Skip to main content
SpringerLink
Log in

Changing Concepts on the Role of Blood Pressure Reduction in Stroke Prevention with the Focus on β-Blocking Agents

  • Chapter
  • First Online:
Blood Pressure and Arterial Wall Mechanics in Cardiovascular Diseases

  • 1948 Accesses

Abstract

In a recent meta-analysis, we investigated effects of β-blockers versus other classes of antihypertensive drugs on central hemodynamic measurements and explored the impact of heart rate on central hemodynamics and the risk of stroke. The pooled estimates of nine randomized controlled trials (n=754) showed that β-blockers were less efficacious in reducing central augmentation index (cAI) than all the other classes of antihypertensive drugs (8.6 %, P<0.001) and less efficacious in reducing central systolic blood pressure (cSBP) than angiotensin-converting enzyme inhibitors (7.7 mmHg, P=0.02) and angiotensin receptor blockers (3.6 mmHg, P=0.005) but not calcium channel blockers or diuretics (P≥0.50). In a meta-regression analysis of these 9 trials, the baseline-adjusted difference in heart rate between randomized groups was significantly associated with cAI (7.0 % increase for each 10 beats/min decrease in heart rate, P=0.02), which was associated with cSBP (1.2 mmHg increase for each 1 % increase in cAI, P=0.009). In 5 outcome trials, the pooled odds ratio of stroke was 1.23 (P<0.001), which would be accounted for by the difference in cSBP derived from the above meta-regression analysis. These meta-analyses and meta-regression analyses have demonstrated that β-blockers by slowing the heart rate may increase cAI and in turn may decrease cSBP less than other classes of antihypertensive drugs. This mechanism might account for the less reduction in the risk of stroke by β-blockers in hypertension. These findings suggest that central hemodynamics should be measured in the diagnosis and therapeutic monitoring of hypertension, especially when a β-blocker is used.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Staessen JA, Wang JG, Bianchi G, Birkenhäger WH. Essential hypertension. Lancet. 2003;361:1629–41.

    Article  PubMed  Google Scholar 

  2. Collins R, Peto R, MacMahon S, Hebert P, Fiebach NH, Eberlein KA, Godwin J, Qizilbash N, Taylor JO, Hennekens CH. Blood pressure, stroke, and coronary heart disease. Part 2, Short-term reductions in blood pressure: overview of randomised drug trials in their epidemiological context. Lancet. 1990;335:827–38.

    Article  CAS  PubMed  Google Scholar 

  3. Staessen JA, Gąsowski J, Wang JG, Thijs L, Den Hond E, Boissel J, Coope J, Ekbom T, Gueyffier F, Liu L, Kerlikowske K, Pocock S, Fagard RH. Risks of untreated and treated isolated systolic hypertension in the elderly: meta-analysis of outcome trials. Lancet. 2000;355:865–72.

    Article  CAS  PubMed  Google Scholar 

  4. Liu LS, Writing Group of 2010 Chinese Guidelines for the Management of Hypertension. 2010 Chinese guidelines for the management of hypertension. Zhonghua Xin Xue Guan Bing Za Zhi. 2011;39:579–615.

    PubMed  Google Scholar 

  5. Ogihara T, Kikuchi K, Matsuoka H, Fujita T, Higaki J, Horiuchi M, Imai Y, Imaizumi T, Ito S, Iwao H, Kario K, Kawano Y, Kim-Mitsuyama S, Kimura G, Matsubara H, Matsuura H, Naruse M, Saito I, Shimada K, Shimamoto K, Suzuki H, Takishita S, Tanahashi N, Tsuchihashi T, Uchiyama M, Ueda S, Ueshima H, Umemura S, Ishimitsu T, Rakugi H, Japanese Society of Hypertension Committee. The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2009). Hypertens Res. 2009;32:3–107.

    Article  CAS  PubMed  Google Scholar 

  6. Mancia G, Fagard R, Narkiewicz K, Redón J, Zanchetti A, Böhm M, Christiaens T, Cifkova R, De Backer G, Dominiczak A, Galderisi M, Grobbee DE, Jaarsma T, Kirchhof P, Kjeldsen SE, Laurent S, Manolis AJ, Nilsson PM, Ruilope LM, Schmieder RE, Sirnes PA, Sleight P, Viigimaa M, Waeber B, Zannad F, Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). 2013 ESH/ESC Guidelines for the management of arterial hypertension. J Hypertens. 2013;31:1281–357.

    Article  CAS  PubMed  Google Scholar 

  7. Medical Research Council Working Party. MRC trial of treatment of mild hypertension: principal results. Br Med J (Clin Res Ed). 1985;291:97–104.

    Article  Google Scholar 

  8. Dahlof B, Sever PS, Poulter NR, Wedel H, Beevers DG, Caulfield M, Collins R, Kjeldsen SE, Kristinsson A, McInnes GT, Mehlsen J, Nieminen M, O’Brien E, Ostergren J. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet. 2005;366:895–906.

    Article  PubMed  Google Scholar 

  9. Dahlof B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, de Faire U, Fyhrquist F, Ibsen H, Kristiansson K, Lederballe-Pedersen O, Lindholm LH, Nieminen MS, Omvik P, Oparil S, Wedel H. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002;359:995–1003.

    Article  CAS  PubMed  Google Scholar 

  10. Hansson L, Hedner T, Lund-Johansen P, Kjeldsen SE, Lindholm LH, Syvertsen JO, Lanke J, de Faire U, Dahlof B, Karlberg BE. Randomised trial of effects of calcium antagonists compared with diuretics and beta-blockers on cardiovascular morbidity and mortality in hypertension: the Nordic Diltiazem (NORDIL) study. Lancet. 2000;356:359–65.

    Article  CAS  PubMed  Google Scholar 

  11. Messerli FH, Grossman E, Goldbourt U. Are beta-blockers efficacious as first-line therapy for hypertension in the elderly? A systematic review. JAMA. 1998;279:1903–7.

    Article  CAS  PubMed  Google Scholar 

  12. Lindholm LH, Carlberg B, Samuelsson O. Should beta blockers remain first choice in the treatment of primary hypertension? A meta-analysis. Lancet. 2005;366:1545–53.

    Article  CAS  PubMed  Google Scholar 

  13. Wilhelmsen L, Berglund G, Elmfeldt D, Fitzsimons T, Holzgreve H, Hosie J, Hornkvist PE, Pennert K, Tuomilehto J, Wedel H. Beta-blockers versus diuretics in hypertensive men: main results from the HAPPHY trial. J Hypertens. 1987;5:561–72.

    Article  CAS  PubMed  Google Scholar 

  14. Hansson L, Lindholm LH, Ekbom T, Dahlof B, Lanke J, Schersten B, Wester PO, Hedner T, de Faire U. Randomised trial of old and new antihypertensive drugs in elderly patients: cardiovascular mortality and morbidity the Swedish Trial in Old Patients with Hypertension-2 study. Lancet. 1999;354:1751–6.

    Article  CAS  PubMed  Google Scholar 

  15. The IPPPSH Collaborative group. Cardiovascular risk and risk factors in a randomized trial of treatment based on the beta-blocker oxprenolol: the International Prospective Primary Prevention Study in Hypertension (IPPPSH). J Hypertens. 1985;3:379–92.

    Google Scholar 

  16. Pepine CJ, Handberg EM, Cooper-DeHoff RM, Marks RG, Kowey P, Messerli FH, Mancia G, Cangiano JL, Garcia-Barreto D, Keltai M, Erdine S, Bristol HA, Kolb HR, Bakris GL, Cohen JD, Parmley WW. A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease. The International Verapamil-Trandolapril Study (INVEST): a randomized controlled trial. JAMA. 2003;290:2805–16.

    Article  CAS  PubMed  Google Scholar 

  17. UK Prospective Diabetes Study Group. Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. BMJ. 1998;317:713–20.

    Article  PubMed Central  Google Scholar 

  18. Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. BMJ. 2009;338:b1665.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Staessen JA, Wang JG, Thijs L. Cardiovascular protection and blood pressure reduction: a meta-analysis. Lancet. 2001;358:1305–15.

    Article  CAS  PubMed  Google Scholar 

  20. Williams B, Lacy PS, Thom SM, Cruickshank K, Stanton A, Collier D, Hughes AD, Thurston H, O’Rourke M. Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) study. Circulation. 2006;113:1213–25.

    Article  CAS  PubMed  Google Scholar 

  21. Williams B, Lacy PS. Impact of heart rate on central aortic pressures and hemodynamics: analysis from the CAFE (Conduit Artery Function Evaluation) study: CAFE-Heart Rate. J Am Coll Cardiol. 2009;54:705–13.

    Article  PubMed  Google Scholar 

  22. Ding FH, Li Y, Li LH, Wang JG. Impact of heart rate on central hemodynamics and stroke: a meta-analysis of β-blocker trials. Am J Hypertens. 2013;26:118–25.

    Article  CAS  PubMed  Google Scholar 

  23. Pannier BM, Guerin AP, Marchais SJ, London GM. Different aortic reflection wave responses following long-term angiotensin-converting enzyme inhibition and beta-blocker in essential hypertension. Clin Exp Pharmacol Physiol. 2001;28:1074–7.

    Article  CAS  PubMed  Google Scholar 

  24. Deary AJ, Schumann AL, Murfet H, Haydock S, Foo RS, Brown MJ. Influence of drugs and gender on the arterial pulse wave and natriuretic peptide secretion in untreated patients with essential hypertension. Clin Sci (Lond). 2002;103:493–9.

    Article  CAS  Google Scholar 

  25. Morgan T, Lauri J, Bertram D, Anderson A. Effect of different antihypertensive drug classes on central aortic pressure. Am J Hypertens. 2004;17:118–23.

    Article  CAS  PubMed  Google Scholar 

  26. Neal DA, Brown MJ, Wilkinson IB, Byrne CD, Alexander GJ. Hemodynamic effects of amlodipine, bisoprolol, and lisinopril in hypertensive patients after liver transplantation. Transplantation. 2004;77:748–50.

    Article  CAS  PubMed  Google Scholar 

  27. Hirata K, Vlachopoulos C, Adji A, O’Rourke MF. Benefits from angiotensin-converting enzyme inhibitor ‘beyond blood pressure lowering’: beyond blood pressure or beyond the brachial artery. J Hypertens. 2005;23:551–6.

    Article  CAS  PubMed  Google Scholar 

  28. Dhakam Z, McEniery CM, Yasmin, Cockcroft JR, Brown MJ, Wilkinson IB. Atenolol and eprosartan: differential effects on central blood pressure and aortic pulse wave velocity. Am J Hypertens. 2006;19:214–9.

    Article  CAS  PubMed  Google Scholar 

  29. Schneider MP, Delles C, Klingbeil AU, Ludwig M, Kolloch RE, Krekler M, Stumpe KO, Schmieder RE. Effect of angiotensin receptor blockade on central haemodynamics in essential hypertension: results of a randomised trial. J Renin Angiotensin Aldosterone Syst. 2008;9:49–56.

    Article  CAS  PubMed  Google Scholar 

  30. Mackenzie IS, McEniery CM, Dhakam Z, Brown MJ, Cockcroft JR, Wilkinson IB. Comparison of the effects of antihypertensive agents on central blood pressure and arterial stiffness in isolated systolic hypertension. Hypertension. 2009;54:409–13.

    Article  CAS  PubMed  Google Scholar 

  31. Boutouyrie P, Achouba A, Trunet P, Laurent S. Amlodipine-valsartan combination decreases central systolic blood pressure more effectively than the amlodipine-atenolol combination: the EXPLOR study. Hypertension. 2010;55:1314–22.

    Article  CAS  PubMed  Google Scholar 

  32. London GM, Asmar RG, O’Rourke MF, Safar ME. Mechanism(s) of selective systolic blood pressure reduction after a low-dose combination of perindopril/indapamide in hypertensive subjects: comparison with atenolol. J Am Coll Cardiol. 2004;43:92–9.

    Article  CAS  PubMed  Google Scholar 

  33. Dickersin K, Berlin JA. Meta-analysis: state-of-the-science. Epidemiol Rev. 1992;14:154–76.

    CAS  PubMed  Google Scholar 

  34. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–58.

    Article  PubMed  Google Scholar 

  35. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50:1088–101.

    Article  CAS  PubMed  Google Scholar 

  36. Protogerou AD, Stergiou GS, Vlachopoulos C, Blacher J, Achimastos A. The effect of antihypertensive drugs on central blood pressure beyond peripheral blood pressure. Part II: Evidence for specific class-effects of antihypertensive drugs on pressure amplification. Curr Pharm Des. 2009;15:272–89.

    Article  CAS  PubMed  Google Scholar 

  37. Shahin Y, Khan JA, Chetter I. Angiotensin converting enzyme inhibitors effect on arterial stiffness and wave reflections: A meta-analysis and meta-regression of randomised controlled trials. Atherosclerosis. 2012;221:18–33.

    Article  CAS  PubMed  Google Scholar 

  38. MRC Working Party. Medical Research Council trial of treatment of hypertension in older adults: principal results. BMJ. 1992;304:405–12.

    Article  Google Scholar 

  39. Black HR, Elliott WJ, Grandits G, Grambsch P, Lucente T, White WB, Neaton JD, Grimm Jr RH, Hansson L, Lacourciere Y, Muller J, Sleight P, Weber MA, Williams G, Wittes J, Zanchetti A, Anders RJ. Principal results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) trial. JAMA. 2003;289:2073–82.

    Article  CAS  PubMed  Google Scholar 

  40. Zanchetti A, Bond MG, Hennig M, Neiss A, Mancia G, Dal Palu C, Hansson L, Magnani B, Rahn KH, Reid JL, Rodicio J, Safar M, Eckes L, Rizzini P. Calcium antagonist lacidipine slows down progression of asymptomatic carotid atherosclerosis: principal results of the European Lacidipine Study on Atherosclerosis (ELSA), a randomized, double-blind, long-term trial. Circulation. 2002;106:2422–7.

    Article  CAS  PubMed  Google Scholar 

  41. Staessen JA, Wang JG, Thijs L. Cardiovascular prevention and blood pressure reduction: a quantitative overview updated until 1 March 2003. J Hypertens. 2003;21:1055–76.

    Article  CAS  PubMed  Google Scholar 

  42. Epstein BJ, Anderson S. Discordant effects of beta-blockade on central aortic systolic and brachial systolic blood pressure: considerations beyond the cuff. Pharmacotherapy. 2007;27:1322–33.

    Article  CAS  PubMed  Google Scholar 

  43. Elliott WJ, Childers WK. Should beta blockers no longer be considered first-line therapy for the treatment of essential hypertension without comorbidities. Curr Cardiol Rep. 2011;13:507–16.

    Article  PubMed  Google Scholar 

  44. Agabiti-Rosei E, Mancia G, O’Rourke MF, Roman MJ, Safar ME, Smulyan H, Wang JG, Wilkinson IB, Williams B, Vlachopoulos C. Central blood pressure measurements and antihypertensive therapy: a consensus document. Hypertension. 2007;50:154–60.

    Article  CAS  PubMed  Google Scholar 

  45. Hashimoto J, Imai Y, O’Rourke MF. Indices of pulse wave analysis are better predictors of left ventricular mass reduction than cuff pressure. Am J Hypertens. 2007;20:378–84.

    Article  PubMed  Google Scholar 

  46. Cheng HM, Sung SH, Shih YT, Chuang SY, Yu WC, Chen CH. Measurement of central aortic pulse pressure: noninvasive brachial cuff-based estimation by a transfer function vs. a novel pulse wave analysis method. Am J Hypertens. 2012;25:1162–9.

    Article  PubMed  Google Scholar 

  47. Cheng HM, Chuang SY, Sung SH, Yu WC, Pearson A, Lakatta EG, Pan WH, Chen CH. Derivation and validation of diagnostic thresholds for central blood pressure measurements based on long-term cardiovascular risks. J Am Coll Cardiol. 2013;62:1780–7.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Centre for Epidemiological Studies and Clinical Trials, The Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Ruijin 2nd Road 197, Shanghai, 200025, China

    Ji-Guang Wang MD, PhD, Feng-Hua Ding MD, PhD, Li-Hua Li MD & Yan Li MD, PhD

  2. Department of Cardiology, Ruijin Hospital, Shanghai Jiatong University School of Medicine, Ruijin 2nd Road 197, Shanghai, 200025, China

    Feng-Hua Ding MD, PhD

Authors
  1. Ji-Guang Wang MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Feng-Hua Ding MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Li-Hua Li MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yan Li MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ji-Guang Wang MD, PhD .

Editor information

Editors and Affiliations

  1. Hôtel-Dieu Hospital Diagnosis and Therapeutics Center, Paris Descartes University, Paris, Paris, France

    Michel E. Safar

  2. St Vincent Clinic and Hospital, University of New South Wales, Victor Chang Cardiac Research Institute, Darlinghurst, Sydney, New South Wales, Australia

    Michael F. O'Rourke

  3. Department of Cardiology, Ochsner Clinic Foundation, New Orleans, Louisiana, USA

    Edward D. Frohlich

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag London

About this chapter

Cite this chapter

Wang, JG., Ding, FH., Li, LH., Li, Y. (2014). Changing Concepts on the Role of Blood Pressure Reduction in Stroke Prevention with the Focus on β-Blocking Agents. In: Safar, M., O'Rourke, M., Frohlich, E. (eds) Blood Pressure and Arterial Wall Mechanics in Cardiovascular Diseases. Springer, London. https://doi.org/10.1007/978-1-4471-5198-2_38

Download citation

  • DOI: https://doi.org/10.1007/978-1-4471-5198-2_38

  • Published:

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-4471-5197-5

  • Online ISBN: 978-1-4471-5198-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation