The George Institute for Global Health, University of Oxford, Oxford, UK.
The George Institute for Global Health, University of Oxford, Oxford, UK; Institute of Cardiovascular Sciences, University of Manchester, Manchester, UK.
Lancet. 2016 Mar 5;387(10022):957-967. doi: 10.1016/S0140-6736(15)01225-8. Epub 2015 Dec 24.
The benefits of blood pressure lowering treatment for prevention of cardiovascular disease are well established. However, the extent to which these effects differ by baseline blood pressure, presence of comorbidities, or drug class is less clear. We therefore performed a systematic review and meta-analysis to clarify these differences.
For this systematic review and meta-analysis, we searched MEDLINE for large-scale blood pressure lowering trials, published between Jan 1, 1966, and July 7, 2015, and we searched the medical literature to identify trials up to Nov 9, 2015. All randomised controlled trials of blood pressure lowering treatment were eligible for inclusion if they included a minimum of 1000 patient-years of follow-up in each study arm. No trials were excluded because of presence of baseline comorbidities, and trials of antihypertensive drugs for indications other than hypertension were eligible. We extracted summary-level data about study characteristics and the outcomes of major cardiovascular disease events, coronary heart disease, stroke, heart failure, renal failure, and all-cause mortality. We used inverse variance weighted fixed-effects meta-analyses to pool the estimates.
We identified 123 studies with 613,815 participants for the tabular meta-analysis. Meta-regression analyses showed relative risk reductions proportional to the magnitude of the blood pressure reductions achieved. Every 10 mm Hg reduction in systolic blood pressure significantly reduced the risk of major cardiovascular disease events (relative risk [RR] 0·80, 95% CI 0·77-0·83), coronary heart disease (0·83, 0·78-0·88), stroke (0·73, 0·68-0·77), and heart failure (0·72, 0·67-0·78), which, in the populations studied, led to a significant 13% reduction in all-cause mortality (0·87, 0·84-0·91). However, the effect on renal failure was not significant (0·95, 0·84-1·07). Similar proportional risk reductions (per 10 mm Hg lower systolic blood pressure) were noted in trials with higher mean baseline systolic blood pressure and trials with lower mean baseline systolic blood pressure (all ptrend>0·05). There was no clear evidence that proportional risk reductions in major cardiovascular disease differed by baseline disease history, except for diabetes and chronic kidney disease, for which smaller, but significant, risk reductions were detected. β blockers were inferior to other drugs for the prevention of major cardiovascular disease events, stroke, and renal failure. Calcium channel blockers were superior to other drugs for the prevention of stroke. For the prevention of heart failure, calcium channel blockers were inferior and diuretics were superior to other drug classes. Risk of bias was judged to be low for 113 trials and unclear for 10 trials. Heterogeneity for outcomes was low to moderate; the I(2) statistic for heterogeneity for major cardiovascular disease events was 41%, for coronary heart disease 25%, for stroke 26%, for heart failure 37%, for renal failure 28%, and for all-cause mortality 35%.
Blood pressure lowering significantly reduces vascular risk across various baseline blood pressure levels and comorbidities. Our results provide strong support for lowering blood pressure to systolic blood pressures less than 130 mm Hg and providing blood pressure lowering treatment to individuals with a history of cardiovascular disease, coronary heart disease, stroke, diabetes, heart failure, and chronic kidney disease.
National Institute for Health Research and Oxford Martin School.
降低血压治疗预防心血管疾病的益处已得到充分证实。然而，这些效果在基线血压、合并症存在或药物类别方面的差异程度尚不清楚。因此，我们进行了系统评价和荟萃分析以澄清这些差异。
为了进行这项系统评价和荟萃分析，我们在 1966 年 1 月 1 日至 2015 年 7 月 7 日期间搜索了 MEDLINE 中的大规模降压试验，并搜索了医学文献以确定截至 2015 年 11 月 9 日的试验。如果每个研究臂的随访时间至少为 1000 患者年，则所有随机对照降压治疗试验都有资格入选。由于存在基线合并症而没有排除任何试验，并且有适应证以外的抗高血压药物的试验也符合入选条件。我们提取了关于研究特征和主要心血管疾病事件、冠心病、中风、心力衰竭、肾衰竭和全因死亡率等结局的汇总数据。我们使用逆方差加权固定效应荟萃分析来汇总估计值。
我们在表格荟萃分析中确定了 123 项研究，涉及 613815 名参与者。Meta 回归分析表明，相对风险降低与实现的血压降低幅度成正比。收缩压每降低 10mmHg，主要心血管疾病事件的风险显著降低（相对风险[RR]0·80，95%CI 0·77-0·83）、冠心病（0·83，0·78-0·88）、中风（0·73，0·68-0·77）和心力衰竭（0·72，0·67-0·78），在研究人群中，全因死亡率显著降低 13%（0·87，0·84-0·91）。然而，对肾衰竭的影响并不显著（0·95，0·84-1·07）。在基线收缩压较高和基线收缩压较低的试验中，都观察到了类似的比例风险降低（每降低 10mmHg 收缩压）（所有 ptrend>0·05）。除糖尿病和慢性肾脏病外，没有明确证据表明主要心血管疾病事件的比例风险降低与基线疾病史有关，对于这些疾病，虽然风险降低幅度较小，但仍有显著意义。β受体阻滞剂在预防主要心血管疾病事件、中风和肾衰竭方面不如其他药物。钙通道阻滞剂在预防中风方面优于其他药物。在预防心力衰竭方面，钙通道阻滞剂不如利尿剂，而利尿剂优于其他药物类别。113 项试验的偏倚风险被判断为低，10 项试验的偏倚风险为不确定。结果的异质性为低至中度；主要心血管疾病事件的异质性 I（2）统计量为 41%，冠心病为 25%，中风为 26%，心力衰竭为 37%，肾衰竭为 28%，全因死亡率为 35%。
降低血压可显著降低各种基线血压水平和合并症的血管风险。我们的研究结果为将血压降低至收缩压<130mmHg，并为有心血管疾病、冠心病、中风、糖尿病、心力衰竭和慢性肾脏病病史的个体提供降压治疗提供了强有力的支持。
英国国家健康研究所和牛津马丁学院。
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