Blood pressure, stroke, and coronary heart disease. Part 1, prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias

S. MacMahon, R. Peto, R. Collins, J. Godwin, S. MacMahon, J. Cutler, P. Sorlie, R. Abbott, R. Collins, J. Neaton, R. Abbott, A. Dyer, J. Stamler

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The associations of diastolic blood pressure (DBP) with stroke and with coronary heart disease (CHD) were investigated in nine major prospective observational studies: total 420 000 individuals, 843 strokes, and 4856 CHD events, 6-25 (mean 10) years of follow-up. The combined results demonstrate positive, continuous, and apparently independent associations, with no significant heterogeneity of effect among different studies. Within the range of DBP studied (about 70-110 mm Hg), there was no evidence of any "threshold" below which lower levels of DBP were not associated with lower risks of stroke and of CHD. Previous analyses have described the uncorrected associations of DBP measured just at "baseline" with subsequent disease rates. But, because of the diluting effects of random fluctuations in DBP, these substantially underestimate the true associations of the usual DBP (ie, an individual's long-term average DBP) with disease. After correction for this "regression dilution" bias, prolonged differences in usual DBP of 5,7·5, and 10 mm Hg were respectively associated with at least 34%, 46%, and 56% less stroke and at least 21%. 29%, and 37% less CHD. These associations are about 60% greater than in previous uncorrected analyses. (This regression dilution bias is quite general, so analogous corrections to the relations of cholesterol to CHD or of various other risk factors to C H D or to other diseases would likewise increase their estimated strengths.) The DBP results suggest that for the large majority of individuals, whether conventionally "hypertensive" or "normotensive", a lower blood pressure should eventually confer a lower risk of vascular disease.

Original languageEnglish (US)
Pages (from-to)765-774
Number of pages10
JournalThe Lancet
Issue number8692
StatePublished - Mar 31 1990

Bibliographical note

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Throughout the range of usual DBP that was studied (about 70-110 mm Hg), the lower the level of DBP the lower the risks of stroke and of CHD. No direct extrapolation to usual DBP levels much below 70-75 mm Hg is possible, but indirect evidence that the steep relation may continue is provided by adult populations in South America and New Guinea, where the average DBP is only 62-66 mm Hg and the rates of vascular disease are extremely low.29 For populations where stroke or CHD are common, therefore, a substantially lower DBP should eventually confer a substantially lower relative risk of vascular disease. The absolute benefits of a lower blood pressure would be greatest for large countries with high stroke rates (eg, China3O) or CHD rates (eg, USA, USSR31). Indeed, some practicable method of reducing the mean DBP in such populations by even just a few mm Hg might avoid large numbers of premature deaths and disabling strokes. Several such methods may eXiSt,32-3 and collectively these might lower population DBP substantially. There is still, however, an important need for better understanding of the dietary and other determinants of population blood pressure levels. (This might be of particular importance in China, where salt intake30 and stroke mortality3° rates are more than double those in Britain.) Among individuals, the absolute benefits of a lower blood pressure are likely to be greatest for those who, as a consequence of their medical history, age, or other factors, are at special risk of vascular disease. The continuous relation between blood pressure and vascular disease suggests that the eventual reductions in risk produced by moderate blood pressure reductions (eg, with some current antihypertensive treatment regimens) may well be medically worthwhile not only among certain "hypertensive" individuals but also among certain individuals who, although considered "normotensive", are for some other reason (eg, a history of stroke or of myocardial infarction44) at high risk. But, although non-randomised prospective observational studies (appropriately corrected for the regression dilution bias) may, despite the possibility of confounding, be more relevant to the eventual effects of prolonged differences in blood pressure, randomised trials of blood pressure reductions that last just a few years may be more relevant to assessing the speed with which the epidemiologically expected reductions in stroke or CHD risk are produced by a reduction in blood pressure in middle age. Fourteen randomised trials of antihypertensive drug therapy have been conducted, and in part 2 of this report16 their results are reviewed in the context of the prospective observational studies. Data were supplied by J. Neaton, D. Wentworth, University of Minnesota (MRFIT screenees); A. Dyer, C. Ballew, J. Stamler, Northwestern University Medical School (Chicago Heart Association, Western Electric, and People’s Gas); G. Rose, M. Shipley, London School of Hygiene and Tropical Medicine (Whitehall); P. Sorlie, National Heart, Lung and Blood Institute (Puerto Rico and Framingham); R. Abbott, National Heart, Lung and Blood Institute (Honolulu); I Mebane, J. Nelson, National Heart, Lung, and Blood Institute (LRC Prevalence); and A. Aromaa, Finnish SII Mobile Clinic Health Survey (unpublished). Peter Sleight provided encouragement and support. Stephen MacMahon had an overseas fellowship from the National Heart Foundation of Australia, and Rory Collins has a senior research fellowship from the British Heart Foundation. Gale Mead and Lisa Park prepared the typescript.


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