Time to First Cigarette After Waking and Incident Heart Failure: A Dose-Response Analysis from the UK Biobank

Aims We aimed to investigate the association between time to first cigarette after waking (TTFC) and incident heart failure (HF) in a large prospective cohort.​ Methods This study included 229,391 participants from the UK Biobank. Current smokers were categorized by TTFC intervals (<5, 5–15, 30–60, 61–120, >120 minutes). Multivariable Cox proportional hazards models were employed to assess the relationship between TTFC and HF. Joint analyses evaluated the combined associations of TTFC with daily cigarette amount and smoking duration. Subgroup and interaction analyses were conducted by age, sex, BMI, education, and alcohol consumption. Results During a median follow-up of 15.5 years, 6,912 (3.01%) incident HF cases occurred among 229,391 participants. The cohort included 203,653 (88.77%) non-smokers (age 55.9 ± 8.1 years, 41.4% female, 91.5% White ethnicity, 2.7% incident HF cases) and 25,738 (11.23%) current smokers (age 54.5 ± 8.1 years, 49.0% female, 89.1% White ethnicity, 5.7% incident HF cases). A significant dose-dependent relationship was observed between shorter TTFC and HF risk (P for trend < 0.001). Compared with non-smokers, smokers with TTFC <5 minutes exhibited the highest adjusted hazard ratio (HR 2.22, 95% CI 1.58–3.10; P < 0.001), corresponding to an absolute risk difference of 4.03%. Joint analyses showed that among individuals smoking ≤ median cigarettes/day, HF risk increased from HR 1.61 (95% CI: 1.35–1.92; P < 0.001) to 2.25 (1.86–2.72; P < 0.001) across decreasing TTFC categories; among those smoking > median cigarettes/day, the corresponding HRs ranged from 1.95 (1.41–2.69; P < 0.001) to 2.17 (1.74–2.69; P < 0.001). Similar gradients were observed when TTFC was jointly analyzed with smoking duration. Subgroup analyses indicated stronger associations in participants aged <60 years (HR 1.98, 95% CI 1.56–2.51; P < 0.001 for TTFC <15 minutes) than in those ≥60 years (HR 1.55, 95% CI 1.25–1.91; P < 0.001), both compared with non-smokers (P for interaction < 0.001). Conclusion Shorter TTFC is independently and dose-dependently associated with a higher risk of incident HF, even after accounting for smoking burden and comorbidities. TTFC assessment may improve HF risk stratification, particularly in younger individuals.