Low plasma transthyretin risk factor for incident Heart Failure: JAMA

Transthyretin amyloidosis with cardiac involvement is the most common phenotype and is increasingly recognized as an important contributor to heart failure (HF) and mortality in older individuals. Both ATTRm (hereditary transthyretin cardiac amyloidosis) and ATTRwt (wild-type transthyretin cardiac amyloidosis) cardiac amyloidosis may manifest as heart failure (HF). However, whether low plasma transthyretin concentration confers increased risk of incident HF in the general population is unknown. So, researchers evaluated whether low plasma transthyretin concentration is associated with incident HF in the general population. they analyzed the data from 2 similar prospective cohort studies of the Danish general population, the Copenhagen General Population Study (CGPS; n = 9582) and the Copenhagen City Heart Study (CCHS; n = 7385). Participants from both studies were observed for survival time endpoints until March 2017. Data were analyzed from March to June 2019. Researchers also evaluated whether genetic variants in TTR associated with increasing tetramer instability and lower transthyretin concentration and thus associated with a higher risk of HF. Patients were categorized based on the Transthyretin concentration at or below the 5th percentile, between the 5th and 95th percentile (reference), and greater than the 95th percentile (genetic variants in TTR). On median follow-up of 12.6 years in CGPS and 21.7 years in CCHS, 441 individuals (4.6%) in the CGPS and 1122 individuals (15.2%) in the CCHS developed Heart Failure.

Key findings of the study:

♦Using heterozygotes for p.T139M, (the most stable variant of transthyretin) as the reference group, researchers observed a stepwise reduction in transthyretin concentration for wild-type TTR (−16.5%), for p.G26S (−18.1%), and heterozygotes for other variants (p.V142I, p.H110N, and p.D119N; −30.8%)

♦Researchers found Baseline plasma transthyretin concentrations at or below the 5th percentile were associated with incident HF

♦They also noted risk of HF was highest in men with low transthyretin levels

♦They reported corresponding Hazard ratios (HRs) for incident HF were 1.14 for wild-type variants, 1.29 for the p.G26S variant, and 2.04 for other variants.

The authors concluded, "In this study, lower plasma concentrations and genetically determined transthyretin concentrations were associated with a higher risk of incident HF. These results are compatible with a potential mechanistic association between low transthyretin concentration as a marker of tetramer instability and incident HF in the general population".

For further information:

https://jamanetwork.com/journals/jamacardiology/fullarticle/10.1001/jamacardio.2020.5969?guestAccessKey=0133d14f-342f-4721-a047-08ed6dc11a82&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-jamacardiology&utm_content=olf&utm_term=112520