Division of Cardiology, Department of Medicine, Duke University Medical Center and the Duke Molecular Physiology Institute, Duke University, Durham, North Carolina.
Division of Cardiology, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
JAMA Cardiol. 2023 Aug 1;8(8):784-788. doi: 10.1001/jamacardio.2023.1525.
Hereditary transthyretin cardiac amyloidosis is an increasingly recognized cause of heart failure (HF) with distinct treatment. The amyloidogenic pV142I (V122I) variant is present in 3% to 4% of Black individuals in the US and increases the risk for atrial fibrillation (AF), HF, and mortality. Since hereditary transthyretin cardiac amyloidosis demonstrates age-dependent anatomic penetrance, evaluation later in life may identify survivors at particularly high risk.
To estimate age-dependent risks for cardiovascular events with the variant.
DESIGN, SETTINGS, AND PARTICIPANTS: This cohort study analyzed Black participants from the Atherosclerosis Risk in Communities (ARIC) study attending visit 1 (1987-1989) (followed up until 2019; median follow-up, 27.6 years). Data analyses were completed from June 2022 to April 2023.
pV142I carrier status.
The association between the variant and AF, HF hospitalization, mortality, and a composite of HF hospitalization or mortality was modeled by generating 10-year absolute risk differences for each year between ages 53 (the median age at visit 1) and 80 years, adjusting for the first 5 principal components of ancestry and sex. As an example, 5- and 10-year risk differences were specifically estimated for the composite outcome among participants surviving to age 80 years.
Among 3856 Black participants (including 124 carriers) at visit 1, 2403 (62%) were women, 2140 (56%) had hypertension, and 740 (20%) had diabetes, with no differences between groups. The 10-year absolute risk difference between ages 53 and 80 years increased over time for each outcome. Statistical significance for increased 10-year risk difference emerged near ages 65 years for AF, 70 years for HF hospitalization, and 75 years for mortality. Among participants surviving to age 80 years, carriers had a 20% (95% CI, 2%-37%) and 24% (95% CI, 1%-47%) absolute increased risk for HF hospitalization or death at 5 and 10 years, respectively. Thus, at age 80 years, only 4 carriers would need to be identified to attribute 1 HF hospitalization or death over the following decade to the variant.
In this study, age-specific risks were provided for relevant outcomes with the pV142I variant. Despite a relatively benign course during earlier years, Black individuals who carry the pV142I variant surviving into later life may be particularly vulnerable. These data may inform timing for screening, risk counseling to patients, and potential strategies for early targeted therapy.
遗传性转甲状腺素蛋白心脏淀粉样变性是心力衰竭（HF）的一种日益被认识到的病因，具有独特的治疗方法。在美国，3%至4%的黑人个体携带致病变异体 pV142I（V122I），这增加了心房颤动（AF）、HF 和死亡的风险。由于遗传性转甲状腺素蛋白心脏淀粉样变性表现出与年龄相关的解剖学外显率，因此在以后的生活中进行评估可能会发现风险特别高的幸存者。
评估该变体的心血管事件的年龄依赖性风险。
设计、地点和参与者：这项队列研究分析了参加 ARIC 研究第 1 次访视（1987-1989 年）的黑人参与者（随访至 2019 年；中位随访时间 27.6 年）。数据分析于 2022 年 6 月至 2023 年 4 月完成。
pV142I 携带状态。
通过为每个年龄组生成 53 岁（第 1 次访视的中位年龄）至 80 岁之间的 10 年绝对风险差异，对该变体与 AF、HF 住院、死亡以及 HF 住院或死亡的复合结局之间的相关性进行了建模，该模型调整了前 5 个祖先和性别的主成分。例如，在年龄达到 80 岁的参与者中，专门针对复合结局估计了 5 年和 10 年的风险差异。
在第 1 次访视的 3856 名黑人参与者（包括 124 名携带者）中，2403 名（62%）为女性，2140 名（56%）患有高血压，740 名（20%）患有糖尿病，各组之间无差异。对于每种结局，53 岁至 80 岁之间的 10 年绝对风险差异随着时间的推移而增加。AF 的 10 年风险差异增加在接近 65 岁时具有统计学意义，HF 住院的 10 年风险差异在接近 70 岁时具有统计学意义，死亡率的 10 年风险差异在接近 75 岁时具有统计学意义。在年龄达到 80 岁的参与者中，携带者在 5 年和 10 年时发生 HF 住院或死亡的绝对风险分别增加 20%（95%CI，2%-37%）和 24%（95%CI，1%-47%）。因此，在 80 岁时，只需识别出 4 名携带者，就可以归因于接下来十年内的 1 例 HF 住院或死亡与该变体有关。
在这项研究中，提供了与 pV142I 变体相关的特定结局的年龄特异性风险。尽管在早期阶段表现出相对良性的病程，但携带 pV142I 变体并存活到晚年的黑人个体可能特别脆弱。这些数据可能有助于确定筛查时间、向患者提供风险咨询以及制定早期靶向治疗的潜在策略。
