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.

  • Review Article
  • Published:

Antihypertensive therapy and sudden cardiac death, should we expect the unexpected?

Journal of Human Hypertension volume 34, pages 339–345 (2020)Cite this article

Subjects

Abstract

Hypertension (HTN) and sudden cardiac death (SCD) constitute major public health problems accounting for millions of deaths each year worldwide. Both HTN and HTN-induced left ventricular hypertrophy (LVH) have been shown to be independent risk factors for SCD. However, the association between antihypertensive pharmacotherapy and risk of SCD has been under-investigated. Given that antihypertensive pharmacotherapy effectively reduces overall cardiovascular mortality, it would be expected to protect patients from SCD. Nevertheless, available data demonstrate that antihypertensive medications (primarily thiazide diuretics), while effective in reducing the incidence of myocardial infarction, do not confer protection from SCD. The purpose of this review was to present the relationship between HTN, LVH, and SCD and to describe the potential association between antihypertensive pharmacotherapy and risk of SCD.

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: Pathogenesis of ventricular arrhythmogenicity and SCD in patients with HTN.

Similar content being viewed by others

References

  1. Al-Khatib SM, Stevenson WG, Ackerman MJ, Bryant WJ, Callans DJ, Curtis AB, et al. 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Circulation. 2018;138:e272–391.

    PubMed  Google Scholar 

  2. Chugh SS. Sudden cardiac death in 2017: spotlight on prediction and prevention. Int J Cardiol. 2017;237:2–5.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Wong CX, Brown A, Lau DH, Chugh SS, Albert CM, Kalman JM, et al. Epidemiology of sudden cardiac death: global and regional perspectives. Heart Lung Circ. 2019;28:6–14.

    Article  PubMed  Google Scholar 

  4. Niemeijer MN, van den Berg ME, Leening MJ, Hofman A, Franco OH, Deckers JW, et al. Declining incidence of sudden cardiac death from 1990–2010 in a general middle-aged and elderly population: the Rotterdam Study. Heart Rhythm. 2015;12:123–9.

    Article  PubMed  Google Scholar 

  5. Priori SG, Blomstrom-Lundqvist C, Mazzanti A, Blom N, Borggrefe M, Camm J, et al. 2015 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: the task force for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). Eur Heart J. 2015;36:2793–867.

    Article  PubMed  Google Scholar 

  6. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R, Prospective Studies C. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360:1903–13.

    Article  PubMed  Google Scholar 

  7. Shenasa M, Shenasa H. Hypertension, left ventricular hypertrophy, and sudden cardiac death. Int J Cardiol. 2017;237:60–3.

    Article  PubMed  Google Scholar 

  8. Kahan T, Bergfeldt L. Left ventricular hypertrophy in hypertension: its arrhythmogenic potential. Heart. 2005;91:250–6.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Ettehad D, Emdin CA, Kiran A, Anderson SG, Callender T, Emberson J, et al. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet. 2016;387:957–67.

    Article  PubMed  Google Scholar 

  10. Tereshchenko LG, Soliman EZ, Davis BR, Oparil S. Risk stratification of sudden cardiac death in hypertension. J Electrocardiol. 2017;50:798–801.

    Article  PubMed  PubMed Central  Google Scholar 

  11. 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  PubMed  PubMed Central  Google Scholar 

  12. Laukkanen JA, Jennings JR, Kauhanen J, Makikallio TH, Ronkainen K, Kurl S. Relation of systemic blood pressure to sudden cardiac death. Am J Cardiol. 2012;110:378–82.

    Article  PubMed  Google Scholar 

  13. Bogle BM, Ning H, Mehrotra S, Goldberger JJ, Lloyd-Jones DM. Lifetime risk for sudden cardiac death in the community. J Am Heart Assoc. 2016;5:e002398.

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  Google Scholar 

  15. Shenasa M, Shenasa H, El-Sherif N. Left ventricular hypertrophy and arrhythmogenesis. Card Electrophysiol Clin. 2015;7:207–20.

    Article  PubMed  Google Scholar 

  16. Messerli FH. Hypertension and sudden cardiac death. Am J Hypertens. 1999;12:181S–8S.

    Article  CAS  PubMed  Google Scholar 

  17. Levy D, Anderson KM, Savage DD, Balkus SA, Kannel WB, Castelli WP. Risk of ventricular arrhythmias in left ventricular hypertrophy: the Framingham Heart Study. Am J Cardiol. 1987;60:560–5.

    Article  CAS  PubMed  Google Scholar 

  18. Haider AW, Larson MG, Benjamin EJ, Levy D. Increased left ventricular mass and hypertrophy are associated with increased risk for sudden death. J Am Coll Cardiol. 1998;32:1454–9.

    Article  CAS  PubMed  Google Scholar 

  19. Cupples LA, Gagnon DR, Kannel WB. Long- and short-term risk of sudden coronary death. Circulation. 1992;85:I11–8.

    CAS  PubMed  Google Scholar 

  20. Reinier K, Dervan C, Singh T, Uy-Evanado A, Lai S, Gunson K, et al. Increased left ventricular mass and decreased left ventricular systolic function have independent pathways to ventricular arrhythmogenesis in coronary artery disease. Heart Rhythm. 2011;8:1177–82.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Verdecchia P, Angeli F, Cavallini C, Aita A, Turturiello D, De Fano M, et al. Sudden cardiac death in hypertensive patients. Hypertension. 2019;73:1071–8.

    Article  CAS  PubMed  Google Scholar 

  22. Manolis AJ, Beldekos D, Handanis S, Haralabidis G, Hatzissavas J, Foussas S, et al. Comparison of spirapril, isradipine, or combination in hypertensive patients with left ventricular hypertrophy: effects on LVH regression and arrhythmogenic propensity. Am J Hypertens. 1998;11:640–8.

    Article  CAS  PubMed  Google Scholar 

  23. Novo S, Abrignani MG, Novo G, Nardi E, Dominguez LJ, Strano A, et al. Effects of drug therapy on cardiac arrhythmias and ischemia in hypertensives with LVH. Am J Hypertens. 2001;14:637–43.

    Article  CAS  PubMed  Google Scholar 

  24. Wachtell K, Okin PM, Olsen MH, Dahlof B, Devereux RB, Ibsen H, et al. Regression of electrocardiographic left ventricular hypertrophy during antihypertensive therapy and reduction in sudden cardiac death: the LIFE study. Circulation. 2007;116:700–5.

    Article  PubMed  Google Scholar 

  25. 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  PubMed Central  Google Scholar 

  26. Heart Outcomes Prevention Evaluation Study I, Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, et al. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000;342:145–53.

    Article  Google Scholar 

  27. Peters R, Beckett N, Forette F, Tuomilehto J, Clarke R, Ritchie C, et al. Incident dementia and blood pressure lowering in the Hypertension in the Very Elderly Trial cognitive function assessment (HYVET-COG): a double-blind, placebo controlled trial. Lancet Neurol. 2008;7:683–9.

    Article  CAS  PubMed  Google Scholar 

  28. Peart S, Brennan P, Broughton P, Dollery C, Hudson M, Lever A. et al. Medical Research Council trial of treatment of hypertension in older adults: principal results. MRC Working Party. BMJ. 1992;304:405–12.

  29. Hoes AW, Grobbee DE, Peet TM, Lubsen J. Do non-potassium-sparing diuretics increase the risk of sudden cardiac death in hypertensive patients? Recent evidence. Drugs. 1994;47:711–33.

    Article  CAS  PubMed  Google Scholar 

  30. Siscovick DS, Raghunathan TE, Psaty BM, Koepsell TD, Wicklund KG, Lin X, et al. Diuretic therapy for hypertension and the risk of primary cardiac arrest. N Engl J Med. 1994;330:1852–7.

    Article  CAS  PubMed  Google Scholar 

  31. Hoes AW, Grobbee DE, Lubsen J, Man in ‘t Veld AJ, van der Does E, Hofman A. Diuretics, beta-blockers, and the risk for sudden cardiac death in hypertensive patients. Ann Intern Med. 1995;123:481–7.

    Article  CAS  PubMed  Google Scholar 

  32. Alharbi FF, Souverein PC, de Groot MCH, Blom MT, de Boer A, Klungel OH, et al. The impact of serum potassium-influencing antihypertensive drugs on the risk of out-of-hospital cardiac arrest: a case-control study. Br J Clin Pharm. 2017;83:2541–8.

    Article  CAS  Google Scholar 

  33. Taverny G, Mimouni Y, LeDigarcher A, Chevalier P, Thijs L, Wright JM, et al. Antihypertensive pharmacotherapy for prevention of sudden cardiac death in hypertensive individuals. Cochrane Database Syst Rev. 2016;3:CD011745.

    PubMed  Google Scholar 

  34. Le HH, Subtil F, Cerou M, Marchant I, Al-Gobari M, Fall M, et al. A sudden death risk score specifically for hypertension: based on 25 648 individual patient data from six randomized controlled trials. J Hypertens. 2017;35:2178–84.

    Article  CAS  PubMed  Google Scholar 

  35. Krogager ML, Torp-Pedersen C, Mortensen RN, Kober L, Gislason G, Sogaard P, et al. Short-term mortality risk of serum potassium levels in hypertension: a retrospective analysis of nationwide registry data. Eur Heart J. 2017;38:104–12.

    CAS  PubMed  Google Scholar 

  36. Papademetriou V. Diuretics, hypokalemia, and cardiac arrhythmia: a 20-year controversy. J Clin Hypertens (Greenwich). 2006;8:86–92.

    Article  Google Scholar 

  37. Moser M. Diuretics and cardiovascular risk factors. Eur Heart J. 1992;13(Suppl G):72–80.

    Article  PubMed  Google Scholar 

  38. Holland OB, Nixon JV, Kuhnert L. Diuretic-induced ventricular ectopic activity. Am J Med. 1981;70:762–8.

    Article  CAS  PubMed  Google Scholar 

  39. Papademetriou V. Diuretics, hypokalemia, and cardiac arrhythmias: a critical analysis. Am Heart J. 1986;111:1217–24.

    Article  CAS  PubMed  Google Scholar 

  40. Papademetriou V, Burris JF, Notargiacomo A, Fletcher RD, Freis ED. Thiazide therapy is not a cause of arrhythmia in patients with systemic hypertension. Arch Intern Med. 1988;148:1272–6.

    Article  CAS  PubMed  Google Scholar 

  41. Papademetriou V, Price M, Notargiacomo A, Gottdiener J, Fletcher RD, Freis ED. Effect of diuretic therapy on ventricular arrhythmias in hypertensive patients with or without left ventricular hypertrophy. Am Heart J. 1985;110:595–9.

    Article  CAS  PubMed  Google Scholar 

  42. Officers A. Coordinators for the ACRGTA, lipid-lowering treatment to prevent heart attack T: 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). J Am Med Assoc. 2002;288:2981–97.

    Article  Google Scholar 

  43. Furberg C, Wright J, Davis B, Cutler J, Alderman M, Black H. et al. Major cardiovascular events in hypertensive patients randomized to doxazosin vs chlorthalidone: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). ALLHAT Collaborative Research Group. JAMA. 2000;283:1967–75.

  44. Alderman MH, Piller LB, Ford CE, Probstfield JL, Oparil S, Cushman WC, et al. Clinical significance of incident hypokalemia and hyperkalemia in treated hypertensive patients in the antihypertensive and lipid-lowering treatment to prevent heart attack trial. Hypertension. 2012;59:926–33.

    Article  CAS  PubMed  Google Scholar 

  45. Cooper HA, Dries DL, Davis CE, Shen YL, Domanski MJ. Diuretics and risk of arrhythmic death in patients with left ventricular dysfunction. Circulation. 1999;100:1311–5.

    Article  CAS  PubMed  Google Scholar 

  46. Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Bohm M, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2013;34:2159–219.

    Article  PubMed  Google Scholar 

  47. James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). J Am Med Assoc. 2014;311:507–20.

    Article  CAS  Google Scholar 

  48. 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: the task force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension. J Hypertens. 2018;36:1953–2041.

    Article  CAS  PubMed  Google Scholar 

  49. Whelton PK, Carey RM, Aronow WS, Casey DE Jr., Collins KJ, Dennison Himmelfarb C, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. J Am Coll Cardiol. 2018;138:e127–248.

    Article  Google Scholar 

  50. Lip GYH, Coca A, Kahan T, Boriani G, Manolis AS, Olsen MH, et al. Hypertension and cardiac arrhythmias: a consensus document from the European Heart Rhythm Association (EHRA) and ESC Council on Hypertension, endorsed by the Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS) and Sociedad Latinoamericana de Estimulacion Cardiaca y Electrofisiologia (SOLEACE). Europace. 2017;19:891–911.

    Article  PubMed  Google Scholar 

  51. Teo KK, Mitchell LB, Pogue J, Bosch J, Dagenais G, Yusuf S, et al. Effect of ramipril in reducing sudden deaths and nonfatal cardiac arrests in high-risk individuals without heart failure or left ventricular dysfunction. Circulation. 2004;110:1413–7.

    Article  CAS  PubMed  Google Scholar 

  52. Lindholm LH, Dahlof B, Edelman JM, Ibsen H, Borch-Johnsen K, Olsen MH, et al. Effect of losartan on sudden cardiac death in people with diabetes: data from the LIFE study. Lancet. 2003;362:619–20.

    Article  CAS  PubMed  Google Scholar 

  53. Ogihara T, Nakao K, Fukui T, Fukiyama K, Ueshima K, Oba K, et al. Effects of candesartan compared with amlodipine in hypertensive patients with high cardiovascular risks: candesartan antihypertensive survival evaluation in Japan trial. Hypertension. 2008;51:393–8.

    Article  CAS  PubMed  Google Scholar 

  54. Pitt B. The role of beta-adrenergic blocking agents in preventing sudden cardiac death. Circulation. 1992;85:I107–11.

    CAS  PubMed  Google Scholar 

  55. Olsson G, Tuomilehto J, Berglund G, Elmfeldt D, Warnold I, Barber H, et al. Primary prevention of sudden cardiovascular death in hypertensive patients. Mortality results from the MAPHY Study. Am J Hypertens. 1991;4:151–8.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Hypertension Excellence Centre—ESH, Department of Cardiology, LAIKO General Hospital, Athens, Greece

    Elias Sanidas, Konstantinos Malliaras, Dimitrios Papadopoulos, Maria Velliou, Konstantinos Tsakalis, Kanella Zerva & John Barbetseas

Authors
  1. Elias Sanidas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Konstantinos Malliaras
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dimitrios Papadopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maria Velliou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Konstantinos Tsakalis
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kanella Zerva
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. John Barbetseas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Elias Sanidas.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

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

Sanidas, E., Malliaras, K., Papadopoulos, D. et al. Antihypertensive therapy and sudden cardiac death, should we expect the unexpected?. J Hum Hypertens 34, 339–345 (2020). https://doi.org/10.1038/s41371-020-0299-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41371-020-0299-3

This article is cited by

Search

Advanced search

Quick links