(Hypertension. 1997;29:537-538.)
© 1997 American Heart Association, Inc.
Articles |
Blood Pressure Lowering for the Secondary Prevention of Myocardial Infarction and Stroke
the Clinical Trials Research Unit, Department of Medicine, The University of Auckland (New Zealand) (S.M., A.R., B.N.), and the Research Office, Royal North Shore Hospital, University of Sydney (Australia) (J.C.).
Key Words: myocardial infarction • cerebrovascular disorders • blood pressure • antihypertensive agents • Editorial
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Introduction |
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Blood pressure (BP) levels are directly and continuously associated with the risks of both coronary heart disease and stroke in individuals without a history of major cardiovascular disease,1 and randomized trials in patients with hypertension have demonstrated that BP lowering reduces these risks after just a few years of beginning treatment.2 3 The proportional benefits of treatment appear to be similar in higher and lower risk patients, and the absolute benefits therefore increase with the level of absolute risk.3 This raises the possibility that patients at highest absolute risk of myocardial infarction or stroke, namely, those with established coronary or cerebrovascular disease, stand to benefit most from BP lowering.
However, questions about the safety of BP reduction for patients with preexisting cardiovascular disease have been raised following observations of J- and U-shaped associations between BP levels and the risks of recurrent myocardial infarction4 and stroke.5 Until recently, it has been unclear whether the J- and U-shaped associations resulted from low BP causing an increase in recurrent events or from more severe or unstable disease causing a decrease in BP and, independently, an increased risk of recurrence. If the latter were true, it could be hypothesized that the nonlinear associations would be most marked in the first few years of follow-up, when those individuals with the most severe or unstable disease would be at particular risk of recurrence. Additionally, it could be hypothesized that these associations would be less apparent or absent among individuals with less severe, more stable disease.
Two recent reports provide support for these hypotheses. The first describes the association of BP levels with the risk of death from coronary heart disease in 5362 individuals with a history of myocardial infarction.6 In the first 2 years of follow-up (during which 106 coronary deaths were observed), there was no detectable association between systolic BP and coronary mortality and a modestly significant (P=.02) quadratic association between diastolic BP and coronary mortality. However, over a subsequent 14-year period (during which 1110 coronary deaths were observed), there were highly significant linear associations of both systolic and diastolic BPs with the risk of coronary death (P<.00001) that appeared to be independent of other risk factors (age, cholesterol level, and smoking). These strikingly linear associations of BP (systolic, in particular) with coronary death over this long period of follow-up suggest that there may well be benefits of a lower BP for many patients with a history of myocardial infarction and not just those with high BP.
The second report describes the association between BP levels and stroke risk among 2435 individuals with a history of transient ischemic attack or minor stroke.7 Over 4 years of follow-up, there were highly significant linear associations of usual levels of both systolic and diastolic BPs with stroke risk (P<.001). Once again, these associations appeared to be independent of other risk factors (age, sex, smoking, and aspirin use). Throughout the range of usual BP levels studied (systolic, 130 to 160 mm Hg; diastolic, 80 to 90), there was no lower level below which the risks of stroke did not continue to decline, again suggesting that there may be benefits of a lower BP for many of these high-risk patients. The association of diastolic BP with stroke risk in these patients was of similar size to that observed in individuals without a history of cardiovascular disease1 ; a 5–mm Hg difference in usual diastolic BP was associated with a one-third difference in the risk of stroke.
These two reports therefore provide reassurance that the observations of J- and U-shaped associations between BP levels and the risks of recurrent stroke and myocardial infarction are unlikely to indicate harmful effects of low BP. Moreover, they suggest the possibility that a sustained lower BP may be of benefit to many patients with preexisting cardiovascular disease. However, proof that BP lowering reduces the risks of recurrent myocardial infarction and stroke requires evidence from randomized trials. A large number of studies have investigated the long-term effects of BP-lowering drugs on the risk of myocardial infarction in patients with a history of coronary heart disease. Their results indicate beneficial effects of most, though not all, agents among a wide range of individuals with high, average, or below-average BP values.
The benefits conferred by ß-blockers8 among individuals with a history of myocardial infarction are larger than those that would be expected from the modest BP reductions typically produced, and it is therefore highly likely that these agents possess independent cardioprotective effects. Angiotensin-converting enzyme inhibitors may also possess cardioprotective effects that are independent of BP lowering9 ; although the evidence for this is less strong than that for ß-blockers. Several ongoing trials of angiotensin-converting enzyme inhibitors in patients with coronary heart disease should resolve any remaining uncertainty. Conversely, the apparent absence of a cardioprotective effect of short-acting (immediate-release) nifedipine in patients with coronary disease10 11 raises the possibility that some BP-lowering drugs may have independent effects that counteract the benefit of BP lowering. At present, there is still little evidence available from randomized trials about the effects of long-acting or slow-release dihydropyridine-derivative calcium antagonists in patients with coronary heart disease, and the evidence about the effects of nondihydropyridine agents (verapamil and diltiazem),12 although promising,13 is not conclusive.
There are substantially fewer trials of BP lowering in patients with a history of cerebrovascular disease.14 15 16 17 The available data are, once again, promising but inconclusive, perhaps as a consequence of the small BP reductions typically achieved and the limited statistical power of the trials, even in combination, to detect the most plausible effect of treatment.3 In an effort to resolve this uncertainty, a new, large-scale, randomized trial of angiotensin-converting enzyme inhibitor–based therapy in hypertensive and normotensive patients with a history of stroke or transient ischemic attack has begun.18 The trial, endorsed by the World Health Organization–International Society of Hypertension Liaison Committee and conducted by collaborating clinical centers from both Western and Eastern countries, will study at least 6000 individuals over 4 to 5 years to determine the effects of treatment on stroke and other major cardiovascular events. Its results should provide a definitive test of the hypothesis that many patients with cerebrovascular disease, and not just those with hypertension, will benefit from BP lowering.
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Footnotes |
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Reprint requests to Dr Stephen MacMahon, Clinical Trials Research Unit, Department of Medicine, The University of Auckland, Private Bag 92019, Auckland, New Zealand. E-mail macmahon@ctru.auckland.ac.nz
Received July 5, 1996;
first decision July 26, 1996;
first decision August 30, 1996;
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References |
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TopIntroductionReferences |
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1. MacMahon S, Peto R, Cutler J, Collins R, Sorlie P, Neaton J, Abbott R, Godwin J, Dyer A, Stamler J. Blood pressure, stroke and coronary heart disease, part I: effects of prolonged differences in blood pressure. Evidence from nine prospective observational studies corrected for the regression dilution bias. Lancet. 1990;335:765-774.[Medline] [Order article via Infotrieve]
2. Collins R, Peto R, MacMahon S, Herbert P, Fiebach NH, Eberlein KA, Qizilbash N, Taylor J, Hennekens C. Blood pressure, stroke and coronary heart disease, part II: effects of short-term reductions in blood pressure. An overview of the unconfounded randomised drug trials in an epidemiological context. Lancet. 1990;335:827-838.[Medline] [Order article via Infotrieve]
3. MacMahon S, Rodgers A. The effects of antihypertensive treatment on vascular disease: reappraisal of the evidence in 1994. J Vasc Med Biol. 1993;4:265-271.
4. D'Agostino RB, Belanger AJ, Kannel WB, Cruickshank JM. Relation of low diastolic blood pressure to coronary heart disease death in presence of myocardial infarction: the Framingham Study. Br Med J. 1991;303:385-389.
5.
Irie K, Yamaguchi T, Minematsu K, Omae T. The J-curve phenomenon in stroke recurrence. Stroke. 1993;24:1844-1849.
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Flack JM, Neaton J, Grim R, Shih J, Cutler J, Ensrud K, MacMahon S, for the Multiple Risk Factor Intervention Trial Research Group. Blood pressure and mortality among men with prior myocardial infarction. Circulation. 1995;92:2437-2445.
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Rodgers A, MacMahon S, Gamble G, Slattery J, Sandercock P, Warlow C, on behalf of the UK TIA Collaborative Group. Blood pressure is an important predictor of future stroke in individuals with cerebrovascular disease. Br Med J. 1996;313:147.
8. Yusuf S, Peto R, Lewis J, Sleight P. Beta-blockade during and after myocardial infarction: an overview of the randomized trials. Prog Cardiovasc Dis. 1985;17:335-371.
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Lonn E, Yusuf S, Prabhat J, Montague TJ, Teo KK, Benedict CR, Pitt B. Emerging role of angiotensin-converting enzyme inhibitors in cardiac and vascular protection. Circulation. 1994;90:2056-2069.
10.
Furberg CD, Psaty BM, Meyer JV. Nifedipine: dose-related increase in mortality in patients with coronary heart disease. Circulation. 1995;92:1326-1331.
11. Furberg CD, Psaty BM. Nifedipine meta-analysis: correction. Circulation. 1996;93:1475-1476.
12. Yusuf S, Held P, Furberg C. Update of effects of calcium antagonists in myocardial infarction or angina in light of the second Danish Verapamil Infarction Trial (DAVIT-II) and other recent studies. Am J Cardiol. 1991;67:1295-1297.[Medline] [Order article via Infotrieve]
13. Sleight P. Calcium channel blockers after myocardial infarction. Drugs. 1996;51:216-225.[Medline] [Order article via Infotrieve]
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Hypertension-Stroke Cooperative Study Group. Effect of antihypertensive treatment on stroke recurrence. JAMA. 1974;229:409-418.
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Dutch TIA Trial Study Group. Trial of secondary prevention with atenolol after transient ischemic attack or nondisabling ischemic stroke. Stroke. 1993;24:543-548.
17. Eriksson S, Olofsson BO, Wester PO, for the TEST study group. Atenolol in secondary prevention after stroke. Cerebrovasc Dis. 1995;5:21-25.
18. PROGRESS Management Committee. Blood pressure lowering for the secondary prevention of stroke: design and rationale for PROGRESS. J Hypertens. 1996;14Suppl 2:41-46.
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