1.
Dear Editor,
Hypertension remains the leading risk factor for cardiovascular diseases. It increases myocardial workload, leading to compensatory remodeling which may progress to heart failure but these structural and functional changes are often identified only after irreversible damage has occurred. The independent use of high‐sensitivity cardiac troponin T (hs‐cTnT) and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) as biomarkers in cardiovascular disease assessment is already well established.
A study conducted by Wang et al. evaluated independent and combined levels of hs‐cTnT and NT‐proBNP to assess multidimensional echocardiographic features in 1803 hypertensive adults. The dual‐biomarker framework has a strong biological basis as hs‐cTnT identifies subclinical cardiomyocyte injury and NT‐proBNP identifies hemodynamic wall stress, and their combined increase identified more severe structural and functional abnormalities than either biomarker alone [1]. Furthermore, the observed association between higher biomarker levels and markedly elevated ASCVD risk observed indicates that this dual approach is able to detect clinically meaningful risk and serves as a valuable diagnostic tool.
While the authors acknowledge residual confounding as a limitation, several variables known to independently influence levels of hs‐cTnT and NT‐proBNP are not measured and adjusted for. BMI was added as a covariate but this is an imperfect indicator of adiposity. Waist‐to‐hip ratio or waist circumference would be more suitable in future studies, as these measures are more likely to reflect visceral obesity than BMI is [2] and are associated with paradoxical suppression of NT‐proBNP in obese HTN participants [3]. The menopausal status was also not taken into account in the analysis despite 29.7% of participants being women. The mean age of the cohort (51 years) was suggestive of a substantial proportion of women being peri‐ or postmenopausal, among the 536 women enrolled. Postmenopausal estrogen deficiency is known to influence NT‐proBNP levels independent of cardiac pathology. Without accounting for menopausal status, the biomarker‐echocardiography associations in the female subgroup may reflect hormonal influences rather than cardiac remodeling alone [4]. Thyroid dysfunction can also independently elevate both hs‐cTnT and NT‐proBNP, potentially misclassifying participants into higher biomarker categories, which was not accounted in the analysis as well [5].
The second concern is the clinical meaning of the threshold values used for the biomarker. The thresholds used hs‐cTnT >6.43 ng/L and NT‐proBNP >47.40 ng/L were derived from cohort‐based tertile distributions rather than established clinical decision limits. Using the Roche Elecsys assay, the same platform referenced by the authors, the 99th percentile upper reference limit for hs‐cTnT is approximately 14 ng/L [6]. This means that participants even in the highest hs‐cTnT tertile largely remained within conventionally normal clinical ranges. While tertile‐based analyses serve a valuable purpose in epidemiological risk stratification, these thresholds carry limited direct applicability to clinical practice without prospective validation against adverse cardiovascular outcomes.
In conclusion, the findings of this study require further prospective validation, through incorporation of non‐cardiac determinants and the establishment of proper biomarker thresholds against adverse cardiovascular outcomes to support clinical implementation.
Author Contributions
Afrah Shahzad: conceptualization, writing, editing, reviewing. Lubna Ihsan: writing, editing, reviewing
Funding
No funding was received for this work.
Conflicts of Interest
The authors declare no conflicts of interest.
Permission to Reproduce Material From Other Sources
No third‐party material is reproduced in this letter.
Data Availability Statement
Data sharing is not applicable to this letter as no new data were created or analyzed.
References
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Data Availability Statement
Data sharing is not applicable to this letter as no new data were created or analyzed.