Journal
CIRCULATION-CARDIOVASCULAR GENETICS
Volume 8, Issue 6, Pages 832-841Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCGENETICS.115.001225
Keywords
blood pressure; heart rate; hypertension; Mendelian randomization; smoking
Funding
- Academy of Finland [24300796, 139635, 129494, 136895, 263836, 141054, 104781, 120315, 129269, 1114194, 141042]
- MRC [G0000934]
- Wellcome Trust [068545/Z/02, 076113, 092731, WT088806, 086684, WT 084762]
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- National Institute of Allergy and Infectious Diseases
- National Human Genome Research Institute
- National Institute of Child Health and Human Development
- Juvenile Diabetes Research Foundation International (JDRF) [U01 DK062418]
- Department of Health's National Institute for Health Research (NIHR) ('Biomedical Research Centres')
- University of Bristol
- British Heart Foundation [SP/07/008/24066]
- Medical Research Council [MR/J01351X/1, G0800612, G0802736, MC_UU_12013/1, MC_UU_12013/5, MC_UU_12013/6]
- Swiss National Science Foundation [105993, 118308, 139468, 122661]
- GlaxoSmithKline
- Faculty of Biology and Medicine of the University of Lausanne
- Danish Heart Foundation
- Danish Medical Research Council
- Danish Hospital Foundation of Medical Research
- Danish Health Insurance Foundation
- Foundation of E. & M. Wedel-Wedellsborg
- Landsforeningen til Bekampelse af Kredslobssygdomme
- Augustinus Foundation
- Becket Foundation
- Foundation of senior registrar J. L. Boserup
- National Institute on Aging in the US [R01 AG017644, R01AG1764406S1]
- UK Government Department for Communities and Local Government
- UK Government Department for Transport
- UK Government Department for Work and Pensions
- UK Government Department of Health
- UK Government HM Revenue and Customs
- Academy of Finland Center of Excellence in Complex Disease Genetics [213506, 129680]
- Sigrid Juselius Foundation
- ENGAGE (European Network for Genetic and Genomic Epidemiology) [201413]
- Medical Research Fund
- Danish Diabetes Association
- NOVO Foundation
- Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6]
- Scottish Funding Council [HR03006]
- UK's Medical Research Council
- Danish National Research Foundation
- Pharmacy Foundation
- Egmont Foundation
- March of Dimes Birth Defects Foundation
- Health Foundation
- Gene Diet Interactions in Obesity (GENDINOB)
- MRC Population Health Scientist Fellowship [MR/J012165/1]
- Velux Foundation
- Danish Medical Research Council, Danish Agency for Science, Technology and Innovation
- Aase and Ejner Danielsens Foundation
- ALK-Abello' A/S (Horsholm, Denmark)
- Timber Merchant Vilhelm Bangs Foundation
- MEKOS Laboratories (Denmark)
- Research Centre for Prevention and Health
- Capital Region of Denmark
- Finnish Diabetes Research Society
- Samfundet Folkhalsan
- Novo Nordisk Foundation
- Finska Lakaresallskapet
- Signe and Ane Gyllenberg Foundation
- University of Helsinki
- Ministry of Education
- Ahokas Foundation
- Emil Aaltonen Foundation
- Danish Centre for Evaluation and Health Technology Assessment
- Novo Nordisk
- Copenhagen County
- Danish Pharmaceutical Association
- Ib Henriksen foundation
- Health Insurance Foundation [2010 B 131]
- NHS Research and Development Cardiovascular Research Programme
- University Hospital Oulu, Biocenter
- University of Oulu, Finland [75617]
- NHLBI through the STAMPEED program [5R01HL087679-02, 1RL1MH083268-01]
- NIH/NIMH [5R01MH63706:02]
- European Commission [QLG1-CT-2000-01643]
- ENGAGE project [HEALTH-F4-2007-201413]
- EU [277849]
- Medical Research Council, UK [G0500539, G0600705, G1002319, MC_UU_12019/1, K013351]
- MRC, Centenary Early Career Award
- European Research Council [284167]
- Netherlands Organization for Scientific Research (NWO) [904-61-090, 985-10-002, 904-61-193, 480-04-004, 400-05-717, Addiction-31160008, Middelgroot-911-09-032, Spinozapremie 56-464-14192]
- BBRMI-NL (Biobanking and Biomolecular Resources Research Infrastructure)
- VU University's Institutes for Health and Care Research
- Neuroscience Campus Amsterdam
- Bristol-Myers Squibb, USA
- European Union [HEALTH-F2-2009-223004]
- Netherlands Consortium for Healthy Ageing [NGI: 05060810]
- Netherlands Heart Foundation [2001 D 032]
- British Heart Foundation
- Health and Safety Executive
- Department of Health
- National Heart Lung and Blood Institute [NHLBI: HL36310]
- National Institute on Aging, US, NIH [AG13196]
- Agency for Healthcare Policy Research [HS06516]
- John D and Catherine T MacArthur Foundation Research Networks on Successful Midlife Development and Socioeconomic Status and Health
- Economic and Social Research Council International Centre for Life Course Studies in Society and Health [RES-596-28-0001]
- Medical Research Council
- Economic and Social Research Council
- region of Copenhagen, the Faroe Islands and Greenland
- Office for National Statistics
- British Heart Foundation [RG/13/16/30528, RG/13/2/30098, SP/07/008/24066, RG/08/013/25942] Funding Source: researchfish
- Chief Scientist Office [CZD/16/6/4] Funding Source: researchfish
- Economic and Social Research Council [ES/J023299/1, ES/K005774/1] Funding Source: researchfish
- Lundbeck Foundation [R165-2013-15410] Funding Source: researchfish
- Medical Research Council [MR/K013351/1, MC_UU_12013/6, G1001799, G9815508, MR/N01104X/1, G0000934, MC_PC_15018, G0800612, MC_UU_12013/3, MC_UU_12013/1, G1002319, MR/J01351X/1, G0802736, MR/J012165/1, MC_UU_12013/5, G0600705, MR/K023233/1, MC_PC_U127561128, MC_UU_12019/1] Funding Source: researchfish
- Academy of Finland (AKA) [141042, 141042] Funding Source: Academy of Finland (AKA)
- ESRC [ES/K005774/1, ES/J023299/1] Funding Source: UKRI
- MRC [G0000934, MR/N01104X/1, G0600705, MR/J01351X/1, MC_UU_12019/1, MC_PC_U127561128, MC_UU_12013/1, MC_UU_12013/3, MR/K023233/1, MR/K013351/1, MC_UU_12013/6, G1001799, G0800612, G1002319, G0802736, MR/J012165/1, MC_UU_12013/5] Funding Source: UKRI
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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 141317 participants (62666 never, 40669 former, 37982 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 mmHg; 95% confidence interval 0.02; 0.08) and systolic blood pressure (0.08 mmHg; 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.
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