Effect of Smoking on Blood Pressure and Resting Heart Rate: A Mendelian Randomization 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.

Keywords: Mendelian randomization; blood pressure; heart rate; hypertension; smoking.

Figure 1

Association of smoking status with systolic blood pressure (SBP) and diastolic blood pressure (DBP), and resting heart rate (RHR). Former and current smoking status are compared to never smoking status; the difference was estimated by linear regression adjusted for sex and age.

Figure 2

Association of smoking status with hypertension and severe hypertension. Former and current smoking status are compared to never smoking status; the difference was estimated by logistic regression adjusted for sex and age. OR, Odds ratio.

Figure 3

Association of smoking heaviness in current smokers with systolic blood pressure (SBP) and diastolic blood pressure (DBP) and resting heart rate (RHR). The difference per one cigarette per day increase in smoking heaviness was estimated by linear regression adjusted for sex and age.

Figure 4

Mendelian randomisation analysis of the association of the smoking increasing allele (minor allele) of rs1051730/rs16969968 with systolic blood pressure (SBP) and diastolic blood pressure (DBP) and resting heart rate (RHR). Analyses were stratified by smoking status (current, former, and never smoking). The difference per one allele was estimated by linear regression adjusted for sex and age. Overall test for heterogeneity by smoking status: SBP: P=0.656; DBP: P=0.138; RHR: P=0.015;

Figure 5

Mendelian randomisation analysis of the association of the smoking increasing allele (minor allele) of rs1051730/rs16969968 with smoking heaviness in current smokers. The difference (increase in smoking quantity) per one allele was estimated by linear regression adjusted for sex and age.