A systematic review of 113 studies of transthyretin amyloidosis (ATTR) around the world highlighted the disease’s wide-ranging prevalence rates, with stark geographic differences and limited data from certain regions, according to results from a study published recently in Orphanet Journal of Rare Diseases.
Mortality outcomes also varied, with two-year mortality risks for wild-type ATTR cardiomyopathy (ATTR-CM) between 10% and 30% and for variant ATTR-CM between 10% and 52%.
What is ATTR-CM?
Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is a rare progressive disease of the heart muscle that leads to congestive heart failure. It occurs when the transthyretin protein produced by the liver is unstable. Symptoms include fatigue; shortness of breath; irregular heart rate or palpitations; swelling of the legs, ankles and stomach; brain fog; wheezing; and dizziness. It often goes underdiagnosed because of a lack of awareness and knowledge of the disease. There is currently no cure for ATTR-CM.
The findings underscored the need for further research to improve early detection and disease management.
Read more about ATTR-CM testing and diagnosis
“Higher prevalence/incidence of ATTR amyloidosis was observed among men, the elderly, and those with cardiac conditions, thereby suggesting potential target populations to screen for timely diagnosis and treatment initiation,” study authors said. “Robust epidemiological ATTR amyloidosis data requires further investigation in a larger sample of patients with diverse phenotypes across multiple countries and world regions.”
The review analyzed studies published between January 2018 and April 2023, drawing from Medline and Embase databases. It included observational studies, systematic reviews and meta-analyses that reported on epidemiology and mortality of ATTR but excluded clinical trials and commentaries.
Of the 1,458 records initially identified, 113 met the inclusion criteria, with 49 addressing disease prevalence and 64 reporting mortality rates. The majority of studies originated from North America (26) and Europe (16), with smaller contributions from Asia (5) and Australia (2). No studies focused exclusively on ATTR in Africa or South America, revealing a major gap in global epidemiological data.
Prevalence estimates varied significantly by country and population. In the U.S., ATTR-CM was reported at a rate of approximately 6.1 cases per million people. Other country data showed higher rates, including Denmark (14 per million), Finland (18 per million) and Sweden (50 per million). Japan had one of the highest prevalence rates, at 100 per million per year. Hereditary ATTR polyneuropathy was primarily documented in Portugal, with a prevalence of 229.3 per million.
Studies assessing high-risk groups found ATTR in up to 21% of patients with heart failure, and some studies suggested an even higher prevalence in populations with conditions such as aortic stenosis and carpal tunnel syndrome.
The mortality analysis revealed that ATTR amyloidosis predominantly affected older men, with male representation ranging from 56% to 94% in study populations. The disease appeared to be more lethal in patients with hereditary ATTR, with some studies reporting median survival times as short as 12 months. Outcomes varied significantly, with survival estimates extending up to 80 months in some cohorts. The variability may have reflected differences in health care access, diagnostic criteria and treatment availability.
Early detection remained a critical challenge, as many cases went undiagnosed until symptoms became severe. The stark differences in prevalence and survival rates highlighted the need for improved diagnostic tools and increased awareness, particularly in regions with little to no reported data. For patients, this meant that access to specialized care and timely intervention could have significantly affected outcomes, particularly for those with hereditary forms of the disease.
As research continues to evolve, filling the existing knowledge gaps will be essential to refining treatment approaches and improving survival, the study said. Addressing disparities in disease recognition and access to care could lead to earlier diagnoses and better management, ultimately offering hope for those living with ATTR amyloidosis worldwide.
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