Divergent trends in high BMI-associated NHL mortality: An analysis of the globalburden of disease database 1990-2021

Abstract Introduction: Non-Hodgkin lymphoma (NHL) represents one of the most prevalent hematologic malignancies globally, with substantial variation in incidence and mortality across populations. In recent decades, the rising prevalence of obesity has been recognized as a significant modifiable risk factor for NHL development and outcomes. High body mass index (BMI) not only contributes to the growing global burden of NHL but is increasingly associated with elevated mortality risk, with pronounced impacts observed in regions and populations with both high obesity prevalence and limited access to preventive or therapeutic interventions Utilizing data from the Global Burden of Disease 2021 study, this analysis aimed to delineate recent trends and disparities in NHL mortality attributable to high BMI at global, regional, and national levels. Methods: Age-adjusted mortality rates (AAMRs) from 1990 to 2021 were extracted from the Global Burden of Disease database (GBD). Data were stratified by sex (male, female, both) and five location categories based on the Socio-Demographic Index (SDI): High SDI, High- middle SDI, Middle SDI, Low-middle SDI, and Low SDI, as well as a global aggregate. Average annual percentage change (AAPC) in rates over 1990-2021 was estimated using joinpoint regression. The univariate regression analysis assessed the relationship between years and mortality rates for each location, yielding a slope, p-value, and R-squared value. Results: A total of 277,300 deaths occurred due to high BMI-associated NHL. In 2021, the highest AAMR for both sexes was observed in High SDI regions (0.24 per 100,000 people, 95% CI: 0.08 to 0.42), followed by High-middle SDI regions (0.15 per 100,000, 95% CI: 0.05 to 0.27) and the global average (0.15 per 100,000, 95% CI: 0.05 to 0.27). Globally, mortality rates showed a slight increase (AAPC: 0.22%, 95% CI: 0.10% to 0.34%), driven by a significant increase among males (AAPC: 0.39%, 95% CI: 0.29% to 0.49%). In contrast, High SDI regions experienced a significant decline in mortality (AAPC: −0.51%, 95% CI: −0.70% to −0.33%), with females showing a greater decrease (AAPC: −0.70%, 95% CI: −0.91% to −0.49%) than males (AAPC: −0.39%, 95% CI: −0.55% to −0.23%). Conversely, all other SDI regions showed significant increases. The largest increases were in Low-middle SDI regions (AAPC: 2.07%, 95% CI: 1.99% to 2.16%), where females had a higher AAPC (AAPC: 2.23%, 95% CI: 2.14% to 2.32%) than males (AAPC: 1.95%, 95% CI: 1.87% to 2.04%). Middle SDI regions (AAPC: 1.52%, 95% CI: 1.46% to 1.58%), Low SDI regions (AAPC: 1.22%, 95% CI: 1.11% to 1.34%), and High-middle SDI regions (AAPC: 0.75%, 95% CI: 0.65% to 0.84%) also showed significant increases. The univariate regression analysis further supported these trends. A significant negative slope was found for High SDI regions (slope=−0.001, p0.05), indicating a consistent decrease in mortality. In contrast, all other SDI regions showed a significant positive slope, indicating an increase in mortality over time (p0.05 for all). The strongest positive correlation was found in Low-middle SDI regions (R2=0.94), followed by Low SDI (R2=0.77) and Middle SDI regions (R2=0.62). Conclusion: Significant disparities in mortality from high BMI-associated NHL are evident across different SDI regions and between sexes. While high-income regions are experiencing a decline in mortality rates, low- and middle-income regions are seeing a substantial increase, particularly in Low-middle SDI and Low SDI regions. The higher mortality rates for males in High SDI regions and the faster rate of increase among females in Low-middle SDI regions highlight the need for sex-specific public health strategies. Future interventions should be concentrated on low- and middle-income regions to curb the rising burden of this disease.