Abstract
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.