Imperial College London
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DrJamesPeters

Faculty of Medicine, Department of Immunology and Inflammation

Clinical Reader in Rheumatology
 
 
 
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j.peters

 
 
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ICTEM buildingHammersmith Campus

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Publications

Citation

BibTex format

@article{Burgess:2018:10.1001/jamacardio.2018.1470,
author = {Burgess, S and Ference, BA and Staley, JR and Freitag, DF and Mason, AM and Nielsen, SF and Willeit, P and Young, R and Surendran, P and Karthikeyan, S and Bolton, TR and Peters, JE and Kamstrup, P and Tybjærg-Hansen, A and Benn, M and Langsted, A and Schnohr, P and Vedel-Krogh, S and Kobylecki, CJ and Ford, I and Packard, C and Trompet, S and Jukema, JW and Sattar, N and Di, Angelantonio E and Saleheen, D and Howson, JMM and Nordestgaard, BG and Butterworth, AS and Danesh, J and Bargess, S and Overvad, K and Tjønneland, A and Clavel-Chapelon, F and Kaaks, R and Boeing, H and Trichopoulou, A and Ferrari, P and Palli, D and Krogh, V and Panico, S and Tumino, R and Matullo, G and Boer, J and Van, Der Schouw Y and Weiderpass, E and Quiros, JR and Sánchez, MJ and Navarro, C and Moreno-Iribas, C and Arriola, L and Melander, O and Wennberg, P and Wareham, NJ and Key, TJ and Riboli, E},
doi = {10.1001/jamacardio.2018.1470},
journal = {JAMA Cardiology},
pages = {619--627},
title = {Association of LPA variants with risk of coronary disease and the implications for lipoprotein(a)-lowering therapies: A mendelian randomization analysis},
url = {http://dx.doi.org/10.1001/jamacardio.2018.1470},
volume = {3},
year = {2018}
}
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TY  - JOUR
AB  - © 2018 American Medical Association. All rights reserved. IMPORTANCE Human genetic studies have indicated that plasma lipoprotein(a) (Lp[a]) is causally associated with the risk of coronary heart disease (CHD), but randomized trials of several therapies that reduce Lp(a) levels by 25%to 35%have not provided any evidence that lowering Lp(a) level reduces CHD risk. OBJECTIVE To estimate the magnitude of the change in plasma Lp(a) levels needed to have the same evidence of an association with CHD risk as a 38.67-mg/dL (ie, 1-mmol/L) change in low-density lipoprotein cholesterol (LDL-C) level, a change that has been shown to produce a clinically meaningful reduction in the risk of CHD. DESIGN, SETTING, AND PARTICIPANTS A mendelian randomization analysiswas conducted using individual participant data from 5 studies and with external validation using summarized data from 48 studies. Population-based prospective cohort and case-control studies featured 20 793 individuals with CHD and 27 540 controls with individual participant data, whereas summarized data included 62 240 patients with CHD and 127 299 controls. Data were analyzed from November 2016 to March 2018. EXPOSURES Genetic LPA score and plasma Lp(a) mass concentration. MAIN OUTCOMES AND MEASURES Coronary heart disease. RESULTS Of the included study participants, 53%were men, all were of white European ancestry, and the mean age was 57.5 years. The association of genetically predicted Lp(a) with CHD risk was linearly proportional to the absolute change in Lp(a) concentration. A 10-mg/dL lower genetically predicted Lp(a) concentration was associated with a 5.8% lower CHD risk (odds ratio [OR], 0.942; 95%CI, 0.933-0.951; P = 3 × 10-37), whereas a 10-mg/dL lower genetically predicted LDL-C level estimated using an LDL-C genetic score was associated with a 14.5%lower CHD risk (OR, 0.855; 95%CI, 0.818-0.893; P = 2 × 10-12). Thus, a 101.5-mg/dL change (95%CI, 71.0-137.0) in Lp(a) concentration had the sam
AU  - Burgess,S
AU  - Ference,BA
AU  - Staley,JR
AU  - Freitag,DF
AU  - Mason,AM
AU  - Nielsen,SF
AU  - Willeit,P
AU  - Young,R
AU  - Surendran,P
AU  - Karthikeyan,S
AU  - Bolton,TR
AU  - Peters,JE
AU  - Kamstrup,P
AU  - Tybjærg-Hansen,A
AU  - Benn,M
AU  - Langsted,A
AU  - Schnohr,P
AU  - Vedel-Krogh,S
AU  - Kobylecki,CJ
AU  - Ford,I
AU  - Packard,C
AU  - Trompet,S
AU  - Jukema,JW
AU  - Sattar,N
AU  - Di,Angelantonio E
AU  - Saleheen,D
AU  - Howson,JMM
AU  - Nordestgaard,BG
AU  - Butterworth,AS
AU  - Danesh,J
AU  - Bargess,S
AU  - Overvad,K
AU  - Tjønneland,A
AU  - Clavel-Chapelon,F
AU  - Kaaks,R
AU  - Boeing,H
AU  - Trichopoulou,A
AU  - Ferrari,P
AU  - Palli,D
AU  - Krogh,V
AU  - Panico,S
AU  - Tumino,R
AU  - Matullo,G
AU  - Boer,J
AU  - Van,Der Schouw Y
AU  - Weiderpass,E
AU  - Quiros,JR
AU  - Sánchez,MJ
AU  - Navarro,C
AU  - Moreno-Iribas,C
AU  - Arriola,L
AU  - Melander,O
AU  - Wennberg,P
AU  - Wareham,NJ
AU  - Key,TJ
AU  - Riboli,E
DO  - 10.1001/jamacardio.2018.1470
EP  - 627
PY  - 2018///
SN  - 2380-6583
SP  - 619
TI  - Association of LPA variants with risk of coronary disease and the implications for lipoprotein(a)-lowering therapies: A mendelian randomization analysis
T2  - JAMA Cardiology
UR  - http://dx.doi.org/10.1001/jamacardio.2018.1470
VL  - 3
ER  -
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