Systolic Blood Pressure Reduction and Risk of Cardiovascular Disease and Mortality: A Systematic Review and Network Meta-analysis
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Importance: Clinical trials have documented that lowering blood pressure reduces cardiovascular disease and premature deaths. However, the optimal target for reduction of systolic blood pressure (SBP) is uncertain. Objective: To assess the association of mean achieved SBP levels with the risk of cardiovascular disease and all-cause mortality in adults with hypertension treated with antihypertensive therapy. Data Sources: MEDLINE and EMBASE were searched from inception to December 15, 2015, supplemented by manual searches of the bibliographies of retrieved articles. Study Selection: Studies included were clinical trials with random allocation to an antihypertensive medication, control, or treatment target. Studies had to have reported a difference in mean achieved SBP of 5 mm Hg or more between comparison groups. Data Extraction and Synthesis: Data were extracted from each study independently and in duplicate by at least 2 investigators according to a standardized protocol. Network meta-analysis was used to obtain pooled randomized results comparing the association of each 5-mm Hg SBP category with clinical outcomes after adjusting for baseline risk. Main Outcomes and Measures: Cardiovascular disease and all-cause mortality. Results: Forty-two trials, including 144 220 patients, met the eligibility criteria. In general, there were linear associations between mean achieved SBP and risk of cardiovascular disease and mortality, with the lowest risk at 120 to 124 mm Hg. Randomized groups with a mean achieved SBP of 120 to 124 mm Hg had a hazard ratio (HR) for major cardiovascular disease of 0.71 (95% CI, 0.60-0.83) compared with randomized groups with a mean achieved SBP of 130 to 134 mm Hg, an HR of 0.58 (95% CI, 0.48-0.72) compared with those with a mean achieved SBP of 140 to 144 mm Hg, an HR of 0.46 (95% CI, 0.34-0.63) compared with those with a mean achieved SBP of 150 to 154 mm Hg, and an HR of 0.36 (95% CI, 0.26-0.51) compared with those with a mean achieved SBP of 160 mm Hg or more. Likewise, randomized groups with a mean achieved SBP of 120 to 124 mm Hg had an HR for all-cause mortality of 0.73 (95% CI, 0.58-0.93) compared with randomized groups with a mean achieved SBP of 130 to 134 mm Hg, an HR of 0.59 (95% CI, 0.45-0.77) compared with those with a mean achieved SBP of 140 to 144 mm Hg, an HR of 0.51 (95% CI, 0.36-0.71) compared with those with a mean achieved SBP of 150 to 154 mm Hg, and an HR of 0.47 (95% CI, 0.32-0.67) compared with those with a mean achieved SBP of 160 mm Hg or more. Conclusions and Relevance: This study suggests that reducing SBP to levels below currently recommended targets significantly reduces the risk of cardiovascular disease and all-cause mortality. These findings support more intensive control of SBP among adults with hypertension.
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Lowering blood pressure substantially reduces cardiovascular disease risk.
“and lowering BP substantially reduces that risk.5–7”
From International Consensus on Standardized Clinic Blood Pressure Measurement – A Call to Action (2023) · cites this paper as [6]
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“A network meta-analysis of randomized clinical trials reported positive linear relationships between mean achieved systolic BP and risk of CVD and all-cause mortality; lowest risks were observed among those with achieved systolic BP of 120 to 124 mm Hg.8 The 2017 American College of Cardiology/American Heart Associati…”
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Self-citationHypertension management in patients with cardiovascular comorbidities
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Hypertension as a risk factor for atherosclerosis: Cardiovascular risk assessment
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The global burden of hypertension exceeds 1.4 billion people
Egan, B. M., Kjeldsen, S. E., Grassi, G. M., Esler, M., & Mancia, G. (2019) · Journal of Hypertension · doi:10.1097/hjh.0000000000002021 · Cited by 197 · see citing works
“Among adults who were treated and controlled, the mean SBP was approximately 121, which is within the optimal range of 120–124 [11].”
BackgroundKhera, R., Lu, Y., Lu, J., Saxena, A., Nasir, K., Jiang, L., & Krumholz, H. M. (2018) · BMJ · doi:10.1136/bmj.k2357 · Cited by 195 · see citing works
Guideline-Driven Management of Hypertension: An Evidence-Based Update
Carey, R., Wright, J. T., Taler, S., & Whelton, P. (2021) · Circulation Research · doi:10.1161/circresaha.121.318083 · Cited by 146 · see citing works
Self-citationBlood Pressure Control Among US Adults, 2009 to 2012 Through 2017 to 2020
Muntner, P., Miles, M. A., Jaeger, B. C., Hannon, L., Hardy, S. T., Ostchega, Y., Wozniak, G. D., & Schwartz, J. E. (2022) · Hypertension · doi:10.1161/hypertensionaha.122.19222 · Cited by 186 · see citing works
“Three goals were outlined in the Call-to-Action: (1) making hypertension a national priority; (2) ensuring the places where people live, learn, work, and play support hypertension control; and (3) optimizing patient care for hypertension control.”
BackgroundBarbato, E., Azizi, M., Schmieder, R. E., Lauder, L., Böhm, M., Brouwers, S., Bruno, R. M., Dudek, D., Kahan, T., Kandzari, D. E., et al. (2023) · European Heart Journal · doi:10.1093/eurheartj/ehad054 · Cited by 188 · see citing works
“Lowering BP through the use of antihypertensive drugs has been shown to reduce the risk for CV morbidity and all-cause mortality 3,4 .”
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Effect of Exercise Training on Ambulatory Blood Pressure Among Patients With Resistant Hypertension
Lopes, S., Bastos, J. M., Garcia, C., Bertoquini, S., Ribau, V., Teixeira, M., Ribeiro, I. P., Melo, J. B., de Oliveira, J. J. F., de Figueiredo, D. M. P., et al. (2021) · JAMA Cardiology · doi:10.1001/jamacardio.2021.2735 · Cited by 132 · see citing works
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“Development of obesity increases the likelihood of hypertension in childhood leading to future hypertension [45].”
BackgroundRecent Advances in the Management of Autosomal Dominant Polycystic Kidney Disease
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“Recent meta-analyses of clinical trials have supported the SPRINT results (14,15).”
ResultScreening for Hypertension in Adults
Guirguis‐Blake, J., Evans, C. V., Webber, E. M., Coppola, E. L., Perdue, L. A., & Weyrich, M. S. (2021) · JAMA · doi:10.1001/jama.2020.21669 · Cited by 129 · see citing works
Beddhu, S., Chertow, G. M., Greene, T., Whelton, P. K., Ambrosius, W. T., Cheung, A. K., Cutler, J. A., Fine, L. J., Boucher, R. E., Wei, G., et al. (2018) · Journal of the American Heart Association · doi:10.1161/jaha.118.009326 · Cited by 117 · see citing works
Self-citationMorris, N. B., Jay, O., Flouris, A. D., Casanueva, A., Gao, C., Foster, J., Havenith, G., & Nybo, L. (2020) · Environmental Health · doi:10.1186/s12940-020-00641-7 · Cited by 121 · see citing works
Effects of elevated systolic blood pressure on ischemic heart disease: a Burden of Proof study
Razo, C., Welgan, C. A., Johnson, C. O., McLaughlin, S. A., Iannucci, V. C., Rodgers, A., Wang, N., LeGrand, K. E., Sorensen, R. J. D., He, J., et al. (2022) · Nature Medicine · doi:10.1038/s41591-022-01974-1 · Cited by 110 · see citing works
Self-citationThe Effect of Alcohol on Blood Pressure and Hypertension
Fuchs, F. D., & Fuchs, S. C. P. C. (2021) · Current Hypertension Reports · doi:10.1007/s11906-021-01160-7 · Cited by 108 · see citing works
Bundy, J. D., Mills, K. T., Chen, J., Li, C., Greenland, P., & He, J. (2018) · JAMA Cardiology · doi:10.1001/jamacardio.2018.1240 · Cited by 106 · see citing works
Self-citationCasey, D. E., Thomas, R. J., Bhalla, V., Commodore-Mensah, Y. Y., Heidenreich, P. A., Kolte, D. S., Muntner, P., Smith, S. C., Spertus, J. A., Windle, J. R., et al. (2019) · Circulation Cardiovascular Quality and Outcomes · doi:10.1161/hcq.0000000000000057 · Cited by 100 · see citing works
Cluett, J., Blazek, O., Brown, A. L., East, C. A., Ferdinand, K. C., Fisher, N. D. L., Ford, C. D., Griffin, K. A., Mena‐Hurtado, C., Sarathy, H., et al. (2024) · Hypertension · doi:10.1161/hyp.0000000000000240 · Cited by 105 · see citing works
“65,66 With RDN, office and ambulatory SBP decreases of 5 to 10 mm Hg are often achieved and thus could be expected to have a similar risk reduction, 67,68 but further research in this area is needed.”
Bielinis, E., Bielinis, L., Krupińska-Szeluga, S., Łukowski, A., & Takayama, N. (2019) · Forests · doi:10.3390/f10010034 · Cited by 100 · see citing works
“Higher SBP is linked with cardiovascular disease and mortality, making every method that effectively lowers SBP valuable to overall human health [49].”
BackgroundJahrami, H., Faris, M. E., Janahi, A. I., Janahi, M. I., Abdelrahim, D. N., Madkour, M. I., Sater, M. S., Hassan, A. B., & Bahammam, A. S. (2021) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2021.05.002 · Cited by 96 · see citing works
A major mechanism for immunomodulation: Dietary fibres and acid metabolites
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Colantonio, L. D., Booth, J., Bress, A., Whelton, P., Shimbo, D., Levitan, E., Howard, G., Safford, M., & Muntner, P. (2018) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.05.074 · Cited by 81 · see citing works
Self-citationEpidemiology of hypertension in Japan: beyond the new 2019 Japanese guidelines
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JCS 2018 Guideline on Diagnosis of Chronic Coronary Heart Diseases
Yamagishi, M., Tamaki, N., Akasaka, T., Ikeda, T., Ueshima, K., Uemura, S., Otsuji, Y., Kihara, Y., Kimura, K., Kimura, T., et al. (2021) · Circulation Journal · doi:10.1253/circj.cj-19-1131 · Cited by 99 · see citing works
International Consensus on Standardized Clinic Blood Pressure Measurement – A Call to Action
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“the American College of Cardiology and the American Heart Association (ACC/AHA) guidelines [2,43].”
BackgroundAkinyelure, O. P., Jaeger, B. C., Oparil, S., Carson, A. P., Safford, M. M., Howard, G., Muntner, P., & Hardy, S. T. (2023) · Hypertension · doi:10.1161/hypertensionaha.122.20219 · Cited by 88 · see citing works
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Cuff-Less Methods for Blood Pressure Telemonitoring
Bard, D. M., Joseph, J. I., & van Helmond, N. (2019) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2019.00040 · Cited by 84 · see citing works
Cardiovascular Effects of Flavonoids
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Bress, A. P., King, J. B., Kreider, K. E., Beddhu, S., Simmons, D. L., Cheung, A. K., Zhang, Y., Doumas, M. N., Nord, J. W., Sweeney, M. E., et al. (2017) · Diabetes Care · doi:10.2337/dc17-0885 · Cited by 81 · see citing works
“events among participants who achieved SBP 120–124 mmHg compared with all other achieved SBP groups including 130–134, 140–144, 150–154, or 160 mmHg or higher (19).”
BackgroundIs early and fast blood pressure control important in hypertension management?
Volpe, M., Gallo, G., & Tocci, G. (2017) · International Journal of Cardiology · doi:10.1016/j.ijcard.2017.12.026 · Cited by 81 · see citing works
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“…reduce BP even among healthy, normotensive individuals is important, according to recent evidence that lower SBP was associated with reduced cardiovascular risks even within ranges far lower than the hypertension threshold (e.g., as low as 90 mm Hg) (Bundy et al., 2017; Whelton et al., 2020).”
Isometric Exercise Training and Arterial Hypertension: An Updated Review
Edwards, J. J., Coleman, D. A., Ritti‐Dias, R. M., Farah, B. Q., Stensel, D. J., Lucas, S. J. E., Millar, P. J., Gordon, B. D., Cornelissen, V., Smart, N. A., et al. (2024) · Sports Medicine · doi:10.1007/s40279-024-02036-x · Cited by 76 · see citing works
“Regardless of this diagnostic confliction, it is uniformly accepted that sBP and dBP values of 120 mmHg and 80 mmHg are optimal, and increasing pressure beyond this threshold is linearly associated with an escalated risk of CVD [9, 10].”
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Blood Pressure Management in Stroke
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“History of stroke was permitted in the ACCORD-BP trial (Action to Control Cardiovascular Risk in Diabetes Blood Pressure; n=4733).32 Stroke—a secondary outcome—was significantly less common (hazard ratio, 0.59 [95% CI, 0.39–0.89]) in those randomized to the SBP target of <120 mm Hg compared with <140 mm Hg.”
BackgroundInfluentialSelf-citationLonger-Term All-Cause and Cardiovascular Mortality With Intensive Blood Pressure Control
Jaeger, B. C., Bress, A. P., Bundy, J. D., Cheung, A. K., Cushman, W. C., Drawz, P. E., Johnson, K., Lewis, C. E., Oparil, S., Rocco, M. V., et al. (2022) · JAMA Cardiology · doi:10.1001/jamacardio.2022.3345 · Cited by 73 · see citing works
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“26,27 35–37 For example, one estimate suggests that a 2 mm Hg increase in systolic BP can elevate the risk of major cardiovascular disease events by 5%.”
BackgroundHypertension after kidney donation: Incidence, predictors, and correlates
Sanchez, O. A., Ferrara, L. K., Rein, S., Berglund, D. M., Matas, A. J., & Ibrahim, H. N. (2018) · American Journal of Transplantation · doi:10.1111/ajt.14713 · Cited by 73 · see citing works
Trends of blood pressure control in the U.S. during the COVID-19 pandemic
Shah, N. P., Clare, R. M., Chiswell, K., Návar, A. M., Shah, B. R., & Peterson, E. D. (2021) · American Heart Journal · doi:10.1016/j.ahj.2021.11.017 · Cited by 72 · see citing works
Liu, F., Song, T., Yu, P., Deng, N., Guan, Y., Yang, Y., & Ma, Y. (2023) · Journal of Medical Internet Research · doi:10.2196/43809 · Cited by 72 · see citing works
“The sample size was determined through a statistical power analysis based on the change in systolic BP before and after 6 months, as it was the most critical indicator of a patient’s cardiovascular risk profile [56].”
Effect on Treatment Adherence of Distributing Essential Medicines at No Charge
Persaud, N., Bedard, M. J., Boozary, A., Glazier, R. H., Gomes, T., Hwang, S. W., Jüni, P., Law, M. R., Mamdani, M., Manns, B., et al. (2019) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2019.4472 · Cited by 69 · see citing works
- Authors
- Bundy, J. D., Li, C., Stuchlik, P., Bu, X., Kelly, T. N., Mills, K. T., He, H., Chen, J., Whelton, P. K., & He, J.
- Affiliations
- Tulane University (US)
- Corresponding author
- He, Jiang
- ORCID
- Venue
- JAMA Cardiology
- Publisher
- American Medical Association (AMA)
- Published
- 2017-07-01
- Volume
- 2
- Issue
- 7
- Pages
- 775
- ISSN
- 2380-6583 (ISSN-L)
- PMC
- PMC5710614
- OpenAlex
- W2618382346
- Cited by
- 783
- References
- 33
- Citations by year
- 2026: 59 · 2025: 102 · 2024: 96 · 2023: 99 · 2022: 65 · 2021: 95 · 2020: 80 · 2019: 78 · 2018: 73 · 2017: 35
- FWCI
- 56.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA Cardiology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (P20GM109036)
- Fogarty International Center (D43TW009107)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Nursing › Nutrition and Dietetics › Sodium Intake and Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Keywords
- systolic blood pressure, blood pressure targets, hypertension, antihypertensive therapy, cardiovascular disease, all-cause mortality, blood pressure reduction, linear dose-response relationship, cardiovascular risk reduction, cardiovascular disease prevention, cardiovascular disease prevention and treatment
- MeSH terms
- Antihypertensive Agents, Blood Pressure, Cardiovascular Diseases, Humans, Hypertension, Mortality, Patient Care Planning, Systole
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