Methodological Issues in Cohort Studies That Relate Sodium Intake to Cardiovascular Disease Outcomes

Abstract

Background-The results of cohort studies relating sodium (Na) intake to blood pressure-related cardiovascular disease (CVD) are inconsistent. To understand whether methodological issues account for the inconsistency, we reviewed the quality of these studies. Methods and Results-We reviewed cohort studies that examined the association between Na and CVD. We then identified methodological issues with greatest potential to alter the direction of association (reverse causality, systematic error in Na assessment), some potential to alter the direction of association (residual confounding, inadequate follow-up), and the potential to yield false null results (random error in Na assessment, insufficient power). We included 26 studies with 31 independent analyses. Of these, 13 found direct associations between Na and CVD, 8 found inverse associations, 2 found J-shaped associations, and 8 found null associations only. On average there were 3 to 4 methodological issues per study. Issues with greater potential to alter the direction of association were present in all but 1 of the 26 studies (systematic error, 22; reverse causality, 16). Issues with lesser potential to alter the direction of association were present in 18 studies, whereas those with potential to yield false null results were present in 23. Conclusions-Methodological issues may account for the inconsistent findings in currently available observational studies relating Na 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 blood pressure and the few existing general population trials of the effects of Na reduction on CVD. The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.This statement was approved by the American Heart Association Science Advisory and Coordinating Committee on September 26, 2013. A copy of the document is available at http://my.americanheart.org/statements by selecting either the "By Topic" link or the "By Publication Date" link. To purchase additional reprints, call 843-216-2533 or e-mail kelle.ramsay@wolterskluwer.com.The American Heart Association requests that this document be cited as follows: 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.

Salt Sensitivity of Blood Pressure

“…445 The controversy continues because the designs of the epidemiological studies supporting worse cardiovascular morbidity and mortality with diminished salt intake have been plagued by methodological weaknesses, including residual confounding, reverse causation, error in the estimation of sodium intake from dietary recall or from measurement of salt excretion in random samples, and lack of repeated measurements of salt excretion over time. 446 Meta-analyses dealing with the same issue are not devoid of the problems of heterogeneity in the included cohorts, to the point that a 2013 Institute of Medicine committee report stated that "lack of consistency among studies in the methods used for defining sodium intakes at both high and low ends of the range of typical intakes among various population groups precluded deriving a numerical definition for high and low salt intakes" in its findings and conclusions. 447 For decades, most Americans, regardless of age or sex, have had daily sodium intake levels that exceed recommendations, 448,449 and public health approaches have been recommended to help reduce sodium intake in the United States.…”

Worldwide Exposures to Cardiovascular Risk Factors and Associated Health Effects

“…111 Evidence for increased risk of CVD events and deaths associated with high salt intake, however, come from prospective studies, which are affected by limitations related to exposure measurement and reverse causation. 112 As a result, there is broad agreement about the CVD harms of high levels of salt use but debate continues about the optimal low levels of consumption. 113 …”

Dietary Salt and Blood Pressure: Verdict is Clear, so why Any Debate?

“…Low-quality research can usually be exposed by examining the study methodology. 9 Criteria that have been used to identify high-quality research designs include: (1) Assessing usual dietary salt using a valid method for at least one day and preferably multiple days over the study duration, (2) a study duration of at least 1 month when assessing changes in blood pressure and at least 1 year for assessing cardiovascular outcomes, (3) cohort studies that exclude people with disease due to the high likelihood of reverse causality (sick people eat less and die more frequently), and (4) analyses in cohort studies that do not adjust for blood pressure when examining outcomes related to salt causing increased blood pressure. Nearly all the studies that meet these modest quality criteria support salt reduction and have adequate statistical power to show harmful effects of increased dietary salt.…”