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.

Blood pressure targets in the treatment of high blood pressure: a reappraisal of the J-shaped phenomenon

A Corrigendum to this article was published on 08 January 2014

This article has been updated

Abstract

The risk that lowering blood pressure (BP) excessively increases the incidence of cardiovascular disease—the J-shaped phenomenon—has been a matter of concern endorsed by many experts, particularly in patients with coronary heart disease and diabetes. The results of the Action to Control Cardiovascular Risk in Type 2 Diabetes (ACCORD) trial strengthened the idea that it may be futile to lower BP more intensively in patients with diabetes. Nevertheless, there seems to be no direct J-shaped relation between BP-lowering treatment and outcome. Patients with normal or low BP and high or very high cardiovascular risk could have their BP reduced further by treatment. Placebo-controlled clinical trials of BP-lowering agents in patients with BP within normal values and concomitant cardiovascular disease demonstrated consistent reduction of recurrent and newer cardiovascular events. The use of BP agents in such conditions, as in patients with coronary artery disease, heart failure, diabetes and in patients recovered from a stroke has been endorsed by guidelines. Although is likely that there is a J-shaped relationship of BP with outcomes in cohort studies, clinical trials that tested more intensive versus standard goals and clinical trials done with patients with low BP demonstrated that the J-shaped phenomenon should not be a concern in the treatment of high BP.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1
Figure 2
Figure 3
Figure 4

Change history

  • 08 January 2014

    This article has been corrected since online publication and a corrigendum is also printed in this issue.

References

  1. Anderson TW . Re-examination of some of the Framingham blood pressure data. Lancet 1978; 2: 1139–1141.

    CAS  Article  PubMed Central  Google Scholar 

  2. Stewart IM . Relation of reduction in pressure to first myocardial infarction in patients receiving treatment for severe hypertension. Lancet 1979; 1: 861–865.

    CAS  Article  Google Scholar 

  3. Cruickshank JM, Thorp JM, Zacharias FJ . Benefits and potential harm of lowering high blood pressure. Lancet 1987; 1: 581–584.

    CAS  Article  Google Scholar 

  4. Farnett L, Mulrow CD, Linn WD, Lucey CR, Tuley MR . The J-curve phenomenon and the treatment of hypertension. Is there a point beyond which pressure reduction is dangerous? JAMA 1991; 265: 489–495.

    CAS  Article  Google Scholar 

  5. Lindblad U, Rastam L, Ryden L, Ranstam J, Isacsson SO, Berglund G . Control of blood pressure and risk of first acute myocardial infarction: Skaraborg hypertension project. BMJ 1994; 308: 681–686.

    CAS  Article  PubMed Central  Google Scholar 

  6. Owens P, O’Brien E . Hypotension in patients with coronary disease: can profound hypotensive events cause myocardial ischaemic events? Heart 1999; 82: 477–481.

    CAS  Article  PubMed Central  Google Scholar 

  7. Hansson L, Zanchetti A, Carruthers SG, Dahlof B, Elmfeldt D, Julius S et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group. Lancet 1998; 351: 1755–1762.

    CAS  Article  Google Scholar 

  8. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr et al. The seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure: The JNC 7 Report. JAMA 2003; 289: 2560–2571.

    CAS  Article  PubMed Central  Google Scholar 

  9. Mancia G, Laurent S, Agabiti-Roseic E, Ambrosioni E, Burnier M, Caulfield MJ et al. Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document. J Hypertens 2009; 27: 2121–2158.

    CAS  Article  Google Scholar 

  10. Cruickshank JM . Antihypertensive treatment and the J-curve. Cardiovasc Drugs Ther 2000; 14: 373–379.

    CAS  Article  Google Scholar 

  11. ACCORD Study Group, Cushman WC,, Evans GW, Byington RP, Goff DC Jr, Grimm RH Jr et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med 2010; 362: 1575–1585.

    Article  Google Scholar 

  12. Chobanian AV . Mixed messages on blood pressure goals. Hypertension 2011; 57: 1039–1040.

    CAS  Article  Google Scholar 

  13. Mizuno R, Fujimoto S, Saito Y, Okamoto Y . Optimal antihypertensive level for improvement of coronary microvascular dysfunction: the lower, the better? Hypertension 2012; 60: 326–332.

    CAS  Article  Google Scholar 

  14. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R . 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: 1903–1913.

    Article  PubMed Central  Google Scholar 

  15. Fuchs FD, Fuchs SC, Moreira LB, Gus M . Proof of concept in cardiovascular risk: the paradoxical findings in blood pressure and lipid abnormalities. Vasc Health Risk Manag 2012; 8: 437–442.

    Article  PubMed Central  Google Scholar 

  16. 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.

    CAS  Article  PubMed Central  Google Scholar 

  17. Beckett NS, Peters R, Fletcher AE, Staessen JA, Liu L, Dumitrascu D et al HYVET Study Group. Treatment of hypertension in patients 80 years of age or older. N Engl J Med 2008; 358: 1887–1898.

    CAS  Article  Google Scholar 

  18. Langer RD, Ganiats TG, Barrett-Connor E . Paradoxical survival of elderly men with high blood pressure. BMJ 1989; 298: 1356–1358.

    CAS  Article  PubMed Central  Google Scholar 

  19. Okumiya K, Matsubayashi K, Wada T, Fujisawa M, Osaki Y, Doi Y et al. A U-shaped association between home systolic blood pressure and four-year mortality in community-dwelling older men. J Am Geriatr Soc 1999; 47: 1415–1421.

    CAS  Article  Google Scholar 

  20. Werle MH, Moriguchi E, Fuchs SC, Bruscato NM, de Carli W, Fuchs FD . Risk factors for cardiovascular disease in the very elderly: results of a cohort study in a city in southern Brazil. Eur J Cardiovasc Prev Rehabil 2011; 18: 369–377.

    Article  PubMed Central  Google Scholar 

  21. Glynn RJ, L’Italien GJ, Sesso HD, Jackson EA, Buring JE . Development of predictive models for long-term cardiovascular risk associated with systolic and diastolic blood pressure. Hypertension 2002; 39: 105–110.

    CAS  Article  Google Scholar 

  22. Psaty BM, Furberg CD, Kuller LH, Cushman M, Savage PJ, Levine D et al. Association between blood pressure level and the risk of myocardial infarction, stroke, and total mortality: the cardiovascular health study. Arch Intern Med 2001; 161: 1183–1192.

    CAS  Article  PubMed Central  Google Scholar 

  23. van Bemmel T, Holman ER, Gussekloo J, Blauw GJ, Bax JJ, Westendorp RG . Low blood pressure in the very old, a consequence of imminent heart failure: the Leiden 85-plus Study. J Hum Hypertens 2009; 23: 27–32.

    CAS  Article  Google Scholar 

  24. Odden MC, Peralta CA, Haan MN, Covinsky KE . Rethinking the association of high blood pressure with mortality in elderly adults: the impact of frailty. Arch Intern Med 2012; 172: 1162–1168.

    Article  PubMed Central  Google Scholar 

  25. Messerli FH, Mancia G, Conti CR, Hewkin AC, Kupfer S, Champion A et al. Dogma disputed: can aggressively lowering blood pressure in hypertensive patients with coronary artery disease be dangerous? Ann Intern Med 2006; 144: 884–893.

    Article  PubMed Central  Google Scholar 

  26. Kai H, Ueno T, Kimura T, Adachi H, Furukawa Y, Kita T et al CREDO-Kyoto Investigators. Low DBP may not be an independent risk for cardiovascular death in revascularized coronary artery disease patients. J Hypertens 2011; 29: 1889–1896.

    CAS  Article  PubMed Central  Google Scholar 

  27. Davis EM, Appel LJ, Wang X, Greene T, Astor BC, Rahman M et al African American Study of Kidney Disease and Hypertension Research Collaborative Group. Limitations of analyses based on achieved blood pressure: lessons from the African American study of kidney disease and hypertension trial. Hypertension 2011; 57: 1061–1068.

    CAS  Article  PubMed Central  Google Scholar 

  28. Fuchs FD . Blood pressure-lowering drugs: essential therapy for some patients with normal blood pressure. Expert Rev Cardiovasc Ther 2004; 2: 771–775.

    CAS  Article  PubMed Central  Google Scholar 

  29. The Heart Outcomes Prevention Evaluation Study Investigators. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Lancet 2000; 355: 253–259.

    Article  Google Scholar 

  30. Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G and The Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med 2000; 342: 145–153.

    CAS  Article  PubMed Central  Google Scholar 

  31. Fox KM and EURopean trial on reduction of cardiac events with Perindopril in stable coronary Artery disease Investigators. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet 2003; 362: 782–788.

    CAS  Article  Google Scholar 

  32. PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack. Lancet 2001; 358: 1033–1041.

    Article  Google Scholar 

  33. The SOLVD investigators. Effect of enalapril on mortality and development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Eng J Med 1992; 327: 685–691.

    Article  Google Scholar 

  34. The SOLVD investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Eng J Med 1991; 325: 669–677.

    Article  Google Scholar 

  35. Pfeffer MA, Braunwald E, Moye LA, Basta L, Brown EJ Jr, Cuddy TE et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction: results of the Survival and Ventricular Enlargement Trial. The SAVE Investigators. N Eng J Med 1992; 327: 669–677.

    CAS  Article  Google Scholar 

  36. Thompson AM, Hu T, Eshelbrenner CL, Reynolds K, He J, Bazzano LA . Antihypertensive treatment and secondary prevention of cardiovascular disease events among persons without hypertension: a meta-analysis. JAMA 2011; 305: 913–922.

    CAS  Article  PubMed Central  Google Scholar 

  37. Fuchs FD, Fuchs SC, Moreira LB, Gus M, Nóbrega AC, Poli-de-Figueiredo CE et al. Prevention of hypertension in patients with pre-hypertension: protocol for the PREVER-prevention trial. Trials 2011; 12: 65.

    CAS  Article  PubMed Central  Google Scholar 

  38. The CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. N Eng J Med 1987; 316: 1429–1435.

    Article  Google Scholar 

  39. Reboldi G, Gentile G, Angeli F, Ambrosio G, Mancia G, Verdecchia P . Effects of intensive blood pressure reduction on myocardial infarction and stroke in diabetes: a meta-analysis in 73,913 patients. J Hypertens 2011; 29: 1253–1269.

    CAS  Article  Google Scholar 

  40. McBrien K, Rabi DM, Campbell N, Barnieh L, Clement F, Hemmelgarn BR et al. Intensive and standard blood pressure targets in patients with type 2 diabetes mellitus: systematic review and meta-analysis. Arch Intern Med 2012; 172: 1296–1303.

    Article  PubMed Central  Google Scholar 

  41. Smith SC Jr, Benjamin EJ, Bonow RO, Braun LT, Creager MA, Franklin BA et al World Heart Federation and the Preventive Cardiovascular Nurses Association. AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients with Coronary and other Atherosclerotic Vascular Disease: 2011 update: a guideline from the American Heart Association and American College of Cardiology Foundation. Circulation 2011; 124: 2458–2473.

    Article  PubMed Central  Google Scholar 

Download references

Acknowledgements

This study was supported, in part, by the National Institute of Science and Technology for Health Technology Assessment (IATS)—CNPq/Brazil.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to F D Fuchs.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Fuchs, F., Fuchs, S. Blood pressure targets in the treatment of high blood pressure: a reappraisal of the J-shaped phenomenon. J Hum Hypertens 28, 80–84 (2014). https://doi.org/10.1038/jhh.2013.78

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jhh.2013.78

Keywords

  • J-shaped phenomenon
  • blood pressure treatment
  • blood pressure targets

Further reading

Search

Quick links