PuSH - Publikationsserver des Helmholtz Zentrums München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Ross, S.* ; D'Mello, M.* ; Anand, S.S.* ; Eikelboom, J.* ; CARDIoGRAMplusC4D Consortium (Gieger, C. ; Meitinger, T. ; Peters, A.) ; Stewart, A.F.R.* ; Samani, N.J.* ; Roberts, R.* ; Paré, G.*

Effect of bile acid sequestrants on the risk of cardiovascular events: A mendelian randomization analysis.

Circ. Cardiovasc. Genet. 8, 618-627 (2015)
Verlagsversion DOI
Free by publisher
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
BACKGROUND: Statins lower low-density lipoprotein cholesterol (LDL-C) and risk of coronary artery disease (CAD), but they may be ineffective or not tolerated. Bile acid sequestrants (BAS) reduce LDL-C, yet their clinical efficacy on CAD remains controversial. METHODS AND RESULTS: We conducted a systematic review and meta-analysis of randomized controlled trials to assess the effect of cholestyramine and colesevelam. We then used Mendelian randomization to estimate the effect of BAS on reducing the risk of CAD. First, we quantified the effect of rs4299376 (ABCG5/ABCG8), which affects the intestinal cholesterol absorption pathway targeted by BAS and then we used these estimates to predict the effect of BAS on CAD. Nineteen randomized controlled trials with a total of 7021 study participants were included. Cholestyramine 24 g/d was associated with a reduction in LDL-C of 23.5 mg/dL (95% confidence interval [CI] -26.8,-20.2; N=3806) and a trend toward reduced risk of CAD (odds ratio 0.81, 95% CI 0.70-1.02; P=0.07; N=3806), whereas colesevelam 3.75 g/d was associated with a reduction in LDL-C of 22.7 mg/dL (95% CI -28.3, -17.2; N=759). Based on the findings that rs4299376 was associated with a 2.75 mg/dL decrease in LDL-C and a 5% decrease in risk of CAD outcomes, we estimated that cholestyramine was associated with an odds ratio for CAD of 0.63 (95% CI 0.52-0.77; P=6.3×10(-6)) and colesevelam with an odds ratio of 0.64 (95% CI 0.52-0.79, P=4.3×10(-5)), which were not statistically different from BAS clinical trials (P>0.05). CONCLUSIONS: The cholesterol lowering effect of BAS may translate into a clinically relevant reduction in CAD.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
4.600
1.100
42
48
Tags
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern

Zusatzinfos bearbeiten
Eigene Tags bearbeiten
Privat
Eigene Anmerkung bearbeiten
Privat
Auf Publikationslisten für
Homepage nicht anzeigen
Als besondere Publikation
markieren
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Cholesterol-lowering Drugs ; Coronary Artery Disease ; Genetics ; Lipids ; Mendelian Randomization; Coronary-Heart-Disease; Biliary Cholesterol Secretion; Colesevelam Hydrochloride; Primary Hypercholesterolemia; Controlled Trial; Familial Hypercholesterolemia; Association Analyses; Dietary-Cholesterol; Combination Therapy; Ldl Cholesterol
Sprache englisch
Veröffentlichungsjahr 2015
HGF-Berichtsjahr 2015
ISSN (print) / ISBN 1942-325X
e-ISSN 1942-3268
Zeitschrift Circulation: Cardiovascular Genetics
Quellenangaben Band: 8, Heft: 4, Seiten: 618-627 Artikelnummer: , Supplement: ,
Verlag Lippincott Williams & Wilkins
Verlagsort Hagerstown, Md
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology (EPI)
Institute of Human Genetics (IHG)
POF Topic(s) 30202 - Environmental Health
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-504091-004
G-500700-001
G-504000-001
DOI 10.1161/CIRCGENETICS.114.000952
WOS ID WOS:000360305600011
Erfassungsdatum 2015-10-07
[➜Korrektur melden]