Department of Medicine III, Saarland University Hospital, Homburg, Saarland, Germany; Department of Medicine I, University of Würzburg, Würzburg, Bavaria, Germany; Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA.
Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
JACC Heart Fail. 2023 Sep;11(9):1189-1199. doi: 10.1016/j.jchf.2023.02.003. Epub 2023 Mar 5.
Long-term data on cardiovascular disease (CVD) and mortality in female carriers of the transthyretin (TTR) V122I (pV142I) variant, one of the most common variants of hereditary transthyretin cardiac amyloidosis, are sparse and the effects of blood pressure, heart rate, body mass index, and physical activity on CVD outcomes remain largely unknown.
The aim was to first examine the relationship of TTR V122I (pV142I) carrier status with CVD and mortality and second to investigate the effects of blood pressure, heart rate, body mass index, and physical activity in a large cohort of postmenopausal women.
The study population consisted of 9,862 non-Hispanic Black/African American women, 9,529 noncarriers and 333 TTR V122I carriers, enrolled in the Women's Health Initiative at 40 centers in the United States. Women were generally healthy and postmenopausal at the time of enrollment (1993-1998). CVD was defined as a composite endpoint consisting of coronary heart disease, stroke, acute heart failure or CVD death, and all-cause mortality. CVD cases were based on self-reported annual mailed health updates. All information was centrally adjudicated by trained physicians. HRs and 95% CIs were obtained from adjusted Cox proportional hazards models.
Among 9,862 Black female participants (mean age: 62 years [IQR: 56-67 years]), the population frequency of the TTR V122I variant was 3.4% (333 variant carriers and 9,529 noncarriers). During a mean follow-up of 16.1 years (IQR: 9.7-22.2 years), incident CVD occurred in 2,229 noncarriers and 96 carriers, whereas 2,689 noncarriers and 108 carriers died. In adjusted models including demographic, lifestyle, and medical history covariates, TTR V122I carriers were at higher risk of the composite endpoint CVD (HR: 1.52; 95% CI: 1.22-1.88), acute heart failure (HR: 2.21; 95% CI: 1.53-3.18), coronary heart disease (HR: 1.80; 95% CI: 1.30-2.47), CVD death (HR: 1.70; 95% CI: 1.26-2.30), and all-cause mortality (HR: 1.28; 95% CI: 1.04-1.56). The authors found a significant interaction by age but not by blood pressure, heart rate, body mass index, or physical activity.
Black female TTR V122I (pV142I) carriers have a higher CVD and all-cause mortality risk compared to noncarriers. In case of clinical suspicion of amyloidosis, they should be screened for TTR V122I (pV142I) carrier status to ensure early treatment onset.
载脂蛋白 Transthyretin（TTR）V122I（pV142I）变异体（遗传性转甲状腺素蛋白心脏淀粉样变最常见的变异体之一）的女性患者发生心血管疾病（CVD）和死亡的长期数据很少，血压、心率、体重指数和体力活动对 CVD 结局的影响在很大程度上仍不清楚。
首先研究 TTR V122I（pV142I）携带者状态与 CVD 和死亡率的关系，其次在一个大型绝经后妇女队列中研究血压、心率、体重指数和体力活动的影响。
研究人群由 9862 名非西班牙裔黑人和/或非洲裔美国女性组成，9529 名非携带者和 333 名 TTR V122I 携带者，在美国 40 个中心参加妇女健康倡议。这些女性在入组时通常健康且处于绝经后状态（1993-1998 年）。CVD 定义为复合终点，包括冠心病、中风、急性心力衰竭或 CVD 死亡和全因死亡率。CVD 病例基于每年邮寄的健康更新报告。所有信息均由经过培训的医生进行集中审查。风险比（HR）和 95%置信区间（CI）通过调整后的 Cox 比例风险模型获得。
在 9862 名黑人女性参与者（平均年龄：62 岁[IQR：56-67 岁]）中，TTR V122I 变异体的人群频率为 3.4%（333 名变异体携带者和 9529 名非携带者）。在平均 16.1 年（IQR：9.7-22.2 年）的随访期间，9529 名非携带者中有 2229 名和 333 名携带者发生了 CVD，而 2689 名非携带者中有 2689 名和 108 名携带者死亡。在包括人口统计学、生活方式和病史协变量的调整模型中，TTR V122I 携带者发生复合 CVD 终点（HR：1.52；95%CI：1.22-1.88）、急性心力衰竭（HR：2.21；95%CI：1.53-3.18）、冠心病（HR：1.80；95%CI：1.30-2.47）、CVD 死亡（HR：1.70；95%CI：1.26-2.30）和全因死亡率（HR：1.28；95%CI：1.04-1.56）的风险更高。作者发现年龄存在显著的交互作用，但血压、心率、体重指数或体力活动没有显著的交互作用。
与非携带者相比，TTR V122I（pV142I）变异体的黑人女性患 CVD 和全因死亡率的风险更高。如果临床怀疑淀粉样变性，应筛查 TTR V122I（pV142I）携带者状态，以确保早期开始治疗。
