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Carpal Tunnel Syndrome and Amyloidosis, HF, and Adverse CV Outcomes
Study Questions:
What is the association of amyloidosis, heart failure (HF), and other adverse cardiovascular (CV) outcomes associated with carpal tunnel syndrome (CTS)?
Methods:
Using data from Danish national registries, all Danish residents who underwent surgery for CTS from 1996 to 2012 were evaluated. Patients with known amyloidosis or HF were excluded. For comparison, patients who underwent CTS surgery were sex- and age-matched to a cohort from the general Danish population. The exposure of interest was surgery for CTS. The primary outcomes were: 1) diagnosis of amyloidosis, and 2) hospitalization for HF. The exposure and outcomes were assessed by review of Danish procedure codes and International Classification of Diseases, 10th edition diagnosis codes. The secondary outcomes were atrial fibrillation, atrioventricular block (AVB), and permanent pacemaker (PPM) and/or implantable cardioverter-defibrillator (ICD) implantation. Covariates included in the analyses were socioeconomic status (education, household income), comorbidities, and concomitant pharmacotherapy. An additional sensitivity analysis was performed between patients with CTS who developed HF and patients with HF in the absence of CTS. In this analysis, the authors examined risk of death.
Results:
The study population consisted of 56,032 patients who underwent surgery for CTS and their age- and sex-matched controls. The median age was 53.9 years (interquartile range, 43.3-65.9 years) and 67.9% were women. CTS patients had a higher prevalence of hypertension and ischemic heart disease and used more pharmacotherapies than the control subjects. CTS was associated with a higher cumulative incidence of amyloidosis compared to control subjects (adjusted hazard ratio (HR), 12.12; 95% confidence interval [CI], 4.37-33.60). The absolute risk of amyloidosis was low, with a cumulative incidence of 0.10% over 10 years in the CTS group compared to 0.006% in the control subjects. CTS also was associated with an increased risk of HF compared with control subjects: cumulative incidence was 5.3% at 10 years for the CTS group compared to 3.2% for control subjects, with an adjusted HR of 1.54 (95% CI, 1.45-1.64). Cumulative mortality was similar among the CTS and control groups (adjusted HR, 0.89; 95% CI, 0.86-0.92). Secondary outcomes were higher in the CTS group compared to the control group, including atrial fibrillation (adjusted HR, 1.36; 95% CI, 1.28-1.45), AVB (adjusted HR, 1.43; 95% CI, 1.20-1.72), and PPM or ICD (adjusted HR, 1.39; 95% CI, 1.18-1.62). The risk of death in patients with CTS and HF compared to those subjects with HF in the absence of CTS was lower in years 0-7 of follow-up after HF developed (adjusted HR, 0.90; 95% CI, 0.85-0.96); however, mortality risk was higher after 7 years (adjusted HR, 1.38; 95% CI, 1.12-1.70).
Conclusions:
CTS was associated with a 12-fold higher risk of diagnosed amyloidosis compared to control subjects, and CTS patients had a higher risk of HF. The overall absolute risk of diagnosed amyloidosis was low (cumulative incidence, 0.10%). There was also an increased risk of atrial fibrillation, AVB, and PPM/ICD implantation in patients with CTS. Patients with CTS and HF had a lower short-term but higher long-term mortality compared to subjects with HF in the absence of CTS.
Perspective:
CTS is common in patients with amyloidosis. The authors provide observational data describing the association between CTS and amyloidosis, and also describe an association among CTS and adverse CV outcomes commonly associated with amyloidosis. Although the absolute risk of the diagnosis of amyloidosis was low in this cohort, the data presented show a significant association (12-fold) of CTS with amyloidosis. While this was an observational study of a relatively homogenous (Danish) population and is thereby limited in assessing causality and applicability to other populations (some of which would have a higher prevalence of amyloidosis), this work suggests that CTS may be an early marker for adverse CV events and amyloidosis.
Keywords: Amyloidosis, Arrhythmias, Cardiac, Atrial Fibrillation, Atrioventricular Block, Carpal Tunnel Syndrome, Coronary Artery Disease, Defibrillators, Implantable, General Surgery, Heart Failure, Hypertension, Myocardial Ischemia, Pacemaker, Artificial, Risk Assessment, Secondary Prevention
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