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Greater Risk of Heart Failure Seen in Individuals With Smoking History


In this Mendelian randomization study, higher odds of developing heart failure were seen in regular vs never smokers and in current vs former smokers.

A higher risk for developing heart failure was recently linked to regular and current smokers compared with never and former smokers, according to findings presented in ESC Heart Failure.

Particularly, a genetic predisposition to smoking and a higher lifetime smoking burden increased the odds of developing the disease. Smoking burden was defined as length of time having smoked and cigarettes smoked per day. The authors investigated the likelihood of heart failure as it related to 3 smoking statuses (ever smoking, lifelong smoking duration, smoking cessation) and 4 smoking phenotypes (smoking initiation, age at initiation of regular smoking, cigarettes per day, smoking cessation). This is an area that requires exploration, they noted.

“Cigarette smoking has been associated with a higher risk of heart failure throughout observational studies,” the authors stated. “However, whether the total smoking burden and smoking cessation have causal effects on heart failure risk requires further exploration.”

Overall, the individuals (n = 47,309 with heart failure; n = 930,014 controls) were included in this analysis, and among them, higher odds ratios (ORs) were seen among ever regular smokers vs never smokers and current smokers vs former smokers for developing heart failure:

  • Ever vs never smokers: 1.28 (95% CI, 1.22-1.36; P = 1.5 × 10-18)
  • Current vs former smokers: 1.25 (95% CI, 1.09-1.44; P = 1.6 × 10-3)

Similar results were seen when accounting for a genetic liability to smoking more cigarettes daily (OR, 1.37; 95% CI, 1.20-1.58; P = 6.4 × 10-6) and having a higher composite lifetime smoking index (OR, 1.49; 95% CI, 1.31-1.70; P = 2.5 x 10-9).

No link was found between the genetically predicted age at initiation of regular smoking and heart failure (OR, 0.71; 95% CI, 0.48-1.06; P = .10), but a positive correlation was seen for every 1 SD increase (ie, for current smokers, 8 cigarettes/day) in genetically instrumented cigarettes per day and risk of heart failure (OR, 1.37; 95% CI, 1.20-1.58; P = 6.4 × 10-6). Also, a 49% greater risk was seen when considering lifetime smoking index (OR, 1.49; 95% CI, 1.31-1.70; P = 2.5 × 10-9).

For this Mendelian randomization (MR) study, the authors extracted genetic variant data linked to smoking from the GWAS and Sequencing Consortium of Alcohol and Nicotine Use, a composite lifetime smoking index was derived from the UK Biobank, and the Heart Failure Molecular Epidemiology for Therapeutic Targets Consortium provided the associations between smoking phenotype and heart failure. MR, the authors pointed out, “is a genetic epidemiological method to explore the causal effect of an exposure on disease outcome, using genetic variants as instrumental variables.”

The associations they saw remained even after adjusting, individually and collectively, for body mass index, type 2 diabetes, lipid levels, and blood pressure—all known heart failure risk factors.

“This MR study indicated that genetic predisposition to ever smoking and to a higher lifetime smoking burden is associated with a higher risk of heart failure,” the authors conclude. “Our findings point to a potentially causal role of smoking in the pathogenesis of heart failure and highlight the importance of smoking cessation strategies to decrease the risk of heart failure.”

The inability of the investigators to evaluate associations between different regular smoking durations and smoking cessation with heart failure, the possibility of smoking’s impact being mediated by other disease pathways, and that most of the study participants were of European ancestry introduced limitations on the generalizability of these findings.


Lu Y, Xu Z, Georgakis MK, Wang Z, Lin H, Zheng L. Smoking and heart failure: a Mendelian randomization and mediation analysis. ESC Heart Fail. Published online March 3, 2021. doi: 10.1002/ehf2.13248

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