本文由小咖机器人翻译整理

期刊来源：JAMA

原文链接：https://doi.org/10.1001/jama.2024.4467

摘要内容如下：

重要性

个体队列研究一致认为，甲状腺素运载蛋白（TTR）基因的淀粉样蛋白V142I变异体（存在于3%至4%的美国黑人个体中）会增加心力衰竭（HF）和死亡风险。考虑到已建立的和新出现的靶向治疗，准确定义相关临床结果的携带者风险和估计人群疾病负担非常重要。

目标

为了更好地确定疾病携带者在生命中期至晚期的自然史，评估变异修饰因子，并估计美国人群的心血管负担。

设计、设置和参与者

全美共有4项大型观察性研究（平均[SD]，随访15.5[8.2]年）纳入了23338名自我报告的最初无心衰的黑人参与者。数据分析在2023年5月至2024年2月之间进行。

曝光

V142i载体状态（N=754，3.2%）。

主要成果和措施

因心衰住院（包括射血分数降低和维持的亚型）和全因死亡率。通过生成50至90岁之间每个年龄的10年风险比来分析结果。使用精算方法，估计携带者状态的平均存活率，并使用美国人口普查数据将其应用于2022年美国人口。

结果

在23338名参与者中，基线时的平均（SD）年龄为62（9）岁，76.7%为女性。到63岁时，心衰住院的10年携带者风险增加，主要由射血分数降低的心衰引起，到72岁时，10年全因死亡风险增加。只有年龄（而不是性别或其他选择变量）改变了变量的风险，估计寿命减少的范围从50岁时的1.9年（95%CI，0.6-3.1）到81岁时的2.8年（95%CI，2.0-3.6）。基于这些数据，估计435851名50-95岁之间的美国黑人携带者预计累计损失957505年的寿命（95%CI，534475-1380535）。

结论和相关性

在自我报告的黑人个体中，男性和女性V142I携带者面临相似且实质性的心衰住院风险，主要是射血分数降低和死亡，具有陡峭的年龄依赖性外显率。描述V142I变异体、祖先、种族的社会结构和健康的生物或社会决定因素对心血管疾病的个体贡献和复杂的相互作用值得进一步研究。

英文原文如下：

Abstracts

Importance  Individual cohort studies concur that the amyloidogenic V142I variant of the transthyretin (TTR) 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.

Objectives  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.

Design, Setting, and Participants  A total of 23 338 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.

Exposure  V142I carrier status (n = 754, 3.2%).

Main Outcomes and Measures  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.

Results  Among the 23 338 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, 435 851 estimated US Black carriers between ages 50 and 95 years are projected to cumulatively lose 957 505 years of life (95% CI, 534 475-1 380 535) due to the variant.

Conclusions and Relevance  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.

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