Muscle Quality and Validated Walking Speed Cut‐Offs: Missing Links in the NT ‐ proBNP –Sarcopenia Association

We read with interest the cross-sectional study by Sato et al. [1] reporting that higher serum NT-proBNP levels are associated with sarcopenia and its components in middle-aged and older Japanese community-dwellers. The authors have provided valuable population-based evidence linking a cardiac biomarker to muscle deterioration. However, two methodological omissions deserve critical discussion, as they may significantly alter the interpretation of the findings and limit clinical generalizability. One concern relates to the definition of sarcopenia, which was based solely on skeletal muscle mass index (SMI) without any measure of muscle quality. Emerging evidence indicates that NT-proBNP correlates more strongly with muscle radiodensity—a surrogate for intramuscular adipose infiltration and fibrosis—than with muscle area alone. In the Multi-Ethnic Study of Atherosclerosis, Tristão Parra et al. [2] demonstrated that after adjustment for muscle density and inflammatory markers, the association between NT-proBNP and muscle area was attenuated to the null, whereas the inverse association with muscle density remained robust. Similarly, Wang et al. [3] recently reported that in patients with heart failure, elevated NT-proBNP levels are inversely associated with muscle fiber cross-sectional area, muscle stem cell content, and capillary density—all indices of muscle quality that are not captured by SMI. By focusing exclusively on muscle mass, Sato et al. may have substantially underestimated the true burden of NT-proBNP-associated muscle deterioration and missed a potential mechanistic pathway linking cardiac stress to functional decline. It is therefore suggested that the authors re-examine their data using available surrogates of muscle quality (e.g., calf circumference adjusted for BMI, or phase angle from bioelectrical impedance analysis) if such measures were collected. A further issue concerns the auxiliary indicator of low maximal walking speed (< 1.59 m/s, defined as the 25th percentile of the study population), which lacks external validation and clinical interpretability. While comfortable walking speed thresholds (e.g., 1.0 m/s) are widely validated, no universally accepted prognostic cut-off exists for maximal walking speed. The value 1.59 m/s is notably higher than the 1.13 m/s threshold associated with fall risk in community-dwelling older adults [4, 5]. This discrepancy likely arises from the relatively young age range (40–74 years) and a healthy cohort bias. More importantly, no mediation analysis was performed to examine whether maximal walking speed—or walking speed reserve—explains part of the NT-proBNP–sarcopenia association. Given that lower-limb skeletal muscle pump function is known to mediate the relationship between cardiac function and exercise capacity [6], a formal test of mediation would have strengthened the causal narrative. Without such analysis, the observed association between elevated NT-proBNP and slower maximal walking speed remains ambiguous: it could reflect cardiac-induced inactivity, or conversely, impaired muscle pump function increasing cardiac preload and NT-proBNP. Finally, although the cross-sectional design was acknowledged as a limitation by the authors, existing longitudinal data could have been used to contextualize their findings. A 2026 community-based study by Kato et al. [7] demonstrated that high NT-proBNP levels predict lower physical function independent of sarcopenia over time, while Tao et al. [8] reported that muscle loss partially mediates the association between NT-proBNP and mortality in hospitalized older adults. The CIRCS cohort, from which the present data were drawn, is a dynamic prospective study with ongoing follow-up, offering a direct opportunity to test whether baseline NT-proBNP predicts incident sarcopenia. Such analyses are encouraged in future work. In summary, Sato et al. have provided important cross-sectional evidence, but the omission of muscle quality indices, the use of a non-validated percentile-based cut-off for maximal walking speed, and the missed opportunity for mediation and prospective analyses limit the interpretability of their findings. Addressing these gaps would substantially advance the field from description toward mechanistic and clinical insight. T.C. and Q.W. conceived the letter concept, performed the literature analysis, and drafted the manuscript. H.D. and X.L. critically revised the manuscript for important intellectual content and provided supervision. All authors approved the final version and agree to be accountable for all aspects of the work. The authors have nothing to report. The authors have nothing to report. The authors have nothing to report. The authors have nothing to report. The authors declare no conflicts of interest. Data sharing is not applicable to this article as no new data were created or analyzed in this correspondence.