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

Educational Objective
To assess the association between blood pressure–lowering treatment and death and cardiovascular disease at different blood pressure levels.
1 Credit CME
Key Points

Question  What is the association between treatment to lower blood pressure and death and cardiovascular disease at different blood pressure levels?

Findings  In this systematic review and meta-analysis, including 74 trials and more than 300 000 patients, treatment to lower blood pressure was associated with a reduced risk for death and cardiovascular disease if baseline systolic blood pressure was 140 mm Hg or above. Below 140 mm Hg, the treatment effect was neutral in primary preventive trials, but with possible benefit on nonfatal cardiovascular events in trials of patients with coronary heart disease.

Meaning  Systolic blood pressure of 140 mm Hg or higher should be treated to prevent death and cardiovascular disease, whereas treatment may be considered in patients with coronary heart disease and systolic blood pressure below 140 mm Hg, but not for primary prevention.


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.

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Article Information

Corresponding Author: Mattias Brunström, MD, Department Public Health and Clinical Medicine, Umeå University, Mail Code 901 87- SE, Umeå, Sweden (mattias.brunstrom@umu.se).

Accepted for Publication: August 31, 2017.

Correction: This article was corrected on January 2, 2018, to include links to an Invited Commentary.

Published Online: November 13, 2017. doi:10.1001/jamainternmed.2017.6015

Authors Contributions: Both authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis

Study concept and design: Both authors.

Acquisition, analysis, or interpretation of data: Both authors.

Drafting of the manuscript: Both authors.

Critical revision of the manuscript for important intellectual content: Both authors.

Statistical analysis: Both authors.

Obtained funding: Both authors.

Study supervision: Carlberg.

Conflict of Interest Disclosures: None reported.

Funding/Support: This study was supported by the Avtal om Läkarutbildning och medicinsk Forskning (ALF) agreement (for medical education and research) from Västerbotten County Council; by Visare Norr, an industry-independent fund supporting regional collaboration between County Councils in Northern Sweden; and by Norrländska Hjärtfonden.

Role of the Funder/Sponsor: The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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