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Relationship Between Stroke Relative Risk and Change in Systolic Blood Pressure: The Misuse of Meta-Regression

Relationship Between Stroke Relative Risk and Change in Systolic Blood Pressure: The Misuse of Meta-Regression To the Editor: In their recent review on the relationship between change in blood pressure and risk of stroke, Lawes et al1 reported that a 31% relative risk reduction (RRR) may be expected from a 10 mm Hg decrease in systolic blood pressure (SBP). This point estimate was derived from a meta-regression based on 7 metaanalyses of 47 controlled clinical trials, regressing the pooled RRR against the average difference in SBP change between treatment groups. Out of the 7 meta-analyses used in the meta-regression, 3 compared an active treatment versus placebo, 1 a more intensive versus less intensive treatment, and 3 compared 2 different classes of antihypertensive treatments. The authors emphasized that for a 10 mm Hg decrease in SBP, the 31% RRR estimated from clinical trial results is (nicely!) consistent with the 25% to 36% RRR observed in populationbased epidemiological cohorts. The conclusion is that the effect obtained by pharmacological treatments to decrease SBP may directly translate into a decrease in stroke risk at a population level. I would be cautious about these results. First, the authors should have given a 95% CI around their 31% point estimate, which I calculated to be (12.2%–49.8%); ie, covering a quite wide spectrum of values. Second, and more problematic, is the choice of the control groups in their meta-analysis. For example, in 1 of the 7 meta-analyses, -blockers and/or diuretics were compared with calcium antagonists, yielding a RR of 1.08 (95% CI, 0.99 to 1.16) for an average decrease in SBP of 1 mm Hg. As well, the authors could arbitrarily have chosen to compare calcium antagonists to -blockers/diuretics, yielding a RR of 0.92 (ie, 1/1.08) for an average increase in SBP of 1 mm Hg. Using the latter comparison in the meta-regression instead of the former provides an estimated relationship between RRR and SBP difference of 22% (95% CI, 14% to 30%), quite different from the published 31% . Third, if instead of using pooled RR and average SBP effects from the 7 meta-analyses they had used the raw results observed in the 47 trials to perform the meta-regression, the estimated slope would have been equal to 22% (95% CI, 14% to 30%). If blocker/diuretic and calcium antagonist groups were reversed as above, the slope would have further decreased to 17% (95% CI, 7% to 21%). Meta-regression is subject to several potential pitfalls. Appropriate modeling methods should be used,2 with cautious interpretation of the results.3 A fundamental difficulty with metaregression may be the choice of the reference group such that all treatment comparisons have common meaningful effects across trials4 (eg, active treatment versus placebo, high dose treatment versus low dose treatment). As exemplified here, situations exist where no obvious reference group can be identified for some comparisons, leading to different results depending on which reference group was arbitrarily considered. In short, the 31% reduction in stroke risk for 10 mm Hg SBP reduction published by Lawes et al is subject to important variations depending on the analysis performed. It should not be taken for truth in future medical papers. Florent Boutitie, PhD Biostatistics Unit Hospices Civils Lyon, France