Pavuluri, Sai Swetha

e15722 Background: Despite overall improvements in colorectal cancer (CRC) outcomes, concerning trends have emerged in younger populations. We examined two decades of US mortality data to characterize age-specific trajectory differences and identify inflection points in the epidemiologic landscape of CRC. Methods: Using CDC WONDER data (1999–2020), we analyzed age-adjusted CRC mortality rates (ICD-10: C18–C20) stratified by age: early-onset (≤44 years) versus late-onset (≥45 years). Joinpoint regression analysis (Version 5.4.0.0) with permutation testing identified significant trend changes. Annual Percent Change (APC) estimates with 95% confidence intervals assessed temporal patterns, with statistical significance set at α = 0.05. Results: Late-onset CRC (≥45 years): Mortality rates declined substantially from 69.26 to 40.49 per 100,000, representing a 41.6% reduction. A critical inflection point occurred in 2014 (95% CI: 2011–2015), marking a deceleration in the rate of improvement. The pre-2014 period showed robust decline (APC: −3.06%; 95% CI: −3.18 to −2.93; p < 0.000001), which slowed significantly post-2014 (APC: −1.61%; 95% CI: −2.12 to −1.09; p = 0.000006)—a 47% reduction in the pace of mortality improvement.Early-onset CRC (≤44 years): In stark contrast, mortality rates increased from 0.92 to 1.13 per 100,000, representing a 22.8% rise. No inflection points were identified; instead, a persistent upward trajectory characterized the entire 22-year period (APC: +0.78%; 95% CI: +0.54 to +1.02; p = 0.000001). This yielded a continuous, unabated increase in deaths among young adults. Conclusions: This analysis reveals a troubling paradox in US colorectal cancer mortality: while older adults experienced substantial but decelerating improvements, young adults faced steadily worsening outcomes throughout the study period. The 2014 inflection point in older adults, coinciding with slowed screening expansion and potential changes in risk factor prevalence, coupled with the relentless rise in early-onset mortality, signals an urgent need to reassess prevention strategies, lower screening age thresholds, and investigate biological and environmental drivers of early-onset disease. The nearly 23% increase in mortality among those ≤44 years represents a growing public health crisis demanding immediate action.

Abstract Background Sleep disorders are increasingly recognized as important risk factors for cardiovascular disease (CVD), yet their contribution to cardiovascular mortality remains insufficiently examined at the population level. This study aimed to evaluate long-term trends in CVD mortality where sleep disorders were identified as contributing causes of death. Methods We analyzed U.S. national mortality data from 1999 to 2020 among individuals aged 15 to 84 years. Cases were selected where CVD (ICD-10: I11.0, I11.9, I20-I25, I48, I49.0, I49.9, I50.0, I50.1, I50.9) was the underlying cause and sleep disorders (ICD-10: G47.0-G47.3) were listed as contributing causes. Joinpoint regression was employed to assess temporal changes in age-adjusted mortality rates (AARs), with standard errors provided in the input data and model selection performed using Weighted BIC. APCs were estimated using the Empirical Quantile Method with 5001 resamples. Results A total of 118,440 deaths were included across 22 annual time points. Joinpoint regression identified two significant inflection points (2005 and 2018). From 1999 to 2005, AARs increased sharply (APC = 14.47%; 95% CI: 11.56-19.54; p = 0.0016), followed by a slower rise from 2005 to 2018 (APC = 6.62%; 95% CI: 4.23-10.83; p &lt; 0.000001), and a renewed acceleration from 2018 to 2020 (APC = 11.54%; 95% CI: 7.01-14.12; p &lt; 0.000001). Males had more than twice the AAR compared to females (3.00 vs. 1.31 per 100,000). Black individuals had the highest burden by race (AAR = 2.55), and geographic variation ranged widely from 0.70 in New York to 3.38 in Wyoming. Conclusions Over two decades, cardiovascular mortality with contributory sleep disorders has risen significantly, with widening demographic and geographic disparities. These findings reinforce that sleep disorders are not merely comorbidities but pivotal, modifiable drivers of cardiovascular morbidity and mortality. Untreated sleep conditions such as insomnia, obstructive sleep apnea, and circadian disruptions exacerbate autonomic dysfunction, inflammation, hypertension, and metabolic dysregulation. Addressing sleep health must become a core component of cardiovascular risk reduction strategies, both in clinical practice and public health policy. Failure to integrate sleep disorder screening, diagnosis, and management into CVD care pathways risks perpetuating a preventable and growing burden of disease. This abstract is funded by: None

Abstract Obesity is a major and growing driver of cardiovascular disease (CVD) in the United States, contributing to hypertension, diabetes, dyslipidemia, and structural cardiac changes that elevate the risk of ischemic heart disease, heart failure, and stroke. After decades of declining CVD mortality, recent national trends show a concerning reversal, coinciding with record-high obesity prevalence. We quantified national trends and disparities in obesity-related CVD mortality from 1999–2020 using de-identified death certificate data from the CDC WONDER database for U.S. residents aged 15–84 years, including deaths with circulatory disease (ICD-10 I00–I99) as the underlying cause and obesity (E66.0–E66.9) as a contributing cause. Age-adjusted mortality rates (AAMR) standardized to the 2000 U.S. population were analyzed using joinpoint regression to estimate annual percent change (APC) and detect inflection points. From 1999–2018, AAMR rose from 2.75 to 6.61 per 100,000 (APC 4.79%; 95% CI 4.60–4.98), followed by a significant post-2018 acceleration (APC 11.05%; 95% CI 6.76–15.51) to 8.36 in 2020. Mortality was highest among adults 65–74 years, males, Black Americans, and nonmetropolitan residents, with a 5.1-fold state variation. Young adults (15–24 years) had the largest relative increase (+210%). The 2020 surge was independent of COVID-19 mortality, indicating gaps in chronic disease management. These results highlight a growing obesity-related CVD mortality burden, with widening disparities by age, sex, race, and geography, emphasizing urgent, equity-focused prevention and targeted interventions.