Effect of Smoking on Blood Pressure and Resting Heart Rate: A Mendelian Randomisation Meta-Analysis in the CARTA Consortium

Allan Linneberg; Rikke K Jacobsen; Tea Skaaby; Amy E Taylor; Meg E Fluharty; Jørgen L Jeppesen; Johan H Bjørngaard; Bjørn O Åsvold; Maiken E Gabrielsen; Archie Campbell; Riccardo E Marioni; Meena Kumari; Pedro Marques-Vidal; Marika Kaakinen; Alana Cavadino; Iris Postmus; Tarun Veer Singh Ahluwalia; S Goya Wannamethee; Jari Lahti; Katri Räikkönen; Aarno Palotie; Andrew Wong; Christine Dalgård; Ian Ford; Yoav Ben-Shlomo; Lene Christiansen; Kirsten O Kyvik; Diana Kuh; Johan G Eriksson; Peter H Whincup; Hamdi Mbarek; Eco J C de Geus; Jacqueline M Vink; Dorret I Boomsma; George Davey Smith; Debbie A Lawlor; Aliaksei Kisialiou; Alex McConnachie; Sandosh Padmanabhan; J Wouter Jukema; Chris Power; Elina Hyppönen; Martin Preisig; Gerard Waeber; Peter Vollenweider; Tellervo Korhonen; Tiina Laatikainen; Veikko Salomaa; Jaakko Kaprio; Mika Kivimäki; Blair H Smith; Caroline Hayward; Thorkild I A Sørensen; Betina H Thuesen; Naveed Sattar; Richard W Morris; Pål R Romundstad; Marcus R Munafò; Marjo-Riitta Jarvelin; Lise Lotte N Husemoen

doi:10.1161/CIRCGENETICS.115.001225

Effect of Smoking on Blood Pressure and Resting Heart Rate: A Mendelian Randomisation Meta-Analysis in the CARTA Consortium

Allan Linneberg, Rikke K Jacobsen, Tea Skaaby, Amy E Taylor, Meg E Fluharty, Jørgen L Jeppesen, Johan H Bjørngaard, Bjørn O Åsvold, Maiken E Gabrielsen, Archie Campbell, Riccardo E Marioni, Meena Kumari, Pedro Marques-Vidal, Marika Kaakinen, Alana Cavadino, Iris Postmus, Tarun Veer Singh Ahluwalia, S Goya Wannamethee, Jari Lahti, Katri RäikkönenAarno Palotie, Andrew Wong, Christine Dalgård, Ian Ford, Yoav Ben-Shlomo, Lene Christiansen, Kirsten O Kyvik, Diana Kuh, Johan G Eriksson, Peter H Whincup, Hamdi Mbarek, Eco J C de Geus, Jacqueline M Vink, Dorret I Boomsma, George Davey Smith, Debbie A Lawlor, Aliaksei Kisialiou, Alex McConnachie, Sandosh Padmanabhan, J Wouter Jukema, Chris Power, Elina Hyppönen, Martin Preisig, Gerard Waeber, Peter Vollenweider, Tellervo Korhonen, Tiina Laatikainen, Veikko Salomaa, Jaakko Kaprio, Mika Kivimäki, Blair H Smith, Caroline Hayward, Thorkild I A Sørensen, Betina H Thuesen, Naveed Sattar, Richard W Morris, Pål R Romundstad, Marcus R Munafò, Marjo-Riitta Jarvelin, Lise Lotte N Husemoen

55 Citations (Scopus)

Abstract

Background-Smoking is an important cardiovascular disease risk factor, but the mechanisms linking smoking to blood pressure are poorly understood. Methods and Results-Data on 141 317 participants (62 666 never, 40 669 former, 37 982 current smokers) from 23 population-based studies were included in observational and Mendelian randomization meta-analyses of the associations of smoking status and smoking heaviness with systolic and diastolic blood pressure, hypertension, and resting heart rate. For the Mendelian randomization analyses, a genetic variant rs16969968/rs1051730 was used as a proxy for smoking heaviness in current smokers. In observational analyses, current as compared with never smoking was associated with lower systolic blood pressure and diastolic blood pressure and lower hypertension risk, but with higher resting heart rate. In observational analyses among current smokers, 1 cigarette/day higher level of smoking heaviness was associated with higher (0.21 bpm; 95% confidence interval 0.19; 0.24) resting heart rate and slightly higher diastolic blood pressure (0.05 mm Hg; 95% confidence interval 0.02; 0.08) and systolic blood pressure (0.08 mm Hg; 95% confidence interval 0.03; 0.13). However, in Mendelian randomization analyses among current smokers, although each smoking increasing allele of rs16969968/rs1051730 was associated with higher resting heart rate (0.36 bpm/allele; 95% confidence interval 0.18; 0.54), there was no strong association with diastolic blood pressure, systolic blood pressure, or hypertension. This would suggest a 7 bpm higher heart rate in those who smoke 20 cigarettes/day. Conclusions-This Mendelian randomization meta-analysis supports a causal association of smoking heaviness with higher level of resting heart rate, but not with blood pressure. These findings suggest that part of the cardiovascular risk of smoking may operate through increasing resting heart rate.

Original language	English
Journal	Circulation: Cardiovascular Genetics
Volume	8
Pages (from-to)	832-841
Number of pages	10
ISSN	1942-325X
DOIs	https://doi.org/10.1161/CIRCGENETICS.115.001225
Publication status	Published - 1 Dec 2015

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10.1161/CIRCGENETICS.115.001225

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Linneberg, A., Jacobsen, R. K., Skaaby, T., Taylor, A. E., Fluharty, M. E., Jeppesen, J. L., Bjørngaard, J. H., Åsvold, B. O., Gabrielsen, M. E., Campbell, A., Marioni, R. E., Kumari, M., Marques-Vidal, P., Kaakinen, M., Cavadino, A., Postmus, I., Ahluwalia, T. V. S., Wannamethee, S. G., Lahti, J., ... Husemoen, L. L. N. (2015). Effect of Smoking on Blood Pressure and Resting Heart Rate: A Mendelian Randomisation Meta-Analysis in the CARTA Consortium. Circulation: Cardiovascular Genetics, 8, 832-841. https://doi.org/10.1161/CIRCGENETICS.115.001225

Linneberg, A, Jacobsen, RK, Skaaby, T, Taylor, AE, Fluharty, ME, Jeppesen, JL, Bjørngaard, JH, Åsvold, BO, Gabrielsen, ME, Campbell, A, Marioni, RE, Kumari, M, Marques-Vidal, P, Kaakinen, M, Cavadino, A, Postmus, I, Ahluwalia, TVS, Wannamethee, SG, Lahti, J, Räikkönen, K, Palotie, A, Wong, A, Dalgård, C, Ford, I, Ben-Shlomo, Y, Christiansen, L, Kyvik, KO, Kuh, D, Eriksson, JG, Whincup, PH, Mbarek, H, de Geus, EJC, Vink, JM, Boomsma, DI, Davey Smith, G, Lawlor, DA, Kisialiou, A, McConnachie, A, Padmanabhan, S, Jukema, JW, Power, C, Hyppönen, E, Preisig, M, Waeber, G, Vollenweider, P, Korhonen, T, Laatikainen, T, Salomaa, V, Kaprio, J, Kivimäki, M, Smith, BH, Hayward, C, Sørensen, TIA, Thuesen, BH, Sattar, N, Morris, RW, Romundstad, PR, Munafò, MR, Jarvelin, M-R & Husemoen, LLN 2015, 'Effect of Smoking on Blood Pressure and Resting Heart Rate: A Mendelian Randomisation Meta-Analysis in the CARTA Consortium', Circulation: Cardiovascular Genetics, vol. 8, pp. 832-841. https://doi.org/10.1161/CIRCGENETICS.115.001225

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title = "Effect of Smoking on Blood Pressure and Resting Heart Rate: A Mendelian Randomisation Meta-Analysis in the CARTA Consortium",

abstract = "Background-Smoking is an important cardiovascular disease risk factor, but the mechanisms linking smoking to blood pressure are poorly understood. Methods and Results-Data on 141 317 participants (62 666 never, 40 669 former, 37 982 current smokers) from 23 population-based studies were included in observational and Mendelian randomization meta-analyses of the associations of smoking status and smoking heaviness with systolic and diastolic blood pressure, hypertension, and resting heart rate. For the Mendelian randomization analyses, a genetic variant rs16969968/rs1051730 was used as a proxy for smoking heaviness in current smokers. In observational analyses, current as compared with never smoking was associated with lower systolic blood pressure and diastolic blood pressure and lower hypertension risk, but with higher resting heart rate. In observational analyses among current smokers, 1 cigarette/day higher level of smoking heaviness was associated with higher (0.21 bpm; 95% confidence interval 0.19; 0.24) resting heart rate and slightly higher diastolic blood pressure (0.05 mm Hg; 95% confidence interval 0.02; 0.08) and systolic blood pressure (0.08 mm Hg; 95% confidence interval 0.03; 0.13). However, in Mendelian randomization analyses among current smokers, although each smoking increasing allele of rs16969968/rs1051730 was associated with higher resting heart rate (0.36 bpm/allele; 95% confidence interval 0.18; 0.54), there was no strong association with diastolic blood pressure, systolic blood pressure, or hypertension. This would suggest a 7 bpm higher heart rate in those who smoke 20 cigarettes/day. Conclusions-This Mendelian randomization meta-analysis supports a causal association of smoking heaviness with higher level of resting heart rate, but not with blood pressure. These findings suggest that part of the cardiovascular risk of smoking may operate through increasing resting heart rate.",

author = "Allan Linneberg and Jacobsen, {Rikke K} and Tea Skaaby and Taylor, {Amy E} and Fluharty, {Meg E} and Jeppesen, {J{\o}rgen L} and Bj{\o}rngaard, {Johan H} and {\AA}svold, {Bj{\o}rn O} and Gabrielsen, {Maiken E} and Archie Campbell and Marioni, {Riccardo E} and Meena Kumari and Pedro Marques-Vidal and Marika Kaakinen and Alana Cavadino and Iris Postmus and Ahluwalia, {Tarun Veer Singh} and Wannamethee, {S Goya} and Jari Lahti and Katri R{\"a}ikk{\"o}nen and Aarno Palotie and Andrew Wong and Christine Dalg{\aa}rd and Ian Ford and Yoav Ben-Shlomo and Lene Christiansen and Kyvik, {Kirsten O} and Diana Kuh and Eriksson, {Johan G} and Whincup, {Peter H} and Hamdi Mbarek and {de Geus}, {Eco J C} and Vink, {Jacqueline M} and Boomsma, {Dorret I} and {Davey Smith}, George and Lawlor, {Debbie A} and Aliaksei Kisialiou and Alex McConnachie and Sandosh Padmanabhan and Jukema, {J Wouter} and Chris Power and Elina Hypp{\"o}nen and Martin Preisig and Gerard Waeber and Peter Vollenweider and Tellervo Korhonen and Tiina Laatikainen and Veikko Salomaa and Jaakko Kaprio and Mika Kivim{\"a}ki and Smith, {Blair H} and Caroline Hayward and S{\o}rensen, {Thorkild I A} and Thuesen, {Betina H} and Naveed Sattar and Morris, {Richard W} and Romundstad, {P{\aa}l R} and Munaf{\`o}, {Marcus R} and Marjo-Riitta Jarvelin and Husemoen, {Lise Lotte N}",

year = "2015",

month = dec,

day = "1",

doi = "10.1161/CIRCGENETICS.115.001225",

language = "English",

volume = "8",

pages = "832--841",

journal = "Circulation: Cardiovascular Genetics",

issn = "1942-325X",

publisher = "Lippincott Williams & Wilkins",

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TY - JOUR

T1 - Effect of Smoking on Blood Pressure and Resting Heart Rate

T2 - A Mendelian Randomisation Meta-Analysis in the CARTA Consortium

AU - Linneberg, Allan

AU - Jacobsen, Rikke K

AU - Skaaby, Tea

AU - Taylor, Amy E

AU - Fluharty, Meg E

AU - Jeppesen, Jørgen L

AU - Bjørngaard, Johan H

AU - Åsvold, Bjørn O

AU - Gabrielsen, Maiken E

AU - Campbell, Archie

AU - Marioni, Riccardo E

AU - Kumari, Meena

AU - Marques-Vidal, Pedro

AU - Kaakinen, Marika

AU - Cavadino, Alana

AU - Postmus, Iris

AU - Ahluwalia, Tarun Veer Singh

AU - Wannamethee, S Goya

AU - Lahti, Jari

AU - Räikkönen, Katri

AU - Palotie, Aarno

AU - Wong, Andrew

AU - Dalgård, Christine

AU - Ford, Ian

AU - Ben-Shlomo, Yoav

AU - Christiansen, Lene

AU - Kyvik, Kirsten O

AU - Kuh, Diana

AU - Eriksson, Johan G

AU - Whincup, Peter H

AU - Mbarek, Hamdi

AU - de Geus, Eco J C

AU - Vink, Jacqueline M

AU - Boomsma, Dorret I

AU - Davey Smith, George

AU - Lawlor, Debbie A

AU - Kisialiou, Aliaksei

AU - McConnachie, Alex

AU - Padmanabhan, Sandosh

AU - Jukema, J Wouter

AU - Power, Chris

AU - Hyppönen, Elina

AU - Preisig, Martin

AU - Waeber, Gerard

AU - Vollenweider, Peter

AU - Korhonen, Tellervo

AU - Laatikainen, Tiina

AU - Salomaa, Veikko

AU - Kaprio, Jaakko

AU - Kivimäki, Mika

AU - Smith, Blair H

AU - Hayward, Caroline

AU - Sørensen, Thorkild I A

AU - Thuesen, Betina H

AU - Sattar, Naveed

AU - Morris, Richard W

AU - Romundstad, Pål R

AU - Munafò, Marcus R

AU - Jarvelin, Marjo-Riitta

AU - Husemoen, Lise Lotte N

PY - 2015/12/1

Y1 - 2015/12/1

N2 - Background-Smoking is an important cardiovascular disease risk factor, but the mechanisms linking smoking to blood pressure are poorly understood. Methods and Results-Data on 141 317 participants (62 666 never, 40 669 former, 37 982 current smokers) from 23 population-based studies were included in observational and Mendelian randomization meta-analyses of the associations of smoking status and smoking heaviness with systolic and diastolic blood pressure, hypertension, and resting heart rate. For the Mendelian randomization analyses, a genetic variant rs16969968/rs1051730 was used as a proxy for smoking heaviness in current smokers. In observational analyses, current as compared with never smoking was associated with lower systolic blood pressure and diastolic blood pressure and lower hypertension risk, but with higher resting heart rate. In observational analyses among current smokers, 1 cigarette/day higher level of smoking heaviness was associated with higher (0.21 bpm; 95% confidence interval 0.19; 0.24) resting heart rate and slightly higher diastolic blood pressure (0.05 mm Hg; 95% confidence interval 0.02; 0.08) and systolic blood pressure (0.08 mm Hg; 95% confidence interval 0.03; 0.13). However, in Mendelian randomization analyses among current smokers, although each smoking increasing allele of rs16969968/rs1051730 was associated with higher resting heart rate (0.36 bpm/allele; 95% confidence interval 0.18; 0.54), there was no strong association with diastolic blood pressure, systolic blood pressure, or hypertension. This would suggest a 7 bpm higher heart rate in those who smoke 20 cigarettes/day. Conclusions-This Mendelian randomization meta-analysis supports a causal association of smoking heaviness with higher level of resting heart rate, but not with blood pressure. These findings suggest that part of the cardiovascular risk of smoking may operate through increasing resting heart rate.

AB - Background-Smoking is an important cardiovascular disease risk factor, but the mechanisms linking smoking to blood pressure are poorly understood. Methods and Results-Data on 141 317 participants (62 666 never, 40 669 former, 37 982 current smokers) from 23 population-based studies were included in observational and Mendelian randomization meta-analyses of the associations of smoking status and smoking heaviness with systolic and diastolic blood pressure, hypertension, and resting heart rate. For the Mendelian randomization analyses, a genetic variant rs16969968/rs1051730 was used as a proxy for smoking heaviness in current smokers. In observational analyses, current as compared with never smoking was associated with lower systolic blood pressure and diastolic blood pressure and lower hypertension risk, but with higher resting heart rate. In observational analyses among current smokers, 1 cigarette/day higher level of smoking heaviness was associated with higher (0.21 bpm; 95% confidence interval 0.19; 0.24) resting heart rate and slightly higher diastolic blood pressure (0.05 mm Hg; 95% confidence interval 0.02; 0.08) and systolic blood pressure (0.08 mm Hg; 95% confidence interval 0.03; 0.13). However, in Mendelian randomization analyses among current smokers, although each smoking increasing allele of rs16969968/rs1051730 was associated with higher resting heart rate (0.36 bpm/allele; 95% confidence interval 0.18; 0.54), there was no strong association with diastolic blood pressure, systolic blood pressure, or hypertension. This would suggest a 7 bpm higher heart rate in those who smoke 20 cigarettes/day. Conclusions-This Mendelian randomization meta-analysis supports a causal association of smoking heaviness with higher level of resting heart rate, but not with blood pressure. These findings suggest that part of the cardiovascular risk of smoking may operate through increasing resting heart rate.

U2 - 10.1161/CIRCGENETICS.115.001225

DO - 10.1161/CIRCGENETICS.115.001225

M3 - Journal article

C2 - 26538566

SN - 1942-325X

VL - 8

SP - 832

EP - 841

JO - Circulation: Cardiovascular Genetics

JF - Circulation: Cardiovascular Genetics

ER -

Effect of Smoking on Blood Pressure and Resting Heart Rate: A Mendelian Randomisation Meta-Analysis in the CARTA Consortium

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