Interaction between Alcohol Consumption and Cigarette Smoking in Association With the Risk of Chronic Limb Threatening Ischaemia

OBJECTIVE: The association between alcohol consumption and peripheral arterial disease (PAD) remains conflicting. Further, although alcohol consumption and smoking are highly correlated habits, interaction between these two factors is rarely studied. This study examined these two factors in association with risk of chronic limb threatening ischaemia (CLTI), which is the most severe form of PAD. METHODS: The Singapore Chinese Health Study, a prospective, population based cohort of middle aged and older adults, recruited 63 257 participants between 1993 and 1998. CLTI cases were identified via linkage to the nationwide hospital database to 31 December 2017. Multivariable Cox proportional hazards models were used to evaluate hazard ratio (HR) and 95% confidence interval (CI) for an association with CLTI risk. RESULTS: A total of 1 097 CLTI cases were identified after a median follow up of 20.6 years. Compared with non-drinkers (less than one drink/week), low to moderate alcohol consumption (one to nine drinks/week) was associated with reduced CLTI risk among non-smokers (HR 0.71, 95% CI 0.55 - 0.91), but not among smokers (HR 1.04, 95% CI 0.77 - 1.41) (p for interaction = .055). Conversely, higher alcohol consumption of ten or more drinks/week was linked to increased risk among current smokers (HR 1.48, 95% CI 1.00 - 2.20) and among non-smokers (HR 1.54, 95% CI 0.98 - 2.40), albeit less precisely. In joint analysis, compared with those who neither smoked nor drank alcohol, reduced risk was observed only in non-smokers with one to nine drinks/week (HR 0.71, 95% CI 0.56 - 0.92), while the highest risk was observed in smokers who drank ten or more drinks/week (HR 2.15, 95% CI 1.48 - 3.13). CONCLUSION: Alcohol and smoking may interact to increase the risk of CLTI such that low to moderate alcohol consumption may only be associated with a lower risk in non-smokers but not in smokers.