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:

Combined effect of visit-to-visit variations in heart rate and systolic blood pressure on all-cause mortality in hypertensive patients

Abstract

Elevated resting heart rate (RHR) and systolic blood pressure (SBP) are independent risk factors for all-cause mortality in hypertensive patients. However, the association of the visit‐to‐visit variation (VVV) in SBP and RHR with the risk of mortality in hypertensive patients remains unknown. The aim of this study was to investigate the effects of the VVVs in SBP and RHR on the risk of all-cause mortality. We enrolled 16,602 hypertensive patients from the Kailuan cohort study who underwent three health examinations from 2006 to 2010. The VVVs in SBP and RHR were defined by the coefficient of variation, standard deviation, variability independent of the mean, and average real variability. High variability was defined as the highest quartile of variability. Participants were classified numerically according to the number of high-variability parameters (e.g., a score of 2 indicated high variability in two parameters). Cox proportional hazards models were used to estimate hazard ratios for mortality. High VVVs in SBP and RHR were associated with an increased risk of all-cause mortality in hypertensive patients. In the multivariable-adjusted model comparing a score of 0 with a score of 2, the hazard ratios (95% confidence intervals (CIs)) for all-cause mortality were 1.38 (1.11–1.69), 1.52 (1.24–1.87), 1.32 (1.07–1.63), and 1.43 (1.16–1.75) using the coefficient of variation, standard deviation, variability independent of the mean, and average real variability, respectively. High VVVs in SBP and RHR constituted an independent risk factor for all-cause mortality in hypertensive patients. High VVVs in SBP and RHR additively increased the risk of all-cause mortality in hypertensive patients.

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

Access options

Buy this article

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

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Rapsomaniki E, Timmis A, George J, Pujades-Rodriguez M, Shah AD, Denaxas S, et al. Blood pressure and incidence of twelve cardiovascular diseases: lifetime risks, healthy life-years lost, and age-specific associations in 1.25 million people. Lancet. 2014;383:1899–911.

    Article  Google Scholar 

  2. Saxena A, Minton D, Lee DC, Sui X, Fayad R, Lavie CJ, et al. Protective role of resting heart rate on all-cause and cardiovascular disease mortality. Mayo Clin Proc. 2013;88:1420–6.

    Article  Google Scholar 

  3. Ho JE, Larson MG, Ghorbani A, Cheng S, Coglianese EE, Vasan RS, et al. Long-term cardiovascular risks associated with an elevated heart rate: the Framingham Heart Study. J Am Heart Assoc. 2014;3:e000668.

    PubMed  PubMed Central  Google Scholar 

  4. Böhm M, Robertson M, Borer J, Ford I, Komajda M, Mahfoud F, et al. Effect of visit-to-visit variation of heart rate and systolic blood pressure on outcomes in chronic systolic heart failure: results from the systolic heart failure treatment with the if inhibitor ivabradine trial (SHIFT) Trial. J Am Heart Assoc. 2016;5:e002160.

    Article  Google Scholar 

  5. Yang X, Hidru TH, Wang B, Han X, Li H, Wu S, et al. The link between elevated long-term resting heart rate and SBP variability for all-cause mortality. J Hypertens. 2019;37:84–91.

    Article  CAS  Google Scholar 

  6. Mehlum MH, Liestøl K, Kjeldsen SE, Julius S, Hua TA, Rothwell PM, et al. Blood pressure variability and risk of cardiovascular events and death in patients with hypertension and different baseline risks. Eur Heart J. 2018;39:2243–51.

    Article  CAS  Google Scholar 

  7. Wang A, Wu J, Zhou Y, Guo X, Luo Y, Wu S, et al. Measures of adiposity and risk of stroke in China: a result from the Kailuan study. PLoS ONE. 2013;8:e61665.

    Article  CAS  Google Scholar 

  8. Wang B, Li H, Han X, Yang Y, Chen Y, Li W, et al. Elevated long term resting heart rate variation is associated with increased risk of all-cause mortality in Northern China. Sci Rep. 2017;7:8043.

    Article  Google Scholar 

  9. Floyd JS, Sitlani CM, Wiggins KL, Wallace E, Suchy-Dicey A, Abbasi SA, et al. Variation in resting heart rate over 4 years and the risks of myocardial infarction and death among older adults. Heart. 2015;101:132–8.

    Article  Google Scholar 

  10. Stevens SL, Wood S, Koshiaris C, Law K, Glasziou P, Stevens RJ, et al. Blood pressure variability and cardiovascular disease: systematic review and meta-analysis. BMJ. 2016;354:i4098.

    Article  Google Scholar 

  11. Mancia G, Schumacher H, Böhm M, Redon J, Schmieder RE, Verdecchia P, et al. Relative and combined prognostic importance of on-treatment mean and visit-to-visit blood pressure variability in ONTARGET and TRANSCEND patients. Hypertension. 2017;70:938–48.

    Article  CAS  Google Scholar 

  12. Wu C, Shlipak MG, Stawski RS, Peralta CA, Psaty BM, Harris TB, et al. Visit-to-visit blood pressure variability and mortality and cardiovascular outcomes among older adults: the health, aging, and body composition study. Am J Hypertens. 2017;30:151–8.

    Article  CAS  Google Scholar 

  13. Chang TI, Reboussin DM, Chertow GM, Cheung AK, Cushman WC, Kostis WJ, et al. Visit-to-visit office blood pressure variability and cardiovascular outcomes in SPRINT (systolic blood pressure intervention trial). Hypertension. 2017;70:751–8.

    Article  CAS  Google Scholar 

  14. Gao S, Hendrie HC, Wang C, Stump TE, Stewart JC, Kesterson J, et al. Redefined blood pressure variability measure and its association with mortality in elderly primary care patients. Hypertension. 2014;64:45–52.

    Article  CAS  Google Scholar 

  15. White WB. Relevance of blood pressure variation in the circadian onset of cardiovascular events. J Hypertens Suppl. 2003;21:S9–15.

    Article  CAS  Google Scholar 

  16. Heidland UE, Strauer BE. Left ventricular muscle mass and elevated heart rate are associated with coronary plaque disruption. Circulation. 2001;104:1477–82.

    Article  CAS  Google Scholar 

  17. Nagareddy PR, Rajput PS, Vasudevan H, McClure B, Kumar U, Macleod KM, et al. Inhibition of matrix metalloproteinase-2 improves endothelial function and prevents hypertension in insulin-resistant rats. Br J Pharmacol. 2012;165:705–15.

    Article  CAS  Google Scholar 

  18. Ciobanu AO, Gherghinescu CL, Dulgheru R, Magda S, Dragoi Galrinho R, Florescu M, et al. The impact of blood pressure variability on subclinical ventricular, renal and vascular dysfunction, in patients with hypertension and diabetes. Maedica. 2013;8:129–36.

    PubMed  PubMed Central  Google Scholar 

  19. Diaz KM, Veerabhadrappa P, Kashem MA, Thakkar SR, Feairheller DL, Sturgeon KM, et al. Visit-to-visit and 24-h blood pressure variability: association with endothelial and smooth muscle function in African Americans. J Hum Hypertens. 2013;27:671–7.

    Article  CAS  Google Scholar 

  20. Zhang L, Li F, Zhi G, Zhang B, Chen YD. NADPH oxidase contributes to the left ventricular dysfunction induced by sinoaortic denervation in rats. Free Radic Res. 2015;49:57–66.

    Article  Google Scholar 

  21. Mangoni AA, Mircoli L, Giannattasio C, Ferrari AU, Mancia G. Heart rate-dependence of arterial distensibility in vivo. J Hypertens. 1996;14:897–901.

    Article  CAS  Google Scholar 

  22. Mircoli L, Mangoni AA, Giannattasio C, Mancia G, Ferrari AU. Heart rate-dependent stiffening of large arteries in intact and sympathectomized rats. Hypertension. 1999;34:598–602.

    Article  CAS  Google Scholar 

  23. Tan I, Butlin M, Spronck B, Xiao H, Avolio A. Effect of heart rate on arterial stiffness as assessed by pulse wave velocity. Curr Hypertens Rev. 2018;14:107–22.

    PubMed  Google Scholar 

  24. Papaioannou TG, Oikonomou E, Lazaros G, Christoforatou E, Vogiatzi G, Tsalamandris S, et al. The influence of resting heart rate on pulse wave velocity measurement is mediated by blood pressure and depends on aortic stiffness levels: insights from the Corinthia study. Physiol Meas. 2019;40:055005.

    Article  Google Scholar 

  25. Satoh M, Hosaka M, Asayama K, Kikuya M, Ohkubo T. Association between N-terminal pro B-type natriuretic peptide and day-to-day blood pressure and heart rate variability in a general population: the Ohasama study. J Hypertens. 2015;33:1536–41

  26. Rodrigues AB, Gismondi RA, Lagoeiro A, Cecilio AM, Marques D, Arita R, et al. Association between B-type natriuretic peptide and within-visit blood pressure variability. Clin Cardiol. 2018;41:778–81

Download references

Acknowledgements

We thank all of the members of the Kailuan Study Group for their contributions, the participants who contributed their data, and Liwen Bianji, Edanz Editing China (www.liwenbianji.cn/ac), for editing the English text of a draft of this manuscript.

Author information

Authors and Affiliations

Authors

Contributions

MXZ had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: MXZ, MW, CW, SY, YL, SZ, CY. Acquisition, analysis, or interpretation of data: MXZ, SW, and HX. Drafting of the manuscript: MXZ, SW, and HX. Critical revision of the manuscript for important intellectual content: all authors. Statistical analysis: MXZ. Supervision: SW and HX.

Corresponding authors

Correspondence to Shouling Wu or Hao Xue.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

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

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhao, M., Yao, S., LI, Y. et al. Combined effect of visit-to-visit variations in heart rate and systolic blood pressure on all-cause mortality in hypertensive patients. Hypertens Res 44, 1291–1299 (2021). https://doi.org/10.1038/s41440-021-00695-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41440-021-00695-1

Keywords

This article is cited by

Search

Quick links