Risk and Prognosis of Cancer After Lower Limb Arterial Thrombosis

Background: Venous thromboembolism can be a presenting symptom of cancer, but the association between lower limb arterial thrombosis and cancer is unknown. We therefore examined cancer risk and prognosis of cancer in patients with lower limb arterial thrombosis. Methods: Using nationwide population-based Danish medical registries, we identified all patients diagnosed with first-time lower limb arterial thrombosis (1994−2013) and followed them until the occurrence of any subsequent cancer diagnosis, emigration, death, or November 30, 2013, whichever came first. We computed standardized incidence ratios with 95% confidence intervals as the observed number of cancers relative to the expected number based on national incidence rates by sex, age, and calendar year. To examine the prognostic impact of lower limb arterial thrombosis on all-cause mortality after cancer, we constructed a matched comparison cohort of patients who had cancer without lower limb arterial thrombosis. Results: Among 6600 patients with lower limb arterial thrombosis, we observed 772 subsequent cancers. The risk of any cancer was 2.5% after 6 months of follow-up, increasing to 17.9% after 20 years. During the first 6 months of follow-up, the standardized incidence ratio of any cancer was 3.28 (95% confidence interval, 2.79–3.82). The standardized incidence ratio remained elevated during 7 to 12 months (1.42; 95% confidence interval, 1.09–1.83) and beyond 12 months (1.14; 95% confidence interval, 1.05–1.24). The strongest associations were found for lung cancer and other smoking-related cancers. Lower limb arterial thrombosis also was associated with increased all-cause mortality after colon, lung, urinary bladder, and breast cancer, but not after prostate cancer. Conclusions: Lower limb arterial thrombosis was a marker of occult cancer, especially lung cancer, and was an adverse prognostic factor for mortality in common cancers.