Musculoskeletal events and risk of amyloidosis in the general population

Abstract

IMPORTANCE

In patients diagnosed with cardiomyopathy, certain musculoskeletal events are considered “red flags” for amyloidosis. In the general population, more information about the usefulness of musculoskeletal events for predicting risk of amyloidosis is needed, because early pharmacological intervention may reduce amyloidosis risk.

Objective

To determine if musculoskeletal events were associated with an increased risk of incident amyloidosis in the general population.

Design, Setting, and Participants

A Danish Nationwide Cohort (DNC), with external and internal validation in two large prospective studies of the general population, the UK Biobank (UKBB) and the Copenhagen General Population Study (CGPS). DNC included 8,122,667 individuals followed for amyloidosis from January 1996 until December 2021. UKBB included 501,723 individuals and CGPS included 106,897 individuals followed from the examination date (2006-2010 in UKBB and 2003-2015 in CGPS) until death or the end of follow-up (October 2022 in UKBB and December 2021 in CGPS).

Exposures

Seven musculoskeletal events identified from International Classification of Disease (ICD) or procedure codes.

Main Outcomes and Measures

Incident amyloidosis identified by ICD codes.

Results

During a median follow-up of 21.9 and 13.6 years, 1,842 and 522 individuals were diagnosed with amyloidosis in the DNC and UKBB, respectively. Carpal tunnel syndrome, spinal stenosis, trigger digit, and hip osteoarthritis were associated with amyloidosis in both studies, with hazard ratios (HRs) ranging from 2.43(95% confidence interval, 1.97-3.00) for spinal stenosis to 7.83(6.54-9.36) for carpal tunnel syndrome. Two or more versus no musculoskeletal events were associated with HRs of 9.80(7.72-12.5) in the DNC, 17.2(4.98-59.5) in the CGPS, and 5.89(2.62-13.2) in the UKBB. At 80 years, >1 in 200 individuals with any musculoskeletal event had amyloidosis. Median time from event to amyloidosis diagnosis was 8.6 years in both the DNC and UKBB, ranging from 6.36 years for carpal tunnel syndrome to 11.3 years for trigger digit.

Conclusions and Relevance

Carpal tunnel syndrome, spinal stenosis, trigger digit, and hip osteoarthritis were associated with substantially higher risk of incident amyloidosis in the general population with median time to amyloidosis diagnosis of 8.6 years. More events predicted higher risk. These findings are important since early pharmacological intervention may reduce amyloidosis risk.