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High blood pressure with elevated resting heart rate: a high risk “Sympathetic” clinical phenotype

Hypertension Research volume 46, pages 2318–2325 (2023)Cite this article

Abstract

Epidemiological studies have unequivocally shown that elevated heart rate values measured at rest have an adverse prognostic impact in the hypertensive patient, being associated with an increased risk of cardiovascular events and complications. In recent years new data have been collected on this issue, strengthening the clinical relevance of elevated heart rate as a specific hypertensive phenotype. The present paper will review old and new data on the prognostic importance of resting tachycardia in the hypertensive patient. It will also examine the role of the sympathetic nervous system in the development of this alteration as well as its therapeutic implications. The different approaches to dynamically assess heart rate values in the clinical setting will be finally discussed.

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References

  1. Gillman MW, Kannel WB, Belanger A, D’Agostino RB. Influence of heart rate on mortality among persons with hypertension: the Framingham study. Am Heart J. 1993;125:1148–54.

    Article  CAS  PubMed  Google Scholar 

  2. Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, et al. 2018 ESC/ESH guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension. Eur Heart J. 2018;39:3021–104.

    Article  PubMed  Google Scholar 

  3. Mancia G, Kreutz R, Brunström M, Burnier M, Grassi G, Januszewicz A, et al. 2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension Endorsed by the European Renal Association (ERA) and the International Society of Hypertension (ISH). J Hypertens. 2023. https://doi.org/10.1097/HJH.0000000000003480. Online ahead of print.

  4. Grassi G, Vailati S, Bertinieri G, Seravalle G, Stella ML, Dell’Oro R, et al. Heart rate as marker of sympathetic activity. J Hypertens. 1998;16:1635–9.

    Article  CAS  PubMed  Google Scholar 

  5. Cohn JN, Levine TB, Olivari MT, Garberg V, Lura D, Francis GS, et al. Plasma norepinephrine as a guide to prognosis in patients with congestive heart failure. N. Engl J Med. 1984;311:819–23.

    Article  CAS  PubMed  Google Scholar 

  6. Tage-Jensen U, Henriksen JH, Christensen E, Widding A, Ring-Larsen H, Christensen NJ. Plasma catecholamine level and portal venous pressure as guides to prognosis in patients with cirrhosis. J Hepatol. 1988;6:350–8.

    Article  CAS  PubMed  Google Scholar 

  7. Rouleau J, Packer M, Moye L, De Champlain M, Bichet D, Klein M, et al. Prognostic value of neurohumoral activation in patients with an acute myocardial infarction: effect of Captopril. J Am Coll Cardiol. 1994;24:583–91.

    Article  CAS  PubMed  Google Scholar 

  8. Benedict CR, Shelton B, Johnstone DE, Francis G, Greenberg B, Konstam M, et al. Prognostic significance of plasma norepinephrine in patients with asymptomatic left ventricular dysfunction. SOLVD Investigators. Circulation. 1996;94:690–7.

    Article  CAS  PubMed  Google Scholar 

  9. Reuben DB, Talvi SLA, Rowe JW, Seeman TE. High urinary catecholamine excretion predicts mortality and functional decline in high functioning, community dwelling older persons: MacArthur studies of successful aging. J Gerontol. 2000;55:M618–M625.

    Article  CAS  Google Scholar 

  10. Sander D, Winbeck K, Klingelhofer J, Etgen T, Conrad B. Prognostic relevance of pathological sympathetic activation after acute thromboembolic stroke. Neurology. 2001;57:833–8.

    Article  CAS  PubMed  Google Scholar 

  11. Zoccali C, Mallamaci F, Parlongo S, Cutrupi S, Benedetto FA, Tripepi G, et al. Plasma norepinephrine predicts survival and incident cardiovascular events in patients with end-stage renal disease. Circulation. 2002;105:1354–9.

    Article  CAS  PubMed  Google Scholar 

  12. Vesalainen RK, Kantola IM, Airaksinen KEJ, Tahynainen KUO, Kaila TJ. Vagal cardiac activity in essential hypertension: the effects of metoprolol and ramipril. Am J Hypertens. 1998;11:649–58.

    Article  CAS  PubMed  Google Scholar 

  13. Petkovich BW, Vega J, Thomas S. Vagal modulation in hypertension. Curr Hypertens Rep. 2015;17:532.

    Article  PubMed  Google Scholar 

  14. Mancia G, Grassi G. The autonomic nervous system in hypertension. Circ Res. 2014;114:1804–14.

    Article  CAS  PubMed  Google Scholar 

  15. Grassi G, Esler M. How to assess sympathetic activity in humans. J Hypertens. 1999;17:719–34.

    Article  CAS  PubMed  Google Scholar 

  16. Grassi G, Quarti-Trevano F, Seravalle G, Dell’Oro R, Facchetti R, Mancia G. Association between the European Society of Cardiology/European Society of Hypertension heart rate thresholds for cardiovascular risk and neuroadrenergic markers. Hypertension. 2020;76:577–82.

    Article  CAS  PubMed  Google Scholar 

  17. Grassi G, Seravalle G, Vanoli J, Facchetti R, Spaziani D, Mancia G. Relationships between sympathetic markers and heart rate thresholds for cardiovascular risk in chronic heart failure. Clin Res Cardiol. 2023;112:59–67.

    Article  CAS  PubMed  Google Scholar 

  18. Seravalle G, Vanoli J, Molisano C, Merati V, Grassi G. Heart rate thresholds for cardiovascular risk and sympathetic activation in the metabolic syndrome. Acta Diabetol. 2022;59:1429–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Seravalle G, Facchetti R, Cappellini C, Annaloro A, Gelfi E, Grassi G. Elevated heart rate as sympathetic biomarker in human obesity. Nutr Metab Cardiovasc Dis. 2022;32:2367–74.

    Article  CAS  PubMed  Google Scholar 

  20. Grassi G, Fowler B, Scali B, Rossi F, Motto E, Pieruzzi F, et al. Sympathetic activation and heart rate tresholds for cardiovascular risk in chronic kidney disease. J Hypertens. 2022;40:1530–6.

    Article  CAS  PubMed  Google Scholar 

  21. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Benetos A, Rudnichi A, Thomas F, Safar M, Guize L. Influence of heart rate on mortality in a French population: role of age, gender, and blood pressure. Hypertension. 1999;33:44–52.

    Article  CAS  PubMed  Google Scholar 

  23. Wang A, Chen S, Wang C, Zhou Y, Wu Y, Xing A, et al. Resting heart rate and risk of cardiovascular diseases and all-cause death: the Kailuan study. PLoS One. 2014;9:e110985.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Jensen MT, Marott JL, Allin KH, Nordestgaard BG, Jensen GB. Resting heart rate is associated with cardiovascular and all-cause mortality after adjusting for inflammatory markers: the Copenhagen City Heart Study. Eur J Prev Cardiol. 2012;19:102–8.

    Article  PubMed  Google Scholar 

  25. Castagno D, Skali H, Takeuchi M, Swedberg K, Yusuf S, Granger CB, et al. Association of heart rate and outcomes in a broad spectrum of patients with chronic heart failure: results from the CHARM (Candesartan in Heart Failure: Assessment of Reduction in Mortality and morbidity) program. J Am Coll Cardiol. 2012;59:1785–95.

    Article  PubMed  Google Scholar 

  26. Bohm M, Schumacher H, Teo KK, Lonn EM, Mahfoud F, Ukena C, et al. Resting heart rate and cardiovascular outcomes in diabetic and nondiabetic individuals at high cardiovascular risk analysis from the ONTARGET/ TRANSCEND trials. Eur Heart J. 2020;41:231–8.

    Article  PubMed  Google Scholar 

  27. Hillis GS, Woodward M, Rodgers A, Chow CK, Li Q, Zoungas S, et al. Resting heart rate and the risk of death and cardiovascular complications in patients with type 2 diabetes mellitus. Diabetologia. 2012;55:1283–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Palatini P. Resting heart rate as a cardiovascular risk factor in hypertension. Am J Hypertens. 2012;34:307–17.

    Article  Google Scholar 

  29. Palatini P, Parati G, Virdis A, Reboldi G, Masi S, Mengozzi A, et al. High heart rate amplifies the risk of cardiovascular mortality associated with elevated uric acid. Eur Prev Cardiol. 2021;14:zwab023.

    Google Scholar 

  30. Mancia G, Masi S, Palatini P, Tsioufis C, Grassi G. Elevated heart rate and cardiovascular risk in hypertension. J Hypertens. 2021;39:1060–9.

    Article  CAS  PubMed  Google Scholar 

  31. Cuspidi C, Sala C, Casati A, Bombelli M, Grassi G, Mancia G. Clinical and prognostic value of hypertensive cardiac damage in the PAMELA study. Hypertens Res. 2017;40:329–35.

    Article  PubMed  Google Scholar 

  32. Vaz M, Jennings G, Turner A, Cox H, Lambert G, Esler M. Regional sympathetic nervous activity and oxygen consumption in obese normotensive human subjects. Circulation. 1997;96:3423–9.

    Article  CAS  PubMed  Google Scholar 

  33. Grassi G. Sympathetic overdrive and cardiovascular risk in the metabolic syndrome. Hypertens Res. 2006;29:839–47.

    Article  CAS  PubMed  Google Scholar 

  34. Mancia G, Kjeldsen SE, Kreutz R, Pathak A, Grassi G, Esler MD. Individualized beta-blocker treatment for high blood pressure dictated by medical comorbidities. Indications beyond the 2018 European Society of Cardiology/European Society of Hypertension guidelines. Hypertension. 2022;79:1153–66.

    Article  CAS  PubMed  Google Scholar 

  35. Flannery G, Gehrig-Mills R, Billah B, Krum H. Analysis of randomised controlled trials on the effect of magnitude of heart rate reduction on clinical outcomes in patients with systolic chronic heart failure receiving beta-blockers. Am J Cardiol. 2008;101:865–9.

    Article  CAS  PubMed  Google Scholar 

  36. Herman M, Donovan J, Tran M, McKenna B, Gore JM, Goldberg RJ, et al. Use of beta blockers and effects on heart rate and blood pressure post-acute coronary syndromes:are we on target? Am Heart J. 2009;158:784–94.

    Article  Google Scholar 

  37. Kolloch R, Legler UF, Champion A, Cooper-Dehoff RM, Handberg E, Zhou Q, et al. Impact of resting heart rate on outcomes in hypertensive patients with coronary artery disease: findings from the International VErapamil-SR/trandolapril STudy (INVEST). Eur Heart J. 2008;29:1327–34.

    Article  PubMed  Google Scholar 

  38. Lonn EM, Rambihar S, Gao P, Custodis FF, Sliwa K, Teo KK, et al. Heart rate is associated with increased risk of major cardiovascular events, cardiovascular and all-cause death in patients with stable chronic cardiovascular disease: an analysis of ONTARGET/TRANSCEND. Clin Res Cardiol. 2014;103:149–59.

    Article  PubMed  Google Scholar 

  39. Palatini P, Thijs L, Staessen JA, Fagard RH, Bulpitt CJ, Clement DL, et al. Predictive value of clinic and ambulatory heart rate for mortality in elderly subjects with systolic hypertension. Arch Intern Med. 2002;162:2313–21.

    Article  PubMed  Google Scholar 

  40. Julius S, Palatini P, Kjeldsen SE, Zanchetti A, Weber MA, McInnes GT, et al. Usefulness of heart rate to predict cardiac events in treated patients with high-risk systemic hypertension. Am J Cardiol. 2012;109:685–92.

    Article  PubMed  Google Scholar 

  41. Grassi G, Turri C, Vailati S, Dell’Oro R, Mancia G. Muscle and skin sympathetic nerve traffic during the "white-coat" effect. Circulation. 1999;100:222–5.

    Article  CAS  PubMed  Google Scholar 

  42. Palatini P, Winnicki M, Santonastaso M, De Venuto G, Zanata G, Bertolo O, et al. Reproducibility of heart rate measured in the clinic and with 24-hour intermittent recorders. Am J Hypertens. 2000;13:92–98.

    Article  CAS  PubMed  Google Scholar 

  43. Palatini P, Reboldi G, Beilin LJ, Eguchi K, Imai Y, Kario K, et al. Predictive value of night-time heart rate for cardiovascular events in hypertension. The ABP-International study. Int J Cardiol. 2012;168:1490–5.

    Article  Google Scholar 

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Author notes

  1. These authors contributed equally: Guido Grassi, Raffaella Dell’Oro

Authors and Affiliations

  1. Clinica Medica, Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy

    Guido Grassi, Raffaella Dell’Oro, Michele Bombelli, Cesare Cuspidi & Fosca Quarti-Trevano

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  1. Guido Grassi
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Correspondence to Guido Grassi.

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Grassi, G., Dell’Oro, R., Bombelli, M. et al. High blood pressure with elevated resting heart rate: a high risk “Sympathetic” clinical phenotype. Hypertens Res 46, 2318–2325 (2023). https://doi.org/10.1038/s41440-023-01394-9

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  • DOI: https://doi.org/10.1038/s41440-023-01394-9

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