Hazard ratios (HRs) for alcohol consumption were calculated separately within each study using Cox regression models, stratified by sex and with adjustment for known confounders: age, smoking status (current vs non-current) and history of diabetes. To account for EPIC-CVD's case-cohort design (which was used because lipids and other cardiovascular disease biomarkers were measured only in the case-cohort subset and not the full EPIC cohort), the Cox models for cardiovascular disease events were adapted using Prentice weights and stratified by centre.26 For the four case-control studies nested within prospective cohorts of the ERFC, odds ratios were calculated using, as appropriate, conditional or unconditional logistic regression models, taking into account relevant matching factors. Study-specific estimates were then pooled across studies by random-effects meta-analysis.27 We tested for violation of the proportional hazards assumption by including time interactions with alcohol consumption. To avoid model overfitting, studies with fewer than five incident cases of a particular outcome were excluded from analyses of that particular outcome.
