Transthyretin Tetramer Destabilization and Increased Mortality in the General Population

Area of Science:

• Cardiology
• Genetics
• Epidemiology

Background:

• Transthyretin tetramer destabilization is a key factor in transthyretin cardiac amyloidosis, a significant cause of death in older adults.
• This condition is often underrecognized, highlighting the need for better understanding of its broader mortality implications.

Purpose of the Study:

• To investigate the association between transthyretin tetramer destabilization and all-cause and cardiovascular mortality in the general population.
• To determine if genetic variants and plasma transthyretin levels can serve as indicators of mortality risk.

Main Methods:

• A cohort study analyzed genetic data from over 100,000 individuals in the Danish general population (CCHS and CGPS).
• Observational data on plasma transthyretin levels were analyzed in a subsample.
• Follow-up extended until December 2018, with mortality data from national registries.

Main Results:

• Genetic analyses showed that individuals with less stable transthyretin tetramers had a higher risk of all-cause and cardiovascular mortality.
• Lower plasma transthyretin levels, observed in individuals with less stable tetramers, were associated with increased all-cause mortality.
• A trend of increasing mortality risk was observed with increasing tetramer destabilization.

Conclusions:

• Transthyretin tetramer destabilization is associated with increased all-cause and cardiovascular mortality in the Danish general population.
• These findings suggest that measuring transthyretin destabilization could help in early detection of transthyretin amyloidosis.
• Early identification and treatment of transthyretin amyloidosis can improve patient prognosis.