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The J-curve in hypertension

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Abstract

The J-curve debate has continued for 25 years. Dependency upon observational and retrospective studies has confused the issue; only the full publication of data from the prospective, randomized Hypertension Optimal Treatment (HOT) study has thrown genuine light on the problem. Many examples of the J-curve relationship between blood pressure and cardiovascular/noncardiovascular events are due to reverse causality, where underlying disease (eg, poor left ventricular function, poor general health, poorly compliant/stiff arteries) is the cause of both the low blood pressure and the increased risk of both cardiovascular and noncardiovascular events. The J-curve in patients with stiff arteries (wide pulse pressure) may be exacerbated by treatment. From the full publication of the HOT study database it is now reasonable to conclude that for nonischemic hypertensive subjects the therapeutic lowering of diastolic blood pressure (DBP) to the low 80s mm Hg is beneficial, but it is safe (though unproductive) to go lower. However, in the presence of coronary artery disease (limited coronary flow reserve) there is a J-curve relationship between treated DBP and myocardial infarction, but not for stroke. In such high-risk (for myocardial infarction) cases it would be prudent to avoid lowering DBP to below the low 80s mm Hg.

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References and Recommended Reading

  1. Lew EA: High blood pressure, other risk factors and longevity: the insurance viewpoint. Am J Med 1973, 35:281–294.

    Article  Google Scholar 

  2. McMahon, S, Peto R, Curler J, et al.: Blood pressure, stroke, and coronary heart disease. Part 1. Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet 1990, 335:765–774.

    Article  Google Scholar 

  3. Prospective Studies Collaboration: Age-specific relevance of usual blood pressure to vascular mortality: a meta-analyses of individual data for one million adults in 61 prospective studies. Lancet 2002, 360:1903–1913. In 1 million subjects with no previous vascular disease usual BP is strongly and directly related to vascular (and overall) mortality, without any evidence of a threshold down to at least 115/75 mm Hg.

    Article  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  6. Green KG: Optimised blood pressure. Lancet 1979, 2:33.

    Article  PubMed  CAS  Google Scholar 

  7. Strandgaard S, Haunso S: Why does anti-hypertensive treatment prevent stroke but not myocardial infarction. Lancet 1987, 2:658–661.

    Article  PubMed  CAS  Google Scholar 

  8. Strandgaard S: Autoregulation of cerebral blood flow in hypertensive patients. The modifying influence of prolonged antihypertensive treatment on the tolerance to acute, druginduced hypotension. Circulation 1976, 53:720–727.

    PubMed  CAS  Google Scholar 

  9. Romero JC, Ruilhope LM, Bentley MD, et al.: Comparison of the effects of calcium antagonists and converting enzyme inhibitors on renal function under normal and hypertensive conditions. Am J Cardiol 1988, 62:59G-68G.

    Article  PubMed  CAS  Google Scholar 

  10. Hricik DE, Browning PJ, Kopelman R, et al.: Captopril — induced functional renal insufficiency in patients with bilateral renalartery stenosis. New Engl J Med 1983, 308:373–376.

    Article  PubMed  CAS  Google Scholar 

  11. Spiers CJ, Dollery CT, Inman WH, et al.: Post-marketing surveillance of enalapril. II. Investigation of the potential role of enalapril in deaths with renal failure. BMJ 1988, 297:830–832.

    Google Scholar 

  12. Gorlin R: Dynamic vascular factors in the genesis of myocardial ischaemia. J Am Coll Cardiol 1983, 1:897–906.

    Article  PubMed  CAS  Google Scholar 

  13. Klocke FJ: Measurements of coronary flow reserve: defining pathophysiology versus making decisions about patient care. Circulation 1987, 76:1183–1189.

    PubMed  CAS  Google Scholar 

  14. Buffington CW: Haemodynamic determinants of ischemic myocardial dysfunction in the presence of coronary stenosis in dogs. Anesthesiolgy 1985, 63:651–652.

    Article  CAS  Google Scholar 

  15. Collins P, Cruickshank JM, Keegan J, Fox K: Acute blood pressure reduction causes impairment of left ventricular function in hypertensive patients with coronary heart disease and left ventricular hypertrophy. Eur Hear J 1991, 12:242.

    Article  Google Scholar 

  16. Owens P, O’Brien E: Hypotension in patients with coronary heart disease: can profound hypotensive events cause myocardial ischemic events. Heart 1999, 82:477–481.

    PubMed  CAS  Google Scholar 

  17. Strauer BE: Left ventricular hypertrophy and coronary flow reserve. In Left Ventricular Hypertrophy and Its Regression. Edited by Cruickshank JM, Messerli FH. London: Science Press; 1992:49–60.

    Google Scholar 

  18. Schwartzkopff B, Mundhenke M, Strauer BE: Remodelling of intramyocardial arterioles and extracellular matrix in patients with arterial hypertension and impaired coronary reserve. Eur Heart J 1995, 16:82–86.

    PubMed  Google Scholar 

  19. Pepi M, Alimento M, Maltagliati A, Guazzi MD: Cardiac hypertrophy in hypertension. Repolarization abnormalities elicited by rapid lowering of pressure. Hypertension 1998, 11:84–91.

    Google Scholar 

  20. Polese A, DeCesare N, Montorsi P, et al.: Upward shift of the lower range of coronary flow autoregulation in hypertensive patients with hypertrophy of the left ventricle. Circulation 1991, 83:845–853.

    PubMed  CAS  Google Scholar 

  21. Cruickshank JM, Polese A: Left ventricular hypertrophy and the possible harmful effects of the excessive lowering of diastolic blood pressure. In Left Ventricular Hypertrophy and its Regression. Edited by Cruickshank JM, Messerli FH. London: Science Press; 1992:61–69.

    Google Scholar 

  22. Coope J, Warrender TS: Randomized trial of treatment of hypertension in elderly patients in primary care. Br Med J 1986, 293:1145–1151.

    CAS  Google Scholar 

  23. D’Agostino RB, Belanger AJ, Kannel WB, Cruickshank JM: Relation of low diastolic blood pressure to coronary heart disease death in the presence of myocardial infarction: the Framingham Study. BMJ 1991, 303:385–389.

    PubMed  CAS  Google Scholar 

  24. Flack JM, Neaton J, Grimm R, et al.: Blood pressure and mortality among men with prior myocardial infarction. Circulation 1995, 92:2437–2445.

    PubMed  CAS  Google Scholar 

  25. Boutitie F, Gueyffier F, Pockock S, et al.: J-shaped relationship between blood pressure and mortality in hypertensive patients: new insights from a meta-analysis of individualpatient data. Ann Intern Med 2002, 136:438–448. In a meta-analysis of seven randomized trials, involving 40,223 hypertensive patients (mean age 68 years), there was a J-curved relationship between DBP and SBP and cardiovascular and noncardiovascular deaths. The J-curve was thought to be due to poor health and not related to antihypertensive treatment.

    PubMed  Google Scholar 

  26. Amery A, Birkenhager W, Brixko P, et al.: Mortality and morbidity results from the European Working Party on High Blood Pressure in the Elderly trial (EWPHE). Lancet 1985, 1:1349–1354.

    Article  PubMed  CAS  Google Scholar 

  27. Hypertension Detection and Follow-up Program (HDFP) Cooperative Group: Five year findings of the hypertension detection and follow-up program. 1. Reduction in mortality in persons with high blood pressure, including mild hypertension. JAMA 1979, 242:2562–2571.

    Article  Google Scholar 

  28. Medical Research Council Working Party: MRC trial of treatment of mild hypertension: principal results. BMJ 1985, 291:97–104.

    Google Scholar 

  29. Medical Research Council Working Party: Medical research council trial of treatment of hypertension in older adults: principal results. BMJ 1992, 304:405–412.

    Article  Google Scholar 

  30. SHEP Cooperative Group: Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA 1991, 265:3255–3264.

    Article  Google Scholar 

  31. Dahlof B, Lindholm LH, Hansson L, et al.: Morbidity and mortality in the Swedish Trial in Old Patients with Hypertension (STOP — Hypertension). Lancet 1991, 338:1231–1235.

    Article  Google Scholar 

  32. Glynn RJ, Field TS, Rosner B, et al.: Evidence for a positive linear relation between blood pressure and mortality in elderly people. Lancet 1995, 345:825–829.

    Article  PubMed  CAS  Google Scholar 

  33. O’Rourke M: From theory into practice: arterial haemodynamics in clinical hypertension. J Hypertens 2002, 20:1901–1915.

    Article  PubMed  CAS  Google Scholar 

  34. Boutouyrie P, Tropeano AI, Asmar R, et al.: Aortic stiffness is an independent predictor of primary coronary events in hypertensive patients. Hypertension 2002, 39:10–15.

    Article  PubMed  CAS  Google Scholar 

  35. Fang J, Madhaven S, Cohen H, Alderman MH: Measures of blood pressure and myocardial infarction in treated hypertensive patients. J Hypertens 1995, 13:413–419.

    Article  PubMed  CAS  Google Scholar 

  36. Benetos A, Safar M, Rudnichi A, et al.: Pulse-pressure: a predictor of long-term cardiovascular mortality in a French male population. Hypertension 1997, 30:1410–1415.

    PubMed  CAS  Google Scholar 

  37. Mitchell GF, Moye LA, Braunwald E, et al.: Sphygmomanometrically determined pulse-pressure is a powerful independent predictor of recurrent events after myocardial infarction in patients with impaired left ventricular function, SAVE investigators. Circulation 1997, 96:4254–4260.

    PubMed  CAS  Google Scholar 

  38. Chae CU, Pfeffer MA, Glynn RJ, et al.: Increased pulse-pressure and risk of heart failure in the elderly. JAMA 1999, 281:634–639.

    Article  PubMed  CAS  Google Scholar 

  39. Domanski MJ, Davis BR, Pfeffer MA, et al.: Isolated systolic hypertension. Prognostic information provided by pulsepressure. Hypertension 1999, 34:375–380.

    PubMed  CAS  Google Scholar 

  40. Frankin SS, Khan SA, Wong ND, et al.: Is pulse-pressure useful in predicting risk for coronary heart disease. The Framingham Study. Circulation 1999, 100:354–360.

    Google Scholar 

  41. Lee ML, Rosner BA, West ST: Relationship of blood pressure to cardiovascular death: the effects of pulse-pressure in the elderly. Ann Epidemiol 1999, 9:101–107.

    Article  PubMed  CAS  Google Scholar 

  42. Millar JA, Lever AF, Burke V: Pulse-pressure as a risk factor for cardiovascular events in the MRC Mild Hypertension Trial. J Hypertens 1999, 17:1065–1072.

    Article  PubMed  CAS  Google Scholar 

  43. Sesso HD, Stampfer MJ, Rosner B, et al.: Two-year changes in blood pressure and subsequent risk of cardiovascular disease in men. Circulation 2000, 102:307–312.

    PubMed  CAS  Google Scholar 

  44. Benetos A, Thomas F, Safar ME, et al.: Should diastolic and systolic blood pressure be considered for cardiovascular risk evaluation: a study in middle-aged men and women. J Am Coll Cardiol 2001, 37:163–168.

    Article  PubMed  CAS  Google Scholar 

  45. Franklin SS, Larson MG, Khan SA, et al.: Does the relation of blood pressure to coronary heart disease change with aging. The Framingham Heart Study. Circulation 2001, 103:1245–1249.

    PubMed  CAS  Google Scholar 

  46. Khattar RS, Swales JD, Dore C, et al.: Effect of aging on the prognostic significance of ambulatory systolic, diastolic and pulse-pressure in essential hypertension. Circulation 2001, 104:783–789.

    PubMed  CAS  Google Scholar 

  47. Psaty BM, Furberg CD, Kuller LH, et al.: Association between blood pressure level and the risk of myocardial infarction, stroke, and total mortality. Arch Intern Med 2001, 161:1183–1192.

    Article  PubMed  CAS  Google Scholar 

  48. Thomas F, Bean K, Provost J-C, et al.: Combined effects of heart rate and pulse-pressure on cardiovascular mortality according to age. J Hypertens 2001, 19:863–869.

    Article  PubMed  CAS  Google Scholar 

  49. Vaccarino V, Berger AK, Abramson J, et al.: Pulse-pressure and risk of cardiovascular events in the Systolic Hypotension in the Elderly Program (SHEP). Am J Cardiol 2001, 88:980–986.

    Article  PubMed  CAS  Google Scholar 

  50. Verdecchia P, Schillaci G, Reboldi G, et al.: Different prognostic impact of 24-hour mean blood pressure and pulse-pressure on stroke and coronary artery disease in essential hypertension. Circulation 2001, 103:2579–2584.

    PubMed  CAS  Google Scholar 

  51. Borghi C, Dormi A, Ambrosini E, Gaddi A, on behalf of the Brisighella Heart Study Working Party: Relative role of systolic, diastolic and pulse-pressure as risk factors for cardiovascular events in the Brisighella Heart Study. J Hypertens 2002, 20:1737–1742.

    Article  PubMed  CAS  Google Scholar 

  52. Domanski M, Mitchell G, Pfeffer M, et al.: Pulse-pressure and cardiovascular disease-related mortality. Follow-up study of MRFIT. JAMA 2002, 287:2677–2683.

    Article  PubMed  Google Scholar 

  53. Gasowski J, Fagard RH, Staessen JA, et al.: Pulsatile blood pressure component as a predictor of mortality in hypertension; a meta-analysis of clinical trial control groups. J Hypertens 2002, 20:145–151.

    Article  PubMed  CAS  Google Scholar 

  54. Klassen PS, Lowrie EG, Reddam DN, et al.: Association between pulse-pressure and mortality in patients undergoing maintenance haemodialysis. JAMA 2002, 287:1548–1555.

    Article  PubMed  Google Scholar 

  55. Schram MT, Kostense PJ, van Dijk RAJM: Diabetes, pulsepressure and cardiovascular mortality: the Hoorn Study. J Hypertens 2002, 20:1743–1751.

    Article  PubMed  CAS  Google Scholar 

  56. Staessen JA, Thijs L, O’Brien ET, et al.: Ambulatory pulse-pressure as predictor of outcome in older patients with systolic hypertension. Am J Hypertens 2002, 15:835–843.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  58. Farnett L, Mulrow CD, Linn WD, et al.: The J-curve phenomenon and the treatment of hypertension. JAMA 1991, 265:489–495.

    Article  PubMed  CAS  Google Scholar 

  59. Fletcher AE, Beevers DG, Bulpitt CJ, et al.: The relationship between a low treated blood pressure and IHD mortality: a report from the DHSS Hypertension Care Computing Project. J Hum Hypertens 1988, 2:11–15.

    PubMed  CAS  Google Scholar 

  60. Cooper SP, Hardy RJ, Labarthe DR, et al.: The relation between degree of blood pressure reduction and mortality among hypertensives in the Hypertension Detection and Follow-up Program. Am J Epidemiol 1988, 127:387–402.

    PubMed  CAS  Google Scholar 

  61. Waller PC, Isles CG, Lever AF, et al.: Does therapeutic reduction of diastolic blood pressure cause death from coronary heart disease. J Hum Hypertens 1988, 2:7–10.

    PubMed  CAS  Google Scholar 

  62. Alderman MH, Ooi WL, Madhavan S: Treatment-induced blood pressure reduction and the risk of myocardial infarction. JAMA 1989, 262:920–924.

    Article  PubMed  CAS  Google Scholar 

  63. Samuelsson O, Wilhelmsen L, Anderson OK, et al.: Cardiovascular morbidity in relation to change in blood pressure and serum cholesterol levels in treated hypertension results from the Primary Prevention Trial in Gotelorg, Sweden. JAMA 1987, 258:1768–1776.

    Article  PubMed  CAS  Google Scholar 

  64. 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, 3:379–392.

    Article  Google Scholar 

  65. Report by the Management Committee of the Australian Therapeutic Trial in Mild Hypertension: Untreated mild hypertension. Lancet 1982, 1:185–191.

    Google Scholar 

  66. Berglund G: Goals of anti-hypertensive therapy: is there a point beyond which reduction is dangerous. Am J Hypertens 1989, 2:586–593.

    PubMed  CAS  Google Scholar 

  67. Wilhelmsen L, Berglund G, Elmfeldt D, et al.: Beta-blockers versus diuretics in hypertensive men: main results from the HAPPY trial. J Hypertens 1987, 5:561–572.

    Article  PubMed  CAS  Google Scholar 

  68. Samuelsson OG, Wilhelmsen LW, Pennert KM, et al.: The Jshaped relationship between coronary heart disease and achieved blood pressure level in treated hypertension: further analysis of 12 years of follow up of treated hypertensives in the Primary Prevention Trial in Gothenberg, Sweden. J Hypertens 1990, 8:847–855.

    Article  Google Scholar 

  69. McClosky LW, Psaty BM, Koepsell TD, Aagaard GN: Level of blood pressure and risk of myocardial infarction among treated hypertensives. Arch Intern Med 1992, 152:513–520.

    Article  Google Scholar 

  70. Lindblad U, Rostam L, Ryder L, et al.: Control of blood pressure and the risk of first acute myocardial infarction: Skaraborg hypertension project. BMJ 1994, 308:681–686.

    PubMed  CAS  Google Scholar 

  71. Somes GW, Pahor M, Shorr RI, et al.: The role of diastolic blood pressure when treating isolated systolic hypertension. Arch Intern Med 1999, 159:2004–2009.

    Article  PubMed  CAS  Google Scholar 

  72. Boutitie F, Gueyffler F, Pockock S, et al., for the INDIANA Project: J-shaped relationship between blood pressure and mortality in hypertensive patients: new insights from a metaanalysis of individual patient data. Ann Intern Med 2002, 136:438–448.

    PubMed  Google Scholar 

  73. Hansson L, Zanchetti A, Carruthers SG, et al., for the HOT Study Group: Effects of intensive blood pressure lowering and low dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomized trial. Lancet 1998, 351:1755–1762. This prospective study, in 18,790 hypertensive subjects, randomized patients to an assigned target DBP of = 90 mm Hg, = 85 mm Hg, = 80 mm Hg, and followed up for a mean of 3.8 years. It was concluded that there were benefits (fewer cardiovascular events) in lowering DBP to 82.6 mm Hg, but that it was safe to reduce DBP further.

    Article  PubMed  CAS  Google Scholar 

  74. Hansson L, Zanchetti, on behalf of the HOT Executive Committee: Hypertension Optimal Treatment (HOT) trial. Lancet 1998, 352:574–575.

    Article  Google Scholar 

  75. Avanzini F, Marchioli R, Alli C, Tognoni G: Hypertension Optimal Treatment (HOT) trial. Lancet 1998, 352:571–572.

    Article  PubMed  CAS  Google Scholar 

  76. Cruickshank JM: Hypertension Optimal Treatment (HOT) trial. Lancet 1998, 352:573–574.

    Article  PubMed  CAS  Google Scholar 

  77. Cruickshank JM: Antihypertensive treatment and the J-curve. Cardiovasc Drugs Ther 2000, 14:373–379. This publication included previously unpublished data from the HOT study which related to the 3010 hypertensive patients with ischemic heart disease. It concluded that for ischemic, in contrast to nonischemic, hypertensive patients there was a J-curved relationship between DBP and CHD (but not stroke), and that excessive lowering of DBP in these cases may be unsafe in terms of increasing the risk of MI.

    Article  PubMed  CAS  Google Scholar 

  78. O’ Rourke M: Arterial stiffening and vascular/ventricular interaction. J Hum Hypertens 1994, 8(Suppl 1):S9-S15.

    Google Scholar 

  79. Cruickshank JM: Losartan for cardiovascular disease in patients with and without diabetes in the LIFE Study. Lancet 2002, 359:2200–2201.

    Article  PubMed  Google Scholar 

  80. Dahlöf B, Devereux RB, Kjeldsen SE, et al., for the LIFE Study group: Cardiovascular morbidity and mortality in the Losartan Intervention for Endpoint reduction in hypertension study (LIFE): a randomized trial against atenolol. Lancet 2002, 359:995–1003.

    Article  PubMed  Google Scholar 

  81. MAPHY Steering Committee: MAPHY and the two arms of HAPPHY. JAMA 1989, 262:3272–3273.

    Article  Google Scholar 

  82. 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, 317:713–720.

    Google Scholar 

  83. Cushman WC, Materson BJ, Williams D, Reda DJ, for the Veterans Affairs Cooperative Study Group on Antihypertensive Agents: Pulse pressure changes with six classes of antihypertensive agents in a randomized, controlled trial. Hypertension 2001, 38:953–954.

    PubMed  CAS  Google Scholar 

  84. Simon AC, Levenson J, Bouthier JD, Safar ME: Effects of chronic administration of enalapril and propranolol on the large arteries in essential hypertension. J Cardiovasc Pharmacol 1985, 7:856–861.

    Article  PubMed  CAS  Google Scholar 

  85. Cruickshank JM, Lewis J, Moore V, Dodd C: Reversibility of left ventricular hypertrophy by differing types of antihypertensive therapy. J Hum Hypertens 1992, 6:85–90.

    PubMed  CAS  Google Scholar 

  86. Safar ME, London GM: Therapeutic studies and arterial stiffness in hypertension: recommendations of the European Society of Hypertension. The Clinical Committee of Arterial Structure and Function. Working Group on Vascular Structure and Function of the European Society of Hypertension. J Hypertens 2000, 18:1527–1535.

    Article  PubMed  CAS  Google Scholar 

  87. The ALLHAT officers and Coordinators for the ALLHAT Collaborative Research Group: Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic. JAMA 2002, 288:2981–2997. This large prospective, randomized study in 33,357 high-risk hypertensives (mean age 66.9 years) concluded that compared to calcium channel blockers and ACE inhibitors, thiazide-type diuretics are superior in preventing one or more major forms of cardiovascular disease, are less expensive, and should be the first step antihypertensive therapy.

    Article  Google Scholar 

  88. Progress Collaborative Group: Randomized trial of a perindopril-based blood pressure-lowering regimen among 6105 individuals with previous stroke or transient ischemic attacks. Lancet 2001, 358:1033–1041. Hypertensive and nonhypertensive subjects with a past history of stroke or transient ischemic attacks gained benefit from a blood pressure-lowering regimen in terms of a significant reduction in the risk of a further stroke.

    Article  Google Scholar 

  89. Cruickshank JM: The lowering of blood pressure after stroke. Lancet 2001, 358:1994.

    Article  PubMed  CAS  Google Scholar 

  90. McMahon S, Rodgers A, Neal B, et al.: The lowering of blood pressure after stroke. Lancet 2001, 358:1994–1995.

    Article  Google Scholar 

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Cruickshank, J. The J-curve in hypertension. Curr Cardiol Rep 5, 441–452 (2003). https://doi.org/10.1007/s11886-003-0105-1

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