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

Circ Cardiovasc Genet
Authors
Keywords
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.

Year of Publication
2015
Journal
Circ Cardiovasc Genet
Volume
8
Issue
6
Pages
832-41
Date Published
2015 Dec
ISSN
1942-3268
URL
DOI
10.1161/CIRCGENETICS.115.001225
PubMed ID
26538566
PubMed Central ID
PMC4684098
Links
Grant list
R01 MH063706 / MH / NIMH NIH HHS / United States
WT 084762 / Wellcome Trust / United Kingdom
RG/13/2/30098 / British Heart Foundation / United Kingdom
R01 HL036310 / HL / NHLBI NIH HHS / United States
G0600705 / Medical Research Council / United Kingdom
MR/J012165/1 / Medical Research Council / United Kingdom
R01 HL087679 / HL / NHLBI NIH HHS / United States
MC_UU_12013/3 / Medical Research Council / United Kingdom
MC_UU_12013/6 / Medical Research Council / United Kingdom
G0802736 / Medical Research Council / United Kingdom
092731 / Wellcome Trust / United Kingdom
5R01MH63706:02 / MH / NIMH NIH HHS / United States
AG13196 / AG / NIA NIH HHS / United States
K013351 / Medical Research Council / United Kingdom
MC_UU_12019/1 / Medical Research Council / United Kingdom
1RL1MH083268-01 / MH / NIMH NIH HHS / United States
MC_UU_12013/1 / Medical Research Council / United Kingdom
G0500539 / Medical Research Council / United Kingdom
102215 / Wellcome Trust / United Kingdom
076113 / Wellcome Trust / United Kingdom
R37 AG013196 / AG / NIA NIH HHS / United States
MR/K023233/1 / Medical Research Council / United Kingdom
U01 DK062418 / DK / NIDDK NIH HHS / United States
092731 / Medical Research Council / United Kingdom
284167 / European Research Council / International
MC_PC_15018 / Medical Research Council / United Kingdom
HL36310 / HL / NHLBI NIH HHS / United States
CZD/16/6/4 / Chief Scientist Office / United Kingdom
MC_PC_U127561128 / Medical Research Council / United Kingdom
R01AG017644 / AG / NIA NIH HHS / United States
R01AG1764406S1 / AG / NIA NIH HHS / United States
SP/07/008/24066 / British Heart Foundation / United Kingdom
UL1 TR001425 / TR / NCATS NIH HHS / United States
R01 AG017644 / AG / NIA NIH HHS / United States
MR/K013351/1 / Medical Research Council / United Kingdom
R01 AG013196 / AG / NIA NIH HHS / United States
R01 DA018673 / DA / NIDA NIH HHS / United States
068545/Z/02 / Wellcome Trust / United Kingdom
5R01HL087679-02 / HL / NHLBI NIH HHS / United States
HS06516 / HS / AHRQ HHS / United States
RG/13/16/30528 / British Heart Foundation / United Kingdom
RL1 MH083268 / MH / NIMH NIH HHS / United States
WT088806 / Wellcome Trust / United Kingdom
G1002319 / Medical Research Council / United Kingdom
MC_UU_12013/5 / Medical Research Council / United Kingdom
G0000934 / Medical Research Council / United Kingdom
G0800612 / Medical Research Council / United Kingdom
G9815508 / Medical Research Council / United Kingdom
086684 / Wellcome Trust / United Kingdom
MR/J01351X/1 / Medical Research Council / United Kingdom