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.

  • Letter
  • Published:

Incidence and prognosis of cardiac conduction system diseases in hypertension: the STEP trial

Nature Aging volume 4, pages 483–490 (2024)Cite this article

Subjects

Abstract

Patients with cardiac conduction system diseases (CSD) may have increased incidence and mortality of cardiovascular events. Here we report a post hoc analysis of the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) randomized clinical trial (ClinicalTrials.gov number, NCT03015311) concerning the effect of intensive blood pressure (BP) control on the incidence of new-onset CSD and the prognostic implications of preexisting or new-onset CSD. The incidence of new-onset CSD was similar in the intensive (n = 205, 6.42%) and standard (n = 188, 5.94%) treatment arms. Participants with preexisting CSD had a higher risk for acute decompensated heart failure. Increased age, male sex and increased body mass index were independently associated with increased risk for new-onset CSD. Our results suggest that intensive BP control may not reduce the incidence of new-onset CSD compared with standard BP control.

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: Multivariable clinical predictors of incident CSD.

Similar content being viewed by others

Data availability

The data are not publicly available due to restrictions of ethical approval requirements and the current national general data protection regulations of this study. Instructions for applying for data access are detailed at https://www.nejm.org/doi/suppl/10.1056/NEJMoa2111437/suppl_file/nejmoa2111437_data-sharing.pdf. The complete de-identified patient data set underlying this article will be shared on reasonable request to the corresponding author.

Code availability

Survival 3.3.1 in R version 4.1.2 was used to perform Cox regression model and Fine–Gray subdistribution hazard model, and to conduct inverse probability weighting. Complete codes of R software (version 4.1.2) are available from the corresponding author on reasonable request.

References

  1. Chow, G. V., Marine, J. E. & Fleg, J. L. Epidemiology of arrhythmias and conduction disorders in older adults. Clin. Geriatr. Med. 28, 539–553 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  2. De Bacquer, D., De Backer, G. & Kornitzer, M. Prevalences of ECG findings in large population based samples of men and women. Heart 84, 625–633 (2000).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Nyholm, B. C. et al. Fascicular heart blocks and risk of adverse cardiovascular outcomes: Results from a large primary care population. Heart Rhythm 19, 252–259 (2022).

    Article  PubMed  Google Scholar 

  4. Kiehl, E. L. et al. Effect of left ventricular conduction delay on all-cause and cardiovascular mortality (from the PRECISION Trial). Am. J. Cardiol. 124, 1049–1055 (2019).

    Article  PubMed  Google Scholar 

  5. Zhang, Z. M. et al. Different patterns of bundle-branch blocks and the risk of incident heart failure in the Women’s Health Initiative (WHI) study. Circ. Heart Fail. 6, 655–661 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Zhang, Z. M. et al. Mortality risk associated with bundle branch blocks and related repolarization abnormalities (from the Women’s Health Initiative [WHI]). Am. J. Cardiol. 110, 1489–1495 (2012).

    Article  PubMed  Google Scholar 

  7. Badheka, A. O. et al. QRS duration on electrocardiography and cardiovascular mortality (from the National Health and Nutrition Examination Survey-III). Am. J. Cardiol. 112, 671–677 (2013).

    Article  PubMed  Google Scholar 

  8. Stephenson, K. et al. Long-term outcomes of left bundle branch block in high-risk survivors of acute myocardial infarction: the VALIANT experience. Heart Rhythm 4, 308–313 (2007).

    Article  PubMed  Google Scholar 

  9. Lund, L. H. et al. Age, prognostic impact of QRS prolongation and left bundle branch block, and utilization of cardiac resynchronization therapy: findings from 14,713 patients in the Swedish Heart Failure Registry. Eur. J. Heart Fail. 16, 1073–1081 (2014).

    Article  PubMed  Google Scholar 

  10. Mandyam, M. C., Soliman, E. Z., Heckbert, S. R., Vittinghoff, E. & Marcus, G. M. Long-term outcomes of left anterior fascicular block in the absence of overt cardiovascular disease. JAMA 309, 1587–1588 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Calò, L. et al. Left posterior fascicular block and increased risk of sudden cardiac death in young people. J. Am. Coll. Cardiol. 77, 1143–1145 (2021).

    Article  PubMed  Google Scholar 

  12. Aro, A. L. et al. Intraventricular conduction delay in a standard 12-lead electrocardiogram as a predictor of mortality in the general population. Circ. Arrhythm. Electrophysiol. 4, 704–710 (2011).

    Article  PubMed  Google Scholar 

  13. Cheng, S. et al. Long-term outcomes in individuals with prolonged PR interval or first-degree atrioventricular block. JAMA 301, 2571–2577 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Magnani, J. W. et al. Electrocardiographic PR interval and adverse outcomes in older adults: the Health, Aging, and Body Composition study. Circ. Arrhythm. Electrophysiol. 6, 84–90 (2013).

    Article  PubMed  Google Scholar 

  15. Kusumoto, F. M. et al. 2018 ACC/AHA/HRS guideline on the evaluation and management of patients with bradycardia and cardiac conduction delay: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation 140, e382–e482 (2019).

    PubMed  Google Scholar 

  16. Davies, M. & Harris, A. Pathological basis of primary heart block. Br. Heart J. 31, 219–226 (1969).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Díez, J. Mechanisms of cardiac fibrosis in hypertension. J. Clin. Hypertens. 9, 546–550 (2007).

    Article  Google Scholar 

  18. Schneider, J. F., Thomas, H. E. Jr., Kreger, B. E., McNamara, P. M. & Kannel, W. B. Newly acquired left bundle-branch block: the Framingham study. Ann. Intern. Med. 90, 303–310 (1979).

    Article  CAS  PubMed  Google Scholar 

  19. Schneider, J. F. et al. Newly acquired right bundle-branch block: the Framingham study. Ann. Intern. Med. 92, 37–44 (1980).

    Article  CAS  PubMed  Google Scholar 

  20. Bussink, B. E. et al. Right bundle branch block: prevalence, risk factors, and outcome in the general population: results from the Copenhagen City Heart Study. Eur. Heart J. 34, 138–146 (2013).

    Article  PubMed  Google Scholar 

  21. Jeong, J. H. et al. Incidence of and risk factors for bundle branch block in adults older than 40 years. Korean J. Intern. Med. 19, 171–178 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  22. Dewland, T. A. et al. Effect of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) on conduction system disease. JAMA Intern. Med. 176, 1085–1092 (2016).

    Article  PubMed  Google Scholar 

  23. Okin, P. M., Kjeldsen, S. E. & Devereux, R. B. Effect of antihypertensive therapy on development of incident conduction system disease in hypertensive patients. J. Hypertens. 37, 629–635 (2019).

    Article  CAS  PubMed  Google Scholar 

  24. Frimodt-Møller, E. K. et al. Association between intensive vs standard blood pressure control and incident left ventricular conduction disease: a post hoc analysis of the SPRINT randomized clinical trial. JAMA Cardiol. 8, 612–616 (2023).

    Article  PubMed  Google Scholar 

  25. Shan, R. et al. Prevalence and risk factors of atrioventricular block among 15 million Chinese health examination participants in 2018: a nation-wide cross-sectional study. BMC Cardiovasc. Disord. 21, 289 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  26. Qiao, Q. et al. Bundle branch block and nonspecific intraventricular conduction delay prevalence using Chinese nationwide survey data. J. Int. Med. Res. 50, 3000605221119666 (2022).

  27. Pfister, R., Michels, G., Cairns, R., Schneider, C. A. & Erdmann, E. Incidence of new onset bundle branch block and atrial fibrillation in patients with type 2 diabetes and macrovascular disease: an analysis of the PROactive study. Int. J. Cardiol. 153, 233–234 (2011).

    Article  PubMed  Google Scholar 

  28. Frimodt-Møller, E. K. et al. Lifestyle habits associated with cardiac conduction disease. Eur. Heart J. 44, 1058–1066 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  29. Ioannou, A., Papageorgiou, N., Singer, D. & Missouris, C. G. Registry report of the prevalence of ECG abnormalities and their relation to patient characteristics in an asymptomatic population. QJM 111, 875–879 (2018).

    Article  CAS  PubMed  Google Scholar 

  30. De Bacquer, D., De Backer, G., Kornitzer, M. & Blackburn, H. Prognostic value of ECG findings for total, cardiovascular disease, and coronary heart disease death in men and women. Heart 80, 570–577 (1998).

    Article  PubMed  PubMed Central  Google Scholar 

  31. Fuchs, F. D. & Whelton, P. K. High blood pressure and cardiovascular disease. Hypertension 75, 285–292 (2020).

    Article  CAS  PubMed  Google Scholar 

  32. Gaba, P. et al. Mortality in patients with right bundle-branch block in the absence of cardiovascular disease. J. Am. Heart Assoc. 9, e017430 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  33. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 288, 2981–2997 (2002).

  34. Alventosa-Zaidin, M. et al. Right bundle branch block: prevalence, incidence, and cardiovascular morbidity and mortality in the general population. Eur. J. Gen. Pract. 25, 109–115 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Zhang, S. et al. Strategy of blood pressure intervention in the elderly hypertensive patients (STEP): rational, design, and baseline characteristics for the main trial. Contemp. Clin. Trials 89, 105913 (2020).

    Article  PubMed  Google Scholar 

  36. Zhang, W. et al. Trial of intensive blood-pressure control in older patients with hypertension. N. Engl. J. Med. 385, 1268–1279 (2021).

    Article  CAS  PubMed  Google Scholar 

  37. D’Agostino, R. B. Sr. et al. General cardiovascular risk profile for use in primary care: the framingham heart study. Circulation 117, 743–753 (2008).

    Article  PubMed  Google Scholar 

  38. Fine, J. P. & Gray, R. J. A proportional hazards model for the subdistribution of a competing risk. J. Am. Stat. Assoc. 94, 496–509 (1999).

    Article  Google Scholar 

  39. Seaman, S. R. & White, I. R. Review of inverse probability weighting for dealing with missing data. Stat. Methods Med. Res. 22, 278–295 (2013).

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors sincerely thank all members of the STEP trial research team for their efforts and contributions to this research. This work was supported by Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2021-I2M-1-007), National High Level Hospital Clinical Research Funding (2022-GSP-GG-5, 2022-GSP-PT-12), National Natural Science Foundation of China (project ID. 81825002), Beijing Outstanding Young Scientist Program (project ID, BJJWZYJH01201910023029), Beijing Municipal Science and Technology Commission (project IDs, Z191100006619106 and Z201100005620006) and the key project of Science and Technology Innovation Project of China Academy of Chinese Medical Sciences (project ID, CI2021A00920). Y.Z. was supported by National Nature Science Foundation of China (82170388 and 82370300), Shanghai Technology Research Leader Program (21XD1434700), the Cardiac Rehabilitation Fund by the International Medical Exchange Foundation (Z-2019-42-1908-3) and a grant for the construction of Innovative Flagship Hospital for Integrated Traditional Chinese and Western Medicine (ZY(2021-2023)-0205-05). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

Author information

Author notes

  1. These authors contributed equally: Song Zhao, Yue Deng.

Authors and Affiliations

  1. Department of Cardiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China

    Song Zhao, Shikai Yu, Jun Han & Yi Zhang

  2. Hypertension Center, Fuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Yue Deng & Jun Cai

  3. Hypertension Center, Beijing Anzhen Hospital, Capital Medical University, Beijing, China

    Yixuan Wang

Authors
  1. Song Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yue Deng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yixuan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shikai Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jun Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jun Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yi Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Y.Z. and J.C. designed the study. S.Z. drafted the paper. Y.D. and Y.W. coded and analyzed the data. Y.Z. and J.C. supervised the study and revised the paper. S.Y. and J.H. revised the paper for important intellectual content.

Corresponding authors

Correspondence to Jun Cai or Yi Zhang.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Aging thanks Sanjay Kaul and Nicholas Pajewski for their contribution to the peer review of this work.

Additional information

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

Extended data

Extended Data Fig. 1 The flow of the study sample.

Abbreviations: ECG, electrocardiogram; CSD, conduction system diseases.

Supplementary information

Supplementary Information

Supplementary Tables 1–7 and Strengthening the Reporting of Observational Studies in Epidemiology statement.

Reporting Summary

Source data

Source Data Fig. 1

Statistical results data.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhao, S., Deng, Y., Wang, Y. et al. Incidence and prognosis of cardiac conduction system diseases in hypertension: the STEP trial. Nat Aging 4, 483–490 (2024). https://doi.org/10.1038/s43587-024-00591-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s43587-024-00591-6

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing