Associations of urinary zinc with incident peripheral artery disease and amputation in the Strong Heart Study.

Abstract

Background and aims: Urinary zinc has been associated with cardiometabolic endpoints, including diabetes and cardiovascular disease, but evidence for peripheral artery disease (PAD) is limited. We evaluated prospective associations between urinary zinc and incident PAD and amputation events in the Strong Heart Study (SHS), a large epidemiological cohort of American Indian adults in the United States.

Methods: A total of 2,045 PAD-free and 2,180 amputation-free participants were included at baseline (1989-91), (mean age 56 years, 61% female). PAD (defined as ankle brachial index < 0.9 or > 1.4) and diabetes-related amputation events were collected through two SHS visits over 10 years. Odds ratios (OR) of PAD and amputation by baseline urinary zinc levels adjusted by creatinine (µg/g) were evaluated with progressively adjusted logistic regression models.

Results: 344 participants developed PAD and 23 underwent diabetes-related amputations. The ORs (95% CI) per one interquartile range increment in baseline urinary zinc levels were 1.29 (1.10, 1.51) and 2.36 (1.43, 3.90) for incident PAD and amputation, respectively, when adjusting for sociodemographic and clinical risk factors. Estimates were attenuated by further adjusting for diabetes status (OR: 1.16 (0.98, 1.38) for incident PAD), and fasting plasma glucose (OR: 1.09 (0.91, 1.31) and OR: 1.39 (0.76, 2.54) for incident PAD and amputation, respectively). Associations between urinary zinc levels and incident PAD were stronger among participants with diabetes at baseline (OR: 1.43 (1.11, 1.86)).

Conclusions: We identify prospective associations between higher urinary zinc levels and increased risk of PAD and amputation in the SHS, with stronger effects among participants with diabetes.

Supplementary information: The online version contains supplementary material available at 10.1007/s44417-025-00005-0.