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Investigating Canada’s Guidance on Alcohol and Health risk zones and major chronic disease in Canadian adults: A target trial emulation approach Claire Benny* Claire Benny Vanessa DeRubeis Erin Hobin Laura Anderson Brendan T. Smith

Introduction: Canada’s updated Guidance on Alcohol and Health (the Guidance) warns that no amount of alcohol is healthy. Randomized studies on alcohol intake are largely unethical, so causal inference methods are necessary to estimate risk. This study aimed to assess if drinking in line with lower risk zones outlined in the Guidance was protective against major chronic disease in Canadian adults.

Methods: Data were from the Canadian Longitudinal Study on Aging from 2011 to 2021. This study employed a target trial emulation approach with marginal structural Cox proportional hazards modelling to assess the research aim. Participants (n=11,724) were categorized as corresponding to “low” (>0 to 2 standard drinks weekly), “moderate” (3-6 drinks weekly), or “increasingly high” (7+ drinks) risk based on the Guidance. Outcomes included a composite measure of major chronic disease and specific major chronic diseases (i.e., cancer, heart disease, stroke, type 2 diabetes, COPD).

Results: Low-risk drinking was protective against major chronic disease (HR: 0.91, 95% CI: 0.88-0.95) and moderate risk drinking was not protective against chronic disease compared to increasingly high risk drinking. Contrastingly, both low and moderate risk drinking were protective against cancer (HR: 0.93, 95% CI 0.90-0.95; HR: 0.96, 95% CI: 0.93-0.98, respectively), heart disease (HR: 0.93, 95% CI: 0.90-0.96; HR: 0.94, 95% CI: 0.92-0.97, respectively), stroke (HR: 0.94, 95% CI: 0.91-0.96; HR: 0.95, 95% CI: 0.92-0.97, respectively); type 2 diabetes (HR: 0.92, 95% CI: 0.89-0.95; HR: 0.93, 95% CI: 0.91-0.96, respectively); and COPD (HR: 0.93, 95% CI: 0.91-0.96; HR: 0.95, 95% CI: 0.93-0.98).

Conclusion: This study used novel causal inference methods to substantiate that drinking in low and moderate risk zones is protective against chronic disease compared to increasingly high risk drinking. The findings provide important implications for reducing alcohol intake for chronic disease prevention.