Disproportionate Risk of Cancer Following Diagnosis of Peripheral Artery Disease

Cancer and cardiovascular disease (CVD) are leading causes of death and share multiple risk factors. Population-level and mechanistic studies support a causal association between CVD and cancer. Recent preclinical studies suggest that peripheral arterial disease (PAD) may confer unique cancer risks. However, the specific contribution of PAD to cancer incidence-and whether this risk exceeds that of other CVD types-remains unclear.

The objective of the study was to test whether PAD is an independent risk factor for cancer and whether it is associated with a greater cancer risk than other forms of CVD.

We conducted a retrospective cohort study using the MarketScan Research Database (2013-2023). Adults aged ≥40 years with ≥36 months of continuous coverage were classified as having PAD, non-PAD CVD, or no CVD. The primary outcome was time to incident cancer, analyzed using an inverse probability of treatment-weighted Fine-Gray subdistribution hazard model adjusted for shared risk factors.

Our cohort included 87,594 individuals with PAD, 917,680 with non-PAD CVD, and 4,303,899 without CVD. Multivariable-adjusted inverse probability of treatment-weighted regression controlling for shared risk factors demonstrated that patients with PAD had a greater risk of cancer than individuals with non-PAD CVD (subdistribution HR: 1.027; 95% CI: 1.001-1.053; P = 0.044) and those without CVD (subdistribution HR: 1.158; 95% CI: 1.129-1.187; P < 0.0001). Individual analysis of the 20 most common cancers demonstrated associations of PAD with specific malignancies.

Patients with PAD experience a higher risk of multiple forms of cancer after controlling for shared risk factors.