Association Between Occupational Physical Work Exposure and Wild-Type Transthyretin Cardiomyopathy

The incidence of transthyretin wild-type amyloid cardiomyopathy (ATTRwt-CM) is increasing. Previous findings suggest an association between mechanical stress and ATTRwt-CM.

This study aimed to assess differences in employment history, occupational mechanical exposures, comorbidity, and mortality between patients with ATTRwt-CM compared with a matched general population cohort.

Patients diagnosed with ATTRwt-CM between 2016 and 2023 were matched 1:5 by age and sex with controls randomly selected from the Danish general population. Outcomes were minimum 3 years of previous agricultural or other general physical demanding employment, predicted median upper and lower body mechanical exposures, and cardiovascular and all-cause mortality. Conditional Poisson regression was used to estimate incidence rate ratios (IRRs).

A total of 258 patients with ATTRwt-CM were matched with 1,290 controls. ATTRwt-CM patients had a higher prevalence of cardiovascular comorbidities (atrial fibrillation and aortic stenosis) and orthopedic conditions (carpal tunnel syndrome, lumbar spinal stenosis, and lower limb arthrosis). Agricultural employment (28% vs 8%; IRR: 3.35; 95% CI: 2.55-4.39) and greater upper body mechanical workload exposures were more common among patients with ATTRwt-CM than among controls. Three-year cardiovascular mortality (13% vs 5%; IRR: 3.38; 95% CI: 1.97-5.83) and all-cause mortality (33% vs 21%; IRR: 1.93; 95% CI: 1.48-2.50) were higher in patients with ATTRwt-CM.

ATTRwt-CM was associated with greater occupational upper-body mechanical stress. While a causal relationship cannot be established due to study design, the results are hypothesis generating for the development of ATTRwt-CM. Additionally, ATTRwt-CM patients had a greater burden of orthopedic and cardiovascular comorbidities including increased cardiovascular mortality.