Background Carpal tunnel syndrome (CTS) has been recognized as a potential early manifestation of systemic amyloidosis; however, its prognostic implications for cardiovascular and renal outcomes remain unclear. Methods Using the TriNetX global federated research network, we conducted a retrospective cohort study of patients with bilateral CTS between January 2006 and December 2024. Among 221 902 eligible individuals, 2099 had concomitant amyloidosis. After 1:1 propensity score matching for demographics, comorbidities, medications, and laboratory variables, 1957 matched pairs were analyzed. Outcomes included major adverse cardiovascular events, 3‐point major adverse cardiovascular events, heart failure, arrhythmia, dialysis initiation, and major adverse kidney events. Cox proportional hazards models and Kaplan–Meier analyses were performed. Results Compared with patients with CTS and amyloidosis (reference group), those without amyloidosis had significantly lower risks of major adverse cardiovascular events (adjusted hazard ratio aHR, 0.41 95% CI, 0.28–0.59), 3‐point major adverse cardiovascular events (aHR, 0.26 95% CI, 0.19–0.35), heart failure (aHR, 0.45 95% CI, 0.30–0.64), arrhythmia (aHR, 0.50 95% CI, 0.35–0.69), dialysis initiation (aHR, 0.51 95% CI, 0.37–0.95), and major adverse kidney events (aHR, 0.28 95% CI, 0.25–0.99; all P <0.05). Kaplan–Meier curves demonstrated consistently lower event‐free survival in the amyloidosis group. Sensitivity analyses across alternative modeling strategies yielded directionally consistent results. The median diagnostic delay from CTS to amyloidosis was 3.3 years (interquartile range, 1.4–5.7) and was shorter in the posttafamidis era. Conclusions Systemic amyloidosis is associated with substantially increased cardiovascular and renal risks among patients with CTS, highlighting the importance of heightened clinical vigilance and earlier recognition.
Wang et al. (2026) studied this question.