ArticlesAge-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies*
Introduction
The observed relationships between blood pressure and vascular disease mortality in particular epidemiological studies are subject to appreciable random error, especially at lower blood pressure levels, for which the mortality rates are relatively low. As a consequence, different studies may produce apparently very different results, and unduly selective emphasis on some and not on others could introduce substantial biases. Hence, both to limit purely random errors and to minimise selective biases, meta-analyses of the observational studies of these relations are needed. By combining data from many studies, such meta-analyses can assess reliably the relevance of blood pressure to disease risk in a wide range of circumstances (including the extremes of the usual blood pressure distribution, and different ages). The present collaborative meta-analysis1 differs from previous meta-analyses2, 3, 4 in several ways that increase its reliability and informativeness: (i) it is large, involving 120 000 deaths among one million participants in 61 cohorts (with parallel analyses of the Multiple Risk Factor Intervention Trial [MRFIT] observational study5 that involve a further 17 000 vascular deaths); (ii) individual records are available for each of the participants in each study, allowing detailed analyses; (iii) individuals with pre-existing vascular disease recorded were excluded, limiting any effects of disease on blood pressure (ie, avoiding “reverse causality”); (iv) cause-specific mortality data, together with age at death, are generally available; and (v) information on 286 000 repeat measurements made during prolonged follow-up allows appropriate time-dependent correction for “regression dilution”.2, 6
Typically in prospective studies of the relevance to disease of risk factors such as blood pressure, various characteristics of a cohort are recorded at an initial baseline survey and these baseline characteristics of individuals who subsequently develop a particular disease are then compared with those of individuals who do not. But, because of fluctuations in the measured values of a risk factor at baseline, such comparisons often substantially underestimate the strength of the real association between the “usual” (ie, long-term average) level of that risk factor during a particular exposure period and the disease rate during that same, or a later, period.2 This regression dilution effect may be caused by measurement error, by short-term biological variability (including both transient fluctuations and any diurnal or seasonal variation), or by longer-term within-person fluctuations or trends in risk factor values (which may occur for several reasons, including physical activity, diet, treatment, disease, or age). Information from repeat measurements of the risk factor after just a year or two in a reasonably representative sample of individuals can be used to correct for the effects not only of random measurement error but also of short-term variability in risk factor levels.2 If, however, the aim is to estimate the usual risk factor levels 5, 10, or 15 years later then corrections based on remeasurements made relatively soon after baseline may not allow properly for the effects of longer-term within-person variability or trends. Moreover, since the interval between the baseline survey and the occurrence of an event in prospective studies is typically longer among those who suffer events at older ages, such underestimation may well be greater in the elderly. In order to make appropriate time-dependent corrections for these effects of regression dilution, remeasurements during prolonged follow-up can be used to estimate the usual risk factor levels at some particular fixed interval prior to death in each decade of age.6
Hence, by combination of individual participant data from many prospective observational studies in a systematic meta-analysis that is appropriately corrected for time-dependent regression dilution, the present report characterises, with greater precision and less bias than has previously been possible, the age-specific and sex-specific relevance of the usual blood pressure to the subsequent rates of death from stroke, ischaemic heart disease (IHD), other vascular causes, and the aggregate of all non-vascular causes.
Section snippets
Study selection criteria and data collection
As described previously,1 collaboration was sought from the investigators of all prospective observational studies in which data on blood pressure, blood cholesterol, date of birth (or age), and sex had been recorded at a baseline screening visit, and in which cause and date of death (or age at death) had been routinely sought for all screenees during more than 5000 person-years of follow-up (see appendix A; http://image.thelancet.com/extras/01art8300webappendixA.pdf). Relevant studies were
Study populations
Individual records for each of 958 074 participants in 61 studies were included in this meta-analysis, with 70% of the participants from Europe, 20% from North America or Australia, and the remainder from Japan or China (table Al in appendix A). During 12·7 million person-years at risk (mean of 12 years to death), there were 11 960 deaths attributed to stroke, 34 283 attributed to IHD, 10 092 attributed to other vascular causes, and 60 797 attributed to non-vascular causes (while a further 5584
Continuous positive associations between blood pressure and disease risk
In the present meta-analysis of data from 61 prospective observational studies on deaths from vascular disease among individuals without known vascular disease at baseline (and in parallel analyses of the large MRFIT study), blood pressure is associated strongly with the age-specific mortality rates from stroke, almost as strongly with the mortality rates from IHD and with those from other vascular causes, and much less strongly (although still positively) with the age-specific mortality rates
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Collaborators listed at end of paper.