Sex Differences in Wild-Type Transthyretin Amyloidosis: An Analysis from the Transthyretin Amyloidosis Outcomes Survey (THAOS)

Courtney M Campbell, Samantha LoRusso, Angela Dispenzieri, Arnt V Kristen, Mathew S Maurer, Claudio Rapezzi, Olivier Lairez, Brian Drachman, Pablo Garcia-Pavia, Martha Grogan, Doug Chapman, Leslie Amass, THAOS investigators, Michele Emdin, Mazen Hanna, Olga Azevedo, Calogero Lino Cirami, Daniel Jacoby, Jose Gonzalez Costello, David Slosky, Henning Moelgaard, Scott Hummel, Jose Nativi-Nicolau, Srinivas Murali, Nowell Fine, Eun-Seok Jeon, Sanjiv Shah, Ronald Witteles, Daniel Lenihan, Marcia Waddington-Cruz, Yoshiki Sekijima, Jose Tallaj, Christopher Mueller, Johan Van Cleemput, Violaine Planté-Bordeneuve, Hans Nienhuis, Dianna Quan, David Steidley, Hartmut Schmidt, Jonas Wixner, Michael Polydefkis, Jeffrey Ralph, Hector Ventura, Sasa Zivkovic, Burkhard Gess, Roberto Fernandéz Torrón, Stephen Gottlieb, William Cotts, James Tauras, Nitasha Sarswat, Juan González Moreno, Yesim Parman, Jin Luo, Courtney M Campbell, Samantha LoRusso, Angela Dispenzieri, Arnt V Kristen, Mathew S Maurer, Claudio Rapezzi, Olivier Lairez, Brian Drachman, Pablo Garcia-Pavia, Martha Grogan, Doug Chapman, Leslie Amass, THAOS investigators, Michele Emdin, Mazen Hanna, Olga Azevedo, Calogero Lino Cirami, Daniel Jacoby, Jose Gonzalez Costello, David Slosky, Henning Moelgaard, Scott Hummel, Jose Nativi-Nicolau, Srinivas Murali, Nowell Fine, Eun-Seok Jeon, Sanjiv Shah, Ronald Witteles, Daniel Lenihan, Marcia Waddington-Cruz, Yoshiki Sekijima, Jose Tallaj, Christopher Mueller, Johan Van Cleemput, Violaine Planté-Bordeneuve, Hans Nienhuis, Dianna Quan, David Steidley, Hartmut Schmidt, Jonas Wixner, Michael Polydefkis, Jeffrey Ralph, Hector Ventura, Sasa Zivkovic, Burkhard Gess, Roberto Fernandéz Torrón, Stephen Gottlieb, William Cotts, James Tauras, Nitasha Sarswat, Juan González Moreno, Yesim Parman, Jin Luo

Abstract

Introduction: Wild-type transthyretin amyloidosis (ATTRwt amyloidosis) is a progressive disease resulting from the accumulation of wild-type transthyretin (TTR) amyloid fibrils, and is diagnosed primarily in males. This analysis examined sex differences in patients with ATTRwt amyloidosis from the Transthyretin Amyloidosis Outcomes Survey (THAOS).

Methods: THAOS is an ongoing, global, longitudinal, observational survey of patients with transthyretin amyloidosis, including both inherited and wild-type disease, and asymptomatic carriers of TTR mutations. THAOS data were analyzed to identify potential differences in demographic and clinical characteristics between males and females with ATTRwt amyloidosis (data cutoff: August 1, 2021).

Results: Of 1386 patients with ATTRwt amyloidosis, 84 (6%) were female and 1302 (94%) were male. Females had a higher median age at enrollment (80 vs. 78 years; p = 0.002) and symptom onset (75 vs. 73 years; p = 0.045) than males. Mean left ventricular (LV) ejection fraction was higher (53% vs. 48%; p = 0.001) and mean LV diastolic diameter lower (42 vs. 46 mm; p < 0.001) in females versus males, but sex was not identified as a predictor of LV mean wall thickness adjusted for height (beta coefficient - 0.22; p = 0.460) or a predominantly cardiac phenotype (odds ratio 1.60; p = 0.191). Modified polyneuropathy disability scores differed between groups (p < 0.001), with a larger proportion of scores ≥ IIIa among females (23% vs. 7%).

Conclusions: Females with ATTRwt amyloidosis in THAOS tended to present at a later age and showed signs of less severe cardiac impairment and more severe walking impairment.

Trial registration: ClinicalTrials.gov: NCT00628745.

Keywords: ATTRwt amyloidosis; Registry; Sex; Transthyretin Amyloidosis Outcomes Survey.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Cumulative incidence of ATTR-CM according to sex. The cumulative incidence curve showed that female patients tended to develop ATTR-CM at a later age. ATTR amyloidosis transthyretin amyloidosis; ATTR-CM transthyretin amyloid cardiomyopathy

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Source: PubMed

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