Relationship between follow-up systolic blood pressure variability and the risk of all-cause mortality in Chinese elderly: a retrospective cohort study
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摘要:
目的 探讨中国老年人随诊间收缩压变异性(systolic blood pressure variability, SBPV)和全因死亡风险的关系。 方法 基于2008―2018年中国纵向健康长寿调查(Chinese longitudinal healthy longevity survey, CLHLS)的跟踪数据集，选取≥65岁、有连续3次收缩压(systolic blood pressure, SBP)记录且随访至2018年的老年人作为研究对象。采用Cox比例风险回归模型分析老年人随诊间SBPV与全因死亡风险的关系; 按性别、年龄亚组分析以评估随诊间SBPV的交互作用; 最后，在模型中加入限制性立方样条(restricted cubic spline, RCS)探究两者的剂量-反应关系。 结果 (1)共纳入2 582名老年人，平均年龄为78(71，86)岁，其中男性1 253人(48.5%)。在平均3.29年的随访期间，共有739例(28.6%)老年人死亡; (2)校正相关混杂因素后，随诊间SBPV与全因死亡风险之间呈正相关，差异有统计学意义(P ＜ 0.05);(3)亚组分析显示: 性别、年龄对不同随诊间SBPV水平与全因死亡风险的关联未发现效应修饰作用(P交互作用≥0.100);(4)RCS结果显示，随诊间SBPV与全因死亡风险之间的剂量-反应关系在男性和女性中一致，全因死亡风险随随诊间SBPV增大而线性升高(P总趋势SBPV ＜ 0.001, P非线性SBPV>0.05)。在不同年龄分组中，＜70岁组的随诊间SBPV与全因死亡风险呈正线性关系，而其余年龄组两者均无剂量-反应关系(年龄 ＜ 70岁组: P总趋势SBPV ＜ 0.001, P非线性SBPV>0.05; 其余年龄组: P总趋势SBPV>0.05, P非线性SBPV>0.05)。 结论 中国老年人随诊间SBPV与全因死亡风险相关，其独立于随访期间平均SBP。除了检测老年人群的SBP外，还应关注其就诊以来SBP的波动情况。 Abstract:Objective To investigate the relationship between follow-up systolic blood pressure variability (SBPV) and the risk of all-cause mortality in older adults across China. Methods Based on the follow-up dataset of the 2008-2018 China longitudinal healthy longevity survey (CLHLS), older adults aged 65 years or older with three consecutive times of recorded systolic blood pressure (SBP) and followed up until 2018 were selected as study subjects. A Cox regression analysis model was used to analyze the relationship between follow-up SBPV and all-cause mortality in older adults; analyses were conducted by gender and age subgroups to assess the interaction of follow-up SBPV; and finally, restricted cubic spline (RCS) was added to the model to explore the dose-response relationship between the two. Results (1) A total of 2 582 older adults were enrolled, including 1 253 (48.5%) males with a median age of 78 (71, 86) years. A total of 739 (28.6%) older adults died during a mean follow-up period of 3.29 years. (2) After correcting for relevant confounders, there was a significant positive association between follow-up SBPV and the risk of all-cause mortality (P ＜ 0.05). (3) Subgroup analyses showed no effect modification of gender and age on the association between different follow-up SBPV levels and the risk of all-cause mortality (Pinteraction≥0.100). (4) Restricted cubic spline results showed that the dose-response relationship between follow-up SBPV and the risk of all-cause mortality was consistent in both gender, with the risk of all-cause mortality increasing linearly with increasing follow-up SBPV. (Poverall SBPV ＜ 0.001, Pnon-linearity SBPV>0.05). Among the different age subgroups, follow-up SBPV was positively and linearly associated with the risk of all-cause mortality among those aged ＜ 70 years, while there was no dose-response relationship between the two in the remaining age subgroups (＜ 70 years old: Poverall SBPV ＜ 0.001, Pnon-linearity SBPV>0.05; remaining age groups: Poverall SBPV>0.05, Pnon-linearity SBPV>0.05). Conclusions Follow-up SBPV was significantly associated with the risk of all-cause mortality in the elderly in China, which was independent of mean follow-up systolic blood pressure. In addition to detecting systolic blood pressure in the elderly population, attention should be paid to fluctuations in systolic blood pressure since the long-term visit. -
图 2 随诊间SBPV(SD、CV、VIM)与全因死亡风险的亚组分析结果
HR：风险比；SD：标准差；CV：变异系数；VIM：独立于均值的变异系数；SBP：收缩压；SBPV：收缩压变异性。
Figure 2. Subgroup analysis results of follow-up SBPV (SD, CV, VIM) and all-cause mortality risk
HR: hazard ratio; SD: standard deviation; CV: coefficient of variation; VIM: coefficient of variation independent of the mean; SBP: systolic blood pressure; SBPV: systolic blood pressure variability.
图 3 老年人群随诊间SBPV(SD、CV、VIM)与全因死亡风险的剂量-反应关系
HR：风险比；SD：标准差；CV：变异系数；VIM：独立于均值的变异系数；SBP：收缩压。
Figure 3. Dose-response relationship between follow-up SBPV (SD, CV, VIM) and all-cause death risk in the elderly population
HR: hazard ratio; SD: standard deviation; CV: coefficient of variation; VIM: coefficient of variation independent of the mean; SBP: systolic blood pressure.
图 4 男性老年人群随诊间SBPV(SD、CV、VIM)与全因死亡风险的剂量-反应关系
HR：风险比；SD：标准差；CV：变异系数；VIM：独立于均值的变异系数；SBP：收缩压。
Figure 4. Dose-response relationship between follow-up SBPV (SD, CV, VIM) and all-cause death risk in male elderly population
HR: hazard ratio; SD: standard deviation; CV: coefficient of variation; VIM: coefficient of variation independent of the mean; SBP: systolic blood pressure.
图 5 女性老年人群随诊间SBPV(SD、CV、VIM)与全因死亡风险的剂量-反应关系
HR：风险比；SD：标准差；CV：变异系数；VIM：独立于均值的变异系数；SBP：收缩压。
Figure 5. Dose-response relationship between follow-up SBPV (SD, CV, VIM) and all-cause death risk in female elderly population
HR: hazard ratio; SD: standard deviation; CV: coefficient of variation; VIM: coefficient of variation independent of the mean; SBP: systolic blood pressure.
图 6 ＜ 70岁老年人群随诊间SBPV(SD、CV、VIM)与全因死亡风险的剂量-反应关系
HR：风险比；SD：标准差；CV：变异系数；VIM：独立于均值的变异系数；SBP：收缩压。
Figure 6. Dose-response relationship between follow-up SBPV (SD, CV, VIM) and risk of all-cause death in elderly people ＜ 70 years old
HR: hazard ratio; SD: standard deviation; CV: coefficient of variation; VIM: coefficient of variation independent of the mean; SBP: systolic blood pressure.
图 7 70~＜80岁老年人群随诊间SBPV(SD、CV、VIM)与全因死亡风险的剂量-反应关系
HR：风险比；SD：标准差；CV：变异系数；VIM：独立于均值的变异系数；SBP：收缩压。
Figure 7. Dose-response relationship between follow-up SBPV (SD, CV, VIM) and risk of all-cause death in the elderly aged 70- ＜ 80
HR: hazard ratio; SD: standard deviation; CV: coefficient of variation; VIM: coefficient of variation independent of the mean; SBP: systolic blood pressure.
图 8 ≥80岁老年人群随诊间SBPV(SD、CV、VIM)与全因死亡风险的剂量-反应关系
HR：风险比；SD：标准差；CV：变异系数；VIM：独立于均值的变异系数；SBP：收缩压。
Figure 8. Dose-response relationship between follow-up SBPV (SD, CV, VIM) and risk of all-cause death in the elderly aged 80 years and above
HR: hazard ratio; SD: standard deviation; CV: coefficient of variation; VIM: coefficient of variation independent of the mean; SBP: systolic blood pressure.
表 1 2 582名老年人口的基线特征
Table 1. Baseline characteristics of the 2 582 elderly population
变量Variable 合计 ① Total ① (n=2 582) 死亡组 ① Death group ① (n=739) 存活组 ① Survival group ① (n=1 843) Z/$ \chi^2$值value P值value 性别Gender 1.019 0.313 男性Male 1 253(48.5) 371(50.2) 883(47.9) 女性Female 1 329(51.5) 368(49.8) 960(52.1) 年龄/岁Age/years 78(71, 86) 86(78, 92) 74(70, 82) -19.784 ＜ 0.001 吸烟史History of smoking 4.965×10-29 0.989 从不吸烟Never smoke 1 996(77.3) 572(77.4) 1 425(77.3) 曾经或至今吸烟Ever smoked or still smoked 586(22.7) 167(22.6) 418(22.7) 饮酒史History of alcohol consumption 0.043 0.836 从不饮酒Never drink alcohol 1 995(77.3) 566(76.6) 1 428(77.5) 曾经或至今饮酒Previous or current alcohol consumption 587(22.7) 173(23.4) 415(22.5) BMI/(kg·m-2) 20.3(18.3, 22.6) 19.8(17.8, 21.8) 20.5(18.6, 22.9) 6.014 ＜ 0.001 基线SBP /mmHg Baseline SBP/mmHg 125.0(117.5, 131.5) 125.0(117.5, 131.5) 125.0(117.5, 131.5) 0.617 0.537 糖尿病Diabetes 57(2.2) 12(1.6) 44(2.4) 1.112 0.292 高血压Hypertensive 258(10.0) 55(7.4) 171(9.3) 2.002 0.157 SBP随访均值/mmHg SBP follow-up mean value/mmHg 130.7(123.7, 138.3) 131.2(123.2, 139.0) 130.5(123.8, 138.1) -0.564 0.572 SBP首末差值/mmHg SBP first and last differences/mmHg -11(-26, 1) -11(-26, 3) -11(-26, 0) -0.900 0.368 SBP-SD/mmHg 12.8(7.7, 19.3) 13.7(8.6, 20.0) 12.4(7.5, 19.0) -3.060 0.002 SBP-CV 9.9(6.1, 14.6) 10.4(6.8, 15.6) 9.6(5.9, 14.3) -3.236 0.001 SBP-VIM 13.0(5.9, 14.3) 13.5(9.1, 19.8) 12.7(7.9, 18.5) -3.291 ＜ 0.001 注：SD，标准差；CV，变异系数；VIM，独立于均值的变异系数；SBP，收缩压；SBPV，收缩压变异性。
①以人数(占比/%)或M(P25, P75)表示。Note: SD, standard deviation; CV, coefficient of variation; VIM, coefficient of variation independent of the mean; SBP, systolic blood pressure; SBPV, systolic blood pressure variability.
① Number of people (proportion/%) or M(P25, P75).
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表 2 老年人群随诊间SBPV(SD、CV、VIM)与全因死亡风险的关联性分析结果
Table 2. Correlation analysis results of follow-up SBPV (SD, CV, VIM) and all-cause death risk in the elderly population
SBPV指标Indicators of variability 模型Model HR值value(95% CI) P值value SD(每增加一个单位的标准差) SD (Per 1 SD) 模型1 Model 1 1.194(1.102~1.295) ＜ 0.001 模型2 Model 2 1.094(1.008~1.184) 0.033 CV(每增加一个单位的标准差) CV (Per 1 SD) 模型1 Model 1 1.177(1.092~1.270) ＜ 0.001 模型2 Model 2 1.085(1.006~1.168) 0.041 VIM(每增加一个单位的标准差) VIM (Per 1 SD) 模型1 Model 1 1.167(1.086~1.255) ＜ 0.001 模型2 Model 2 1.076(1.008~1.156) 0.040 注：HR，风险比；SD，标准差；CV，变异系数；VIM，独立于均值的变异系数；SBPV, 收缩压变异性。
模型1，根据平均随访SBP和SBP首末差值进行调整；模型2，HR对模型1中的变量进行了调整，对性别、年龄、吸烟史、饮酒史、BMI和是否患有高血压、糖尿病进行了额外调整。
Note: HR, hazard ratio; SD, standard deviation; CV, coefficient of variation; VIM, coefficient of variation independent of the mean; SBPV, systolic blood pressure variability.
Model 1, adjusted for mean follow-up SBP and first-and last-differences in SBP; Model 2, HR adjusted for variables in model 1 with additional adjustments for gender, age, history of smoking, history of alcohol consumption, BMI, and presence of hypertension and diabetes.
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