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From single risks to causal pathways: future directions for early cardiovascular biomarker research

Hypertension Research volume 49, pages 1064–1065 (2026)Cite this article

We read with great interest the recent article by Jacobs et al., titled “Profiling endothelial function, oxidative stress and inflammatory biomarkers in individuals with various cardiovascular risk factors: the African-PREDICT study” [1]. This systematic investigation into the independent associations between various cardiovascular risk factors and a range of circulating biomarkers in a young, apparently healthy population provides valuable insights into the early origins of cardiovascular disease (CVD). The rigorous design and forward-looking perspective of this work are highly commendable. While acknowledging the significant contributions of this study, we would like to offer several constructive suggestions for future research. We hope to engage the authors in a discussion on how to further leverage the potential of the African-PREDICT cohort and advance this field of study.

The study successfully delineates independent associations of individual risk factors through meticulous statistical adjustment—a notable methodological strength. However, clinically, CVD risk factors often co-occur and may exert synergistic effects. We propose that future analyses consider introducing the concept of “cardiovascular risk burden.” For instance, calculating the number of risk factors per participant and examining the dose-response relationship between this simple score and biomarker levels could be highly informative. Furthermore, applying statistical interaction models to test whether specific risk combinations (e.g. “central adiposity + smoking” or “low HDL-C + elevated blood pressure”) lead to synergistic alterations in biomarkers would help identify young subpopulations exposed to “high-risk cocktails.” Such individuals may represent those earliest affected by vascular impairment and most in need of targeted interventions, thereby enabling more precise preventive strategies.

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Reference

  1. Jacobs A, Kruger R, Smith W, Mokhaneli MC, Mels CMC. Profiling endothelial function, oxidative stress and inflammatory biomarkers in individuals with various cardiovascular risk factors: the African-PREDICT study. Hypertens Res. 2025. https://doi.org/10.1038/s41440-025-02392-9.

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Authors and Affiliations

  1. The First Clinical College, Changzhi Medical College, Changzhi, Shanxi, China

    Yi Zhang

  2. The First Regiment, School of Basic Medicine, Fourth Military Medical University, Xi’an, China

    Junyu Lu

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  1. Yi Zhang
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  2. Junyu Lu
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YZ and JYL contributed in writing the first draft. JYL revised the manuscript. All authors reviewed the manuscript.

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Correspondence to Junyu Lu.

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Zhang, Y., Lu, J. From single risks to causal pathways: future directions for early cardiovascular biomarker research. Hypertens Res 49, 1064–1065 (2026). https://doi.org/10.1038/s41440-025-02476-6

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