Ravindrarajah Rathi, Hazra Nisha C, Hamada Shota, Charlton Judith, Jackson Stephen H D, Dregan Alex, Gulliford Martin C
From Department of Primary Care and Public Health Sciences (R.R., N.C.H., S.H., J.C., A.D., M.C.G.), Department of Clinical Gerontology (J.C., S.H.D.J.), King's College London, UK; Research Department, Institute for Health Economics and Policy, Association for Health Economics Research and Social Insurance and Welfare, Tokyo, Japan (S.H.); and National Institute for Health Research Biomedical Research Centre at Guy's and St Thomas' National Health Service Foundation Trust, London, UK (A.D., M.C.G.).
Circulation. 2017 Jun 13;135(24):2357-2368. doi: 10.1161/CIRCULATIONAHA.116.026687. Epub 2017 Apr 21.
Clinical trials show benefit from lowering systolic blood pressure (SBP) in people ≥80 years of age, but nonrandomized epidemiological studies suggest lower SBP may be associated with higher mortality. This study aimed to evaluate associations of SBP with all-cause mortality by frailty category >80 years of age and to evaluate SBP trajectories before death.
A population-based cohort study was conducted using electronic health records of 144 403 participants ≥80 years of age registered with family practices in the United Kingdom from 2001 to 2014. Participants were followed for ≤5 years. Clinical records of SBP were analyzed. Frailty status was classified using the e-Frailty Index into the categories of fit, mild, moderate, and severe. All-cause mortality was evaluated by frailty status and mean SBP in Cox proportional-hazards models. SBP trajectories were evaluated using person months as observations, with mean SBP and antihypertensive treatment status estimated for each person month. Fractional polynomial models were used to estimate SBP trajectories over 5 years before death.
During follow-up, 51 808 deaths occurred. Mortality rates increased with frailty level and were greatest at SBP <110 mm Hg. In fit women, mortality was 7.7 per 100 person years at SBP 120 to 139 mm Hg, 15.2 at SBP 110 to 119 mm Hg, and 22.7 at SBP <110 mm Hg. For women with severe frailty, rates were 16.8, 25.2, and 39.6, respectively. SBP trajectories showed an accelerated decline in the last 2 years of life. The relative odds of SBP <120 mm Hg were higher in the last 3 months of life than 5 years previously in both treated (odds ratio, 6.06; 95% confidence interval, 5.40-6.81) and untreated (odds ratio, 6.31; 95% confidence interval, 5.30-7.52) patients. There was no evidence of intensification of antihypertensive therapy in the final 2 years of life.
A terminal decline of SBP in the final 2 years of life suggests that nonrandomized epidemiological associations of low SBP with higher mortality may be accounted for by reverse causation if participants with lower blood pressure values are closer, on average, to the end of life.
临床试验表明，降低80岁及以上人群的收缩压（SBP）有益，但非随机流行病学研究表明，较低的SBP可能与较高的死亡率相关。本研究旨在评估80岁以上不同衰弱类别中SBP与全因死亡率的关联，并评估死亡前的SBP轨迹。
采用基于人群的队列研究，使用2001年至2014年在英国家庭医生处登记的144403名80岁及以上参与者的电子健康记录。对参与者随访≤5年。分析SBP的临床记录。使用电子衰弱指数将衰弱状态分为健康、轻度、中度和重度。在Cox比例风险模型中，按衰弱状态和平均SBP评估全因死亡率。以人月为观察单位评估SBP轨迹，估计每个月的平均SBP和抗高血压治疗状态。采用分数多项式模型估计死亡前5年的SBP轨迹。
随访期间，发生51808例死亡。死亡率随衰弱程度增加而升高，在SBP<110 mmHg时最高。在健康女性中，SBP为120至139 mmHg时，死亡率为每100人年7.7例；SBP为110至119 mmHg时，死亡率为15.2例；SBP<110 mmHg时，死亡率为22.7例。对于严重衰弱的女性，相应的死亡率分别为16.8例、25.2例和39.6例。SBP轨迹显示在生命的最后2年加速下降。在生命的最后3个月，SBP<120 mmHg的相对比值在接受治疗（比值比，6.06；95%置信区间，5.40 - 6.81）和未接受治疗（比值比，6.31；95%置信区间，5.30 - 7.52）的患者中均高于5年前。在生命的最后2年，没有证据表明抗高血压治疗强度增加。
生命最后2年SBP的终末下降表明，如果平均而言，血压值较低的参与者更接近生命终点，那么低SBP与较高死亡率之间的非随机流行病学关联可能是由反向因果关系导致的。
