Abstract
BACKGROUND: Peripheral artery disease (PAD), particularly premature PAD, remains understudied. It is still unclear whether premature PAD exhibits distinct risk profiles and survival outcomes compared with nonpremature PAD. We aimed to compare risk factors and long-term mortality between premature and nonpremature PAD using two large cohorts.</p>
METHODS: In this study, we analyzed data from the UK Biobank (N = 348,766) and the U.S. National Health and Nutrition Examination Survey (NHANES; N = 6539). Premature PAD was defined using a sex-specific age cutoff (men <55 years, women <65 years), with sensitivity analyses using a 50-year cutoff. Participants were classified into three groups: no PAD, premature PAD, and nonpremature PAD groups. Multinomial logistic regression assessed associations between risk factors and PAD subtypes. Cox proportional hazards models estimated associations of PAD subtypes with all-cause and cardiovascular mortality risks.</p>
RESULTS: Patients with premature PAD were predominantly female with fewer cardiometabolic comorbidities. Peripheral neuropathy was a strong risk factor specifically for premature PAD (UK Biobank: odds ratio [OR] = 3.96, 95% confidence interval [CI]: 2.73-5.73; NHANES: OR = 2.01, 95% CI: 1.28-3.17), whereas nonpremature PAD showed no significant association (UK Biobank: OR = 1.32, 95% CI: 0.66-2.65; NHANES: OR = 0.87, 95% CI: 0.65-1.16). Over a mean follow-up period of 13.2 (UK Biobank) and 14.9 (NHANES) years, unadjusted analyses showed the highest mortality in nonpremature PAD among the three groups. However, after full adjustment for potential confounders, the patterns of mortality shifted. Premature PAD had a higher all-cause mortality risk (UK Biobank: hazard ratio [HR] = 2.15, 95% CI: 1.93-2.39; NHANES: HR = 2.15, 95% CI: 1.41-3.29) than nonpremature PAD (UK Biobank: HR = 1.91, 95% CI: 1.75-2.09; NHANES: HR = 1.52, 95% CI: 1.28-1.80). Premature PAD also had a higher cardiovascular mortality risk (UK Biobank: HR = 3.10, 95% CI: 2.33-4.13; NHANES: HR = 4.33, 95% CI: 2.47-7.57) vs nonpremature PAD (UK Biobank: HR = 2.26, 95% CI: 1.76-2.88; NHANES: HR = 1.66, 95% CI: 1.34-2.07). This was further confirmed in a direct comparison among patients with PAD, which showed that premature PAD carried a significantly higher risk of cardiovascular mortality than nonpremature PAD.</p>
CONCLUSIONS: Premature PAD exhibited distinct risk profiles and had higher adjusted long-term mortality than nonpremature PAD, particularly from cardiovascular causes. Future studies are needed to investigate the mechanisms underlying these differences.</p>