Critical Limb Ischemia Related to Toxic Metal Levels in the Strong Heart Study

Kishan Bhatt, VP&S Class of 2025

Name: Kishan Bhatt
School: Vagelos College of Physicians and Surgeons, Class of 2025
Mentor: Ana Navas-Acien, MD, MPH, PhD

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Toxic metal exposure has been associated with peripheral artery disease (PAD) and diabetes among American Indian (AI) communities in the Strong Heart Study, which is a prospective, longitudinal cohort study. The most advanced stage of PAD is critical limb ischemia (CLI) of the lower limbs, and its poor long-term prognosis can require amputation in severe cases. PAD rates among AIs are significantly higher than among other populations. This study aimed to evaluate the association between creatine-adjusted urine levels of six metals (arsenic, cadmium, molybdenum, selenium, tungsten, and zinc) and amputation status among AIs in the Northern and Southern Plains and the Southwest. We included 2,728 participants from 13 AI communities who were examined at baseline at three centers between 1989 and 1991. The prevalence of amputation was increased in study participants with PAD and/or with diabetes. We used logistic regression models comparing the prevalence of amputation by tertile urinary metal levels in the Strong Heart Study population. Comparing the highest to lowest tertile of zinc levels, the odds ratio of amputation status was 4.95 (95% CI: 1.46, 16.81). This finding was robust across models that adjusted for demographic, lifestyle, and clinical variables. The result also remained significant after a sensitivity analysis that adjusted for fasting glucose levels (a proxy for diabetes control). Other metals such as arsenic, cadmium, and tungsten showed non-significant increased risk of amputation. Our results invite further analysis on the linkage between zinc metabolism,
diabetes, and CLI severity.