Methodological Issues in Cohort Studies that Relate Sodium Intake to Cardiovascular Disease Outcomes: Implications for Research, Practice, and Policy
Disclosure: Dr. Labarthe has nothing to disclose.
Pub Date: Monday, Feb. 10, 2014
Author: Darwin R. Labarthe, MD, MPH, PhD
Affiliation: Northwestern University
Cobb LK, Anderson CAM, Elliott P, Hu FB, Liu K, Neaton JD, Whelton PK, Woodward M, Appel LJ; on behalf of the American Heart Association Council on Lifestyle and Metabolic Health. Methodological issues in cohort studies that relate sodium intake to cardiovascular disease outcomes: a science advisory from the American Heart Association. [published online ahead of print February 10, 2014]. Circulation. doi: 10.1161/CIR.0000000000000015.
Current average sodium intake by the U.S. population has been estimated as more than 3,400 mg/day.1 The recommendation of the Dietary Guidelines for Americans 2010 (DGA 2010) is to “Reduce daily sodium intake to less than 2,300 milligrams (mg) and further reduce intake to 1,500 mg among persons who are 51 and older and those of any age who are African American or have hypertension, diabetes, or chronic kidney disease. The 1,500 mg recommendation applies to about half of the U.S. population, including children, and the majority of adults.”2, p 34
The Institute of Medicine (IOM), in A Population-Based Policy and Systems Change Approach to Prevent and Control Hypertension, found “the evidence base to support policies to reduce dietary sodium as a means to shift the population distribution of blood pressure levels in the population convincing.”3, p 8 The report cited the Congressional directive to the Centers for Disease Control and Prevention (CDC) to take action to reduce sodium intake and proposed that the agency take active leadership with government and industry to achieve the levels proposed by DGA 2010.
A second IOM report in 2010, Strategies to Reduce Sodium Intake in the United States, declared the current level of sodium intake to be “simply too high to be safe for consumers given the chronic disease risks associated with sodium intake for all population segments.”4, pp 2-3 The findings of this report were presented in the context of the Dietary Guidelines for Americans 2005, which had previously recommended sodium intakes less than 2,300 mg/day for the general population age 2 years and older, and no more than 1,500 mg/day for individuals with hypertension, African Americans, and middle-aged and older adults.5 This report recommended adoption of mandatory food industry standards to limit sodium content of processed and restaurant foods as the primary strategy to reduce population-level sodium intake, in a graduated, step-wise manner.
Both of these IOM reports emphasized the public health importance of hypertension. The latter report noted that hypertension is “extraordinarily common: 32 percent of adult Americans have hypertension, and roughly another third have pre-hypertension. The costs of these health conditions are staggering. Estimates place the direct and indirect costs of hypertension at $73.4 billion in 2009.”4, p ix Furthermore, the report cites recent modeling studies projecting reductions in the burden and costs of hypertension, coronary heart disease and myocardial infarction, and stroke through reductions in population sodium intake.6,7
Recommendations for substantial reductions in population-level sodium intake have been made by Federal and voluntary health agencies in the U.S., as well as the World Health Organization, from 1969 to the present, as catalogued by the IOM.4,8 Some have questioned the appropriateness of these recommendations, on grounds of a possible lack of benefit, or even production of harm, from recommended reductions in population-level sodium intake, leading to a recent IOM report, Sodium Intake in Populations – Assessment of Evidence.9
The evidence cited elsewhere10 as supporting these concerns is based primarily on data taken from cohort studies with baseline estimates of individual-level sodium intake and follow-up to identify cardiovascular events. There is wide variation among the results of these analyses as to the presence, and if present the direction, of an association between sodium intake of individuals and cardiovascular disease (CVD) events. Inconsistencies in the findings might be a consequence of well-known methodological issues inherent in such studies.
To evaluate the quality and import of the reported findings, the American Heart Association charged an expert group to review this body of evidence and consider these issues. The accompanying AHA Science Advisory is the report of their review.11
The AHA Science Advisory
The group identified 26 studies meeting all criteria for review. Of the 31 independent analyses related to these studies, findings were mixed: a direct association (higher sodium intake, higher event rate) in 13, inverse association in 8, J-shaped association in 2, and no association in 8.
The report discusses 6 methodological issues of concern and stratifies them in three levels according to their potential impact on the finding of association: greatest potential to alter the direction of association (reverse causality and systematic error in sodium intake assessment); some potential to alter the direction (residual confounding and inadequate follow-up); and potential to yield false null findings (random error in sodium intake assessment and insufficient power).
The expert group found 3 to 4 instances of these methodological issues in each analysis. When evaluated in relation to the 4 types of result (direct, inverse, J-shaped, or null), issues with greatest potential or some potential to alter the direction of association were common regardless of the direction of the findings. Most common of all were issues likely to lead to false-negative findings – 5 of 8 null results being accompanied by high levels of random error and 5 of 7 having less than 80% power to find association if present. Reports often provided insufficient information to evaluate adequately the crucial aspect of sodium intake assessment, as well as other aspects of study quality. Among the more recent reports (8 of 12 published after 2010), persons recruited to the studies were sick patients, in whom a relation between sodium intake and subsequent events, had one been found, may not apply to the general population.
The committee concluded that “Methodological issues may account for the inconsistent findings in currently available observational studies relating Na [sodium] to CVD. Until well-designed cohort studies in the general population are available, it remains appropriate to base Na guidelines on the robust body of evidence linking Na with elevated BP and the few existing population trials of Na reduction on CVD.”11
A large body of evidence establishes a causal relation between levels of sodium intake and blood pressure, including reduction in blood pressure following reduction in sodium intake.
Hypertension, or high blood pressure, is a significant public health problem in the US and worldwide. Major health expenditures are required for its detection, evaluation, and treatment as well as for treating its consequences in CVD morbidity and mortality. It is not merely a surrogate for those later outcomes; its prevention is a major priority among national and global public health policies for CVD and NCD prevention.2,12 Two broad public health strategies – one remedial, seeking to control already-raised blood pressure, and the other primordial, seeking to prevent high blood pressure in the first place – are available to address this massive public health challenge.13
The remedial strategy, in this case through control of hypertension, remains to be fully achieved for the majority of those who have it. Success in reaching national and global targets for hypertension control will require increased access to effective long-term management, chiefly through medication; efforts toward this goal are being intensified. Reduction of sodium intake is an important concomitant of drug treatment and can in some cases obviate the need for medication. So, even the remedial strategy depends for its fullest impact on reducing sodium content of processed and restaurant foods to increase consumer choice of low-sodium food purchases.
Regarding the primordial strategy, population-wide reduction of sodium intake is the principal public health intervention to prevent hypertension in the first place. For example, reduction of sodium intake in the U.S. of 20% by 2017 is a key community-level intervention target within the Million Hearts™ Initiative,14 and a 30% reduction by 2025 is a target of the WHO Global NCD Action Plan.12
Current U.S. and global policy recommendations for reduction of sodium intake are based on the overall strength of the total body of evidence of public health benefit. These recommendations have not been altered on the basis of the reports reviewed by the AHA expert group.
Further research, based on more rigorous methods, may include evaluation of the impact of sodium reduction policies, as in the National Sodium Reduction Initiative centered in New York City15; the impact on stroke events of sodium reduction in the 600+ randomized community intervention trial, the China Rural Health Initiative16 (personal communication, Nicole Li, George Institute, Beijing, October 2013); or analysis of new longitudinal observational data based on 24-hour urine collections, including duplicate samples, planned for the next cycle of the National Health and Nutrition Examination Survey (personal communication, Janelle Gunn, Centers for Disease Control and Prevention, November 2013.)
Several key points emerge from this detailed evaluation:
Due to methodological issues, the evidence presented to date on the question of sodium intake in relation to CVD events is limited and does not rise to a level to alter current sodium-reduction policies for prevention and control of hypertension.
- CDC. Vital signs: Prevalence, treatment, and control of hypertension – United States, 1999-2002 and 2005-2008. MMWR 2011;60:103-108.
- U.S. Department of Agriculture and U.S. Department of Health and Human Services. Dietary Guidelines for Americans, 2010. 7th Edition, Washington, DC: U.S. Government Printing Office, December 2010.
- IOM (Institute of Medicine). A Population-Based Policy and Systems Change Approach to Prevent and Control Hypertension. Washington, DC: The National Academies Press, 2010.
- IOM (Institute of Medicine). Strategies to Reduce Sodium Intake in the United States. Washington, DC: The National Academies Press, 2010.
- U.S. Department of Agriculture/U.S. Department of Health and Human Services). 2005. Dietary Guidelines for Americans. 6th ed., Home and Garden Bulletin No. 232. Washington, DC: U.S. Government Printing Office.
- Palar K, Sturm R. Potential societal savings from reduced sodium consumption in the U.S. population. Am J Health Prom 2009;24:49-57.
- Bibbins-Domingo K, Chertow GM, Coxson PG, Moran A, Lightwood JM, Pletcher MJ, Goldman L. Projected effect of dietary salt reductions on future cardiovascular disease. N Engl J Med 2010;362:590-599.
- Whelton PK, Appel LJ, Sacco RL, Anderson CAM, Antman EM, Campbell N, Dunbar SB, Frohlich ED, Hall JE, Jessup M, Labarthe DR, MacGregor GA, Sacks FM, Stamler J, Vafiadis DK, Van Horn LV. Sodium, blood pressure, and cardiovascular disease: Further evidence supporting the American Heart Association sodium reduction recommendations. Circulation 2012;126:2880-2889.
- IOM (Institute of Medicine). Sodium Intake in Populations. Assessment of Evidence. Washington, DC: The National Academies Press, 2013.
- O’Donnell MJ, Mente A, Smyth A, Yusuf S. Salt intake and cardiovascular disease: Why are the data inconsistent? Eur Heart J 2013;34:1034-1040.
- Cobb LK, Anderson CAM, Elliott P, Hu FB, Liu K, Neaton JD, Whelton PK, Woodward M, Appel LJ; on behalf of the American Heart Association Council on Lifestyle and Metabolic Health. Methodological issues in cohort studies that relate sodium intake to cardiovascular disease outcomes: a science advisory from the American Heart Association. [published online ahead of print February 10, 2014]. Circulation. doi: 10.1161/CIR.0000000000000015.
- World Health Organization. WHO Global NCD Action Plan 2013-2020. Geneva, Switzerland: World Health Organization, 2013.
- Labarthe DR, Dunbar SB. Global cardiovascular health promotion and disease prevention: 2013 and beyond. Circulation 2012;126:479-485.
- Frieden TR, Berwick DM. The “Million Hearts™” Initiative – preventing heart attacks and strokes. N Engl J Med 2011;365:e27.
- National Salt Reduction Initiative Coordinated by the New York City Health Department. Appendix G. In: IOM (Institute of Medicine). Strategies to Reduce Sodium Intake in the United States. Washington, DC: The National Academies Press, 2010.
- Li N, Yan LL, Niu W, Labarthe D, Feng X, Shi J, Zhang J, Zhang R, Zhang Y, Chu H, Neiman A, Engelgau M, Elliott P, Wu Y, Neal B. A large-scale cluster randomized trial to determine the effects of community-based dietary sodium reduction—the China Rural Health Initiative Sodium Reduction Study. Am Heart J 2013;166:815-822.
-- The opinions expressed in this commentary are not necessarily those of the editors or of the American Heart Association --