Mortality in patients with premature lower extremity atherosclerosis

Abstract

Lower extremity peripheral artery disease occurs mostly in the elderly and is associated with high mortality. Limited data are available regarding long-term mortality in patients with premature lower extremity atherosclerosis (PLEA). Our objective was to determine the all-cause mortality and its predictors in younger PLEA patients. We studied patients with severe PLEA who were <55 years of age at diagnosis and treated at a single academic vascular center between 1998 and 2010. Data were collected prospectively at the initial evaluation for vascular care. National Death Index and hospital records were used to determine all-cause mortality. Demographic and clinical characteristics were summarized using count (%), mean (standard deviation), or median (interquartile range), and associations with aspirin use were tested using χ2 test, t-test, or Wilcoxon test. Survival times were estimated using Kaplan-Meier estimates, and associations with covariates were tested using simple and multivariable Cox proportional hazards models. A total of 564 patients were analyzed (46% female; 20% nonwhite; mean age 49.4 [6.4] years). Ninety-five percent of patients had ≥2 cardiovascular risk factors, 31% had coronary artery disease (CAD), and 10% had a history of cancer. During median follow-up of 5.6 years (interquartile range, 2.3-8.3 years), 108 deaths (19%) were recorded. Two-year estimated mortality (standard error) was 6% (0.01), and 5-year estimated mortality was 16% (0.02). In univariate regression analysis, patient age (P=.04), prior amputation (P<.01), history of cancer (P=.03), and established CAD (P=.04) were associated with increased risk of mortality. Aspirin use and lipid-lowering therapy at the time of first evaluation were associated with improved survival (P<.01 and P=.02, respectively). A multivariable Cox proportional hazards model identified age (hazard ratio [HR] for 5-year increase, 1.17; 95% CI, 1.01-1.36; P=.04), prior amputation (HR, 1.99; 95% CI, 1.18-3.34; P=.01), history of cancer (HR, 2.35; 95% CI, 1.36-4.07; P<.01), and CAD (HR, 1.76; 95% CI, 1.16-2.67; P<.01) as independent predictors of mortality in patients with PLEA. Importantly, history of aspirin use had a significant protective effect (HR, 0.45; 95% CI, 0.30-0.69; P<.01). The impact of lipid-lowering therapy was no longer significant in multivariable modeling. Patients with PLEA demonstrate high all-cause mortality. No traditional cardiovascular risk factors predicted mortality. Aspirin therapy at the time of first evaluation was a significant and independent predictor of improved survival in patients with PLEA.