Abstract
Unlike the brain, oxygen extraction for the heart is almost maximal at rest, so lowering coronary filling pressure (DBP) below the lower limit of autoregulation with antihypertensive drugs can lead to myocardial ischemia. This situation is exacerbated by the presence of coronary stenosis, which if more than 85% means that coronary flow reserve is virtually zero (particularly in the presence of LVH). Such patients experience a fall in coronary flow and ischemia when DBP is acutely lowered to less than the mid-80s. Ischemic episodes on the 24-hour Hotler monitor in treated hypertensives are often immediately preceded by a hypotensive episode.
The “J-curve” debate has been going for over 20 years. Those that deny a J-curve relationship between treated DBP and myocardial infarction (MI) quote the continuous DBP/MI relationship seen in the large cohort of MRFIT screenees (with ischemic patients weeded out). However, the actual MRFIT (and similar HDFP) study patients with abnormal ECGs (ischemia or LVH), in contrast to those with normal ECGs, in the special-care group experienced an excess of coronary events associated with a DBP 5 mmHg lower than the referred-care group. Other studies, including the prospective HOT study, have indicated that ischemic hypertensives gain optimal results when DBP is lowered to the mid- to low 80s; below this level, the frequency of MI increases. This treatment-induced J-curve should not be confused with Nature's untreated J-curve, which results from the association of a low DBP (wide pulse-pressure) due to aging, noncompliant arteries, and an increasing frequency of ischemic events.
A reasonable conclusion from most treatment studies (including HOT) is that in nonischemic hypertensives there is little point in lowering DBP below the mid- to low 80s in terms of MI prevention—though it is safe to do so. In contrast, ischemic hypertensives should not have their DBP lowered to less than the mid- to low 80s for fear of increasing the risk of MI.
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References
Stewart IMcDG. Relation of reduction in pressure to first myocardial infarction in patients receiving treatment for severe hypertension. Lancet 1979;1:861-865.
Hansson L, Zanchetti A, Carruthers SG, 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. Lancet 1998;351:1755-1762.
Kaplan N. J-curve not burned off by HOT study. Lancet 1998;351:1748-1749.
Stewart IMcDG. Beta adrenoceptor blockade and the incidence of myocardial infarction during treatment of severe hypertension. Br J Clin Pharmacol 1982;13:91-93.
Anderson TW. Re-examination of some of the Framingham blood pressure data. Lancet 1978;2:1139-1141.
Berglund G. Goals of hypertensive therapy; is there a point beyond which pressure reduction is dangerous? Am J Hypertens 1989;2:586-593.
Cruickshank JM. Coronary flow reserve and the J-curve relation between diastolic blood pressure and myocardial infarction. Lancet 1987;1:581-584.
Cruickshank JM. Coronary flow reserve and the J-curve relation between diastolic blood pressure and myocardial infarction. Br Med J 1988;297:1227-1230.
Farnett L, Mulrow CD, Linn WD, Lucey CR, Tuley MR. The J-curve phenomenon and the treatment of hypertension. JAMA 1991;265:489-495.
Multiple Risk Factor Intervention Trial (MRFIT). Baseline rest ECG abnormalities, antihypertensive treatment, and mortality in the multiple risk factor intervention trial. Am J Cardiol 1985;55:1-15.
Langford HG. Further analyses of the Hypertension Detection and Follow-up Program (HDFP). Drugs 1986;31(1):23-28.
Cohen JD, Butler SM, Cutler JA, Neaton JD for the MRFIT Research Group. Relationship between blood pressure change and mortality among MRFIT hypertensives. Circulation 1991;84(Suppl II):134-137.
Strandgaard S, HaunsøS. Why does antihypertensive treatment prevent stroke but not myocardial infarction? Lancet 1987;2:658-661.
Pepi M, Alimento M, Maltagliati A, Guazzi MD. Cardiac hypertrophy in hypertension. Repolarisation abnormalities elicited by rapid lowering of pressure. Hypertension 1988;11:84-91.
Collins P, Cruickshank JM, Keegan J, Fox K. Acute blood pressure reduction causes an impairment of left ventricular function in hypertensive patients with coronary heart disease and left ventricular hypertrophy. Euro Heart J 1991;12 (Suppl):242.
Polese A, De Cesare 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.
Cruickshank JM, Polese A (with permission of Kannel WV). Left ventricular hypertrophy and the possible harmful effect of the excessive lowering of diastolic blood pressure. In: Cruickshank JM, Messerli FH, eds. Left Ventricular Hypertrophy and its Regression. London: Science Press, 1992;61-69.
Owens P, O'Brien E. Hypotension in patients with coronary disease: can profound hypotensive events cause myocardial ischemic events? Heart 1999;82:477-481.
Kannel WB, Cupples A, D'Agostino RB, Stokes J. Hypertension, antihypertensive treatment and sudden coronary death: the Framingham Study. Hypertension 1988;11 (Suppl II):II45-II50.
McInnes G. The J-curve: a sceptic's viewpoint. Dialogues Cardiol 1989;1:1-8.
McMahon S, Peto R, Cutler 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.
Kjekshus JK. Comments-beta blockers: heart rate reduction a mechanism of benefit. Euro Heart J 1985; 6(Suppl A):29-30.
Kjekshus JK. Importance of heart rate in determining beta-blocker efficacy in acute and long term acute myocardial infarction interventional trials. Am J Cardiol 1986;57:43F-49F.
Jugdutt BI. Intravenous nitroglycerine unloading in acute myocardial infarction. Am J Cardiol1991;68:52D-63D.
Sleight P. Blood pressures, hearts and U-shaped curves. Lancet 1997;349:362.
Witteman JCM, Grobbee DE, Valkenburg HA, et al. J-shaped relation between change in diastolic blood pressure and progression of aortic atherosclerosis. Lancet 1994;343:504-507.
Coope J. Hypertension: the cause of the J-curve. J Hum Hypertens 1990;4:1-4.
Staessen J, Bulpitt C, Clement D, et al. Relation between mortality and treated blood pressure in elderly patients with hypertension: report of the European Working Party on High Blood Pressure in the Elderly. Br Med J 1989;298:1552-1556.
Somes GW, Pahor M, Shorr RI, Cushman WC, Applegate WB. The role diastolic blood pressure when treating isolated systolic hypertension. Arch Intern Med 1999;159(17):2004-2009.
Hansson L, Zanchetti A on behalf of the HOT Executive Committee. Hypertension Optimal Treatment (HOT) trial. Lancet 1998;352:574-575.
Avanzini F, Marchioli R, Alli C, Tognoni G. Hypertension Optimal Treatment (HOT) trial. Lancet 1998;352:571-572.
Cruickshank JM. Hypertension Optimal Treatment (HOT) trial. Lancet 1998;352:573-574.
UK Prospective Diabetes Study Group. High blood pressure and risk of macrovascular and microvascular complications in type II diabetes. UKPDS 38. Br Med J 1998;317:703-713.
Australian Therapeutic Trial in Mild Hypertension. Report by the Management Committee: untreated mild hypertension. Lancet 1982;1:185-191.
IPPPSH Collaborative Group. Cardiovascular risk and risk factors in a randomised trial of treatment based on the beta blocker oxprenolol: the International Prospective Primary Prevention Study in Hypertension (IPPPSH). J Hypertens 1985;3:379-392.
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Cruickshank, J.M. Antihypertensive Treatment and the J-curve. Cardiovasc Drugs Ther 14, 373–380 (2000). https://doi.org/10.1023/A:1007856014581
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DOI: https://doi.org/10.1023/A:1007856014581