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(Hypertension. 2004;43:393.)
© 2004 American Heart Association, Inc.
Scientific Contribution |
From Pennington Biomedical Research Center (D.W. H., G.A.B.), Baton Rouge, La; EndocrineHypertension Division and Channing Laboratory (F.M.S.), Department of Medicine, Brigham and Womens Hospital and Harvard Medical School and Nutrition Department, Harvard School of Public Health, Boston, Mass; National Heart, Lung, and Blood Institute (E.O.), Bethesda, Md; Duke Hypertension Center and the Sarah W. Stedman Nutrition and Metabolism Center (L.P.S., P.-H.L.), Duke University School of Medicine, Durham, NC; Kaiser Permanente Center for Health Research (M.A.), Portland, Ore; and Welch Center for Prevention, Epidemiology, and Clinical Research (L.J.A., E.R.M), Johns Hopkins University, Baltimore, Md.
Correspondence to Dr Lawrence J. Appel, Welch Center, Johns Hopkins University, Suite 2-600, 2024 East Monument St, Baltimore, MD 21205. E-mail lappel{at}jhmi.edu
| Abstract |
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Key Words: diet sodium lipids cholesterol blood pressure hypertension
| Introduction |
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The Dietary Approaches to Stop Hypertension (DASH)Sodium trial provided an opportunity to examine the effect of dietary sodium on serum lipids at sodium levels typically consumed and with sufficient power to detect small differences because of large sample size. The DASH dietary pattern is rich in fruits, vegetables, and low-fat dairy foods, emphasizes fish, poultry, and whole grains, and is reduced in fats, red meat, sweets, and sweetened beverages. We previously showed that the DASH diet and sodium reduction substantially lowered blood pressure in men and women with prehypertension (above optimal blood pressure and high normal blood pressure) and stage 1 hypertension compared with a control diet typical of what many Americans consume.1012 We also reported that the DASH diet significantly lowered total cholesterol and LDL and HDL cholesterols, without significantly increasing triglyceride concentrations.13 The purpose of this report is to determine the effects on serum lipids of 3 levels of dietary sodium in participants eating either a diet typical of many Americans or the DASH dietary pattern. Effects on serum lipids of the DASH diet at 3 levels of sodium are also examined.
| Methods |
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During a 2-week run-in period, eligible persons ate the control diet at the higher sodium level. Participants were then randomly assigned to eat 1 of 2 dietary patterns for 90 days using a parallel group design. Within the assigned diet, participants ate foods with higher, intermediate, and lower levels of sodium for 30 consecutive days each. The order of the sodium levels was random. Energy intake was adjusted for each participant when necessary to maintain body weight throughout the study. Four clinical centers, a coordinating center, and the National Heart, Lung, and Blood Institute collaborated on the trial. The clinical centers conducted the trial in 4 or 5 cohorts of participants.
The 2 dietary patterns were a control diet constructed to be typical of what many Americans eat and the DASH diet, which emphasizes fruits, vegetables, and low-fat dairy foods, includes whole grains, poultry, fish, and nuts, and is reduced in fats, red meat, sweets, and sugar-containing beverages.10,15 The nutrient composition of the diets was validated and monitored by chemical analysis. The control and the DASH dietary patterns were composed with the higher, intermediate, and lower sodium levels. Participants were provided all their food for the duration of the study.
The primary outcome was blood pressure measured at the end of each 30-day intervention feeding period. A prespecified secondary objective of the DASHSodium trial was to assess the impact of study interventions on total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride concentrations. The total cholesterol-to-HDL cholesterol ratio is also reported but was not prespecified in the protocol. The study was approved by the Institutional Review Board at each center, with written informed consent given by all participants.
Participant Eligibility
Adults aged 22 years or older who had a blood pressure of 120 to 159 mm Hg systolic and 80 to 95 mm Hg diastolic averaged over 3 screening visits were eligible to participate. The trial targeted 50% enrollment of blacks and women. Exclusion criteria included a history of heart disease, renal insufficiency, poorly controlled hyperlipidemia (total cholesterol greater than 260 mg/dL), insulin-requiring or poorly controlled diabetes, special dietary requirements, intake of more than 14 alcoholic drinks per week, or use of antihypertensive drugs or other medications that would affect blood pressure or nutrient metabolism.
Measurements
Blood samples were collected from participants after an approximate 12-hour fast at baseline and during the final week of each 30-day period of defined dietary sodium level. Baseline samples were collected during screening (ie, before the run-in period while the participant was on his/her usual diet). Blood samples were collected into serum separator tubes and centrifuged in a refrigerated centrifuge for 15 minutes at 1500g. The resulting serum was frozen at -70°C and shipped in batches to the Core Laboratory for Clinical Studies at Washington University School of Medicine, St. Louis, Mo. Specimens were analyzed by enzymatic kits on the Hitachi 917 analyzer for total triglycerides (Roche TGGB kit), total cholesterol (Miles-Technicon kit), and HDL cholesterol (Miles-Technicon cholesterol kit) after precipitation of apoB-containing lipoproteins with dextran sulfate. LDL cholesterol was estimated by the Friedewald equation for specimens with total triglyceride concentration below 400 mg/dL.16 The core laboratory is standardized for lipid measurements through the National Institutes of Health National Heart, Lung, Blood InstituteCenters for Disease Control Lipid Standardization Program.17
Energy and nutrient intake of participants were calculated from the assigned menus according to participants energy levels, from unit foods, and from logs that provided information on alcohol intake using Moores Extended Nutrition (MENu) database (version 3.1, 1997; Pennington Biomedical Research Foundation, Baton Rouge, La).
Dietary adherence was assessed by review of daily diaries, observation of on-site meal consumption, and measurement of 24-hour urinary excretion of sodium, potassium, phosphorus, and urea nitrogen. Participants and dietary staff were blinded to outcome data; personnel involved in collection of outcome data were blinded to diet assignment. Details of other measurements made during the trial are published elsewhere.11,14
Statistical Analysis
We used generalized estimating equations (GEE) to model lipid levels as a function of diet and sodium level while adjusting for cohort and clinical center. Baseline lipid levels were included as part of the design matrix, so that estimates of the DASH diet effect are net of baseline differences between participants in the DASH and control diet arms. The sodium contrasts are made within subjects and thus automatically incorporate baseline levels.
Linearity of the effects of sodium within the control diet or the DASH diet was assessed by comparing the change in lipids from the higher level to the intermediate level of sodium with the change from the intermediate level to the lower level of sodium; a significant test indicated deviation from linearity, that is, the change in lipids from the higher to the intermediate levels of sodium was not equivalent to the change from the intermediate to the lower level of sodium. Interaction terms of sodium level by diet assignment were included to test whether lipid changes from the 3 sodium levels were different between the 2 diets. The analytic model included effects for 4 clinical centers and 5 feeding cohorts, and therefore the diet and sodium main effects and interactions, were all adjusted for potential site effects and time trends. A one-period carry-over effect was also included in the model for completeness, but it had no impact on the estimates of the diet and sodium estimated effects. The GEE model allows for intercorrelation among outcome measures on the same individual, as occurs in this crossover design, and is the same analytic model we used to analyze the effects of diet and sodium on blood pressure.11,12 Conventional 2-sided probability values are reported here for diet effects within sodium levels and for the sodium levels separately within the DASH and control diets. No adjustments were made for multiple comparisons.
The trials sample size provided 85% power at a 2-sided significance level of 0.05 to detect differences between the higher and lower sodium levels of 0.14 mmol/L for total cholesterol, 0.12 mmol/L for LDL cholesterol, 0.04 mmol/L for HDL cholesterol, 0.12 mmol/L for triglycerides, and 0.15 for total/HDL cholesterol ratio. These reflect differences in cholesterol of 3% to 4%, in triglycerides of 12%, and in the ratio of 3%.
| Results |
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The calculated energy and nutrient intakes of the participants on the 2 diets are shown in Table 2. Except for sodium, intakes were similar at all 3 levels of sodium, so the average is shown.
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Mean baseline lipid levels were virtually identical for participants in the 2 diet arms (Table 1). There was no significant effect of dietary sodium on total cholesterol with either the control or the DASH diet (Figure 1a). The DASH diet lowered total cholesterol similarly and significantly, by 0.4 to 0.5 mmol/L, at every level of sodium intake (each P<0.0001). As with total cholesterol, there was no significant effect of sodium level on LDL cholesterol (Figure 1b). At each sodium level, the DASH diet lowered LDL cholesterol similarly and significantly, by 0.3 to 0.4 mmol/L (each P<0.0001). Sodium level did not significantly affect HDL cholesterol with either the control or the DASH diet. However, the DASH diet lowered HDL cholesterol by 0.08 to 0.10 mmol/L at the 3 sodium levels (each P<0.0001).
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Serum triglycerides were slightly higher by 0.06 mmol/L during lower compared with higher sodium intake with the control diet (P=0.07) (Figure 1d). With the DASH diet, triglycerides showed no pattern across sodium levels. The DASH diet did not significantly affect triglyceride concentrations.
The ratio of total cholesterol-to-HDL cholesterol was slightly but significantly higher during lower than higher and during lower than intermediate sodium intake with the control diet, ie, 4.63 for lower, 4.53 for intermediate, and 4.53 for higher (P=0.04 for lower versus higher) (Figure 1e). Among individuals eating the DASH diet, there was no significant sodium effect on the ratio. There was a trend toward a lower ratio for the DASH diet with lower sodium intake compared with the control diet with lower sodium (P=0.09) but not with intermediate or higher sodium intake. The ratio was similar for the DASH diet with lower sodium and the control diet with higher sodium (4.49 and 4.53, respectively).
Tests for deviation from linearity were non-significant for serum lipids and the ratio of total cholesterol-to-HDL cholesterol. Tests for interactions between sodium level and diet were not significant, indicating that the effects of sodium level on serum lipids and the total cholesterol-to-HDL cholesterol ratio did not differ between the control and DASH diets.
| Discussion |
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Changes in total cholesterol, LDL cholesterol, and HDL cholesterol between the higher and the two lower levels of sodium were small and non-significant with the control diet and were totally absent with the DASH diet. The difference in LDL cholesterol between the intermediate and lower sodium levels on the control diet approached statistical significance (P=0.052). However, this finding should not be overly interpreted, because there was no doseresponse; in other words, the lowest LDL concentration was observed at the intermediate sodium level. Changes in triglycerides between the higher and lower sodium levels were somewhat larger than in the total, LDL, and HDL cholesterol concentrations with the control diet, although still not significant or clinically relevant, and virtually non-existent with the DASH diet. All these findings were observed under conditions of energy balance, low alcohol intake, and sedentary activity levels.
A meta-analysis18 reported significant 4% to 5% increases in total cholesterol and LDL cholesterol from sodium reduction. However, previous studies that have shown increases in total cholesterol and/or LDL cholesterol tended to be those in which the low sodium level was extremely low, at 20 mmol/d, compared with a very high intake of 200 to 300 mmol/d.79,19 Other studies that used a more moderate sodium reduction of 50 to 80 mmol/d versus 130 to 200 mmol/d tended to report no significant mean increase in total cholesterol and/or LDL cholesterol, with changes ranging from -0.2 mmol/L to +0.1 mmol/L,8,2023 although one study reported a net increase of 0.45 mmol/L in total cholesterol, primarily because of the large reduction in total cholesterol at the higher sodium level (-0.18 change with lower sodium versus -0.63 mmol/L change with higher sodium).24 Reported changes in HDL cholesterol among these studies were inconsistent, supporting the conclusion from the meta-analysis that low sodium intake does not change HDL cholesterol. Similarly, triglyceride concentrations in the studies cited changed by small amounts with low sodium intake, some negatively, and none was significant. Other reviews concluded that there were no adverse effects of moderate sodium reduction on blood lipids.3,25
Changing sodium levels between the higher and lower level and between the intermediate and lower levels, but not between the higher and intermediate level, resulted in a small increase in the total cholesterol-to-HDL cholesterol ratio of 0.10 (P=0.04) with the control diet. No change in ratio related to sodium reduction was observed with the DASH diet. Two other studies reporting on the total cholesterol-to-HDL cholesterol ratio (or its inverse) found no significant adverse effects from sodium reduction.21,24 In the DASHSodium trial, it is doubtful that the increased total cholesterol-to-HDL cholesterol ratio in the control diet is clinically relevant, especially in light of the non-significant changes in either total cholesterol or HDL cholesterol from sodium reduction. Furthermore, because the total cholesterol-to-HDL cholesterol ratio was not a protocol-specified outcome variable, there is also the possibility of a type 1 (false-positive) error.
The results from the present study showed that the DASH diet, compared with the control diet, significantly decreased serum lipoprotein concentrations without increasing triglyceride concentrations at all 3 levels of sodium. Sodium level did not influence the effects of the DASH diet on serum lipoproteins. Total cholesterol decreased by 0.4 to 0.5 mmol/L, LDL cholesterol by 0.3 to 0.4 mmol/L, and HDL cholesterol by 0.1 mmol/L. These decreases were similar to those found in the earlier DASH trial (0.35 mmol/L for total cholesterol, 0.28 mmol/L for LDL cholesterol, and 0.09 mmol/L for HDL cholesterol),13 which was conducted at a sodium level similar to the higher sodium level in the present DASHSodium trial (136 versus 142 mmol/L sodium, respectively). The earlier DASH trial observed a small, non-significant increase in triglycerides (0.04 mmol/L), whereas the present DASHSodium trial observed small non-significant changes in triglycerides of 0.06, -0.02, and 0.03 mmol/L from the DASH diet compared with the control diet at higher, intermediate, and lower sodium levels. Hence, the DASH diet, which is high in fiber and complex carbohydrates, might prevent the increase in triglycerides that otherwise occurs with diets rich in carbohydrates.13
The reductions in total cholesterol and LDL cholesterol observed with the DASH diet compared with the control diet in both the DASH and DASHSodium trials are beneficial. Using the DASH data,13 we previously calculated that the decrease in total cholesterol, even with the decrease in HDL cholesterol, coupled with the substantial decrease in blood pressure that accompanied the DASH diet, would result in a decrease in 10-year coronary heart disease risk of approximately 12% for those eating the DASH diet, in contrast to a 1% increase for those on the control diet. The lipid results from the DASHSodium trial are likely to yield similar, if not greater, predicted risk reduction given that lipid changes were slightly better and blood pressure was reduced the most with the combination of the DASH diet with lower sodium compared with the control diet with higher sodium. Nevertheless, it is important for epidemiologic studies to help determine the clinical relevance of reduced HDL cholesterol concentrations when accompanied by decreased total cholesterol or LDL cholesterol concentrations.
Perspectives
Moderate sodium reduction has no adverse effects on blood lipids. Thus, sodium reduction would be expected to decrease overall cardiovascular risk when consuming a diet similar to what many Americans consume or when consuming the DASH diet because of the salutary effect on blood pressure from sodium reduction.
| Acknowledgments |
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Received September 30, 2003; first decision October 27, 2003; accepted December 4, 2003.
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