Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Effect of intensive blood pressure lowering on left atrial remodeling in the SPRINT

Hypertension Research volume 44, pages 1326–1331 (2021)Cite this article

Abstract

Upstream therapy of atrial remodeling may decrease atrial fibrillation and associated thromboembolism. We examined the impact of intensive BP lowering on ECG-defined left atrial abnormalities in the SPRINT. SPRINT was a randomized clinical trial comparing outcomes when a systolic BP of <120 mmHg (standard treatment) was the target. We included SPRINT participants without baseline atrial fibrillation who had a technically interpretable baseline ECG and at least one follow-up ECG. The primary outcome was incident left atrial abnormality, defined as P-wave terminal force in V1 (PTFV1) > 4000 μV × ms. Secondary outcomes were regression of the left atrial abnormality and the change in PTFV1 from baseline across follow-up ECGs. Cox regression was used to examine the associations between treatment assignment and incident left atrial abnormality and its regression. We used linear mixed models to examine the changes in PTFV1. Of 9361 SPRINT participants, 7738 qualified for this analysis, of whom 5544 did not have baseline left atrial abnormalities. Intensive BP management was not associated with incident left atrial abnormality (HR, 0.96; 95% CI, 0.87–1.07) or regression of the baseline left atrial abnormality (HR, 1.09; 95% CI, 0.98–1.21). The change in PTFV1 from baseline through follow-up did not differ significantly between treatment groups (difference in μV × ms per year, 6; 95% CI, −67 to 79). Thus, among patients in a randomized clinical trial, we found no difference in the progression or regression of ECG-defined left atrial abnormalities with intensive BP management compared to standard BP management.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Iwasaki YK, Nishida K, Kato T, Nattel S. Atrial fibrillation pathophysiology: implications for management. Circulation. 2011;124:2264–74.

    Article  CAS  Google Scholar 

  2. Heijman J, Voigt N, Nattel S, Dobrev D. Cellular and molecular electrophysiology of atrial fibrillation initiation, maintenance, and progression. Circulation Res. 2014;114:1483–99.

    Article  CAS  Google Scholar 

  3. Abed HS, Wittert GA, Leong DP, Shirazi MG, Bahrami B, Middeldorp ME, et al. Effect of weight reduction and cardiometabolic risk factor management on symptom burden and severity in patients with atrial fibrillation: a randomized clinical trial. JAMA. 2013;310:2050–60.

    Article  CAS  Google Scholar 

  4. Kamel H, Okin PM, Longstreth WT Jr., Elkind MS, Soliman EZ. Atrial cardiopathy: a broadened concept of left atrial thromboembolism beyond atrial fibrillation. Future Cardiol. 2015;11:323–31.

    Article  CAS  Google Scholar 

  5. Andlauer R, Seemann G, Baron L, Dossel O, Kohl P, Platonov P, et al. Influence of left atrial size on p-wave morphology: differential effects of dilation and hypertrophy. Europace. 2018;20:iii36–44.

    Article  Google Scholar 

  6. Morris JJ Jr, Estes EH Jr, Whalen RE, Thompson HK Jr, McIntosh HD. P-wave analysis in valvular heart disease. Circulation. 1964;29:242–52.

    Article  Google Scholar 

  7. Scott CC, Leier CV, Kilman JW, Vasko JS, Unverferth DV. The effect of left atrial histology and dimension on p wave morphology. J Electrocardiol. 1983;16:363–6.

    Article  CAS  Google Scholar 

  8. Soliman EZ, Prineas RJ, Case LD, Zhang ZM, Goff DC Jr. Ethnic distribution of ecg predictors of atrial fibrillation and its impact on understanding the ethnic distribution of ischemic stroke in the atherosclerosis risk in communities (aric) study. Stroke. 2009;40:1204–11.

    Article  Google Scholar 

  9. Eranti A, Aro AL, Kerola T, Anttonen O, Rissanen HA, Tikkanen JT, et al. Prevalence and prognostic significance of abnormal p terminal force in lead v1 of the ECG in the general population. Circulation Arrhythmia Electrophysiol. 2014;7:1116–21.

    Article  Google Scholar 

  10. Tereshchenko LG, Henrikson CA, Sotoodehnia N, Arking DE, Agarwal SK, Siscovick DS, et al. Electrocardiographic deep terminal negativity of the p wave in v(1) and risk of sudden cardiac death: the atherosclerosis risk in communities (aric) study. J Am Heart Assoc. 2014;3:e001387.

    Article  Google Scholar 

  11. Hancock EW, Deal BJ, Mirvis DM, Okin P, Kligfield P, Gettes LS, et al. Aha/accf/hrs recommendations for the standardization and interpretation of the electrocardiogram: part V—electrocardiogram changes associated with cardiac chamber hypertrophy: a scientific statement from the american heart association electrocardiography and arrhythmias committee, council on clinical cardiology; the american college of cardiology foundation; and the heart rhythm society. Endorsed by the international society for computerized electrocardiology. J Am Coll Cardiol. 2009;53:992–1002.

    Article  Google Scholar 

  12. Kamel H, Hunter M, Moon YP, Yaghi S, Cheung K, Di Tullio MR, et al. Electrocardiographic left atrial abnormality and risk of stroke: Northern Manhattan study. Stroke. 2015;46:3208–12.

    Article  Google Scholar 

  13. Kamel H, Soliman EZ, Heckbert SR, Kronmal RA, Longstreth WT Jr., Nazarian S, et al. P-wave morphology and the risk of incident ischemic stroke in the multi-ethnic study of atherosclerosis. Stroke. 2014;45:2786–8.

    Article  Google Scholar 

  14. Kamel H, O’Neal WT, Okin PM, Loehr LR, Alonso A, Soliman EZ. Electrocardiographic left atrial abnormality and stroke subtype in aric. Ann Neurol. 2015;78:670–8.

    Article  CAS  Google Scholar 

  15. Wright JT Jr, Williamson JD, Whelton PK, Snyder JK, Sink KM, Rocco MV, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373:2103–16.

    Article  CAS  Google Scholar 

  16. Ambrosius WT, Sink KM, Foy CG, Berlowitz DR, Cheung AK, Cushman WC, et al. The design and rationale of a multicenter clinical trial comparing two strategies for control of systolic blood pressure: the Systolic Blood Pressure Intervention Trial (SPRINT). Clin Trials. 2014;11:532–46.

    Article  Google Scholar 

  17. Hommel G. A stagewise rejective multiple test procedure based on a modified bonferroni test. Biometrika. 1988;75:383–6.

    Article  Google Scholar 

  18. Staszewsky L, Wong M, Masson S, Raimondi E, Gramenzi S, Proietti G, et al. Left atrial remodeling and response to valsartan in the prevention of recurrent atrial fibrillation: the GISSI-AF echocardiographic substudy. Circ Cardiovasc Imaging. 2011;4:721–8.

    Article  Google Scholar 

  19. Kapelios CJ, Murrow JR, Nuhrenberg TG, Montoro Lopez MN. Effect of mineralocorticoid receptor antagonists on cardiac function in patients with heart failure and preserved ejection fraction: a systematic review and meta-analysis of randomized controlled trials. Heart Fail Rev. 2019;24:367–77.

    Article  CAS  Google Scholar 

  20. McNamara DA, Aiad N, Howden E, Hieda M, Link MS, Palmer D, et al. Left atrial electromechanical remodeling following 2 years of high-intensity exercise training in sedentary middle-aged adults. Circulation. 2019;139:1507–16.

    Article  Google Scholar 

  21. Edelmann F, Gelbrich G, Dungen HD, Frohling S, Wachter R, Stahrenberg R, et al. Exercise training improves exercise capacity and diastolic function in patients with heart failure with preserved ejection fraction: results of the ex-dhf (exercise training in diastolic heart failure) pilot study. J Am Coll Cardiol. 2011;58:1780–91.

    Article  Google Scholar 

  22. Chen LY, Bigger JT, Hickey KT, Chen H, Lopez-Jimenez C, Banerji MA, et al. Effect of intensive blood pressure lowering on incident atrial fibrillation and p-wave indices in the accord blood pressure trial. Am J Hypertens. 2016;29:1276–82.

    Article  Google Scholar 

  23. Snyder ML, Soliman EZ, Whitsel EA, Gellert KS, Heiss G. Short-term repeatability of electrocardiographic p wave indices and pr interval. J Electrocardiol. 2014;47:257–63.

    Article  Google Scholar 

  24. Soliman EZ, Rahman AF, Zhang ZM, Rodriguez CJ, Chang TI, Bates JT, et al. Effect of intensive blood pressure lowering on the risk of atrial fibrillation. Hypertension. 2020;75:1491–6.

    Article  CAS  Google Scholar 

Download references

Funding

The SPRINT is funded with federal funds from the National Institutes of Health (NIH), including the National Heart, Lung, and Blood Institute (NHLBI), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Institute on Aging (NIA), and the National Institute of Neurological Disorders and Stroke (NINDS), under contract numbers HHSN268200900040C, HHSN268200900046C, HHSN268200900047C, HHSN268200900048C, HHSN268200900 049C, and Inter-Agency Agreement Number A-HL-13-002-001. It was also supported in part with resources and the use of facilities through the Department of Veterans Affairs. SPRINT investigators acknowledge the contribution of the study. Medications (azilsartan and azilsartan combined with chlorthalidone) were from Takeda Pharmaceuticals International, Inc. All components of the SPRINT study protocol were designed and implemented by the investigators. The investigative team collected, analyzed, and interpreted the data. All aspects of article writing and revision were carried out by the coauthors. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, the US Department of Veterans Affairs, or the United States Government. For a full list of contributors to SPRINT, please see the supplementary acknowledgment list: https://www.sprinttrial.org/public/dspScience.cfm. We also acknowledge the support from the following Clinical and Translational Science Awards funded by the National Center for Advancing Translational Sciences of the NIH: Case Western Reserve University: UL1TR000439, Ohio State University: UL1RR025755, University of Pennsylvania: UL1RR024134 and UL1TR000003, Boston University: UL1RR025771, Stanford University: UL1TR000093, Tufts: UL1RR025752, UL1TR000073 and UL1TR001064, University of Illinois: UL1TR000050, University of Pittsburgh: UL1TR000005, UT Southwestern University: 9U54TR000017-06, University of Utah: UL1TR000105-05, Vanderbilt University: UL1 TR000445, George Washington University: UL1TR000075, University of California, Davis: UL1 TR000002, University of Florida: UL1 TR000064, University of Michigan: UL1TR000433, and Tulane University: P30GM103337 COBRE Award NIGMS. The views expressed in this article are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; National Institutes of Health; or the United States Department of Health and Human Services or of the Veterans Administration.

Author information

Authors and Affiliations

  1. Clinical and Translational Neuroscience Unit, Feil Family Brain and Mind Research Institute, Department of Neurology, Weill Cornell Medicine, New York, NY, USA

    Hooman Kamel

  2. Departments of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA

    Akm Fazlur Rahman

  3. Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA

    Wesley T. O’Neal

  4. Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA

    Cora E. Lewis

  5. Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

    Cora E. Lewis

  6. Epidemiological Cardiology Research Center, Department of Epidemiology and Prevention, Division of Public Health Sciences and Department of Medicine, Section on Cardiology, Wake Forest School of Medicine, Winston-Salem, NC, USA

    Elsayed Z. Soliman

Authors
  1. Hooman Kamel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Akm Fazlur Rahman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wesley T. O’Neal
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Cora E. Lewis
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Elsayed Z. Soliman
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conception and design of study: all authors. Data collection: CEL, EZS. Statistical analysis: AFR. Interpretation of data: all authors. Drafting of manuscript: HK. Revision of manuscript for important intellectual content.

Corresponding author

Correspondence to Hooman Kamel.

Ethics declarations

Conflict of interest

HK serves as co-PI for the NIH-funded ARCADIA trial (NINDS U01NS095869), which receives an in-kind study drug, Eliquis®, from the BMS-Pfizer Alliance and ancillary study support from Roche Diagnostics; serves as a Deputy Editor for JAMA Neurology; serves as a steering committee member of Medtronic’s Stroke AF trial (uncompensated); serves on an endpoint adjudication committee for a trial of empagliflozin for Boehringer-Ingelheim; and has served on an advisory board for Roivant Sciences related to factor XI inhibition.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kamel, H., Rahman, A.F., O’Neal, W.T. et al. Effect of intensive blood pressure lowering on left atrial remodeling in the SPRINT. Hypertens Res 44, 1326–1331 (2021). https://doi.org/10.1038/s41440-021-00713-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41440-021-00713-2

Keywords

This article is cited by

Search

Advanced search

Quick links