A systematic review and meta-analysis of 130,000 individuals shows smoking does not modify the association of APOE genotype on risk of coronary heart disease

Michael V Holmes; Ruth Frikke-Schmidt; Daniela Melis; Robert Luben; Folkert W Asselbergs; Jolanda M A Boer; Jackie Cooper; Jutta Palmen; Pia Horvat; Jorgen Engmann; Ka-Wah Li; N Charlotte Onland-Moret; Marten H Hofker; Meena Kumari; Brendan J Keating; Jaroslav A Hubacek; Vera Adamkova; Ruzena Kubinova; Martin Bobak; Kay-Tee Khaw; Børge G Nordestgaard; Nick Wareham; Steve E Humphries; Claudia Langenberg; Anne Tybjaerg-Hansen; Philippa J Talmud

doi:10.1016/j.atherosclerosis.2014.07.038

A systematic review and meta-analysis of 130,000 individuals shows smoking does not modify the association of APOE genotype on risk of coronary heart disease

Michael V Holmes, Ruth Frikke-Schmidt, Daniela Melis, Robert Luben, Folkert W Asselbergs, Jolanda M A Boer, Jackie Cooper, Jutta Palmen, Pia Horvat, Jorgen Engmann, Ka-Wah Li, N Charlotte Onland-Moret, Marten H Hofker, Meena Kumari, Brendan J Keating, Jaroslav A Hubacek, Vera Adamkova, Ruzena Kubinova, Martin Bobak, Kay-Tee KhawBørge G Nordestgaard, Nick Wareham, Steve E Humphries, Claudia Langenberg, Anne Tybjaerg-Hansen, Philippa J Talmud

Department of Clinical Medicine

19 Citations (Scopus)

Abstract

BACKGROUND: Conflicting evidence exists on whether smoking acts as an effect modifier of the association between APOE genotype and risk of coronary heart disease (CHD).

METHODS AND RESULTS: We searched PubMed and EMBASE to June 11, 2013 for published studies reporting APOE genotype, smoking status and CHD events and added unpublished data from population cohorts. We tested for presence of effect modification by smoking status in the relationship between APOE genotype and risk of CHD using likelihood ratio test. In total 13 studies (including unpublished data from eight cohorts) with 10,134 CHD events in 130,004 individuals of European descent were identified. The odds ratio (OR) for CHD risk from APOE genotype (ε4 carriers versus non-carriers) was 1.06 (95% confidence interval (CI): 1.01, 1.12) and for smoking (present vs. past/never smokers) was OR 2.05 (95%CI: 1.95, 2.14). When the association between APOE genotype and CHD was stratified by smoking status, compared to non-ε4 carriers, ε4 carriers had an OR of 1.11 (95%CI: 1.02, 1.21) in 28,789 present smokers and an OR of 1.04 (95%CI 0.98, 1.10) in 101,215 previous/never smokers, with no evidence of effect modification (P-value for heterogeneity = 0.19). Analysis of pack years in individual participant data of >60,000 with adjustment for cardiovascular traits also failed to identify evidence of effect modification.

CONCLUSIONS: In the largest analysis to date, we identified no evidence for effect modification by smoking status in the association between APOE genotype and risk of CHD.

Original language	English
Journal	Atherosclerosis
Volume	237
Issue number	1
Pages (from-to)	5-12
Number of pages	8
ISSN	0021-9150
DOIs	https://doi.org/10.1016/j.atherosclerosis.2014.07.038
Publication status	Published - 1 Dec 2014

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Holmes, M. V., Frikke-Schmidt, R., Melis, D., Luben, R., Asselbergs, F. W., Boer, J. M. A., Cooper, J., Palmen, J., Horvat, P., Engmann, J., Li, K-W., Onland-Moret, N. C., Hofker, M. H., Kumari, M., Keating, B. J., Hubacek, J. A., Adamkova, V., Kubinova, R., Bobak, M., ... Talmud, P. J. (2014). A systematic review and meta-analysis of 130,000 individuals shows smoking does not modify the association of APOE genotype on risk of coronary heart disease. Atherosclerosis, 237(1), 5-12. https://doi.org/10.1016/j.atherosclerosis.2014.07.038

A systematic review and meta-analysis of 130,000 individuals shows smoking does not modify the association of APOE genotype on risk of coronary heart disease. / Holmes, Michael V; Frikke-Schmidt, Ruth; Melis, Daniela et al.

In: Atherosclerosis, Vol. 237, No. 1, 01.12.2014, p. 5-12.

Research output: Contribution to journal › Journal article › Research › peer-review

Holmes, MV, Frikke-Schmidt, R, Melis, D, Luben, R, Asselbergs, FW, Boer, JMA, Cooper, J, Palmen, J, Horvat, P, Engmann, J, Li, K-W, Onland-Moret, NC, Hofker, MH, Kumari, M, Keating, BJ, Hubacek, JA, Adamkova, V, Kubinova, R, Bobak, M, Khaw, K-T, Nordestgaard, BG, Wareham, N, Humphries, SE, Langenberg, C, Tybjaerg-Hansen, A & Talmud, PJ 2014, 'A systematic review and meta-analysis of 130,000 individuals shows smoking does not modify the association of APOE genotype on risk of coronary heart disease', Atherosclerosis, vol. 237, no. 1, pp. 5-12. https://doi.org/10.1016/j.atherosclerosis.2014.07.038

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title = "A systematic review and meta-analysis of 130,000 individuals shows smoking does not modify the association of APOE genotype on risk of coronary heart disease",

abstract = "BACKGROUND: Conflicting evidence exists on whether smoking acts as an effect modifier of the association between APOE genotype and risk of coronary heart disease (CHD).METHODS AND RESULTS: We searched PubMed and EMBASE to June 11, 2013 for published studies reporting APOE genotype, smoking status and CHD events and added unpublished data from population cohorts. We tested for presence of effect modification by smoking status in the relationship between APOE genotype and risk of CHD using likelihood ratio test. In total 13 studies (including unpublished data from eight cohorts) with 10,134 CHD events in 130,004 individuals of European descent were identified. The odds ratio (OR) for CHD risk from APOE genotype (ε4 carriers versus non-carriers) was 1.06 (95% confidence interval (CI): 1.01, 1.12) and for smoking (present vs. past/never smokers) was OR 2.05 (95%CI: 1.95, 2.14). When the association between APOE genotype and CHD was stratified by smoking status, compared to non-ε4 carriers, ε4 carriers had an OR of 1.11 (95%CI: 1.02, 1.21) in 28,789 present smokers and an OR of 1.04 (95%CI 0.98, 1.10) in 101,215 previous/never smokers, with no evidence of effect modification (P-value for heterogeneity = 0.19). Analysis of pack years in individual participant data of >60,000 with adjustment for cardiovascular traits also failed to identify evidence of effect modification.CONCLUSIONS: In the largest analysis to date, we identified no evidence for effect modification by smoking status in the association between APOE genotype and risk of CHD.",

author = "Holmes, {Michael V} and Ruth Frikke-Schmidt and Daniela Melis and Robert Luben and Asselbergs, {Folkert W} and Boer, {Jolanda M A} and Jackie Cooper and Jutta Palmen and Pia Horvat and Jorgen Engmann and Ka-Wah Li and Onland-Moret, {N Charlotte} and Hofker, {Marten H} and Meena Kumari and Keating, {Brendan J} and Hubacek, {Jaroslav A} and Vera Adamkova and Ruzena Kubinova and Martin Bobak and Kay-Tee Khaw and Nordestgaard, {B{\o}rge G} and Nick Wareham and Humphries, {Steve E} and Claudia Langenberg and Anne Tybjaerg-Hansen and Talmud, {Philippa J}",

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T1 - A systematic review and meta-analysis of 130,000 individuals shows smoking does not modify the association of APOE genotype on risk of coronary heart disease

AU - Holmes, Michael V

AU - Frikke-Schmidt, Ruth

AU - Melis, Daniela

AU - Luben, Robert

AU - Asselbergs, Folkert W

AU - Boer, Jolanda M A

AU - Cooper, Jackie

AU - Palmen, Jutta

AU - Horvat, Pia

AU - Engmann, Jorgen

AU - Li, Ka-Wah

AU - Onland-Moret, N Charlotte

AU - Hofker, Marten H

AU - Kumari, Meena

AU - Keating, Brendan J

AU - Hubacek, Jaroslav A

AU - Adamkova, Vera

AU - Kubinova, Ruzena

AU - Bobak, Martin

AU - Khaw, Kay-Tee

AU - Nordestgaard, Børge G

AU - Wareham, Nick

AU - Humphries, Steve E

AU - Langenberg, Claudia

AU - Tybjaerg-Hansen, Anne

AU - Talmud, Philippa J

PY - 2014/12/1

Y1 - 2014/12/1

N2 - BACKGROUND: Conflicting evidence exists on whether smoking acts as an effect modifier of the association between APOE genotype and risk of coronary heart disease (CHD).METHODS AND RESULTS: We searched PubMed and EMBASE to June 11, 2013 for published studies reporting APOE genotype, smoking status and CHD events and added unpublished data from population cohorts. We tested for presence of effect modification by smoking status in the relationship between APOE genotype and risk of CHD using likelihood ratio test. In total 13 studies (including unpublished data from eight cohorts) with 10,134 CHD events in 130,004 individuals of European descent were identified. The odds ratio (OR) for CHD risk from APOE genotype (ε4 carriers versus non-carriers) was 1.06 (95% confidence interval (CI): 1.01, 1.12) and for smoking (present vs. past/never smokers) was OR 2.05 (95%CI: 1.95, 2.14). When the association between APOE genotype and CHD was stratified by smoking status, compared to non-ε4 carriers, ε4 carriers had an OR of 1.11 (95%CI: 1.02, 1.21) in 28,789 present smokers and an OR of 1.04 (95%CI 0.98, 1.10) in 101,215 previous/never smokers, with no evidence of effect modification (P-value for heterogeneity = 0.19). Analysis of pack years in individual participant data of >60,000 with adjustment for cardiovascular traits also failed to identify evidence of effect modification.CONCLUSIONS: In the largest analysis to date, we identified no evidence for effect modification by smoking status in the association between APOE genotype and risk of CHD.

AB - BACKGROUND: Conflicting evidence exists on whether smoking acts as an effect modifier of the association between APOE genotype and risk of coronary heart disease (CHD).METHODS AND RESULTS: We searched PubMed and EMBASE to June 11, 2013 for published studies reporting APOE genotype, smoking status and CHD events and added unpublished data from population cohorts. We tested for presence of effect modification by smoking status in the relationship between APOE genotype and risk of CHD using likelihood ratio test. In total 13 studies (including unpublished data from eight cohorts) with 10,134 CHD events in 130,004 individuals of European descent were identified. The odds ratio (OR) for CHD risk from APOE genotype (ε4 carriers versus non-carriers) was 1.06 (95% confidence interval (CI): 1.01, 1.12) and for smoking (present vs. past/never smokers) was OR 2.05 (95%CI: 1.95, 2.14). When the association between APOE genotype and CHD was stratified by smoking status, compared to non-ε4 carriers, ε4 carriers had an OR of 1.11 (95%CI: 1.02, 1.21) in 28,789 present smokers and an OR of 1.04 (95%CI 0.98, 1.10) in 101,215 previous/never smokers, with no evidence of effect modification (P-value for heterogeneity = 0.19). Analysis of pack years in individual participant data of >60,000 with adjustment for cardiovascular traits also failed to identify evidence of effect modification.CONCLUSIONS: In the largest analysis to date, we identified no evidence for effect modification by smoking status in the association between APOE genotype and risk of CHD.

U2 - 10.1016/j.atherosclerosis.2014.07.038

DO - 10.1016/j.atherosclerosis.2014.07.038

M3 - Journal article

C2 - 25173947

SN - 0021-9150

VL - 237

SP - 5

EP - 12

JO - Atherosclerosis

JF - Atherosclerosis

IS - 1

ER -

A systematic review and meta-analysis of 130,000 individuals shows smoking does not modify the association of APOE genotype on risk of coronary heart disease

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