Relative effects of LDL-C on ischemic stroke and coronary disease A Mendelian randomization study

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MARC

Valdes-Marquez, E. (author)

Relative effects of LDL-C on ischemic stroke and coronary disease A Mendelian randomization study

Article/chapterEnglish2019

Publisher, publication year, extent ...

2019-02-20
Ovid Technologies (Wolters Kluwer Health),2019

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LIBRIS-ID:oai:gup.ub.gu.se/280728
https://gup.ub.gu.se/publication/280728URI
https://doi.org/10.1212/wnl.0000000000007091DOI

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Language:English

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SwePubSwePub

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

Objective To examine the causal relevance of lifelong differences in low-density lipoprotein cholesterol (LDL-C) for ischemic stroke (IS) relative to that for coronary heart disease (CHD) using a Mendelian randomization approach. We undertook a 2-sample Mendelian randomization, based on summary data, to estimate the causal relevance of LDL-C for risk of IS and CHD. Information from 62 independent genetic variants with genome-wide significant effects on LDL-C levels was used to estimate the causal effects of LDL-C for IS and IS subtypes (based on 12,389 IS cases from METASTROKE) and for CHD (based on 60,801 cases from CARDIoGRAMplusC4D). We then assessed the effects of LDL-C on IS and CHD for heterogeneity. A 1 mmol/L higher genetically determined LDL-C was associated with a 50% higher risk of CHD (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.32-1.68, p = 1.1 x 10(-8)). By contrast, the causal effect of LDL-C was much weaker for IS (OR 1.12, 95% CI 0.96-1.30, p = 0.14; p for heterogeneity = 2.6 x 10(-3)) and, in particular, for cardioembolic stroke (OR 1.06, 95% CI 0.84-1.33, p = 0.64; p for heterogeneity = 8.6 x 10(-3)) when compared with that for CHD. In contrast with the consistent effects of LDL-C-lowering therapies on IS and CHD, genetic variants that confer lifelong LDL-C differences show a weaker effect on IS than on CHD. The relevance of etiologically distinct IS subtypes may contribute to the differences observed.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Neurovetenskaper hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Neurosciences hsv//eng
density-lipoprotein-cholesterol
risk-factors
heart-disease
genetic-variants
statin therapy
metaanalysis
subtypes
pcsk9
reduction
bmi
Neurosciences & Neurology

Added entries (persons, corporate bodies, meetings, titles ...)

Parish, S. (author)
Clarke, R. (author)
Stari, T. (author)
Worrall, B. B. (author)
Hopewell, J. C. (author)
Slowik, A. (author)
Hofman, A. (author)
Algra, A. (author)
Reiner, A. P. (author)
Doney, A. S. F. (author)
Gschwendtner, A. (author)
Ilinca, A. (author)
Giese, A. K. (author)
Lindgren, A. (author)
Vicente, A. M. (author)
Norrving, B. (author)
Nordestgaard, B. G. (author)
Mitchell, B. D. (author)
Psaty, B. M. (author)
Carty, C. L. (author)
Sudlow, C. L. M. (author)
Anderson, C. (author)
Levi, C. R. (author)
Satizabal, C. L. (author)
Palmer, C. N. A. (author)
Gamble, D. M. (author)
Woo, D. (author)
Saleheen, D. (author)
Ringelstein, E. B. (author)
Valdimarsson, E. M. (author)
Holliday, E. G. (author)
Davies, G. (author)
Chauhan, G. (author)
Pasterkamp, G. (author)
Boncoraglio, G. B. (author)
Kuhlenbaumer, G. (author)
Thorleifsson, G. (author)
Falcone, G. J. (author)
Pare, G. (author)
Schmidt, H. (author)
Delavaran, H. (author)
Markus, H. S. (author)
Aparicio, H. J. (author)
Deary, I. (author)
Cotlarciuc, I. (author)
Fernandez-Cadenas, I. (author)
Meschia, J. F. (author)
Liu, J. M. (author)
Montaner, J. (author)
Pera, J. (author)
Cole, J. (author)
Attia, J. R. (author)
Rosand, J. (author)
Ferro, J. M. (author)
Bis, J. C. (author)
Furie, K. (author)
Stefansson, K. (author)
Berger, K. (author)
Kostulas, K. (author)
Rannikmae, K. (author)
Ikram, M. A. (author)
Benn, M. (author)
Dichgans, M. (author)
Pandolfo, M. (author)
Traylor, M. (author)
Walters, M. (author)
Sale, M. (author)
Nalls, M. A. (author)
Fornage, M. (author)
van Zuydam, N. R. (author)
Sharma, P. (author)
Abrantes, P. (author)
de Bakker, P. I. W. (author)
Higgins, P. (author)
Lichtner, P. (author)
Rothwell, P. M. (author)
Amouyel, P. (author)
Yang, Q. (author)
Malik, R. (author)
Schmidt, R. (author)
Lemmens, R. (author)
van der Laan, S. W. (author)
Pulit, S. L. (author)
Abboud, S. (author)
Oliveira, S. A. (author)
Gretarsdottir, S. (author)
Debette, S. (author)
Williams, S. R. (author)
Bevan, S. (author)
Kittner, S. J. (author)
Seshadri, S. (author)
Mosley, T. (author)
Battey, T. W. K. (author)
Tatlisumak, TurgutGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology(Swepub:gu)xtatlt (author)
Thorsteinsdottir, U. (author)
Thijs, V. N. S. (author)
Longstreth, W. T. (author)
Zhao, W. (author)
Chen, W. M. (author)
Cheng, Y. C. (author)
Isgc,, Isgc, (author)
Göteborgs universitetInstitutionen för neurovetenskap och fysiologi (creator_code:org_t)

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In:Neurology: Ovid Technologies (Wolters Kluwer Health)92:110028-38781526-632X

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By the author/editor: Valdes-Marquez, ...; Parish, S.; Clarke, R.; Stari, T.; Worrall, B. B.; Hopewell, J. C.; show more...; Slowik, A.; Hofman, A.; Algra, A.; Reiner, A. P.; Doney, A. S. F.; Gschwendtner, A.; Ilinca, A.; Giese, A. K.; Lindgren, A.; Vicente, A. M.; Norrving, B.; Nordestgaard, B. ...; Mitchell, B. D.; Psaty, B. M.; Carty, C. L.; Sudlow, C. L. M.; Anderson, C.; Levi, C. R.; Satizabal, C. L.; Palmer, C. N. A.; Gamble, D. M.; Woo, D.; Saleheen, D.; Ringelstein, E. ...; Valdimarsson, E. ...; Holliday, E. G.; Davies, G.; Chauhan, G.; Pasterkamp, G.; Boncoraglio, G. ...; Kuhlenbaumer, G.; Thorleifsson, G.; Falcone, G. J.; Pare, G.; Schmidt, H.; Delavaran, H.; Markus, H. S.; Aparicio, H. J.; Deary, I.; Cotlarciuc, I.; Fernandez-Cadena ...; Meschia, J. F.; Liu, J. M.; Montaner, J.; Pera, J.; Cole, J.; Attia, J. R.; Rosand, J.; Ferro, J. M.; Bis, J. C.; Furie, K.; Stefansson, K.; Berger, K.; Kostulas, K.; Rannikmae, K.; Ikram, M. A.; Benn, M.; Dichgans, M.; Pandolfo, M.; Traylor, M.; Walters, M.; Sale, M.; Nalls, M. A.; Fornage, M.; van Zuydam, N. R ...; Sharma, P.; Abrantes, P.; de Bakker, P. I. ...; Higgins, P.; Lichtner, P.; Rothwell, P. M.; Amouyel, P.; Yang, Q.; Malik, R.; Schmidt, R.; Lemmens, R.; van der Laan, S. ...; Pulit, S. L.; Abboud, S.; Oliveira, S. A.; Gretarsdottir, S ...; Debette, S.; Williams, S. R.; Bevan, S.; Kittner, S. J.; Seshadri, S.; Mosley, T.; Battey, T. W. K.; Tatlisumak, Turg ...; Thorsteinsdottir ...; Thijs, V. N. S.; Longstreth, W. T ...; Zhao, W.; Chen, W. M.; Cheng, Y. C.; Isgc,, Isgc; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Neurosciences

Articles in the publication: Neurology

By the university: University of Gothenburg

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