Effects of Diet and Sodium Intake on Blood Pressure: Subgroup Analysis of the DASH-Sodium Trial

Although epidemiologic data show a direct relation between dietary sodium intake and blood pressure at the population level (1, 2), some experts question the universality of the findings and oppose public health recommendations to decrease sodium intake in the general population (3). Certainly, results from reports on the relationship between sodium and blood pressure among major subgroups vary considerably. Several studies suggest that African Americans and older adults have heightened salt sensitivity (greater blood pressure response to sodium intake) (4-6). Some evidence also indicates increased salt sensitivity in women (7), although other studies do not support this claim (4, 5). The association of sodium intake with cardiovascular morbidity and mortality varies by overweight status (8), perhaps reflecting a differential effect of sodium on blood pressure in overweight persons. Finally, higher dietary intakes of potassium and calcium have been shown to blunt the pressor effects of dietary sodium (9, 10). Dietary factors other than sodium also directly affect blood pressure, and these effects also appear to vary across subgroups. In the Dietary Approaches to Stop Hypertension (DASH) Trial, for example, a diet that had reduced total and saturated fat and was rich in fruits, vegetables, and low-fat dairy foods (the DASH diet) substantially decreased blood pressure compared with a more typical U.S. diet, in the absence of weight change and at sodium intakes approximating current U.S. consumption (11, 12). These effects persisted across all subgroups and were especially pronounced among hypertensive persons, African Americans, and persons who did not drink alcohol (13). The DASH-Sodium Trial examined the effects of reduced sodium intake in the context of the DASH diet and a more typical U.S. diet (14). In that study, highly significant decreases in blood pressure were observed with decreased sodium intake in participants following either diet, and the DASH diet decreased blood pressure at sodium intakes well below the current U.S. average. These results were observed overall and in subgroups defined by ethnicity, sex, and hypertension status (15). We report on more detailed subgroup analyses from the DASH-Sodium Trial, including results for subgroups defined by age, obesity, waist circumference, alcohol intake, and baseline sodium intake. We also report the results of multivariate analyses that demonstrate how these effects vary across subgroups defined jointly by age, ethnicity, sex, and hypertension status. Methods Study Design The DASH-Sodium Trial was a multicenter, randomized feeding trial comparing the effects on blood pressure of three levels of sodium intake and two dietary patterns. The 412 participants were 22 years of age or older and had systolic blood pressures of 120 to 159 mm Hg and diastolic blood pressures of 80 to 95 mm Hg (15). The three levels of sodium intake (lower, intermediate, and higher) varied according to energy intake in a ratio of 1:2:3; target intakes were 50, 100, and 150 mmol/d, respectively, for a 2100-kcal diet. The dietary patterns were a control diet, 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 (11, 14). Participants were recruited in four separate feeding cohorts and were randomly assigned to one of the two dietary patterns by using a parallel-group design. They then ate their assigned diet for three consecutive 30-day intervention feeding periods, during which sodium intake varied among the three levels by a randomly assigned sequence (Figure). Participants ate the control diet at the higher sodium intake during a 2-week run-in period. During the three intervention periods, participants received all their food in the context of the study and were asked not to eat any nonstudy food. Individual energy intake was adjusted to keep body weight stable. Figure. Design of the Dietary Approaches to Stop Hypertension (DASH)-Sodium Trial. Exclusion criteria were heart disease, renal insufficiency, poorly controlled hyperlipidemia or diabetes mellitus, diabetes requiring insulin, special dietary requirements, intake of more than 14 alcoholic drinks/wk, or use of antihypertensive drugs or other medications that would affect blood pressure or nutrient metabolism. The study was approved by the human subjects committees of the clinical centers and coordinating center, and participants gave informed consent. Measurement Protocol Trained staff measured blood pressure at each of three screening visits, on 2 days during the run-in period, and on 5 of the last 9 days of each intervention feeding period. Interim blood pressures were assessed once during each of the first 3 weeks of each intervention feeding period. During screening and the last week of each intervention feeding period, a 24-hour urine collection was obtained. Height and weight were measured, and body mass index was calculated. Baseline physical activity was measured by using a 7-day physical activity recall interview (16). Information on education level, income, alcohol consumption, and family history was obtained by using a questionnaire. Baseline blood pressure was defined as the average of the five preintervention blood pressures. End-of-feeding blood pressures were defined as the average of the five blood pressures at the end of each 30-day intervention feeding period. If no end-of-feeding blood pressure values were available (49 of 1236 possible cases), interim (n = 9) or screening (n = 40) blood pressures were used to impute end-of-feeding blood pressures. Definitions of Subgroups Ethnicity was categorized as African American versus other (primarily non-Hispanic white). Participants were considered hypertensive if their untreated baseline systolic blood pressure was 140 mm Hg or greater and their diastolic blood pressure was 90 mm Hg or greater. (Use of antihypertensive agents was an exclusion criterion [17].) Obesity was defined as body mass index of 30 kg/m2 or greater, and high-risk waist circumference was defined as greater than 102 cm in men and greater than 88 cm in women (18). Age, physical activity, baseline alcohol intake, baseline 24-hour urinary sodium level, and family income were dichotomized at the approximate median. Level of education was dichotomized as high school or less versus more than high school. Statistical Analysis The data were analyzed on an intention-to-treat basis. Given the differential effects of sodium on blood pressure observed in previous analyses among participants eating the DASH diet versus the control diet (15) and because power for subgroup analyses is more limited than for overall analysis, we focused our comparisons on the maximum contrasts (higher versus lower sodium intake with the control diet, DASH diet versus control diet at the higher sodium intake, and the combined effect of DASH diet and lower sodium intake versus control diet and higher sodium intake). We used generalized estimating equations (19) to fit linear models that predicted baseline and end-of-feeding blood pressures as a function of diet (DASH vs. control), sodium level, and subgroup indicators. Different ways of modeling the dietsodium effects and their interactions with the subgroup indicators were used to test specific hypotheses. In particular, two-way interactions of the various dietsodium effects with ethnicity, sex, hypertension status, and age were analyzed to determine the incremental effect on blood pressure in each of these subgroups while controlling for the main and incremental effects of the other subgroups. This model allowed us to estimate various diet-sodium contrasts for each of the 16 subgroups defined by hypertension status, ethnicity, sex, and age. A second set of models examined subgroup variables in a bivariate manner and did not assume simple additivity of subgroup effects. Finally, unadjusted subgroup analyses included main effects and interactions for a single subgroup indicator. All analyses were performed by using the xtgee procedure in Stata software, version 5 (Stata Corp., College Station, Texas) (20) and included adjustment for baseline blood pressure, site, feeding cohort, and carryover effects. An exchangeable covariance matrix was assumed for the repeated measurements for each participant. Unless otherwise stated, a P value less than 0.05 was significant, and all confidence intervals are 95% confidence intervals. Because subgroup analyses were planned to interpret and elucidate the overall study results, they are not adjusted for multiple comparisons. Results Of the 412 participants who underwent randomization, 390 (95%) completed the 12-week intervention feeding period. Adherence to the study diets seemed excellent, and body weight remained stable over time (15). Table 1 shows baseline characteristics of the 412 participants. Mean urinary sodium excretion at screening was 155 mmol/d, a value higher than that found while participants ate higher-sodium diets (142 mmol/d). Table 1. Characteristics of Study Sample Several key subgroups were highly interrelated. Women made up 70% of African-American participants but only 39% of non-African-American participants. Women were more likely to be hypertensive than were men. The percentage of both men and women with hypertension increased sharply with age among non-African-American participants (21% of those 45 years of age vs. 47% of those >45 years of age) but was equally high among older and younger African Americans (43% of those 45 years of age vs. 45% of those >45 years of age). These correlations highlight the potential for confounding in our results and, hence, the importance of the multivariate-adjusted analyses. Effects of the DASH Diet Table 2 shows the effect on systolic blood pressure of the DASH diet compared with the control diet du