Association between the aggregate index of systemic inflammation and peripheral artery disease: NHANES 1999–2004

Peripheral artery disease (PAD) is a common atherosclerotic vascular disorder affecting the lower-extremity arteries, and chronic low-grade inflammation may contribute to its pathophysiology. This study examined the association between the Aggregate Index of Systemic Inflammation (AISI) and PAD in a nationally representative sample of U.S. adults. Data were obtained from the 1999–2004 cycles of the National Health and Nutrition Examination Survey (NHANES) and included 5,453 adults aged ≥ 40 years. PAD was defined as an ankle–brachial index (ABI) < 0.90. AISI was calculated from neutrophil, monocyte, platelet, and lymphocyte counts, and log-transformed AISI [log(AISI)] was used as the primary exposure variable. Survey-weighted multivariable logistic regression was used to assess the association between log(AISI) and the odds of prevalent PAD. Dose–response patterns were evaluated using restricted cubic splines (RCS), and subgroup and sensitivity analyses were performed to examine the robustness of the findings. Among the included participants, 383 had PAD and 5,070 did not have PAD. Participants with PAD were older and had more cardiometabolic comorbidities than those without PAD. Mean log(AISI) was significantly higher in the PAD group than in the non-PAD group (5.79 ± 0.73 vs. 5.58 ± 0.65, P < 0.001). In the fully adjusted model, each 1-unit increase in log(AISI) was associated with higher odds of prevalent PAD (OR = 1.528, 95% CI: 1.205–1.937, P = 0.002). Compared with participants in the lowest log(AISI) quartile, those in the highest quartile had higher odds of prevalent PAD (OR = 2.143, 95% CI: 1.319–3.482, P = 0.006). RCS analysis showed a positive and approximately linear association between log(AISI) and the odds of prevalent PAD (P for overall association = 0.0005; P for nonlinearity = 0.523). Sensitivity analyses excluding C-reactive protein, serum glucose, or both from the adjustment set showed materially consistent results. Subgroup analyses showed no statistically significant interactions across major demographic or clinical strata. Higher log(AISI) was associated with higher odds of prevalent PAD in a nationally representative sample of U.S. adults. Further prospective studies are needed to clarify the temporal and causal nature of this association.