van der Laan, Sander W and Fall, Tove and Soumaré, Aicha and Teumer, Alexander and Sedaghat, Sanaz and Baumert, Jens and Zabaneh, Delilah and van Setten, Jessica and Isgum, Ivana and Galesloot, Tessel E and Arpegård, Johannes and Amouyel, Philippe and Trompet, Stella and Waldenberger, Melanie and Dörr, Marcus and Magnusson, Patrik K and Giedraitis, Vilmantas and Larsson, Anders and Morris, Andrew P and Felix, Janine F and Morrison, Alanna C and Franceschini, Nora and Bis, Joshua C and Kavousi, Maryam and O'Donnell, Christopher and Drenos, Fotios and Tragante, Vinicius and Munroe, Patricia B and Malik, Rainer and Dichgans, Martin and Worrall, Bradford B and Erdmann, Jeanette and Nelson, Christopher P and Samani, Nilesh J and Schunkert, Heribert and Marchini, Jonathan and Patel, Riyaz S and Hingorani, Aroon D and Lind, Lars and Pedersen, Nancy L and de Graaf, Jacqueline and Kiemeney, Lambertus ALM and Baumeister, Sebastian E and Franco, Oscar H and Hofman, Albert and Uitterlinden, André G and Koenig, Wolfgang and Meisinger, Christa and Peters, Annette and Thorand, Barbara and Jukema, J Wouter and Eriksen, Bjørn Odvar and Toft, Ingrid and Wilsgaard, Tom and Onland-Moret, N Charlotte and van der Schouw, Yvonne T and Debette, Stéphanie and Kumari, Meena and Svensson, Per and van der Harst, Pim and Kivimaki, Mika and Keating, Brendan J and Sattar, Naveed and Dehghan, Abbas and Reiner, Alex P and Ingelsson, Erik and den Ruijter, Hester M and de Bakker, Paul IW and Pasterkamp, Gerard and Ärnlöv, Johan and Holmes, Michael V and Asselbergs, Folkert W (2016) Cystatin C and Cardiovascular Disease. Journal of the American College of Cardiology, 68 (9). pp. 934-945. DOI https://doi.org/10.1016/j.jacc.2016.05.092
van der Laan, Sander W and Fall, Tove and Soumaré, Aicha and Teumer, Alexander and Sedaghat, Sanaz and Baumert, Jens and Zabaneh, Delilah and van Setten, Jessica and Isgum, Ivana and Galesloot, Tessel E and Arpegård, Johannes and Amouyel, Philippe and Trompet, Stella and Waldenberger, Melanie and Dörr, Marcus and Magnusson, Patrik K and Giedraitis, Vilmantas and Larsson, Anders and Morris, Andrew P and Felix, Janine F and Morrison, Alanna C and Franceschini, Nora and Bis, Joshua C and Kavousi, Maryam and O'Donnell, Christopher and Drenos, Fotios and Tragante, Vinicius and Munroe, Patricia B and Malik, Rainer and Dichgans, Martin and Worrall, Bradford B and Erdmann, Jeanette and Nelson, Christopher P and Samani, Nilesh J and Schunkert, Heribert and Marchini, Jonathan and Patel, Riyaz S and Hingorani, Aroon D and Lind, Lars and Pedersen, Nancy L and de Graaf, Jacqueline and Kiemeney, Lambertus ALM and Baumeister, Sebastian E and Franco, Oscar H and Hofman, Albert and Uitterlinden, André G and Koenig, Wolfgang and Meisinger, Christa and Peters, Annette and Thorand, Barbara and Jukema, J Wouter and Eriksen, Bjørn Odvar and Toft, Ingrid and Wilsgaard, Tom and Onland-Moret, N Charlotte and van der Schouw, Yvonne T and Debette, Stéphanie and Kumari, Meena and Svensson, Per and van der Harst, Pim and Kivimaki, Mika and Keating, Brendan J and Sattar, Naveed and Dehghan, Abbas and Reiner, Alex P and Ingelsson, Erik and den Ruijter, Hester M and de Bakker, Paul IW and Pasterkamp, Gerard and Ärnlöv, Johan and Holmes, Michael V and Asselbergs, Folkert W (2016) Cystatin C and Cardiovascular Disease. Journal of the American College of Cardiology, 68 (9). pp. 934-945. DOI https://doi.org/10.1016/j.jacc.2016.05.092
van der Laan, Sander W and Fall, Tove and Soumaré, Aicha and Teumer, Alexander and Sedaghat, Sanaz and Baumert, Jens and Zabaneh, Delilah and van Setten, Jessica and Isgum, Ivana and Galesloot, Tessel E and Arpegård, Johannes and Amouyel, Philippe and Trompet, Stella and Waldenberger, Melanie and Dörr, Marcus and Magnusson, Patrik K and Giedraitis, Vilmantas and Larsson, Anders and Morris, Andrew P and Felix, Janine F and Morrison, Alanna C and Franceschini, Nora and Bis, Joshua C and Kavousi, Maryam and O'Donnell, Christopher and Drenos, Fotios and Tragante, Vinicius and Munroe, Patricia B and Malik, Rainer and Dichgans, Martin and Worrall, Bradford B and Erdmann, Jeanette and Nelson, Christopher P and Samani, Nilesh J and Schunkert, Heribert and Marchini, Jonathan and Patel, Riyaz S and Hingorani, Aroon D and Lind, Lars and Pedersen, Nancy L and de Graaf, Jacqueline and Kiemeney, Lambertus ALM and Baumeister, Sebastian E and Franco, Oscar H and Hofman, Albert and Uitterlinden, André G and Koenig, Wolfgang and Meisinger, Christa and Peters, Annette and Thorand, Barbara and Jukema, J Wouter and Eriksen, Bjørn Odvar and Toft, Ingrid and Wilsgaard, Tom and Onland-Moret, N Charlotte and van der Schouw, Yvonne T and Debette, Stéphanie and Kumari, Meena and Svensson, Per and van der Harst, Pim and Kivimaki, Mika and Keating, Brendan J and Sattar, Naveed and Dehghan, Abbas and Reiner, Alex P and Ingelsson, Erik and den Ruijter, Hester M and de Bakker, Paul IW and Pasterkamp, Gerard and Ärnlöv, Johan and Holmes, Michael V and Asselbergs, Folkert W (2016) Cystatin C and Cardiovascular Disease. Journal of the American College of Cardiology, 68 (9). pp. 934-945. DOI https://doi.org/10.1016/j.jacc.2016.05.092
Abstract
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 = 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. 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 = 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. 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.
Item Type: | Article |
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Uncontrolled Keywords: | coronary heart disease; genetics; heart failure; ischemic stroke |
Subjects: | H Social Sciences > H Social Sciences (General) R Medicine > R Medicine (General) |
Divisions: | Faculty of Social Sciences Faculty of Social Sciences > Institute for Social and Economic Research |
SWORD Depositor: | Unnamed user with email elements@essex.ac.uk |
Depositing User: | Unnamed user with email elements@essex.ac.uk |
Date Deposited: | 26 Aug 2016 14:14 |
Last Modified: | 07 Aug 2024 19:49 |
URI: | http://repository.essex.ac.uk/id/eprint/17471 |
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