Common ATTR amyloidosis gene could impair longevity among many Black carriers
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Key takeaways:
- Roughly 3% of the Black U.S. population are carriers of an ATTR amyloidosis-causing gene.
- Among all carriers aged 50 to 95 years, they are estimated to lose nearly 1 million total years of life.
A common cardiac amyloidosis-causing gene believed to be present in around 3% of the Black U.S. population is associated with increased risk for HF hospitalization and death, which increases with age, a speaker reported.
Moreover, the more than 400,000 Black Americans aged 50 to 95 years with the genetic variant are estimated to lose nearly 1 million cumulative years of life, according to research presented at the European Society of Cardiology’s Heart Failure 2024 meeting and published in JAMA.
“Since 3% to 4% of self-identified Black individuals in the United States carry this variant, a significant number are at elevated risk for developing cardiac amyloidosis, being hospitalized for heart failure, and dying several years earlier than expected,” Senthil Selvaraj, MD, advanced heart failure physician-scientist at Duke University School of Medicine, said in a press release. “With our improved understanding of the risks with the variant, future efforts to increase disease awareness and ultimately connect carriers with the disease to effective therapies will be important.”
To better understand disease progression among individuals with the amyloidogenic V1421 variant of the TTR gene — the most common cause of transthyretin cardiac amyloidosis (ATTR-CA) in the presence of a detected genetic variant — Selvaraj and colleagues conducted a pooled analysis of Black participants in four large studies: ARIC, MESA, REGARDS and the Women’s Health Initiative.
The study included data from 23,338 Black participants, of which 3.2% were carriers of the V1421 variant and initially free of HF with available genotyping. The mean age at baseline was 62 years and 77% were women due to a large sample size of participants included from the Women’s Health Initiative.
The proportion of carriers was similar by sex (3% of men vs. 3.3% of women).
Outcomes of interest included first HF hospitalization, HF hospitalization subtypes of either HF with reduced ejection fraction or HF with preserved ejection fraction, all-cause mortality and a composite of HF hospitalization or all-cause mortality.
The researchers reported observing a significant increased 10-year risk for HF in carriers of the ATTR variant gene at age 63 years, HF or death at 65 years and death at 72 years. The increased risk for HF was driven by a 10-year increased risk for HFrEF detected at age 65 years (HR = 2.47; 95% CI, 1.87-3.26; P < .001).
Selvaraj and colleagues noted that age was the only significant modifying risk factor for patients who were carriers, translating to an estimated reduction in longevity ranging from 1.9 years at age 50 years to 2.8 years at age 81 years, according to the study.
Moreover, an estimated 435,851 Black carriers of the gene aged 50 to 95 years in the U.S. are projected to cumulatively lose 957,505 years of life due to the variant.
“We believe these data will inform clinicians and patients regarding risk when these genetic findings are known, either through family screening, medical, or even commercial genetic testing,” Scott D. Solomon, MD, Edward D. Frohlich Distinguished Chair and professor of medicine at Brigham and Women’s Hospital and Harvard Medical School, said in the release. “There are now several potential new therapies for cardiac amyloidosis, and understanding the magnitude of this risk, at the individual and societal level, will help determine which patients might be best suited for novel therapies.”
In a related editorial, Mathew S. Maurer, MD, advanced heart failure and transplant cardiologist in the cardiac amyloidosis program, Seymour, Paul and Gloria Milstein Division of Cardiology at Columbia University Irving Medical Center and NewYork-Presbyterian Hospital, and colleagues discussed access to genetic testing for this variant as well as the need for a culturally sensitive multidisciplinary approach to disease management.
“Genetic testing for TTR variants is currently available as part of direct-to-consumer genetic tests and recently the American College of Medical Genetics’ Secondary Findings Working Group endorsed the return of results from genomic testing for TTR variants,” the authors wrote. “The working group determined that genes associated with conditions that disproportionately affect racial and ethnic minoritized groups, such as TTR V142I, should have return of results even if they are rare or have lower penetrance in the U.S. population as a whole.
“Because we now have effective treatments for ATTR-CA, it is likewise imperative that we develop communication strategies in a culturally sensitive manner regarding the risks and benefits of family cascade testing for first-degree relatives of V142I carrier,” they wrote. “We submit that a multidisciplinary approach will be necessary to adequately address these barriers that will require appropriate, multimodal educational materials and policy changes through advocacy that facilitates access for potentially affected patients, many of whom reside in areas remote from centers of excellence in amyloidosis care”
References:
- Maurer MS, et al. JAMA. 2024;doi:10.1001/jama.2024.2868.
- Researchers show genetic variant common among Black Americans contributes to large cardiovascular disease burden. https://medicalxpress.com/news/2024-05-genetic-variant-common-black-americans.html. Published May 12, 2024. Accessed May 29, 2024.
- Selvaraj S, et al. JAMA. 2024;doi:10.1001/jama.2024.4467.
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Selvaraj S, et al. Late breaking science: registries. Presented at: Heart Failure 2024; May 11-14, 2024; Lisbon, Portugal.
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