Dear Editor, We read with great interest the article by Zhao et al, entitled “Association Between Circulating Selenium Levels and Arterial Stiffness: A Nationwide Cross-Sectional Study”1. Based on data from the National Health and Nutrition Examination Survey (NHANES), the study identifies significant associations between blood selenium (Se) levels and arterial stiffness markers, including the atherogenic index of plasma (AIP). Their exploration of how sex differences influence this association offers valuable insights to the field. The reporting of this work follows the TITAN Guidelines 2025 governing the declaration and use of artificial intelligence2. After careful consideration, we would like to offer two perspectives for further exploration. The study found a significant interaction between sex and the association between Se and the AIP (P = 0.043). This is a notable finding, as it suggests that sex is an important effect modifier. However, the subsequent use of mediation analysis to quantify the role of sex, reporting a 26.49% mediation effect, invites methodological consideration. According to the current methodological consensus, traditional mediation analysis requires the mediator to be a modifiable variable influenced by the exposure. Treating a fixed attribute, such as sex, determined early in life, as a mediator may present conceptual challenges in interpreting causal pathways3,4. This could lead to confusion in the biological interpretation of the results. Thus, it might be valuable to also present the results of a sex-stratified analysis from the fully adjusted model. Specifically, providing the odds ratios and confidence intervals for the Se–high AIP association separately for men and women would be highly informative. This approach would clearly illustrate the sex-specific patterns of association while avoiding potential conceptual disputes. We appreciate that distinguishing between specific chemical species of Se, such as selenoproteins and selenomethionine, is challenging within the constraints of the NHANES database5. Future studies that distinguish between these forms could move beyond the macro-level association of total Se. By delving into specific biological pathways, they may provide a more comprehensive explanation for complex phenomena, such as the U-shaped relationship observed in this study. Finally, advancing precision prevention relies on biomarkers that are both sex-specific and practical for clinical use. Skin and its appendages (such as hair and nails) offer distinct advantages as non-invasive tissues that reflect long-term trace element status6. Incorporating these dermatological parameters could offer practical tools for validating this study’s key findings while creating new avenues for early cardiovascular risk assessment.
Lv et al. (Thu,) studied this question.