{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:00:29Z","timestamp":1790611229488,"version":"4.1.0"},"reference-count":36,"publisher":"American Medical Association (AMA)","issue":"21","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA"],"published-print":{"date-parts":[[2024,6,4]]},"abstract":"<jats:sec id=\"ab-joi240040-4\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>\n                      Individual cohort studies concur that the amyloidogenic V142I variant of the transthyretin (\n                      <jats:italic>TTR<\/jats:italic>\n                      ) gene, present in 3% to 4% of US Black individuals, increases heart failure (HF) and mortality risk. Precisely defining carrier risk across relevant clinical outcomes and estimating population burden of disease are important given established and emerging targeted treatments.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-joi240040-5\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To better define the natural history of disease in carriers across mid to late life, assess variant modifiers, and estimate cardiovascular burden to the US population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-joi240040-6\">\n                    <jats:title>Design, Setting, and Participants<\/jats:title>\n                    <jats:p>A total of 23\u202f338 self-reported Black participants initially free from HF were included in 4 large observational studies across the US (mean [SD], 15.5 [8.2] years of follow-up). Data analysis was performed between May 2023 and February 2024.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-joi240040-7\">\n                    <jats:title>Exposure<\/jats:title>\n                    <jats:p>V142I carrier status (n\u2009=\u2009754, 3.2%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-joi240040-8\">\n                    <jats:title>Main Outcomes and Measures<\/jats:title>\n                    <jats:p>Hospitalizations for HF (including subtypes of reduced and preserved ejection fraction) and all-cause mortality. Outcomes were analyzed by generating 10-year hazard ratios for each age between 50 and 90 years. Using actuarial methods, mean survival by carrier status was estimated and applied to the 2022 US population using US Census data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-joi240040-9\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among the 23\u202f338 participants, the mean (SD) age at baseline was 62 (9) years and 76.7% were women. Ten-year carrier risk increased for HF hospitalization by age 63 years, predominantly driven by HF with reduced ejection fraction, and 10-year all-cause mortality risk increased by age 72 years. Only age (but not sex or other select variables) modified risk with the variant, with estimated reductions in longevity ranging from 1.9 years (95% CI, 0.6-3.1) at age 50 to 2.8 years (95% CI, 2.0-3.6) at age 81. Based on these data, 435\u202f851 estimated US Black carriers between ages 50 and 95 years are projected to cumulatively lose 957\u202f505 years of life (95% CI, 534\u202f475-1\u202f380\u202f535) due to the variant.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-joi240040-10\">\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>Among self-reported Black individuals, male and female V142I carriers faced similar and substantial risk for HF hospitalization, predominantly with reduced ejection fraction, and death, with steep age-dependent penetrance. Delineating the individual contributions of, and complex interplay among, the V142I variant, ancestry, the social construct of race, and biological or social determinants of health to cardiovascular disease merits further investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jama.2024.4467","type":"journal-article","created":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T04:30:39Z","timestamp":1715488239000},"page":"1824","source":"Crossref","is-referenced-by-count":47,"title":["Cardiovascular Burden of the V142I Transthyretin Variant"],"prefix":"10.1001","volume":"331","author":[{"given":"Senthil","family":"Selvaraj","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, North Carolina"},{"name":"Duke Molecular Physiology Institute, Durham, North 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Duke University Medical Center, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ani W.","family":"Manichaikul","sequence":"additional","affiliation":[{"name":"Center for Public Health Genomics, University of Virginia, Charlottesville"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadiya S.","family":"Khan","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine and Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen S.","family":"Rich","sequence":"additional","affiliation":[{"name":"Center for Public Health Genomics, University of Virginia, Charlottesville"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas H.","family":"Mosley","sequence":"additional","affiliation":[{"name":"The MIND Center, University of Mississippi Medical Center, Jackson"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily B.","family":"Levitan","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of Alabama at Birmingham"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pankaj","family":"Arora","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Disease, University of Alabama at Birmingham"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parag","family":"Goyal","sequence":"additional","affiliation":[{"name":"Department of Medicine, Weill Cornell Medicine, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Haring","sequence":"additional","affiliation":[{"name":"Department of Medicine III, Saarland University, Homburg, Saarland, Germany"},{"name":"Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New 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