Wolfgang ; Meisinger, Christa ; Peters, Annette ; Thorand, Barbara ; Jukema, J Wouter ; Eriksen, Bjørn Odvar ; Toft, Ingrid ; Wilsgaard, Tom ; Onland-Moret, N Charlotte ; van der Schouw, Yvonne T ; Debette, Stéphanie ; Kumari, Meena ; Svensson, Per ; van der Harst, Pim ; Kivimaki, Mika ; Keating, Brendan J ; Sattar, Naveed ; Dehghan, Abbas ; Reiner, Alex P ; Ingelsson, Erik ; den Ruijter, Hester M ; de Bakker, Paul I W ; Pasterkamp, Gerard ; Ärnlöv, Johan ; Holmes, Michael V ; Asselbergs, Folkert W
Subjects: Aged ; Alleles ; Cardiovascular disease ; Cardiovascular Diseases - blood ; Cardiovascular Diseases - epidemiology ; Cardiovascular Diseases - genetics ; Causality ; Collaboration ; Community medicine, Social medicine: 801 ; Consortia ; coronary heart disease ; Coronary vessels ; Cystatin C - blood ; Cystatin C - genetics ; Epidemiology ; genetics ; Genomes ; Genotype ; Global Health ; Health and Welfare ; Health risk assessment ; Health sciences: 800 ; Heart attacks ; Heart failure ; Helsefag: 800 ; Humans ; Hälsa och välfärd ; Incidence ; ischemic stroke ; Medical disciplines: 700 ; Medicin och hälsovetenskap ; Medisinske Fag: 700 ; Mendelian Randomization Analysis - methods ; Middle Aged ; Polymorphism, Single Nucleotide ; Prospective Studies ; Quality control ; Risk Factors ; Samfunnsmedisin, sosialmedisin: 801 ; Stroke ; Studies ; VDP
Is Part Of: Journal of the American College of Cardiology, 2016-08, Vol.68 (9), p.934-945
Description: 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. The aim of this study was to use Mendelian randomization to investigate whether cystatin C is causally related to CVD in the general population. 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. 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. 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.
Publisher: United States: Elsevier Limited
Language: English
Identifier: ISSN: 0735-1097
ISSN: 1558-3597
EISSN: 1558-3597
DOI: 10.1016/j.jacc.2016.05.092
PMID: 27561768
Source: GFMER Free Medical Journals
MEDLINE
NORA Norwegian Open Research Archives
Alma/SFX Local Collection
SWEPUB Freely available online

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Cystatin C and Cardiovascular Disease: A Mendelian Randomization Study

Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved. ;Copyright Elsevier Limited Aug 30, 2016 ;info:eu-repo/semantics/openAccess ;ISSN: 0735-1097 ;ISSN: 1558-3597 ;EISSN: 1558-3597 ;DOI: 10.1016/j.jacc.2016.05.092 ;PMID: 27561768

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