INTERSALT Study Research Articles

Jeremiah Stamler, MD (1919-2022).

Jeremiah Stamler, MD (1919-2022).

Urinary sodium-to-potassium ratio and intake of sodium and potassium among men and women from multiethnic general populations: the INTERSALT Study.

The Na/K ratio may be more strongly related to blood pressure and cardiovascular disease than sodium or potassium. The casual urine Na/K ratio can provide prompt on-site feedback, and with repeated measurements, may provide useful individual estimates of the 24-h ratio. The World Health Organization has published guidelines for sodium and potassium intake, but no generally accepted guideline prevails for the Na/K ratio. We used standardized data on 24 h and casual urinary electrolyte excretion obtained from the INTERSALT Study for 10,065 individuals aged 20-59 years from 32 countries (52 populations). Associations between the casual urinary Na/K ratio and the 24-h sodium and potassium excretion of individuals were assessed by correlation and stratification analyses. The mean 24-h sodium and potassium excretions were 156.0 mmol/24 h and 55.2 mmol/24 h, respectively; the mean 24-h urinary Na/K molar ratio was 3.24. Pearson's correlation coefficients (r) for the casual urinary Na/K ratio with 24-h sodium and potassium excretions were 0.42 and -0.34, respectively, and these were 0.57 and -0.48 for the 24-h ratio. The urinary Na/K ratio predicted a 24-h urine Na excretion of <85 mmol/day (the WHO recommended guidelines) with a sensitivity of 99.7% and 94.0%, specificity of 39.5% and 48.0%, and positive predictive value of 96.3% and 61.1% at the cutoff point of 1 in 24 h and casual urine Na/K ratios, respectively. A urinary Na/K molar ratio <1 may be a useful indicator for adherence to the WHO recommended levels of sodium and, to a lesser extent, the potassium intake across different populations; however, cutoff points for Na/K ratio may be tuned for localization.

Abstract 008: Casual and 24-hour Urinary Sodium-to-potassium Ratio and Intakes of Sodium and Potassium Among Men and Women From Multi-ethnic General Populations: The Intersalt Study

Background: Urinary sodium-to-potassium ratio may be more strongly related to blood pressure and cardiovascular disease than either urinary sodium or potassium alone. The casual urine sodium-to-potassium ratio is readily obtained, can provide prompt on-site feedback, and with repeated measurements may provide useful individual estimates of 24-hour urinary sodium-to-potassium ratio. The World Health Organization (WHO) has recently published guidelines for sodium and potassium intakes, but no generally accepted guideline prevails for favorable sodium-to-potassium ratio. Objective: Our primary aim was to compare the level of urinary Na/K ratio with the current recommended levels of Na and K intakes suggested in WHO guidelines. Methods: INTERSALT is an international study on associations of multiple urinary variables, with blood pressure (BP), based on standardized data on 24-hour and casual urinary electrolyte excretion in 10,065 individuals from 52 population samples in 32 countries. The associations between casual urinary sodium-to-potassium ratio and 24-hour urinary sodium and potassium excretion of individuals were assessed by correlation and stratification analysis. Results: Mean 24-hour sodium and potassium excretions were 156.0 mmol/24h and 55.2 mmol/24h; mean 24-hour urinary sodium-to-potassium ratio was 3.24. Pearson-r correlation coefficients of casual urinary sodium-to-potassium ratio with 24-hour sodium and potassium excretions were 0.42 and -0.34, respectively, and these were 0.57 and -0.48 for 24-hour urinary sodium-to-potassium ratio. The proportion of participants with estimated sodium chloride intake below the WHO recommended guideline of 85 mmol/day was 61.1% for those with casual urinary sodium-to-potassium ratio less than 1, and 96.3% where the 24-hour ratio was less than 1. For potassium, the proportion of people with potassium intake more than the WHO recommended guideline of 90 mmol/day was 21.3% where the casual urinary sodium-to-potassium ratio was less than 1 and 28.6% for the 24-hour urinary sodium-to-potassium ratio. Conclusions: Casual urinary sodium-to-potassium ratio less than 1 may be a useful indicator of adherence to the World Health Organization recommended levels of sodium intake, and to a lesser extent potassium intake in diverse different populations.

Estimating 24-h urinary sodium/potassium ratio from casual ('spot') urinary sodium/potassium ratio: the INTERSALT Study.

BackgroundAssociation between casual and 24-h urinary sodium-to-potassium (Na/K) ratio is well recognized, although it has not been validated in diverse demographic groups. Our aim was to assess utility across and within populations of casual urine to estimate 24-h urinary Na/K ratio using data from the INTERSALT Study.MethodsThe INTERSALT Study collected cross-sectional standardized data on casual urinary sodium and potassium and also on timed 24-h urinary sodium and potassium for 10 065 individuals from 52 population samples in 32 countries (1985–87). Pearson correlation coefficients and agreement were computed for Na/K ratio of casual urine against 24-h urinary Na/K ratio both at population and individual levels.ResultsPearson correlation coefficients relating means of 24-h urine and casual urine Na/K ratio were r = 0.96 and r = 0.69 in analyses across populations and individuals, respectively. Correlations of casual urine Na/creatinine and K/creatinine ratios with 24-h urinary Na and K excretion, respectively, were lower than correlation of casual and 24-h urinary Na/K ratio in analyses across populations and individuals. The bias estimate with the Bland–Altman method, defined as the difference between Na/K ratio of 24-h urine and casual urine, was approximately 0.4 across both populations and individuals. Spread around, the mean bias was higher for individuals than populations.ConclusionWith appropriate bias correction, casual urine Na/K ratio may be a useful, low-burden alternative method to 24-h urine for estimation of population urinary Na/K ratio. It may also be applicable for assessment of the urinary Na/K ratio of individuals, with use of repeated measurements to reduce measurement error and increase precision.

The blood pressure-salt sensitivity paradigm: pathophysiologically sound yet of no practical value.

Sodium plays an important pathophysiological role in blood pressure (BP) values and in the development of hypertension, and epidemiological studies such as the Intersalt Study have shown that the increase in BP occurring with age is determined by salt intake. Recently, a meta-analysis of 13 prospective studies has also shown the close relationship between excess sodium intake and higher risk of stroke and total cardiovascular events. However, the BP response to changing salt intake displayed a marked variability, as first suggested by Kawasaki et al. (The effect of high-sodium and low-sodium intakes on blood pressure and other related variables in human subjects with idiopathic hypertension. Am J Med 1978; 64: 193-198) and later by Weinberger et al. (Definitions and characteristics of sodium sensitivity and blood pressure resistance. Hypertension 1986; 8: II127-II134), who recognized the heterogeneity of the BP response to salt and developed the concept of salt sensitivity. We have a large body of evidence in favour of a major role of metabolic and neuro-hormonal factors in determining BP salt sensitivity in association with the effect of genetic variation. There is evidence that salt sensitivity influences the development of organ damage, even independently-at least in part-of BP levels and the occurrence of hypertension. In addition, several observational studies indicate that salt sensitivity is clearly associated with a higher rate of cardiovascular events and mortality, independently of BP levels and hypertension. A cluster of factors with well-known atherogenic potential such as hyperinsulinaemia, dyslipidaemia and microalbuminuria-all known to be prevalent in salt-sensitive hypertension-might at least partially explain the increased cardiovascular risk observed in salt sensitive individuals. The gold standard for the evaluation of BP salt sensitivity is the BP response to a moderate reduction of salt intake for several weeks; nevertheless, these protocols often suffer of poor patient compliance to dietary instructions. To overcome this problem, short-term tests have been proposed that evaluate either large differences in salt intake for a few days or the response to intravenous administration of saline solution and short-acting diuretics. Recently, the use of ambulatory BP measurement has been proposed for the clinical assessment of BP salt sensitivity. Noteworthy, BP salt sensitivity, in whomever or however assessed, behaves as a continuous variable but salt sensitivity is used as a categorical parameter, with salt-sensitive individuals being defined as those with a difference in BP between low- and high-sodium intake >10%, and salt-resistant subjects those in whom BP does not increase or shows an increase <5% under sodium loading. The general conclusion that can and should be drawn from the above considerations is that the paradigm of salt sensitivity, despite its important pathophysiological meaning, is not helpful, so far, to the practising physician in clinical practice nor is it relevant or useful to the design and implementation of a population-based strategy of salt intake reduction; however, further studies are warranted for an accurate assessment of the salt-sensitivity phenotype in clinical practice. In the absence of a population strategy for salt intake reduction, the aim should be the generation of a 'low sodium environment' allowing for a dietary salt intake tailored on true human requirements and not on deleterious lifestyle habits.

Why Does Obesity Lead to Hypertension? Further Lessons from the Intersalt Study

Objectives: To analyze correlations between major determinants of blood pressure (BP), in efforts to generate and compare predictive models that explain for variance in systolic, diastolic, and mean BP amongst participants of the Intersalt study. Methods: Data from the Intersalt study, consisting of nearly 10,000 subjects from 32 different countries, were reviewed and analyzed. Published mean values of 24 hour urinary electrolyte excretion (Na+, K+), 24 hour urine creatinine excretion, body mass index (BMI, kg/m^2), and blood pressure data were extracted and imported into MatlabTM for stepwise linear regression analysis. Results: As shown earlier, strong correlations between urinary sodium excretion (UNaV) and systolic, diastolic and mean blood pressure were noted as well as between UNaV and the age dependent increase in systolic blood pressure. Of interest, BMI and urinary creatinine excretion rate (UCrV) also both correlated with systolic blood pressure, but the ratio of BMI/UCrV, constructed to be a measure of obesity, correlated negatively with systolic blood pressure. Conclusions: Our results offer population-based evidence suggesting that increased size due to muscle mass rather than adiposity may correspond more to blood pressure. Additional data bases will need to be sampled and analyzed to further validate these observations.

Relationship of 24-hr Urinary Na/K ratio to 24-hr Urinary Na and K Excretion in Men and Women from Multi-Ethnic General Populations: the INTERSALT Study.

Relationship of 24-hr Urinary Na/K ratio to 24-hr Urinary Na and K Excretion in Men and Women from Multi-Ethnic General Populations: the INTERSALT Study.

Reduction of sodium intake is a prerequisite for preventing and curing high blood pressure in hypertensive patients - first part: therapy.

The studies on the relation between Na intake and blood pressure were started at the Brookhaven National Laboratories in Upton (New York) by Lewis K Dahl in 1961, however the story goes back to our hunter-gatherer predecessors who, between 750,000 and 10,000 years ago, ate diets proving a Na intake of 690 mg/day. The relevance of this finding became evident when the data of the studies on Yanomamo Indians of Brazil and Venezuela (living in the tropical forest) became available. They showed that in these populations sodium intake averages 1.34±2.01 mEq/24 hours,and that their blood pressure increases from the first to the second decade of life and then tapers down. Studies inc himpanzees, a species genetically similar to humans, the DASH Trial, the Intersalt Study, various meta-analyses, the data in persons with stroke, the blood pressure profile of newborns on low Na intake, and various studies in hypertensives with and without Chronic Kidney Disease, have demonstrated the beneficial effects of a restricted low salt intake alone or as an adjunct to drug therapy on blood pressure profiles.

Abstract MP78: Relationship Between Casual Urinary Sodium/potassium Ratio And 24-h Urinary Sodium/potassium Ratio: The Intersalt Study

Objective: High dietary sodium (Na) and low dietary potassium (K) intakes are associated with adverse blood pressure levels and excess risks of cardiovascular diseases. The Sodium/potassium (Na/K) ratio is a composite index of Na and K. Recently, we found Na/K ratio of casual urine is useful for estimating 24-h urinary Na/K ratio in healthy Japanese participants. However, this finding has not been validated in different ethnic groups. Our aim was to assess the utility across and within populations of casual (spot) urine specimens to estimate 24-h urinary Na/K ratio using data from the International Cooperative Study on Salt, Other Factors, and Blood Pressure (INTERSALT). Methods: The INTERSALT study collected standardized data on casual urinary Na and K concentrations, and also on timed 24-h urinary Na and K excretion for 10,079 men and women ages 20-59 years from 52 population samples in 32 countries. Pearson correlation coefficients and agreement quality analysis (by the Bland-Altman method) were computed for Na/K ratio of casual urine against 24-h urinary Na/K ratio. Results: Overall mean value of Na/K ratio in 24-h urine collections was 3.24. 24-h urinary Na/K ratio and Na/K ratio of casual urine across the 52 population samples were highly correlated: r=0.96 (overall), r=0.96 (men), r=0.95 (women), r=0.94 (ages 20-29), r=0.94 (ages 30-39), r=0.95 (ages 40-49) and r=0.95 (ages 50-59). 24-hour urinary Na/K ratio and Na/K of casual urine across the 10,079 individuals had moderately strong correlations: r=0.69 (overall), r=0.70 (men), r=0.68 (women), r=0.58 (white), r=0.47 (black), r=0.81 (Amerindian), r=0.70 (Asian Indian), r=0.64 (east-Asian), r=0.70 (other ethnicities), r=0.58 (with anti-hypertensive medication use) and r=0.72 (without anti-hypertensive medication use). The bias estimate with the Bland-Altman method, defined as the difference between Na/K of 24-h urine collection and casual urine, was approximately 0.4 across both populations and individuals, independent of age, gender and anti-hypertensive medication use across the 52 population samples. Bias estimates across population samples were 0.39 (overall), 0.42 (men), 0.36 (women), 0.32 (ages 20-29), 0.41 (ages 30-39), 0.37 (ages 40-49) and 0.46 (ages 50-59). Bias estimates for the 10,079 individuals were 0.40 (overall), 0.42 (men), 0.37 (women), 0.33 (white), 0.69 (black), 0.04 (Amerindian), 0.22 (Asian Indian), 0.65 (east-Asian), 0.31 (other ethnicities), 0.45 (with anti-hypertensive medication use) and 0.38 (without anti-hypertensive medication use). Conclusions: These findings indicate that casual urine Na/K ratio is a useful, low-burden, low-cost method alternative to 24-h urine collection for estimation of urinary Na/K ratio across populations of various ethnicities. It is also applicable to individual urinary Na/K ratio.

Is amlodipine more cardioprotective than other antihypertensive drug classes?

Is amlodipine more cardioprotective than other antihypertensive drug classes?

764 SYNERGISTIC EFFECTS OF RENAL DOPAMINE AND GASTRIN RECEPTORS IN HYPERTENSION

764 SYNERGISTIC EFFECTS OF RENAL DOPAMINE AND GASTRIN RECEPTORS IN HYPERTENSION

Statistical Models and Causal Inference: A Dialogue with the Social Sciences (review)

Reviewed by: Statistical Models and Causal Inference: A Dialogue with the Social Sciences Daniel J. Dutton Statistical Models and Causal Inference: A Dialogue with the Social Sciences by David A. Freedman. Edited by David Collier, Jasjeet S. Sekhon, and Philip B. Stark. New York: Cambridge University Press, 2010, 399 pp. This volume is a collection of various works by the late University of California—Berkeley statistician David A. Freedman compiled shortly before his death and edited by his colleagues. Professor Freedman worked on issues in applied statistics and was particularly concerned with their usage in disciplines like epidemiology, political science, and economics. His work in this text is on using mathematics and statistical theory to undo common misconceptions that have emerged in the social sciences around model design and model diagnostic testing. The topics in the book range from valuable elementary arguments presented with sophisticated theory to prove them, to seemingly dated or esoteric presentations of specific topics that may interest only a minority of researchers. The valuable sections definitely outweigh the easily skipped digressions into less popular topics. Freedman’s recommendations for practice are always needed in our fields, which sometimes gloss over the details behind the assumptions we use in modeling. Part 1, “Statistical Modeling: Foundations and Limitations,” presents Freedman’s skeptical attitude toward the use of “causal” models in the statistics. After the first chapter’s introduction to the difference between Bayesian and frequentist statistics, Freedman lays out his thoughts on various established practices in the social sciences. For example, the practice of imagining a population that does not exist on its own (e.g., The homeless population is the process generating homeless people, of which all the homeless people in a city are a sample) is sharply criticized, as are meta-analyses (“Just say no”). Freedman also decries assuming independence of observations outside the context of society, and his recommendations for practice are to avoid imputation processes and understand the assumptions required by models. He closes with the importance of topic-specific understanding when seeking out causal relationships and the futility in using certain forms of data to answer causal questions. Part 2, “Studies in Political Science, Public Policy, and Epidemiology,” despite its promising title, is decidedly weak because of its inclusion of strange topics. For example, the discussion of methods used in the United States Census in 2000 seems out of place, but the lessons from that chapter have some applicability to large datasets in general. The discussion on the United States Geological Service and the prediction of earthquakes is more valuable as a consideration of probability than a social science dialogue. Two chapters deal with conventional wisdom concerning the Intersalt study on hypertension and survival analysis, respectively, and are must-reads for epidemiologists. Part 3, “New Developments: Progress or Regress?,” gets to the root of Freedman’s argument [End Page 537] against the spread of uninformed modeling in social sciences. The two motifs of Freedman’s work— model diagnostics not being a replacement for topic knowledge, and intellectual wrangling of models not being a replacement for better data gathering— are ubiquitous in this section. These motifs are presented in discussions on endogeneity in Probit models, particularly focusing on the inadequacy of Heckman two-step procedures. For epidemiologists, there is an informative discussion on logistic regression, which in the process of a randomized experimental design is shown to be inconsistent and is compared to a more general test. Part 4, “Shoe Leather Revisited,” concludes by reiterating Freedman’s cautions over letting models supersede the reasoning process he claims has been used to make great discoveries throughout modern history (such as Snow’s cholera study). The section also stresses the importance of what Freedman calls “qualitative knowledge.” Such knowledge includes informal reasoning, insights into possible mechanisms or processes creating the data, and substantive understanding that comes from expending effort to understand the question under investigation. Freedman’s arguments are well taken and, in the opinion of the reviewer, classic and well-worn critiques that most practitioners are aware of on some level. The added-value of this text is the explicit statement, through math and argument, of how wrong things can go when the assumptions behind...

Sodium, Potassium, and Target Organ Damage

The relationship between blood pressure (BP) and sodium intake is well documented. Large observational studies have shown that sodium chloride (NaCl) intake is directly related to BP, whereas various interventional studies demonstrated a relationship between the reduction in NaCl intake and magnitude of BP reduction. Similarly, a low-potassium diet is associated with high BP and increased cardiovascular risk. In the Intersalt Study, urinary potassium excretion (a surrogate for intake) was associated with a lower BP after adjustment for various confounders, including urinary sodium excretion. The effects of dietary sodium and potassium on BP are closely related. The first strain of rats bred by Dahl for the trait of “salt sensitivity” demonstrated less NaCl-induced hypertension when potassium intake was high. Well-controlled human studies subsequently showed that the BP-rising effect of extremely high NaCl intake can be blunted by potassium supplementation. Clinical trials showed that potassium supplementation modestly reduces BP, an effect that is, however, enhanced in blacks and in the presence of a high-sodium diet. Conversely, hypertension in potassium deficiency is associated with increased renal sodium reabsorption, whereas sodium restriction may prevent the development of hypertension induced by potassium restriction. Recent literature has identified regulatory pathways of tubular sodium and potassium handling (eg, those mediated by with-no-lysine-kinase 1)1 that may, at least partially, mediate interactions between dietary sodium and potassium on extracellular volume and BP. Importantly, whereas high-sodium/low-potassium intake are associated with hypertension, both have been shown to predict an increased cardiovascular risk even after adjustment for brachial BP and other observed factors, indicating that unmeasured factors played a role. Accumulating evidence indicates that central arterial pulsatile hemodynamic abnormalities predict cardiovascular risk independent of brachial BP in various populations.2 It should be noted that there is a highly variable relationship between brachial pulse pressure (PP) and aortic pulsatile hemodynamics. …

Acculturation, Obesity, and Hypertension Among Female Brazilian Indians

To the Editor: The Amazon is the largest native forest in the word. There, many isolated and relatively unacculturated Amerindian populations still strive to keep their cultures untouched. In a series of reports from 1989 to 1992, one of us (Carvalho) and colleagues of the Intersalt Study have evidenced that both obesity and hypertension were entirely absent among an uncivilized Amazon tribe named Yanomamo.1–5 Moreover, blood pressure did not increase with age, and both salt and alcohol were unknown among this ethnic group. Presently, there are ≈460 000 Indians in Brazil living in 225 villages and speaking 180 languages. They correspond to 0.26% of the Brazilian population and live in preserved areas that represent ≈15% of the country’s territory.6 Approximately 175 000 Brazilian …

Should the Concentration of Vitamin D Be Measured in All Patients With Hypertension?

The importance of vitamin D in a variety of health areas has led to increased interest about the prevalence, etiologies and associated morbidities of hypovitaminosis D. The role of vitamin D in absorption of calcium and bone health is well known, but recent data support additional effects on the immune system, cancer, neuromuscular function, and cardiovascular system, including hypertension [1,2]. Vitamin D is converted to 25-hydroxyvitamin D (25-OH D) in the liver and then again to 1,25 dihydroxyvitamin D (1,25-OH D) in the kidney. While 1,25-OH D is the biologically active form of vitamin D, 25-OH D is considered the best indicator of vitamin D status in the body because it circulates in a higher concentration, has a long half-life and is the substrate for 1,25-OH D production [1]. There are several etiologies of vitamin D deficiency and insufficiency (Table 1). The lack of ultraviolet B radiation from sunlight is the most common reason for vitamin D deficiency - northern latitudes, the winter season, sun protection factors (SPF) in lotions to prevent skin exposure to the sun all contribute to this form of vitamin D deficiency or insufficiency. The most common biochemical definition of vitamin D deficiency is a 25-OH D level less than 20 ng/ml (50 nmol/L) while levels from 21 to 29 ng/ml are considered insufficiency [3]. Surveys show that large minorities (40-45%) of elderly Americans and approximately 50% of post-menopausal women in American are deficient or insufficient in Vitamin D [4]. Prevalence rates go up with increasing age due to lesser quantities of the vitamin D precursor in the skin, 7-dehydrocholesterol and in populations with high levels of melanin in the skin (e.g African-Americans and dark-skinned Hispanic populations) since melanin also impairs the absorption of ultraviolet B radiation (Table 1). Table 1 Common Causes of Vitamin D Deficiency Vitamin D and Cardiovascular Disease Vitamin D deficiency is associated with diabetes, obesity, metabolic syndrome and hypertension [5]. In addition, low 25-OH D levels (< 15 to 20 ng/ml) have been associated with the development of hypertension (6) and cardiovascular events (7). In the Framingham Offspring Study participants followed for a median interval of 5.4 years demonstrated a higher relative risk for a cardiovascular event with lower vitamin D levels (Figure 1). The risk of an event increased by 2.13 in subjects with hypertension with 25-OH D levels less than 15 ng/ml [7]. It is impressive that the general risk for cardiovascular disease associated with vitamin D deficiency is comparable to the Framingham-derived risk ratios if the patient has metabolic syndrome (relative risk of 2.1), hypertension (relative risk of 1.7), dyslipidemia (relative risk of 1.8), increased fibrinogen levels (relative risk of 2.42) and homocysteinemia (relative risk of 1.6) [8-11]. Figure 1 Five-year cardiovascular event rates (%) according to varying levels of 25-hydroxyvitamin D in the Framingham Offspring Study. Rates were adjusted for age and sex and grouped according to the presence or absence of hypertension. Modified from reference ... Vitamin D and Hypertension Epidemiologic association between Vitamin D deficiency and hypertension Data from the INTERSALT study suggest a rise in BP is proportional to distance from the equator [12] while seasonal variations in BP have also been reported in temperate climates [13]. Population studies have shown an inverse relationship between vitamin D levels and hypertension, with increasing incidence of hypertension as Vitamin D levels decrease [6, 14]. The largest database is from Forman and colleagues (6) using 117,730 subjects from the Health Professional follow-up study and the Nurse's Health Studies in which there was a median follow-up period of 4 years for the development of incident hypertension. When comparing those individuals whose 25-0H D levels were 30 ng/ml, the relative risk of developing hypertension was 3.18, with a marked gender difference (6.13 in men and 2.67 in women). Hence, a significant inverse relationship exists between vitamin D and development of hypertension.

Scientific Opinion on the substantiation of health claims related to potassium and maintenance of normal muscular and neurological function (ID 320, 386) and maintenance of normal blood pressure (ID 321) pursuant to Article 13(1) of Regulation (EC) No 1924/2006

Scientific Opinion on the substantiation of health claims related to potassium and maintenance of normal muscular and neurological function (ID 320, 386) and maintenance of normal blood pressure (ID 321) pursuant to Article 13(1) of Regulation (EC) No 1924/2006

Impact of Urine Sodium on Urine Risk Factors for Calcium Oxalate Nephrolithiasis

Increased sodium intake is thought to promote nephrolithiasis by dietary sodium hypercalciuric effects. However, equivocal data exist on whether increased urine sodium actually increases the nephrolithiasis risk. We examined the relationship between urine sodium and urine risk factors for nephrolithiasis. We retrospectively reviewed the records of 880 patients evaluated at a metabolic stone clinic to determine the relationship between urine sodium and urine calcium, volume and calcium oxalate supersaturation. Patients were separated into sodium excretion quintiles. Tests of linear trend were performed by examining the linear contrast in coefficients and using Cuzick's nonparametric linear trend test. Multivariate linear regression with urine sodium as a continuous variable was done to assess the relationship between urine sodium and other urine variables. Tests of linear trend showed that urine calcium and volume increased with increasing urine sodium (each p <0.01) but urine calcium oxalate supersaturation decreased with increasing urine sodium (p <0.01). Multivariate linear regression was adjusted for age, sex, body mass index and urine constituents. Urine sodium was positively associated with urine calcium (beta = 0.28, 95% CI 0.15 to 0.41, p <0.001) but negatively associated with urine calcium oxalate supersaturation (beta = -0.013, 95% CI -0.016 to -0.011, p <0.001). There was a trend toward a positive association of urine sodium and volume (beta = 0.001, 95% CI -0.00019 to 0.002, p = 0.10). Increasing urine sodium does not appear to increase the risk of calcium oxalate nephrolithiasis. Global sodium restriction may not necessarily alter the risk of stone formation, ie cause changes in calcium oxalate urine supersaturation, in patients with a history of nephrolithiasis.

Changes in Urinary Stone Risk Factors in Hypocitraturic Calcium Oxalate Stone Formers Treated With Dietary Sodium Supplementation

We investigated the effects of supplemental dietary sodium on risk factors for urinary stone disease in stone forming patients with hypocitraturia. Ten patients diagnosed with recurrent isolated hypocitraturic calcium urolithiasis were identified. Baseline 24-hour urinalysis was performed with patients on their regular diet, including citrate replacement with 20 mEq potassium citrate 3 times per day. Strict daily dietary logs were kept for a 7-day period, during which patients had normal oral intake and potassium citrate replacement. Patients then received supplemental sodium chloride for 1 week (1 gm orally 3 times per day), in addition to their regular diets and potassium citrate supplementation. Dietary logs were continued and 24-hour urinalysis was performed at the end of 1 week of supplemental sodium. Risk factors for urinary stone disease were compared using the Student t test and ANOVA. Two patients were unable to comply with sodium supplementation based on 24-hour urinalysis and, therefore, they were excluded from study. The remaining 8 patients were analyzed. Patients on supplemental dietary sodium demonstrated significantly increased mean urinary voided volume (933 ml per day above baseline, p <0.05) and mean urinary sodium excretion (66 mEq per day above baseline, p <0.05). There was no statistically significant change in urinary calcium, oxalate or uric acid. The urinary supersaturation relative risk ratio decreased for calcium oxalate stones (0.93 vs 0.63, p <0.05), while those of brushite, struvite and uric acid were not different before vs after supplemental sodium. Dietary sodium supplementation resulted in an increased voided urine volume and decreased the relative risk supersaturation ratio for calcium oxalate stones in patients with a history of hypocitraturic calcium oxalate nephrolithiasis. Urinary calcium excretion as well as other urine parameters that are risk factors for nephrolithiasis was not changed. Sodium restriction may be inappropriate in patients with hypocitraturia and recurrent urinary stones. Sodium supplementation may be beneficial in these patients because it results in voluntary increased fluid intake.

Time to talk salt

Just over a decade ago, the BMJ found itself in the eye of the storm about dietary salt ( BMJ 1996;312:1239-40). We had published the Intersalt study some years previously; it concluded that populations with high average intakes of salt were likely to have higher average blood pressures. But the salt producers' trade organisation, the Salt Institute, had criticised the study's methods and asked the investigators to hand over their raw data for reanalysis. A reanalysis was done—by the original investigators—and published in the BMJ ( BMJ 1996;312:1249-53). The findings were the same. It's worth remembering this skirmish in the war on dietary …

Commentary: Geoffrey Rose's thinking about coronary artery disease

References 1 Doll R, Peto R, Boreham J, Sutherland I. Mortality in relation to smoking: 50 years’ observations on male British doctors. BMJ 2004;328:1519. 2 Belanger C, Speizer FE, Hennekens CH, Rosner B, Willett W, Bain C. The nurses’ health study: current findings. Am J Nurs 1980;80:1333. 3 Keys A, Aravanis C, Blackburn HW et al. Epidemiological studies related to coronary heart disease: characteristics of men aged 40–59 in seven countries. Acta Med Scand Suppl 1966;460:1–392. 4 Mariotti S, Capocaccia R, Farchi G, Menotti A, Verdecchia A, Keys A. Differences in the incidence rate of coronary heart disease between north and south European cohorts of the Seven Countries Study as partially explained by risk factors. Eur Heart J 1982;3:481–87. 5 Rose G. Incubation period of coronary heart disease. Br Med J (Clin Res Ed) 1982;284:1600–1. (Reprinted Int J Epidemiol 2005;34:242–44.) 6 Ross SD, Allen IE, Connelly JE et al. Clinical outcomes in statin treatment trials: a meta-analysis. Arch Intern Med 1999;159: 1793–1802. 7 Vartiainen E, Puska P, Pekkanen J, Tuomilehto J, Jousilahti P. Changes in risk factors explain changes in mortality from ischaemic heart disease in Finland. BMJ 1994;309:23–27. 8 Rose G. Sick individuals and sick populations. Int J Epidemiol 2001;30:427–32. 9 Tuomilehto J, Kuulasmaa K. WHO MONICA Project: assessing CHD mortality and morbidity. Int J Epidemiol 1989;18:S38–S45. 10 The INTERSALT Co-operative Research Group. Sodium, potassium, body mass, alcohol and blood pressure: the INTERSALT Study. J Hypertens Suppl 1988;6:S584–S586. 11 Ounpuu S, Negassa, A,Yusuf S. INTER-HEART: a global study of risk factors for acute myocardial infarction. Am Heart J 2001;141:711–21. 246 INTERNATIONAL JOURNAL OF EPIDEMIOLOGY