Association of Blood Pressure Lowering With Mortality and Cardiovascular Disease Across Blood Pressure Levels: A Systematic Review and Meta-analysis

Abstract

Importance: High blood pressure (BP) is the most important risk factor for death and cardiovascular disease (CVD) worldwide. The optimal cutoff for treatment of high BP is debated.

Objective: To assess the association between BP lowering treatment and death and CVD at different BP levels.

Data sources: Previous systematic reviews were identified from PubMed, the Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effect. Reference lists of these reviews were searched for randomized clinical trials. Randomized clinical trials published after November 1, 2015, were also searched for in PubMed and the Cochrane Central Register for Controlled Trials during February 2017.

Study selection: Randomized clinical trials with at least 1000 patient-years of follow-up, comparing BP-lowering drugs vs placebo or different BP goals were included.

Data extraction and synthesis: Data were extracted from original publications. Risk of bias was assessed using the Cochrane Collaborations assessment tool. Relative risks (RRs) were pooled in random-effects meta-analyses with Knapp-Hartung modification. Results are reported according to PRISMA guidelines.

Main outcomes and measures: Prespecified outcomes of interest were all-cause mortality, cardiovascular mortality, major cardiovascular events, coronary heart disease (CHD), stroke, heart failure, and end-stage renal disease.

Results: Seventy-four unique trials, representing 306 273 unique participants (39.9% women and 60.1% men; mean age, 63.6 years) and 1.2 million person-years, were included in the meta-analyses. In primary prevention, the association of BP-lowering treatment with major cardiovascular events was dependent on baseline systolic BP (SBP). In trials with baseline SBP 160 mm Hg or above, treatment was associated with reduced risk for death (RR, 0.93; 95% CI, 0.87-1.00) and a substantial reduction of major cardiovascular events (RR, 0.78; 95% CI, 0.70-0.87). If baseline SBP ranged from 140 to 159 mm Hg, the association of treatment with mortality was similar (RR, 0.87; 95% CI, 0.75-1.00), but the association with major cardiovascular events was less pronounced (RR, 0.88; 95% CI, 0.80-0.96). In trials with baseline SBP below 140 mm Hg, treatment was not associated with mortality (RR, 0.98; 95% CI, 0.90-1.06) and major cardiovascular events (RR, 0.97; 95% CI, 0.90-1.04). In trials including people with previous CHD and mean baseline SBP of 138 mm Hg, treatment was associated with reduced risk for major cardiovascular events (RR, 0.90; 95% CI, 0.84-0.97), but was not associated with survival (RR, 0.98; 95% CI, 0.89-1.07).

Conclusions and relevance: Primary preventive BP lowering is associated with reduced risk for death and CVD if baseline SBP is 140 mm Hg or higher. At lower BP levels, treatment is not associated with any benefit in primary prevention but might offer additional protection in patients with CHD.

Figure 1.. Effect of Treatment to Lower Blood Pressure (BP) at Different BP Levels in Primary Prevention

RR indicates relative risk; SBP, systolic BP. Different size markers indicate weight. Studies included in the analyses are given in eTable 7 in the Supplement.

Figure 2.. Effect of Treatment to Lower Blood Pressure (BP) in Coronary Heart Disease Trials

CV indicates cardiovascular; MACE, major cardiovascular events; and RR, relative risk. The following trials were included in the analysis: Poole-Wilson et al,¹⁹ Nissen et al,²⁰ Fox and the EUROPA Investigators,²¹ Yusuf et al,²² Rouleau et al,⁸⁵ the MACB Study Group (all outcomes except coronary heart disease and heart failure),⁸⁶ Yusuf et al,²³ Braunwald et al (all outcomes except coronary heart disease),²⁴ Pitt et al (all outcomes except CV mortality),²⁵ Pitt et al (all outcomes except stroke and heart failure),⁸⁷ Teo et al (all outcomes except heart failure),²⁶ and Yusuf et al.²⁷

Figure 3.. Effect of Treatment to Lower Blood Pressure (BP) in Poststroke Trials

CV indicates cardiovascular; MACE, major cardiovascular events; and RR, relative risk. The following trials were included in all the analyses except for heart failure: the Dutch TIA Trial Study Group, Hypertension-Stroke Cooperative Study Group, Yusuf et al, MacMahon et al, Benavente et al, and Eriksson et al. The following trials were included in the heart failure analysis: Hypertension-Stroke Cooperative Study Group, Yusuf et al, and MacMahon et al.