Determinants and Clinical Interpretation of Circulating Transthyretin in ATTR Amyloidosis.

Authors

Toshihiro Tsuruda, Yosuke Suiko, Yunosuke Matsuura, Soichi Komaki, Kohei Moribayashi, Hiroki Tanaka, Masashi Yamaguchi, Kinuko Yamamoto, Michikazu Nakai, Koichi Kaikita

Published in

JACC. Advances. Pages 103047. Jul 23, 2026. Epub Jul 23, 2026.

Abstract

Transthyretin (TTR) amyloidosis (ATTR) ranges from localized to systemic disease, but the clinical interpretation of circulating TTR remains uncertain.
The objective of the study was to characterize serum TTR in ATTR and identify longitudinal determinants, including disease-modifying therapies.
In a single-center cohort, 134 patients with ATTR were enrolled. Serum TTR was measured at baseline (91 treatment-naive patients) and longitudinally during follow-up (347 measurements). Linear mixed-effects models were used to identify clinical and therapeutic determinants of circulating TTR.
Baseline TTR levels declined across clinical stages, from isolated carpal tunnel syndrome to symptomatic heart failure (27 vs 20 mg/dL). In longitudinal mixed-effects analyses, older age (β = -0.310, P < 0.001), inflammation (log₁₀[C-reactive protein+0.1], β = -6.011, P < 0.001), and cardiac stress (log₁₀BNP, β = -1.460, P = 0.033) were independently associated with lower TTR levels, whereas albumin was positively associated (β = 3.041; P < 0.001). Wild-type ATTR showed higher TTR levels than variant ATTR (β = 6.766; P < 0.001). Tetramer stabilizers increased TTR (β = 8.095; P < 0.001), whereas small-interfering RNA therapy reduced TTR levels (β = -13.456; P < 0.001). Following stabilizer initiation, median TTR increased from 21.5 mg/dL to 32.2 mg/dL after >730 days of therapy.
Circulating TTR reflects the integrated effects of systemic status and therapeutic interventions and should not be interpreted as a simple surrogate of ATTR disease severity.

PMID:
42663367
Bibliographic data and abstract were imported from PubMed on 28 Aug 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.