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中年及老年双胞胎静息心率的遗传度及其与死亡率的关联

Heritability of resting heart rate and association with mortality in middle-aged and elderly twins.

作者信息

Jensen Magnus T, Wod Mette, Galatius Søren, Hjelmborg Jacob B, Jensen Gorm B, Christensen Kaare

机构信息

Department of Cardiology, Rigshospitalet, Copenhagen, Denmark.

The Danish Twin Registry, Department of Public Health, University of Southern Denmark, Odense, Denmark.

出版信息

Heart. 2018 Jan;104(1):30-36. doi: 10.1136/heartjnl-2016-310986. Epub 2017 Jun 21.

Abstract

OBJECTIVE

Resting heart rate (RHR) possibly has a hereditary component and is associated with longevity. We used the classical biometric twin study design to investigate the heritability of RHR in a population of middle-aged and elderly twins and, furthermore, studied the association between RHR and mortality.

METHODS

In total, 4282 twins without cardiovascular disease were included from the Danish Twin Registry, hereof 1233 twin pairs and 1816 'single twins' (twins with a non-participating co-twin); mean age 61.7 (SD 11.1) years; 1334 (31.2%) twins died during median 16.3 (IQR 13.8-16.5) years of follow-up assessed through Danish national registers. RHR was assessed by palpating radial pulse.

RESULTS

Within pair correlations for RHR adjusted for sex and age were 0.23 (95% CI 0.14 to 0.32) and 0.10 (0.03 to 0.17) for RHR in monozygotic (MZ) and dizygotic (DZ) twin pairs, respectively. Overall, heritability estimates were 0.23 (95% CI 0.15 to 0.30); 0.27 (0.15 to 0.38) for males and 0.17 (0.06 to 0.28) for females. In multivariable models adjusting for age, gender, body mass index, diabetes, hypertension, pulmonary function, smoking, physical activity and zygosity, RHR was significantly associated with mortality (eg, RHR >90 vs 61-70 beats per min: all-cause HR 1.56 (95% CI 1.21 to 2.03); cardiovascular 2.19 (1.30 to 3.67). Intrapair twin comparison revealed that the twin with the higher RHR was significantly more likely to die first and the probability increased with increase in intrapair difference in RHR.

CONCLUSIONS

RHR is a trait with a genetic influence in middle-aged and elderly twins free of cardiovascular disease. RHR is independently associated with longevity even when familial factors are controlled for in a twin design.

摘要

目的

静息心率(RHR)可能具有遗传成分,且与长寿相关。我们采用经典的双生子生物统计学研究设计,调查中年及老年双生子群体中RHR的遗传度,并进一步研究RHR与死亡率之间的关联。

方法

从丹麦双生子登记处纳入4282名无心血管疾病的双生子,其中包括1233对双生子和1816名“单卵双生子”(其同胞双生子未参与研究);平均年龄61.7(标准差11.1)岁;通过丹麦国家登记处评估,在中位随访16.3(四分位间距13.8 - 16.5)年期间,1334名(31.2%)双生子死亡。通过触诊桡动脉评估RHR。

结果

经性别和年龄调整后,同卵(MZ)双生子对RHR的组内相关系数为0.23(95%置信区间0.14至0.32),异卵(DZ)双生子对RHR的组内相关系数为0.10(0.03至0.17)。总体而言,遗传度估计值为0.23(95%置信区间0.15至0.30);男性为0.27(0.15至0.38),女性为0.17(0.06至0.28)。在调整年龄、性别、体重指数、糖尿病、高血压、肺功能、吸烟、身体活动和双生子类型的多变量模型中,RHR与死亡率显著相关(例如,RHR>90次/分钟与61 - 70次/分钟相比:全因风险比1.56(95%置信区间1.21至2.03);心血管疾病风险比2.19(1.30至3.67)。双生子对内部比较显示,RHR较高的双生子先死亡的可能性显著更高,且随着双生子对内部RHR差异的增加,这种可能性增大。

结论

在无心血管疾病的中年及老年双生子中,RHR是一种受遗传影响的性状。即使在双生子设计中控制了家族因素,RHR仍与长寿独立相关。

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