Log in to MyACC
Sex-Related Cardiac Risk in ATTRv Amyloidosis
Quick Takes
- Some biological characteristic(s) associated with female sex could be protective against myocardial involvement in hereditary transthyretin amyloidosis.
- The higher prevalence of male sex in the predominantly cardiac phenotype, and the association between male sex and severity of cardiac involvement, suggests that male patients are more susceptible to myocardial involvement in ATTRv amyloidosis.
- Additional studies are indicated to better assess potential prognostic factors and delineate the underlying biology of a potential protective mechanism conferred by female sex in hereditary transthyretin amyloidosis.
Study Questions:
What are the associations between sex and genotype, phenotype, and degree of myocardial involvement in wild-type or variant (ATTRv) hereditary transthyretin amyloidosis?
Methods:
The investigators analyzed data from the THAOS (Transthyretin Amyloidosis Outcomes Survey), an ongoing global longitudinal observational survey of patients with ATTR amyloidosis and asymptomatic carriers with TTR mutations. Data from THAOS (data cutoff: January 6, 2020) were analyzed to determine any sex-based differences in genotype, phenotype, and presence of cardiac and neurological symptoms in patients with ATTRv amyloidosis and in patients with ATTRv amyloidosis and cardiomyopathy. Multivariable analysis of the possible determinants of phenotype (by logistic regression) and mean left ventricular wall thickness ([LVWT] divided by height, to normalize for physiologic sex-related differences; by linear regression) was also conducted to assess the independent contribution of sex in patients with ATTRv amyloidosis.
Results:
There were 2,790 patients with ATTRv amyloidosis enrolled in THAOS, with male patients more likely to have symptoms of cardiac involvement and a cardiac phenotype. Male prevalence was greater in patients with more severe cardiac manifestations of disease, as assessed with N-terminal pro–B-type natriuretic peptide, LV ejection fraction, mean LVWT divided by height, and LV mass index divided by height. Sex, age at disease onset, and genotype category were identified by multivariate analyses as risk factors for the development of cardiomyopathy (defined as increased LV septum thickness divided by height).
Conclusions:
The authors concluded that myocardial involvement was more frequent and pronounced in male patients with ATTRv amyloidosis, suggesting that there may be biological characteristics that inhibit myocardial amyloid infiltration in females or facilitate it in males.
Perspective:
This observational study reports that some biological characteristic(s) associated with female sex could be protective against myocardial involvement in ATTRv amyloidosis. Furthermore, the higher prevalence of male sex in the predominantly cardiac phenotype and in cardiogenic mutations, along with the association between male sex and severity of morphological and functional cardiac involvement, suggests that male patients are more susceptible to myocardial involvement in ATTRv amyloidosis. Additional studies are indicated to better assess potential prognostic factors and delineate the underlying biology of a potential protective mechanism conferred by female sex.
Clinical Topics: Anticoagulation Management, Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure, Heart Failure and Cardiac Biomarkers
Keywords: Amyloid, Amyloid Neuropathies, Familial, Biology, Cardiomyopathies, Genotype, Heart Failure, Mutation, Natriuretic Peptide, Brain, Peptide Fragments, Phenotype, Risk Factors, Secondary Prevention, Sex Characteristics, Stroke Volume
< Back to Listings
