Cited by 783Blood Pressure and Hypertension StudiesSodium Intake and HealthCardiovascular Health and Disease Prevention

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Systolic Blood Pressure Reduction and Risk of Cardiovascular Disease and Mortality: A Systematic Review and Network Meta-analysis

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Bundy, Joshua D., Li, Changwei, Stuchlik, Patrick, Bu, Xiaoqing, Kelly, Tanika N., Mills, Katherine T., He, Hua, Chen, Jing, Whelton, Paul K., He, Jiang·2017·JAMA Cardiology

DOI 10.1001/jamacardio.2017.1421PMC PMC5710614

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Abstract

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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“Although there does not appear to be any specific overwhelming evidence in support of this recommendation, it has been stated that it is based on evaluation of the prediabetes cohort in the SPRINT database (diabetics were excluded) as well as the findings from some of the recent meta-analyses.(11,12) It is crucial to…”
Short-Term Effect of Self-Selected Training Intensity on Ambulatory Blood Pressure in Hypertensive Older Women: A Randomized Controlled Trial
Sócrates, J., Browne, R. A. V., Macêdo, G. A. D., Araújo, M. B. F., Paulo-Pereira, R., Cabral, L. L. P., Lucena, B., Farias-Junior, L. F., & Costa, E. C. (2020) · Clinical Interventions in Aging · doi:10.2147/cia.s260134 · Cited by 9
Association between high-altitude polycythemia and hypertension: a cross-sectional study in adults at Tibetan ultrahigh altitudes
Yin, R., Wu, Y., Li, M., Liu, C., Pu, X., & Wen, Y. (2024) · Journal of Human Hypertension · doi:10.1038/s41371-024-00916-3 · Cited by 9
Burden of diseases due to high systolic blood pressure in the Middle East and North Africa region from 1990 to 2019
Safiri, S., Mousavi, S. E., Asghari, K. M., Nejadghaderi, S. A., Aletaha, R., Sullman, M. J. M., Singh, K., Kolahi, A., & Beyranvand, M. R. (2024) · Scientific Reports · doi:10.1038/s41598-024-64563-x · Cited by 10
Prebiotics Improve Blood Pressure Control by Modulating Gut Microbiome Composition and Function: A Systematic Review and Meta-Analysis
Msdi, A. S., Wang, E. M., & Garey, K. W. (2025) · Nutrients · doi:10.3390/nu17152502 · Cited by 12
Semaglutide 2.4 mg Clinical Outcomes in Patients with Obesity or Overweight: A Real-World Retrospective Comparative Cohort Study
Ruseva, A., Michalak, W., Fabricatore, A. N., Hartaigh, B. Ó., Zhao, Z., & Umashanker, D. (2025) · Advances in Therapy · doi:10.1007/s12325-025-03320-6 · Cited by 11
Use of Risk Assessment to Guide Decision-Making for Blood Pressure Management in the Primary Prevention of Cardiovascular Disease: A Scientific Statement From the American Heart Association and American College of Cardiology
Khan, S. S., Abdalla, M., Bello, N. A., Blyler, C. A., Carter, J., Commodore-Mensah, Y. Y., Ferdinand, K. C., Johnson, H. M., Jones, D. W., Khera, A., et al. (2025) · Circulation · doi:10.1161/cir.0000000000001355 · Cited by 13
Impact of the 2017 American College of Cardiology/American Heart Association Guidelines on Prevalence of Hypertension in Ghana
Abariga, S. A., Kibria, G. M. A., & Albrecht, J. S. (2020) · American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.19-0272 · Cited by 9
“because the SBP target of < 130 mmHg reduces total mortality and composite cardiovascular events compared with the SBP of < 140 mmHg.(6,23) There is already a low”
Background
Combined exercise training improves blood pressure at rest and during exercise in young obese prehypertensive men
Phoemsapthawee, J., & Sriton, B. (2021) · The Journal of Sports Medicine and Physical Fitness · doi:10.23736/s0022-4707.20.11222-2 · Cited by 10
Clinical impact of guideline-based practice and patients’ adherence in uncontrolled hypertension
Sohn, I. S., Kim, C.-J., Yoo, B., Kim, B. J., Choi, J. W., Kim, D., Lee, S., Song, W., Jeon, D. W., Jun, T. Y., et al. (2021) · Clinical Hypertension · doi:10.1186/s40885-021-00183-1 · Cited by 9
Diurnal blood pressure loads are associated with lower cognitive performances in controlled-hypertensive elderly individuals
de la Colina, A. N., Wu, R., Desjardins-Crépeau, L., Badji, A., Lamarre-Cliché, M., Doyon, J., Bherer, L., & Girouard, H. (2019) · Journal of Hypertension · doi:10.1097/hjh.0000000000002155 · Cited by 9
Implications of the New 2017 American College of Cardiology/American Heart Association Guidelines for Hypertension
Aronow, W. S. (2019) · Minerva Cardioangiologica · doi:10.23736/s0026-4725.19.04965-x · Cited by 8
Past Sodium Intake, Contemporary Sodium Intake, and Cardiometabolic Health in Southwest Coastal Bangladesh
Naser, A. M., Rahman, M. M., UNICOMB, L. E., Doza, S., Selim, S., Chaity, M., Luby, S. P., Anand, S., Staimez, L. R., Clasen, T., et al. (2020) · Journal of the American Heart Association · doi:10.1161/jaha.119.014978 · Cited by 8
Trends in Cardiometabolic and Cancer Multimorbidity Prevalence and Its Risk With All-Cause and Cause-Specific Mortality in U.S. Adults: Prospective Cohort Study
Yang, L., Sun, J., Zhao, M., Magnussen, C. G., & Xi, B. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.731240 · Cited by 9
Early antihypertensive treatment and clinical outcomes in acute ischemic stroke
He, W. J., Zhong, C., Xu, T., Wang, D., Sun, Y., Bu, X., Chen, C.-S., Wang, J., Ju, Z., Li, Q., et al. (2018) · Journal of Hypertension · doi:10.1097/hjh.0000000000001690 · Cited by 9
Self-citation
Influence of oral administration of kukoamine A on blood pressure in a rat hypertension model
Butts, C. A., HEDDERLEY, D. I., Martell, S., Dinnan, H., Middlemiss-Kraak, S., Bunn, B. J., McGhie, T. K., & Lill, R. E. (2022) · PLoS ONE · doi:10.1371/journal.pone.0267567 · Cited by 8
“Hypertension is one of the leading preventable risk factors for death and disability globally [1, 2].”
Background
Development of a machine learning-based model for predicting individual responses to antihypertensive treatments
Yi, J., Wang, L., Song, J., Liu, Y., Liu, J., Zhang, H., Lu, J., & Zheng, X. (2024) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2024.02.014 · Cited by 8
The impact of interval training on adiponectin to leptin ratios and on blood pressures in severely obese adolescent girls: A randomized controlled trial
Racil, G., Aouichaoui, C., Hawani, A., Signorelli, P., Chamari, K., Migliaccio, G. M., Trabelsi, Y., & Padulo, J. (2024) · Journal of Sports Sciences · doi:10.1080/02640414.2024.2369447 · Cited by 8
“A sedentary lifestyle is a prevalent phenomenon in modern societies, leading to obesity in children and adolescents which has deleterious consequences and escalates the risk of obesity persisting into adulthood (Bundy et al., 2017).”
Influential
Relationship between Carotid Intima-Media Thickness, Periodontal Disease, and Systemic Inflammation Biomarkers in an Adult Population
Uriza, C. L., Roa, N. S., Porras, J. V., Poveda, J. C. V., Otero, L., Ruiz, Á. J., & Arregocés, F. M. E. (2024) · Biomedicines · doi:10.3390/biomedicines12071425 · Cited by 8
“Cytokines can alter various metabolic pathways, including lipid metabolism, potentially leading to an increase in total cholesterol levels and low-density lipoproteins (LDLs) [26–28].”
Background
α‐Mangostin Attenuates Blood Pressure and Reverses Vascular Remodeling by Balancing ACE / AT1R and ACE2 /Ang‐(1–7)/ MasR Axes in Ang II ‐Infused Hypertensive Mice
Xue, Q., Liu, C., Zhang, D., Li, M., & Li, Y. (2024) · Phytotherapy Research · doi:10.1002/ptr.8353 · Cited by 8
Does mean systolic blood pressure less than 130 mm Hg ensure high rates of control to <140/<90 mm Hg? A cross-sectional analysis of two cohorts
Egan, B. M., Sutherland, S. E., Martin, B. P., Riesser, B., Moran, A. E., Rodgers, A., & Rakotz, M. (2025) · BMJ Open · doi:10.1136/bmjopen-2024-090440 · Cited by 8
Highlights of Cardiovascular Disease Prevention Studies Presented at the 2025 American Heart Association Scientific Sessions
Jabbar, A. B. A., Naeem, U., Zulfiqar, K., Ahmed, S., Inam, M., Hinkamp, C. A., Minhas, A. M. K., Slipczuk, L. N., Krittanawong, C., Sahebkar, A., et al. (2026) · Current Atherosclerosis Reports · doi:10.1007/s11883-025-01376-x · Cited by 8
Cardiovascular risk factors in the elderly: a 10-year follow-up survival analysis
de Sousa, T. V., Cavalcante, Á. M. R. Z., Lima, N. X., Souza, J. S., Sousa, A. L. L., Brasil, V. V., VIEIRA, F. V. M., Guimarães, J. V., de Matos, M. A., Silveira, É. A., et al. (2022) · European Journal of Cardiovascular Nursing · doi:10.1093/eurjcn/zvac040 · Cited by 8
The JMJD family of histone demethylase and their intimate links to cardiovascular disease
Xie, J., Lin, H., Zuo, A., Shao, J., Sun, W., Wang, S., Jianda, S., Wang, Y., Luo, Y., Sun, J. M., et al. (2024) · Cellular Signalling · doi:10.1016/j.cellsig.2024.111046 · Cited by 8
Modifiable risk factors of inequalities in hypertension: analysis of 100 million health checkups recipients
Aida, J., Inoue, Y., Tabuchi, T., & Kondo, N. (2024) · Hypertension Research · doi:10.1038/s41440-024-01615-9 · Cited by 10
“Overall, the prevalence of hypertension was lower with this de ﬁ nition compared with the original de ﬁ nition in both men and women (Supplementary Tables 6, 7).”
Efficacy and Safety of Sacubitril/Allisartan for the Treatment of Primary Hypertension
Zhang, W., Zhang, J., Yan, J., Ge, Q., Lu, X., Chen, S.-X., Xu, W., Sun, J.-C., Li, J., Liu, Z.-C., et al. (2024) · JACC Asia · doi:10.1016/j.jacasi.2024.06.002 · Cited by 8
Associations between central and brachial blood pressure in patients with hypertension and aortovascular disease: Implications for clinical practice
Alsomali, A., Lip, G. Y. H., Akhtar, R., Field, M., Grillo, A., Tidbury, N., Leo, D. G., & Proietti, R. (2024) · Current Problems in Cardiology · doi:10.1016/j.cpcardiol.2024.102874 · Cited by 8
Childhood pulse pressure predicts subclinical vascular damage in adulthood
Hou, D., Yan, Y., Liu, J., Zhao, X., Cheng, H., & Mi, J. (2018) · Journal of Hypertension · doi:10.1097/hjh.0000000000001748 · Cited by 8
Estimation System of Blood Pressure Variation with Photoplethysmography Signals Using Multiple Regression Analysis and Neural Network
Cho, S.-I., Negishi, T., Tsuchiya, M., Yasuda, M., & Yokoyama, M. (2018) · International Journal of Fuzzy Logic and Intelligent Systems · doi:10.5391/ijfis.2018.18.4.229 · Cited by 8
“A high BP is the main cause of cardiovascular disease such as stroke and heart disease [11, 12].”
Background
Association of optimal blood pressure with mortality in patients taking antihypertensive medications
Yun, D., Lee, H. S., Choi, W., Chang, H., Son, D., & Lee, J. (2020) · Journal of Clinical Hypertension · doi:10.1111/jch.14034 · Cited by 8
Three-year trajectories of metabolic risk factors predict subsequent long-term mortality in patients with type 2 diabetes
Lin, C., Li, C., Liu, C.-S., Lin, C., Lin, W., Wang, M.-C., Yang, S.-Y., & Li, T. (2021) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2021.108995 · Cited by 8
Self-citation
Cardiovascular risk in patients receiving antihypertensive drug treatment from the perspective of endothelial function
Maruhashi, T., & Higashi, Y. (2022) · Hypertension Research · doi:10.1038/s41440-022-00936-x · Cited by 8
“Effective antihypertensive drug treatment undoubtedly reduces cardiovascular morbidity and mortality in patients with hypertension [3].”
Background
The expanding role of primary care providers in care of individuals with kidney disease
Martin, K. E., Thomas, B. S., & Greenberg, K. I. (2022) · Journal of the National Medical Association · doi:10.1016/j.jnma.2022.05.006 · Cited by 8
Islamic fasting: cardiovascular disease perspective
Naz, H., Haider, R., Rashid, H. U., Haq, Z. U., Malik, J., Zaidi, S. M. J., Ishaq, U., & Trevisan, R. (2022) · Expert Review of Cardiovascular Therapy · doi:10.1080/14779072.2022.2138344 · Cited by 10
Re-Classifying Hypertension in the Venezuelan EVESCAM Database Using 2017 AHA/ACC Criteria: High Prevalence, Poor Control, and Urgent Call for Action
Gonzalez-Rivas, J. P., Mechanick, J. I., Durán, M., Ugel, E., Marulanda, M. I., & Nieto-Martínez, R. E. (2019) · Annals of Global Health · doi:10.5334/aogh.2346 · Cited by 8
“This conspicuous numerically based change is primarily based on the Systolic Blood Pressure Intervention Trial (SPRINT) [5], and supported by other relevant observational studies [2, 6, 7].”
Result
Potential of Stratified Medicine for High Blood Pressure Management
Porcher, R., Tran, V.-T., Blacher, J., & Ravaud, P. (2019) · Hypertension · doi:10.1161/hypertensionaha.119.13749 · Cited by 8
Randomised controlled trials of antihypertensive therapy: does exclusion of orthostatic hypotension alter treatment effect? A systematic review and meta-analysis
Reddin, C., Murphy, R., Hanrahan, C., Loughlin, E. A., Ferguson, J. P., Judge, C. S., Waters, R., Canavan, M. D., Kenny, R. A., & O'Donnell, M. J. (2023) · Age and Ageing · doi:10.1093/ageing/afad044 · Cited by 7
“Previous meta-analyses have shown that blood pressure lowering is associated with a reduced risk of cardiovascular disease, mortality and dementia [68, 69].”
Background
Renin-Angiotensin-Aldosterone System Modulators in Adults with Hypertension: A Network Meta-Analysis of Randomized Controlled Trials
Yi, X., Yang, S., Yang, J., Chen, X., Zhang, A., Zeng, Q., Luo, W., Li, Q., & Hu, J. (2024) · Drugs · doi:10.1007/s40265-024-02092-7 · Cited by 9
“Conversely, lowering BP is effective in preventing all-cause mortality [5, 6].”
Treatment optimisation for blood pressure with single-pill combinations in India (TOPSPIN) – Protocol design and baseline characteristics
Kiru, G., Roy, A., Kondal, D., Chandrasekaran, A. M., Mukherjee, S., Mohan, B., Singh, K., Salwa, H., Christa, E., Lobo, A. S., et al. (2024) · International Journal of Cardiology Cardiovascular Risk and Prevention · doi:10.1016/j.ijcrp.2024.200346 · Cited by 8
Internet-based digital intervention to support the self-management of hypertension compared to usual care: results of the HALCYON randomized controlled trial
Meyer, B., Riepenhausen, A., Betz, L. T., Jauch‐Chara, K., & Reshetnik, A. (2025) · BMC Cardiovascular Disorders · doi:10.1186/s12872-025-04698-5 · Cited by 9
Beneficial effects of Codonopsis lanceolata extract on systolic blood pressure levels in prehypertensive adults: A double‐blind, randomized controlled trial
Shin, Y. K., Hsieh, Y.-S., Han, A. Y., Lee, K., & Seol, G. H. (2019) · Phytotherapy Research · doi:10.1002/ptr.6520 · Cited by 7
“Pre‐HTN was also found to be associated with increases in the risks of stroke morbidity (Huang et al., 2014) and mortality (Bundy et al., 2017), as well as the risks of composite cardiovascular disease, suggesting the need for more intensive control of systolic BP among adultswith pre‐HTN.…”
Background
The association of SBP with mortality in patients with stage 1–4 chronic kidney disease
Zhuo, M., Yang, D., Goldfarb‐Rumyantzev, A. S., & Brown, R. S. (2021) · Journal of Hypertension · doi:10.1097/hjh.0000000000002927 · Cited by 7
“A meta-analysis of 42 randomized controlled trials demonstrated that lowering SBP to 120–124 mmHg was associated with the lowest risk of cardiovascular outcome and mortality in adults treated with antihypertensive therapy [28].”
Background
Beliefs and misconceptions about hypertension disease: A qualitative study among patients in a peri-urban community in Ghana
Otemah, J., Ohene, L. A., Kyei, J. M., & Darkwa, I. O. (2023) · Chronic Illness · doi:10.1177/17423953231199525 · Cited by 7
Development of a risk-prediction model for primary aldosteronism in veterans with hypertension
Ginzberg, S. P., Kalva, S., Wirtalla, C. J., Passman, J. E., Cohen, D. L., Cohen, J. B., & Wachtel, H. (2023) · Surgery · doi:10.1016/j.surg.2023.04.063 · Cited by 7
The effect of cardiorespiratory fitness and habitual physical activity on cardiovascular responses to 2 h of uninterrupted sitting
Paterson, C. A., Stone, K. J., Turner, L. A., Moinuddin, A., Stoner, L. R., & Fryer, S. M. (2024) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00361.2023 · Cited by 7
Association of plasma trans fatty acid concentrations with blood pressure and hypertension in U.S. adults
Luan, M., Tian, Y., Yan, D., & Liang, S. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1373095 · Cited by 7
World Stroke Organization and World Hypertension League position statement on hypertension control strategies in prevention and management of stroke
Pandian, J. D., Sylaja, P. N., Lackland, D. T., Babu, V., Paramasivan, N. K., Sebastian, I. A., Parati, G., Anderson, C. S., Ovbiagele, B. I., Fisher, M., et al. (2024) · International Journal of Stroke · doi:10.1177/17474930241309276 · Cited by 10
Self-citation
Effect of Intensive Blood Pressure Control and Comorbidity Status on the Prognosis of Patients With Hypertension: Insights From SPRINT
Zheng, W., Li, S., Jiang, C., Hao, W., Ai, H., Wang, X., Ma, C., & Nie, S. (2025) · Journal of the American Heart Association · doi:10.1161/jaha.124.036719 · Cited by 7

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: Bundy, Joshua D.
Li, Changwei
Bu, Xiaoqing
Kelly, Tanika N.
Mills, Katherine T.
He, Hua
Chen, Jing
Whelton, Paul K.
He, Jiang
Venue: JAMA Cardiology
Publisher: American Medical Association (AMA)
Published: 2017-07-01
Volume: 2
Issue: 7
Pages: 775
ISSN: 2380-6583 (ISSN-L)
DOI: 10.1001/jamacardio.2017.1421
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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Systolic Blood Pressure Reduction and Risk of Cardiovascular Disease and Mortality: A Systematic Review and Network Meta-analysis

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