Abstract
Importance: The variant V122I is commonly enriched in the transthyretin (TTR) gene in individuals of African ancestry and associated with greater risk of heart failure (HF) in older adulthood, after age 65 years. Prevention of HF may be most effective earlier in life, but whether screening with echocardiography can identify subclinical cardiac abnormalities during middle age to risk-stratify individuals appears to be unknown. Objective: To examine the association between the V122I TTR variant and cardiac structure and function during middle age in those without prevalent HF. Design, Setting, and Participants: This serial cross-sectional study of 875 Black participants in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort was conducted at 4 urban sites across the US. Recruiting was completed in 1985-1986, and follow-up examinations occurred 25 and 30 years later. A subset of Black adults from the CARDIA cohort who underwent TTR genotyping was included. Data analysis was completed from January 2020 to October 2020. Exposures: The V122I TTR genotype. Main Outcomes and Measures: Echocardiographic left ventricular (LV) circumferential and longitudinal systolic strain and LV structure, measured at years 25 and 30 of follow-up. The analyses were adjusted for age, sex, echocardiography quality, genetic ancestry, and field center. Results: Among the 875 Black adults (mean [SD] age, 49.4 [3.8] years at year 25; 543 women [62.1%]), there were 31 individuals who were heterozygous and 1 who was homozygous for the V122I TTR variant. Of the adults who had an echocardiogram at year 25, rates of hypertension (312 [46%]), diabetes (102 [15%]), and current smoking (128 [19%]) were not significantly different between those who did and did not carry V122I TTR. At year 25, there was no difference in LV circumferential strain, longitudinal strain, or LV structure between those who did vs did not carry V122I TTR. At year 30, those who carried V122I TTR had significantly lower absolute LV circumferential strain (mean [SD], 12.4 [4.2] percentage units) compared with those who did not carry the variant (mean [SD], 14.5 [3.7] percentage units). Those who carried V122I TTR also had significantly higher LV mass index values (mean [SD], 97.5 [34.1] g/m2) compared with those who did not (mean [SD], 83.7 [22.6] g/m2) at year 30. Conclusions and Relevance: Carrier status for the V122I TTR variant is associated with subclinical cardiac abnormalities in middle age (worse LV systolic function and higher LV mass) that have been associated with increased risk of incident HF. Midlife screening of individuals who carry V122I TTR with echocardiography may prognosticate risk of symptomatic HF and inform prevention strategies.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 718-722 |
| Number of pages | 5 |
| Journal | JAMA cardiology |
| Volume | 6 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 2021 |
Funding
received research grants from Actelion, AstraZeneca, Corvia, Novartis, and Pfizer and received consulting fees from Abbott, Actelion, AstraZeneca, Amgen, Aria, Axon Therapeutics, Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, Cardiora, CVRx, Cyclerion, Cytokinetics, Eisai, GSK, Imara, Ionis, Ironwood, Keyto, Lilly, Merck, MyoKardia, Novartis, Novo Nordisk, Pfizer, Regeneron, Sanofi, Shifamed, Tenax, and United Therapeutics, of which personal fees from Pfizer and Ionis and research grants from Pfizer were provided during the conduct of the study. Dr Yancy reported spousal employment at Abbott Inc. Dr McNally reported grants from National Institutes of Health and Northwestern University during the conduct of the study; personal fees from AstraZeneca, Avidity, Amgen, Cytokinetics, Invitae, Exonics/Vertex, Tenaya Therapeutics, Janssen, and Pfizer; grants from Solid Biosciences Grant and the Department of Defense to Northwestern outside the submitted work; and being a founder of Ikaika Therapeutics outside of the submitted work. Dr Lloyd-Jones reported grants from the National Institute of Health during the conduct of the study. Dr Khan reported grant KL2TR001424 from the National Center for Advancing Translational Sciences and grant 19TPA34890060 from the American Heart Association during the conduct of the study. No other disclosures were reported. Funding/Support: Dr Sinha is supported by the
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
