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BMJ No 7106 Volume 315 Letters Saturday 23 August 1997 Intersalt dataReply for Intersalt Steering and Editorial Committee(NB: This letter is an extended version of the letter published in the BMJ paper version)
Editor, Michael Alderman cites a 1996 overview of trials but fails to note (a) its report of significant falls in the systolic pressure of non-hypertensive and hypertensive individuals with reduced sodium intake, (b) several criticisms of this overview in the accompanying editorial in JAMA and subsequent correspondence, and (c) findings of larger reductions in blood pressure with reduced sodium intake in other overviews.(1) Contrary to what Alderman says, recommendations for moderate salt reduction in populations are studied judgments by expert groups (British, American, international), including two reports that he co-signed. Alderman states that some antihypertensive drugs "may not be safe," implying similar problems with moderate salt reduction. But prescription of a drug is the addition of a non-physiological agent; lowering salt intake restores favourable physiology by reducing a major food additive that causes disease. When discussing safety, Alderman cites his two papers but fails to note that both his findings could not be replicated and his second was judged, in an accompanying editorial, to have multiple limitations.(3,4) Alexander Macnair states incorrectly that the 1988 Intersalt report showed no significant association of urinary sodium with the prevalence of hypertension. Analysis across the 52 population samples (prior hypothesis) showed that median urinary sodium excretion was significantly related to hypertension (P<0.01). Macnair doubts a correlation between body mass and sodium intake: this was 0.22 for individuals in Intersalt. N E Day, George Davey Smith and Andrew N Phillips, and we agree that uncorrected coefficients underestimate the size of the association of sodium with blood pressure in individuals. They discuss how best to correct for this bias. As Day states, none of their arguments refer to Intersalt cross-population findings. We agree with Day that 'corrections for measurement error are not free of assumptions'; hence we presented uncorrected and multivariate corrected estimates with and without body mass index(2) and gave the methods in detail with extensive sensitivity analyses.(5) (Body mass index is known to correlate highly with other measures of body composition related to obesity.) Because of concerns about possible short term fluctuations, Davey Smith and Phillips call for an estimate of the correlation between change in sodium excretion and change in blood pressure among the 8% of people in whom repeat measurements were obtained. That estimate - published - was 0.15 for systolic pressure and approximately zero for diastolic pressure. Contrary to the arguments of Day and Davey Smith and Phillips, however, this correlation is not sufficient to make the corrections they discuss; estimates of within-person covariance and covariance reliability between sodium and blood pressure are needed. In the Intersalt study, obtaining such estimates validly was not possible due to study design and results: 200 men and women in eight age-sex groups in 52 small population samples; some extreme differences between first and repeat measurements of blood pressure; and a fall in mean blood pressure of 3.3/1.6 mm Hg (systolic/diastolic) over the three weeks between measurements,(5) invalidating the usual assumption of a constant mean. Other databases tell us whether correlated fluctuations exist over a period of around three weeks. Recent analyses from the trials of hypertension prevention study found - as Intersalt assumed - that there was little or no short term covariation of sodium and blood pressure (N Cook, fourth international conference on preventive cardiology, Montreal, 2 July). These data cast further doubt on the thrust of Davey Smith and Phillips's arguments. They indicate that the Intersalt corrected estimates - a sodium intake of 100 mmol/day influences the systolic pressure of individuals by about -3 to -6 mm Hg and the diastolic pressure by 0 to -3 mm Hg - are scientifically sound, although likely still to be underestimates for reasons given in our commentary to Davey Smith and Phillips's paper.(6) In the context of the extensive concordant data from all research disciplines supporting the conclusions that high dietary salt intake has an important role in causing population-wide adverse blood pressure levels, the Intersalt data - both cross-population and within-population - have profound meaning for public policy, as has been widely recognised by unbiased expert groups. We agree with Graham Watt and Julian Tudor Hart that food manufacturers should now institute a gradual reduction of sodium in their products, with clear food labelling. We respond to Keith Rennolls's letter in a separate letter on the BMJ website.
Paul Elliott Professor Department of Epidemiology and Public Health, Jeremiah Stamler
Professor emeritus
Department of Preventive Medicine, Hugo Kesteloot Professor Department of Epidemiology, Michael Marmot Professor Department of Epidemiology and Public Health, On behalf of the Intersalt Cooperative Research Group References 1 Cutler J A, Follman D, Allender P S. Randomised trials of sodium reduction: an overview. Am J Clin Nutr 1997;65(suppl):643-51S. 2 Elliott P, Stamler J, Nichols R, Dyer A R, Stamler R, Kesteloot H, et al for the Intersalt Cooperative Research Group. Intersalt revisited: further analyses of 24 hour sodium excretion and blood pressure within and across populations. BMJ 1996;312:1249-53. 3 Meade T W, Cooper J A, Peart W S. Plasma renin activity and ischemic heart disease. N Engl J Med 1993;329:616-9. 4 Stamler J, Cohen J, Cutler J A, Grandits G, Kjelsberg M, Kuller L, et al for the MRFIT Research Group. Sodium intake and mortality from myocardial infarction: multiple risk factor intervention trial (MRFIT) [abstract]. Can J Cardiol 1997;13(suppl B):272B. 5 Dyer A R, Shipley S, Elliott P for the Intersalt Cooperative Research Group. Urinary electrolyte excretion in 24 hours and blood pressure in the Intersalt study. I. Estimates of reliability. Am J Epidemiol 1994;139:927-39. 6 Davey Smith G, Phillips A N. Inflation in epidemiology: "The proof and measurement of association between two things" revisited. [With commentary by A R Dyer et al.] BMJ 1996;312:1659-64.
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