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

Allan Linneberg*, Rikke K. Jacobsen, Tea Skaaby, Amy E Taylor, Meg E Fluharty, Jørgen L. Jeppesen, Johan H. Bjorngaard, Bjørn O. Åsvold, Maiken E. Gabrielsen, Archie Campbell, Riccardo E. Marioni, Meena Kumari, Pedro Marques-Vidal, Marika Kaakinen, Alana Cavadino, Iris Postmus, Tarunveer S. Ahluwalia, S. Goya Wannamethee, Jari Lahti, Katri RaikkonenAarno Palotie, Andrew Wong, Christine Dalgård, Ian Ford, Yoav Ben-Shlomo, Lene Christiansen, Kirsten O. Kyvik, Diana J L 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 Hypponen, Martin Preisig, Gerard Waeber, Peter Vollenweider, Tellervo Korhonen, Tiina Laatikainen, Veikko Salomaa, Jaakko Kaprio, Mika J Kivimaki, Blair H. Smith, Caroline Hayward, Thorkild Sorensen, Betina H. Thuesen, Naveed Sattar, Richard W. Morris, Pål R. Romundstad, Marcus R. Munafò, Marjo Riitta Jarvelin, Lise Lotte N Husemoen

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

104 Citations (Scopus)
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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 randomisation (MR) meta-analyses of the associations of smoking status and smoking heaviness with systolic and diastolic blood pressure (SBP, DBP), hypertension, and resting heart rate. For the MR 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 SBP, DBP, and lower hypertension risk, but with higher resting heart rate. In observational analyses amongst current smokers, one cigarette/day higher level of smoking heaviness was associated with higher (0.21 beats/minute; 95% CI 0.19; 0.24) resting heart rate, and slightly higher DBP (0.05 mmHg; 95% CI 0.02; 0.08) and SBP (0.08 mmHg; 95% CI 0.03; 0.13). However, in MR analyses amongst current smokers, while each smoking increasing allele of rs16969968/rs1051730 was associated with higher resting heart rate (0.36 beats/minute/allele; 95% CI 0.18; 0.54), there was no strong association with DBP, SBP, or hypertension. This would suggest a 7 beats/minute higher heart rate in those who smoke 20 cigarettes/day.

CONCLUSIONS: -This MR 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 languageEnglish
Pages (from-to)832-841
Number of pages10
JournalCirculation: Cardiovascular Genetics
Issue number6
Early online date4 Nov 2015
Publication statusPublished - 1 Dec 2015

Structured keywords

  • Brain and Behaviour
  • Tobacco and Alcohol


  • Blood pressure
  • heart rate
  • hypertension
  • Mendelian randomization
  • smoking


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