Association of monocyte-lymphocyte ratio with peripheral arterial disease in US participants: a retrospective cross-sectional study

TL;DR

This study found that a blood cell ratio called MLR is linked to peripheral arterial disease, especially below a certain threshold, suggesting it could help assess risk.

Contribution

The study identifies a threshold effect of MLR on PAD risk and confirms its potential as a clinical risk indicator after adjusting for confounders.

Findings

Elevated MLR is associated with increased odds of PAD, particularly below an MLR threshold of 0.343.

The association remains significant in adjusted models and across demographic and clinical subgroups.

Above the MLR threshold of 0.343, no significant association with PAD was observed.

Abstract

Peripheral arterial disease (PAD), a prevalent manifestation of atherosclerosis, is closely linked to systemic inflammation. The monocyte-lymphocyte ratio (MLR), a cost-effective inflammatory biomarker, has shown prognostic value in cardiovascular diseases but remains underexplored in PAD.

This study aimed to investigate the correlation between MLR and the occurrence of PAD.

Utilizing data from the National Health and Nutrition Examination Survey (NHANES) 1999–2004, this retrospective cross-sectional study applied complex survey weighting to generate nationally representative estimates. A total of 2,827 participants aged ≥40 years were included after applying sample exclusions and accounting for missing data. PAD was defined as an ankle-brachial index <0.9. The MLR was calculated from complete blood count data. Weighted multivariable logistic regression models were employed to examine the association between MLR and PAD, with sequential adjustment for sociodemographic, lifestyle, metabolic, and clinical covariates. Weighted restricted cubic spline regression was used to evaluate potential nonlinearity, and a two-piecewise logistic model was applied to identify inflection points through maximum likelihood estimation.

In the weighted sample, the prevalence of PAD was 3.96%. Participants in the highest MLR tertile were older, more often male, and had higher cardiovascular risk profiles. In unadjusted analyses, elevated MLR was strongly associated with PAD (OR = 6.52, 95% CI: 2.60–16.33). However, this association was substantially attenuated after full adjustment for covariates including age (OR = 1.99, 95% CI: 0.78–5.07). Nonlinear analysis revealed a significant threshold effect at an MLR of 0.343 (P for log-likelihood ratio test = 0.009). Below this inflection point, each unit increase in MLR was associated with a 62% higher odds of PAD (OR = 1.62, 95% CI: 1.24–2.11), whereas no significant association was observed above the threshold (OR = 0.94, 95% CI: 0.64–1.38). Subgroup analyses demonstrated consistent associations across demographic and clinical strata, with no significant interaction effects.

This nationally representative analysis identifies a threshold-based association between MLR and PAD. Despite substantial confounding by age, elevated MLR—particularly in the highest tertile—remains an independent indicator of increased PAD risk, supporting its potential utility in clinical risk assessment.

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