Smoking and the comorbidity trajectory of cardiometabolic and mental disorders: A multi-state model

Cardiometabolic diseases (CMDs) and mental disorders (MDs) exhibit high comorbidity and result in a substantial disease burden. The impact of smoking, a risk factor for both diseases, on the comorbidity trajectory remains unclear.

We conducted a prospective cohort study involving 355,488 UK Biobank participants, utilizing multi-state models to explore the potential impact of smoking status on all transition stages. Smoking status were classified as never, previous, and current. Incident CMDs (ischaemic heart disease, stroke, and diabetes) and MDs (depression and anxiety) were ascertained via linkage to hospital inpatient records, primary care data, self-reports, and death registries.

Across all pathway, current smokers had higher transition probabilities than previous smokers and never-smokers. Compared to the effects on incident MDs or CMDs from baseline, current smoking was associated with higher risks of transitions from MDs to comorbid CMDs (HR = 1.63; 95% CI: 1.34-1.98), from CMDs to comorbid MDs (HR = 1.45; 95% CI: 1.20-1.76), and from comorbidity to death (HR = 2.43; 95% CI: 1.79-2.29). In contrast, smoking cessation attenuated this risk (HRs range: 0.45-0.93). Moreover, current and previous smoking were associated with average life expectancy reductions of 6.88 years (95% CI: 4.78-8.98) and 0.84 years (95% CI: 0.59-2.27), respectively, among 45-year-old participants with comorbidity. The associations between smoking and the comorbidity trajectory were robust in sensitivity analyses.

Current smoking has stronger impacts on transitions to comorbidity than on the first occurrence of CMDs or MDs. While current smoking increases the risk of death, smoking cessation mitigates the loss of life expectancy.