Alcohol consumption and cigarette smoking interact to modify the risk of chronic limb-threatening ischaemia (CLTI), the most severe form of peripheral arterial disease (PAD) in a local cohort, as suggested in a study. Specifically, low-to-moderate drinking is protective among individuals who do not smoke, whereas any level of drinking contributes to a risk increase among smokers.
Analysis of data from the Singapore Chinese Health Study showed that compared with having less than one drink per week, one to nine drinks per week was associated with a 29-percent reduction in the risk of CLTI among nonsmokers (hazard ratio [HR], 0.71, 95 percent confidence interval [CI], 0.55–0.91) but a 4-percent risk increase among smokers (HR, 1.04, 95 percent CI, 0.77–1.41; p=0.055 for interaction). [Eur J Vasc Endovasc Surg 2026;doi:10.1016/j.ejvs.2026.06.002]
Meanwhile, having at least 10 drinks per week raised the risk of CLTI both among smokers (HR, 1.48, 95 percent CI, 1.00–2.20) and among nonsmokers (HR, 1.54, 95 percent CI, 0.98–2.40).
In joint analyses in which the combined influence of alcohol and smoking was assessed, nonsmokers consuming one to nine drinks per week were the only ones who showed a reduced risk of CLTI (HR, 0.71, 95 percent CI, 0.56–0.92). Conversely, smokers with an intake of ≥10 drinks per week had the highest CLTI risk (HR, 2.15, 95 percent CI, 1.48–3.13) relative to participants who neither smoked nor consumed alcohol.
The authors argued that smoking may cancel out the cardiovascular benefits associated with light-to-moderate drinking, leaving smokers fully exposed to the risk of CLTI.
“Low-or-moderate alcohol consumption has been associated with increased high-density lipoprotein cholesterol levels, reduced incidence of type 2 diabetes, lower fibrinogen and fibrin D dimer levels, as well as higher tissue plasminogen activator and plasminogen concentrations, all of which could potentially reduce CLTI risk,” the authors said.
“However, these potentially protective effects may be neutralized by smoking, which promotes atherosclerosis through mechanisms such as endothelial dysfunction, smooth muscle cell remodelling, and macrophage phenotypic transformation,” they added.
Furthermore, heavy or binge drinking exerts detrimental effects on most cardiovascular risk factors (eg, lipid profile and blood pressure) and intermediate biomarkers (eg, inflammation and oxidation), contributing to an increased risk of atherosclerosis.
“Therefore, heavy drinking and smoking may jointly enhance CLTI risk through mechanisms such as peripheral atherosclerosis, thrombosis, and microvascular dysfunction,” the authors said.
Overall, the findings underscore the need for public health interventions aimed at controlling alcohol consumption and promoting smoking cessation to reduce the burden of CLTI, according to the authors, noting that the data are observational rather than definitive evidence of causality and cannot yet support a formal clinical recommendation.
The study included 63,134 participants (mean age 56.5 years, 55.8 percent female, 19.5 percent current smokers), with CLTI occurring in 1,097 over a median follow-up of 20.6 years.
At baseline, 81.2 percent of participants consumed fewer than one drink per week (non-drinkers), 9.8 percent consumed one to two drinks per week, 5.9 percent consumed three to nine drinks per week, and 3.1 percent consumed at least 10 drinks per week. Compared with non-drinkers, participants who consumed 10 or more drinks/week were more likely to be men, engage in less physical activity, have lower prevalence of hypertension and diabetes, and be current smokers.