International Journal of Epidemiology · Oct 14, 2026

Comparison of modeling strategies to study the effect of an exposure on changes in continuous outcomes: evaluating the impact of alcohol consumption on changes in cardiometabolic health markers based on the German National Cohort (NAKO)

By Bouka M, Nimptsch K, Grittner U et al.

BACKGROUND: When investigating effects of baseline exposures on changes in continuous outcomes in longitudinal studies, the change-score model is increasingly recommended, while baseline adjustment is debated. Limited empirical evidence exists on the extent to which these choices matter. We examined how different modeling strategies influence estimated effects using alcohol and prospective changes in cardiometabolic health markers as an example. METHODS: We used data from the German National Cohort (NAKO; ∼205 000 participants at baseline, ∼140 000 at 4-5-year follow-up). Participants reported alcohol consumption at baseline (2014-19) and were classified as light, moderate, heavy, former, or never drinkers. Triglycerides (TG), systolic and diastolic blood pressure (SBP and DBP), high-density lipoprotein cholesterol (HDL-C), and glycated hemoglobin were measured at baseline and 5 years later. Longitudinal effects were estimated using a change-score model informed by directed acyclic graphs without baseline adjustment, and compared to a baseline-adjusted model and a model that adjusted for the average of baseline and follow-up (Oldham's). Statistical tests assessed whether changes in the outcome depended on baseline levels. RESULTS: Change-score and Oldham's models produced highly consistent results across all five cardiometabolic markers, whereas baseline-adjusted change-score models yielded different results for all. Statistical tests assessing the relationship between baseline levels and subsequent change did not indicate whether baseline adjustment would materially alter the results. Based on the change-score models, former drinkers had lower 5-year TG change and higher SBP, DBP, and HDL-C changes compared with light drinkers, while heavy drinkers had lower DBP change. CONCLUSION: When exposure precedes the baseline outcome, baseline adjustment in change-score analyses may substantially alter effect estimates.

doi.org/10.1093/ije/dyag245 Open access PubMed 42974917 Populations