Commentary on “Association of Plasma Homocysteine With Peripheral Arterial Disease in Hypertensive Adults: A Cross-Sectional Study”

Abstract

Dear Editor,

We have carefully read the article “Association of Plasma Homocysteine with Peripheral Arterial Disease in Hypertensive Adults: A Cross-Sectional Study,” published recently in your esteemed journal [1]. The main objectives of this examination were to ascertain the association between plasma homocysteine (Hcy) and peripheral artery disease (PAD) and the potential modifier factors in Chinese hypertensive adults. The results of the study indicate a strong relationship: an increase in plasma Hcy is clearly linked to an increase in PAD. Although we acknowledge the added value of the authors’ contribution to the current scientific literature, we argue that a few methodological and interpretative limitations deserve attention to improve the generalizability and robustness of the study's findings.

First, the investigation did not sufficiently consider confounding comorbidities, such as malignancies and autoimmune diseases, that could materially affect patient outcomes.

Second, more laboratory parameters should be included in the study. The overall validity of the conclusions is diminished by the lack of data on other markers such as zinc levels, vitamin B6, vitamin D, vitamin C, serum liver function tests, and ratios such as the monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), systemic inflammatory response index (SIRI), and systemic immune-inflammatory index (SII) [2, 3].

Third, it did not include extensive documentation of the participants’ pharmacological regimens, especially with nonsteroidal anti-inflammatory drugs (NSAIDs) and proton pump inhibitors (PPIs). Exclusion of these important treatment characteristics can lead to bias, and the interpretation of identified associations can be difficult.

Additionally, many key demographic and lifestyle-related factors (e.g., socioeconomic status, education, and opium use) were not accounted for in the analysis, limiting the generalizability of the results. Furthermore, the adjustments made for insulin resistance, exercise, family history of PAD, and heavy metal (lead, cadmium, and arsenic) exposure were inadequate. A more rigorous and precise classification of PAD is also warranted in fortifying the study's methodologic structure [4].

In conclusion, we appreciate the authors’ significant contribution regarding the relationship between plasma Hcy and PAD, but the study could be significantly strengthened if these limitations were acknowledged and addressed.

Mostafa Javanian:conceptualization, investigation, and supervision.Mohammad Barary: investigation, writing–original draft preparation, and writing–review and editing. Mohammad Ranaee: investigation and writing–original draft preparation. Danial Hosseinzadeh: investigation and writing–original draft preparation. Soheil Ebrahimpour: investigation, supervision, and writing–original draft preparation. All authors contributed significantly to the work and approved the final version of the manuscript. Their contributions align with the latest guidelines of the International Committee of Medical Journal Editors.

No ethical approval was required as this letter-to-the-editor article has no original research data.

No patient consent was required as this letter-to-the-editor article did not include any patient data.

The authors declare no conflicts of interest.