Sex-specific vitamin D biomarkers in cardiovascular risk: beyond genetics toward personalized prevention

Dear Editor,

I read with great interest the recent study by Delanghe et al. highlighting the association between DBP polymorphisms and adverse metabolic traits in hypertensive women [1]. Their findings provide compelling evidence for a sex-specific impact of vitamin D binding protein variants on body weight, triglyceride levels, and diabetes prevalence. This work significantly advances our understanding of vitamin D physiology beyond its endocrine actions.

Building on this, our recent consensus emphasizes the need to consider serum vitamin D as an accessible and actionable biomarker of cardiovascular risk, particularly in women [2]. While Delanghe et al. elegantly demonstrate how genetic variability influences vitamin D metabolism and metabolic risk, clinical practice still largely overlooks routine assessment of vitamin D status in cardiovascular prevention [1], 2]. We argue that vitamin D deficiency represents a modifiable metabolic risk factor, especially in sex-specific contexts like menopause, hormone therapy, and obesity [3].

Moreover, I agree with the authors on the relevance of evaluating not only total vitamin D but also bioavailable and free fractions, particularly in populations with DBP polymorphisms. However, as bioavailable vitamin D assays are not yet widely accessible, monitoring total serum 25(OH) D remains a practical clinical tool. In our opinion, vitamin D assessment should complement genetic insights, offering an immediate avenue for intervention through tailored supplementation.

Importantly, both genetic and hormonal contexts modulate cardiovascular risk [4]. The higher metabolic burden observed in DBP 2-2 female carriers echoes prior reports of estrogen’s role in regulating DBP synthesis. This supports the hypothesis that women across menopausal stages or undergoing hormone therapy may benefit from personalized vitamin D thresholds and supplementation targets, rather than a uniform cut-off.

The work by Delanghe et al. reinforces the concept that cardiovascular prevention in women must integrate biomarkers reflecting both genetic predisposition and modifiable factors [1]. Vitamin D assessment, when combined with other sex-specific markers (e.g., lipid profile, adiposity measures, hormonal status), may improve risk stratification and guide preventive strategies [5].

We commend the authors for advancing the field of sex-specific metabolic risk. Future longitudinal studies should clarify whether integrating vitamin D status into risk models improves prediction and outcomes, and whether adjusting supplementation by genotype or hormonal status optimizes cardiovascular prevention in women.