Arterial Stiffness Predicts Death Risk in Over 105 Million US Cancer Survivors

Cancer survivors face elevated cardiovascular disease (CVD) risk driven by treatment-related vascular toxicity, shared risk factors, and accelerated vascular aging. Arterial stiffness, measurable via pulse wave velocity (PWV), is an established predictor of CVD events and death in the general population, but its prognostic value specifically in cancer survivors had not been systematically evaluated. This study fills that gap using a large, nationally representative US dataset.

Using five biennial cycles of NHANES (2009–2018) linked to National Death Index mortality records through December 31, 2019, investigators identified 2,234 unweighted adult cancer survivors representing over 105 million Americans. Estimated PWV (ePWV) was calculated from each participant's age and mean blood pressure using a validated formula derived by the Arterial Stiffness Collaboration. Multivariable Cox regression, Kaplan–Meier survival analysis, restricted cubic splines for dose-response assessment, and maximally selected rank statistics to identify an optimal ePWV cut-point were all employed.

During a median follow-up of 59 months, 435 all-cause and 91 cardiovascular deaths were recorded. Every 1 m/s increment in ePWV was independently associated with a 29% increase in all-cause mortality (HR 1.29, 95% CI 1.19–1.40) and a 46% increase in cardiovascular mortality (HR 1.46, 95% CI 1.20–1.76), after adjustment for demographics, socioeconomic status, traditional CVD risk factors, and baseline CVD. Early vascular aging (EVA), defined as ePWV ≥9.4 m/s, was present in 54.6% of survivors and was most prevalent in rectal, prostate, esophageal, and bladder cancer survivors. An optimal prognostic threshold of ePWV ≥12.05 m/s was identified, above which all-cause mortality risk was 70% higher (HR 1.70, 95% CI 1.35–2.13) and cardiovascular mortality risk was 153% higher (HR 2.53, 95% CI 1.56–4.12). Dose-response analysis revealed a nonlinear relationship, with risk accelerating steeply at higher ePWV values.

The clinical implication is substantial: ePWV requires only routinely collected data—age and blood pressure—making it deployable in virtually any clinical or survivorship setting without specialized equipment. Identifying cancer survivors with EVA or ePWV above 12.05 m/s could trigger earlier cardiovascular surveillance, lifestyle intervention, or pharmacological risk reduction. This positions ePWV as a candidate biomarker for integration into cardio-oncology follow-up protocols.

Key caveats include the observational, cross-sectional measurement of ePWV (a single baseline value), reliance on self-reported cancer diagnosis and comorbidities, and inability to account for specific cancer treatments or duration of survivorship, all of which limit causal inference. Validation in prospective cardio-oncology cohorts with gold-standard carotid-femoral PWV measurements is warranted.