(CSPOT38) Do Multimorbidity, Polypharmacy, and Socioeconomic Position Interact to Increase Colorectal Cancer Mortality? A Danish Nationwide, Population-Based Cohort Study

Background: Multimorbidity, polypharmacy and socioeconomic position (SEP), may impact mortality in individuals undergoing surgery for colorectal cancer (CRC).

Objectives: To evaluate how these factors interactively and individually may impact mortality rates.

Methods: Using Danish health and social registries, we assembled a nationwide, population-based cohort of all individuals who underwent curative surgery for stage I-III CRC between 2001 and 2021. Patients were followed from surgery date until death, emigration, or December 31, 2022. We categorized SEP into three levels: high, medium, and low using a combined measure of liquid assets, education, and cohabitation status. Multimorbidity was defined as the presence of >=2 somatic and/or psychiatric diseases per WHO guidelines and/or polypharmacy as >=5 prescriptions in the six months before CRC surgery. We computed age-sex standardized mortality rates (SMR) per 1,000 person-years and used Cox regression models to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). We computed interaction contrasts to examine the excess mortality risk associated with SEP, multimorbidity, and polypharmacy.

Results: Among 58,169 CRC patients (46% female, median age 72), 30,608 were multimorbid and 39,489 used polypharmacy; 25,851 died during follow-up. Median follow-up was 3.4 years. SMR were lowest in patients with high SEP without multimorbidity or polypharmacy (39.4 per 1,000 person-years, 95%CI=36.0-43.4). Mortality increased with decreasing SEP. Patients with low SEP and polypharmacy had the highest mortality rates (110.0 per 1,000 person-years, 95%CI=104.8-117.7). Compared with high-SEP patients with neither multimorbidity nor polypharmacy, low-SEP patients without multimorbidity or polypharmacy had HR=1.3 (95% CI=1.1–1.5), rising to HR= 2.1 (95% CI=1.9-2.3) for those with polypharmacy, and HR=2.4 (95% CI=1.9-2.3) for those with both multimorbidity and polypharmacy. For patients with multimorbidity but not polypharmacy, the impact of decreasing SEP on the HR was small, changing from HR=1.3 (95% CI=1.1–1.5) to HR=1.5 (95% CI=1.3–1.8). The interaction contrast showed that 10% of mortality was attributed to the interaction among multimorbidity, polypharmacy and SEP.

Conclusions: CRC patients with polypharmacy and multimorbidity had higher mortality rates, especially those with low SEP, when compared with high-SEP patients with neither multimorbidity nor polypharmacy. Multimorbidity alone had limited impact on mortality. Interaction analyses showed a marginally synergistic effect of SEP, multimorbidity, and polypharmacy on mortality.