HTN: Medical Nutrition Therapy (2015)
Kumanyika SK, Cook NR, Cutler JA, Belden L, Brewer A, Cohen JD, Hebert PR, Lasser VI, Raines J, Raczynski J, Shepek L, Diller L, Whelton PK, Yamamoto M; Trials of Hypertension Prevention Collaborative Research Group. Sodium reduction for hypertension prevention in overweight adults: Further results from the Trials of Hypertension Prevention Phase II. J Hum Hypertens. 2005 Jan; 19(1): 33-45.PubMed ID: 15372064
- To study the efficacy of sodium reduction for hypertension prevention in overweight adults for 36 months to 48 months
- To examines the sodium intervention results in detail with respect to adherence, treatment effects and dose response, including exploration of results by ethnicity, gender and genotype at the angiotensinogen locus.
- Healthy men and women
- Aged 30 years to 54 years
- Approximately 110% to 165% of Metropolitan Life Insurance Company weight standards
- DBP between 83mm Hg and 89mm Hg and SBP less than 140mm Hg when nine readings were taken over three visits were averaged.
- Current treatment for hypertension
- Evidence of cardiovascular disease, diabetes mellitus, renal insufficiency or other serious illness
- Current or planned pregnancy
- Unwillingness or inability to adhere to trial procedure.
RecruitmentSubjects recruited from the nine TOHP II clinical centers in diverse regions of the United States: Baltimore, MD; Birmingham, AL; Davis, CA; Jackson, MS; Memphis, TN; Newark, NJ; Portland, OR; Pittsburgh, PA; and St. Louis, MO. A
coordinating center, located in Boston, MA, and the National Heart, Lung, and Blood Institute project office (Bethesda, MD) also participated.
Randomized controlled clinical trial.
Implied with measurements. Data collection staff were different from intervention staff and were kept unaware of the participant's randomization group.
- Participants were given the knowledge and skills necessary to reduce sodium intake through:
- First, one individual counseling session
- Then 10 weekly group counseling sessions
- Then four monthly group counseling sessions
- Then periodic mini-series of intervention sessions on selected topics
- Individual in-person, telephone and mail contacts as needed.
- Interventions were delivered by RDs or other nutrition counselors, with support from behavior psychologists as co-leaders or consultants.
- X2 test
- Log transformation
- Geometric mean computed and SD estimated using delta method
- Linear regression analysis.
Timing of Measurements
- Baseline data collected over a series of three visits spaced seven to 45 days apart
- Follow-up data collected every six months after randomization for at least 36 months, and up to 48 months if randomized early in the study.
- BP (three readings taken per visit) every six months
- Body weight every six months
- Reported use of medications every six months.
- Participants were given the knowledge and skills necessary to reduce sodium intake through individual and group counseling sessions using in-person, telephone and mail contacts as needed. Interventions were delivered by RDs or other nutrition counselors, with support from behavior psychologists as co-leaders or consultants.
- Dietary data collected at 18 months and 36 months from a sub-sample of randomly selected participants with equal representation across the four conditions (single 24-hour recall from 900 and three-day food records from 150)
- Sodium intake measured by sodium excretion in 24-hour urine sample.
- Initial N: N=2,382 subjects
- Attrition (final N): N=956 white (681 males, 275 females) and 203 black (86 males, 117 females). The sodium reduction group had 582 subjects and the control group had 577 subjects.
- Age: Aged 30 years to 54 years (43.3±6.3 years for males, 44.6±5.8 years for females; P<0.001)
- Ethnicity: N=956 white and 203 black subjects.
- Women were less likely than men to be college graduates (38.7% vs. 59.3%, P<0.001)
- Women were less likely than men to be employed full-time (73.6% vs. 95.5%, P<0.001)
- Women were less likely than men to be married (63.3% vs. 82.2%, P<0.001)
- Women were more likely than men to have never smoked (61.8% vs. 50.5%, P<0.001).
AnthropometricsRandomization was not stratified on ethnicity or gender, but groups were comparable.
Boston, Massachusetts and National Institutes of Health. Nine clinical centers located in:
- Baltimore, MD
- Birmingham, AL
- Davis, CA
- Jackson, MS
- Memphis, TN
- Newark, NJ
- Portland, OR
- Pittsburgh, PA
- St. Louis, MO.
Dietary Intakes at Baseline
- Women reported lower calorie intakes than men (1,752±595kcal vs. 2,534±926kcal, P<0.001)
- Women reported higher percent of calories from fat than men (35.6±10.3% vs. 33.7±9.0%, P<0.05)
- Women reported lower Na intakes (mmol) than men (126.8±60.8mmol vs. 189.3±96.9mmol, P<0.001)
- Women reported lower K intakes (mmol) than men (58.9±26.6mmol vs. 84.9±35.5mmol, P<0.001)
- Women reported lower CA intakes (mmol) than men (18.0±14.7mmol vs. 22.1±12.4mmol, P<0.01)
- Women had lower urinary Na (mmol per 24 hours) than men (155.5±62.8mmol vs. 202.7±84.1mmol, P<0.001)
- Women had lower urinary K (mmol per 24 hours) than men (54.1±22.2mmol vs. 72.0±27.7mmol, P<0.001).
Urinary Sodium Excretion (mmol per 24 Hours)
- Decreased significantly in Na reduction vs. controls with net decreases at six months of 51 (95% CI of 28.9, 73.0), 18 months of 42.7 (95% CI of 30.6, 54.8) and 36 months of 40.4 (95% CI of 29.3, 51.5)
- The above decrease was larger for men than women. Na reduction vs. controls in men at six months of 55.8 (95% CI of 26.3, 85.2) and in women of 42.1 (95% CI of 11.8, 72.4); men at 18 months of 53.6 (95% CI of 37.7, 69.6) and women of 21.0 (95% CI of 4.4, 37.6); and men at 36 months of 51.3 (95% CI of 36.8, 65.8) and women of 19.8 (95% CI of 3.6, 35.9)
- Reductions were not sufficient to attain a study design goal of an average excretion of less than 80. Only 21% of participants attained this level of excretion (19% of white men, 24% of black men, 25% of white women and 20% of black women)
- Better attendance at intervention sessions were associated with greater mean Na reduction.
BP (mm Hg)
- Mean BP decreased in both Na reduction and control groups over 36 months
- Decrease in SBP between Na reduction and control groups was significant at six months [mean (SD) -5.1 (8.6) and -2.2 (8.1); (P<0.001)], at 18 months -3.8 (8.1) and -1.8 (7.0); (P<0.001), and at 36 months -0.7 (9.0) and +0.6 (8.5); (P=0.02)
- Decrease in DBP was significant at six months [mean (SD) -4.4 (6.7) and -2.8 (6.1); (P<0.001)] and at 18 months -4.4 (6.5) and -3.2 (5.0); (P=0.002), but not at 36 months -3.0 (6.5) and -2.4 (5.8) in Na reduction vs. control
- Overall reduction in hypertension incidence associated with the Na intervention was 18% (RR) (95% CI) of 0.82 (0.68, 1.00); P=0.048).
- Multivariate analyses (adjusting for the main effects of gender, ethnicity and baseline BP, weight and Na excretion) did not reveal significant interactions for BP effects by ethnicity-gender sub-groups at either 18 months or 36 months (all interaction P-values greater than 0.05)
- Larger net effects for blacks than whites were suggested in several instances (in men for both SBP and DBP at six months and for DBP at 18 months; in women for SBP throughout and for DBP at 18 months and 36 months). However, CI for black men and women were wide.
- Life-table analysis in ethnicity-gender sub-groups indicated that hypertension incidence was the highest for black women. Incidence was lower in Na reduction vs. controls in all four ethnicity-gender sub-groups, but effects were not statistically significant within subgroups. RR (95% CI) from Cox regression were:
- White men: RR of 0.82 (0.63, 1.07)
- Black men: RR of 1.00 (0; 51, 1.94)
- White women: RR of 0.89 (0.60, 1.32)
- Black women: RR of 0.61 (0.36, 1.03).
- These data support the potential public health benefit of sodium reduction for hypertension prevention, but clearly demonstrate that sodium reduction is too difficult for many people to achieve. The reduction in the incidence of hypertension, with parallel reductions in complications and health care costs, that could be achieved through sodium reduction among overweight individuals might be doubled were a greater degree of sodium reduction made more feasible through the types of food supply changes that have been recommended.
- These results should not be construed to suggest that overweight individuals with high normal BP opt for sodium reduction instead of reducing their weight or undertaking other potentially beneficial lifestyle changes. Rather, these findings support the inference that sodium reduction has important potential benefits for BP control even without concurrent weight reduction, and are supported by observational data linking sodium reduction to reductions in cardiovascular mortality in overweight individuals.
|Government:||National Heart, Lung and Blood Institute of the NIH|
Quality Criteria Checklist: Primary Research
|1.||Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)||Yes|
|2.||Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?||Yes|
|3.||Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?||Yes|
|4.||Is the intervention or procedure feasible? (NA for some epidemiological studies)||Yes|
|1.||Was the research question clearly stated?||Yes|
|1.1.||Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?||Yes|
|1.2.||Was (were) the outcome(s) [dependent variable(s)] clearly indicated?||Yes|
|1.3.||Were the target population and setting specified?||Yes|
|2.||Was the selection of study subjects/patients free from bias?||Yes|
|2.1.||Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?||Yes|
|2.2.||Were criteria applied equally to all study groups?||Yes|
|2.3.||Were health, demographics, and other characteristics of subjects described?||Yes|
|2.4.||Were the subjects/patients a representative sample of the relevant population?||Yes|
|3.||Were study groups comparable?||Yes|
|3.1.||Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)||Yes|
|3.2.||Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?||Yes|
|3.3.||Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)||Yes|
|3.4.||If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?||N/A|
|3.5.||If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)||N/A|
|3.6.||If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?||N/A|
|4.||Was method of handling withdrawals described?||No|
|4.1.||Were follow-up methods described and the same for all groups?||Yes|
|4.2.||Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)||No|
|4.3.||Were all enrolled subjects/patients (in the original sample) accounted for?||No|
|4.4.||Were reasons for withdrawals similar across groups?||???|
|4.5.||If diagnostic test, was decision to perform reference test not dependent on results of test under study?||N/A|
|5.||Was blinding used to prevent introduction of bias?||Yes|
|5.1.||In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?||Yes|
|5.2.||Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)||Yes|
|5.3.||In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?||N/A|
|5.4.||In case control study, was case definition explicit and case ascertainment not influenced by exposure status?||N/A|
|5.5.||In diagnostic study, were test results blinded to patient history and other test results?||N/A|
|6.||Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?||Yes|
|6.1.||In RCT or other intervention trial, were protocols described for all regimens studied?||Yes|
|6.2.||In observational study, were interventions, study settings, and clinicians/provider described?||N/A|
|6.3.||Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?||Yes|
|6.4.||Was the amount of exposure and, if relevant, subject/patient compliance measured?||Yes|
|6.5.||Were co-interventions (e.g., ancillary treatments, other therapies) described?||Yes|
|6.6.||Were extra or unplanned treatments described?||Yes|
|6.7.||Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?||Yes|
|6.8.||In diagnostic study, were details of test administration and replication sufficient?||N/A|
|7.||Were outcomes clearly defined and the measurements valid and reliable?||Yes|
|7.1.||Were primary and secondary endpoints described and relevant to the question?||Yes|
|7.2.||Were nutrition measures appropriate to question and outcomes of concern?||Yes|
|7.3.||Was the period of follow-up long enough for important outcome(s) to occur?||Yes|
|7.4.||Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?||Yes|
|7.5.||Was the measurement of effect at an appropriate level of precision?||Yes|
|7.6.||Were other factors accounted for (measured) that could affect outcomes?||Yes|
|7.7.||Were the measurements conducted consistently across groups?||Yes|
|8.||Was the statistical analysis appropriate for the study design and type of outcome indicators?||Yes|
|8.1.||Were statistical analyses adequately described and the results reported appropriately?||Yes|
|8.2.||Were correct statistical tests used and assumptions of test not violated?||Yes|
|8.3.||Were statistics reported with levels of significance and/or confidence intervals?||Yes|
|8.4.||Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?||Yes|
|8.5.||Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?||Yes|
|8.6.||Was clinical significance as well as statistical significance reported?||Yes|
|8.7.||If negative findings, was a power calculation reported to address type 2 error?||N/A|
|9.||Are conclusions supported by results with biases and limitations taken into consideration?||Yes|
|9.1.||Is there a discussion of findings?||Yes|
|9.2.||Are biases and study limitations identified and discussed?||Yes|
|10.||Is bias due to study's funding or sponsorship unlikely?||Yes|
|10.1.||Were sources of funding and investigators' affiliations described?||Yes|
|10.2.||Was the study free from apparent conflict of interest?||Yes|