Polypharmacy as an ordered indicator of therapeutic complexity in a national cardiovascular prevention programme

Background: The prevalence of polypharmacy has been rising worldwide, most studies focuses on older adults. However, little is known about patterns and determinants of polypharmacy in middle-aged individuals engaged in structured national prevention programmes. This exploratory study examines how clinical characteristics, comorbidity structure, and system-level actions relate to increasing medication burden in participants of the Polish Prophylaxis 40 PLUS prevention programme, which focuses on the prevention and early detection of lifestyle-related (civilization) diseases, particularly cardiovascular conditions. Methods: A cohort of 151 adults aged ≥40 years was stratified into three ordinal polypharmacy categories (5, 6, ≥7 drugs). Patients demographics, lifestyle behaviours, blood-pressure measures, ICD-10 comorbidity blocks, and indicators of medical actions were analysed. Ordinal proportional-odds regression (forward and backward stepwise selection) was performed with multimorbidity included as an adjustment covariate. Bootstrap resampling (B = 200) assessed parameter stability. Results: Circulatory system diseases (ICD-10 I) were consistently associated with higher odds of belonging to a higher polypharmacy category (OR 2.3-2.6). Normalisation of previously irregular heart rhythm strongly predicted higher medication burden (OR 6.0-8.4). Sensory system diseases (ICD-10 H) were also positively associated with polypharmacy, whereas nervous-system diseases (ICD-10 G) showed an inverse relationship. Higher baseline diastolic blood pressure was negatively associated with medication count (OR 0.93-0.95 per mmHg). Educational attainment demonstrated a weaker, exploratory positive association. Bootstrap analysis confirmed the robustness of the main predictors (ICD-10 I, ICD-10 G/H, heart-rhythm change, baseline DBP). Conclusion: In middle-aged adults within a Polish national prevention programme, polypharmacy reflects treatment intensity and system-level complexity rather than multimorbidity alone. Cardiovascular disease, rhythm-control interventions, and multi-specialty care were associated with higher medication burden. These findings highlight the importance of integrating structured medication review, targeted deprescribing, and equitable preventive pharmacotherapy into cardiovascular prevention pathways.