Younger Male, Minority Patients With Early-Onset CRC in Urban Settings Face Higher Cardiovascular Death Risk

Young adults with early-onset colorectal cancer (EOCRC), particularly men and non-Hispanic Black and American Indian/Alaskan Native patients living in urban areas, face significantly elevated risks of cardiovascular death, according to a research letter published in the Journal of the American Heart Association.¹

The Intersection of Rising EOCRC and CVD Mortality Trends

While cardiovascular disease (CVD) mortality in the US has plateaued, it has risen in younger populations.² Simultaneously, EOCRC, defined as CRC diagnosed before age 50, has become one of the fastest-growing cancer diagnoses in the country.

Investigators emphasized that the intersection of these 2 trends creates a compounded risk.¹ Prior research has identified CVD as an emerging noncancer cause of death among patients with EOCRC, with those diagnosed before age 50 carrying a standardized mortality ratio for CVD of 2.40 within 2 years of diagnosis, compared with 1.97 for those aged 50 to 70.² Shared risk factors, including obesity and poor diet, alongside cardiotoxic cancer treatments, are thought to contribute to this elevated burden.¹

In addition, prior research in mixed-age CRC populations has identified higher CVD mortality among men, racial and ethnic minorities, and rural residents. However, whether those same disparities hold in a strictly younger patient population and how geography modifies them has remained largely unexplored. The investigators aimed to address that knowledge gap with this analysis.

They used data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program, specifically the Data With Census Tract Attributes file covering 2006 through 2020, to examine CVD-specific survival in patients aged 18 to 49 diagnosed with EOCRC.

The primary outcome was CVD-specific survival, defined using SEER cause-of-death recode categories encompassing diseases of the heart, cerebrovascular diseases, and hypertension without heart disease. Key exposures were sex, rurality, and race and ethnicity. Rurality was derived from SEER's census-tract Urban/Rural Indicator and categorized as all urban (100% urban population), mostly urban (50% to < 100% urban), or rural (< 50% urban).

The researchers calculated age-adjusted CVD mortality rates by sex and race and ethnicity, standardized to the 2000 US population, and used multivariable Fine–Gray competing risk models stratified by rurality to estimate adjusted HRs for CVD death. Models accounted for competing risks and were adjusted for demographic, socioeconomic, cancer stage, treatment, and diagnosis year variables.

CVD Mortality Burden Concentrated Among Men, Minority Patients

The analysis included 83,433 patients with EOCRC, the majority of whom were male (53.5%), non-Hispanic White (54.6%), and aged 40 to 49 years (73.9%). Most of the cohort resided in all-urban areas (66.8%) and lived in medium socioeconomic status census tracts (56.9%). Additionally, most patients had regional-stage disease (30.8%), underwent surgery (80.2%), received chemotherapy (58.3%), and were diagnosed between 2016 and 2020 (35.0%).

The age-adjusted CVD mortality rate was dramatically higher in men than in women: 94.9 vs 18.9 per 100,000 person-years. By race and ethnicity, the highest rates were observed among American Indian/Alaska Native patients (76.1 per 100,000 person-years) and non-Hispanic Black patients (51.9 per 100,000 person-years).

In rurality-stratified competing risk models, men with EOCRC had significantly higher CVD mortality rates in both all-urban areas (HR, 2.14; 95% CI, 1.73–2.64) and rural areas (HR, 1.54; 95% CI, 1.03–2.31) compared with women.

Regarding racial and ethnic disparities, the differences were concentrated in all-urban settings. Compared with non-Hispanic White patients in those areas, non-Hispanic Black patients had a 38% higher rate of CVD death (HR, 1.38; 95% CI, 1.07–1.77), while American Indian/Alaska Native patients faced more than triple the risk (HR, 3.23; 95% CI, 1.42–7.33).

Findings Draw Attention to Cardiovascular Risks Beyond Cancer Outcomes

The researchers acknowledged several limitations, one being that the rurality measure they used captures census-tract urbanicity but does not distinguish frontier or remote geographies, nor does it account for regional rural variation, which may meaningfully affect health care access and outcomes. They noted that their limitations raise the possibility of residual confounding and misclassification while also limiting assessment of shared CVD-EOCRC risk factors and subgroup analyses.

In contrast, the researchers also expressed confidence in their findings, explaining that they shift the attention of the cardio-oncology field toward young urban minority patients, who may face unique care barriers, including health care disengagement, short-term health priorities, and structural challenges such as limited insurance coverage or financial hardship.

"Our findings underscore the disproportionate burden among young racial minorities in all urban settings and provide novel insights to guide cardio-oncology care strategies," the authors concluded. "They emphasize the need for targeted cardio-oncology risk assessment and prevention in younger patients with EOCRC, particularly men and [non-Hispanic Black and American Indian/Alaska Native] patients in urban settings, challenging the assumption that rural populations face greater disparities."

References

1. Tsai MH, Vo JB, Harris RA, et al. Sex, race and ethnicity, and rurality disparities in cardiovascular death among adults with early-onset colorectal cancer: a retrospective cohort analysis. J Am Heart Assoc. Published online May 6, 2026. doi:10.1161/JAHA.126.049282
2. Khan M, Ayaz A. Cardiovascular (CV) mortality in adults diagnosed with colorectal cancer (CRC): a retrospective cohort study. J Am Coll Cardiol. 2025;85:627.