HTN: Medical Nutrition Therapy (2015)

Study Design:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
  • The TONE trial tested whether reduced sodium intake or weight loss can maintain satisfactory medication-treated HTN control in older persons with HTN
  • This article focused solely on the sodium component of TONE and sought to examine:
  1. The effects of a reduced sodium intake in subgroups defined by sex, ethnicity, age and obesity
  2. Dose-response relationships
  3. The effects of a reduced sodium intake on the need/resumption of drug therapy, dietary intake of other nutrients and occurrence of adverse events.
Inclusion Criteria:

Inclusion Criteria

  1. Healthy persons aged 60 to 80 years with systolic BP of less than 145mm Hg and diastolic BP of less than 85mm Hg, while taking one antihypertensive medication
  2. Individuals taking two antihypertensive medications, as long as they were successfully weaned from from one medication during the screening phase.


Exclusion Criteria:

Exclusion Criteria

  1. Use of antihypertensive medication for conditions other than HTN
  2. MI or stroke within six months
  3. Angina pectoris
  4. CHF
  5. Serum creatinine level of more than 176.8µmol per L (more than two mg/dL)
  6. Blood glucose level of more than 14.4mmol per L (over 260mg per dL)
  7. Self-report of more than 14 alcoholic drinks per week.
Description of Study Protocol:

Study Protocol

  • Screening: Medical histories, 24-hour dietary recalls, physical exam, routine lab tests, 24-hour urine collections over two screening visits
  • Randomization: In TONE, overweight participants randomly assigned to one of four groups:
    1. Combined weight loss and reduced sodium (80mmol Na per L)
    2. Reduced sodium alone (80mmol Na per L)
    3. Weight loss alone
    4. Usual lifestyle control group.
  • Non-overweight participants were randomly assigned to:
    1. Reduced sodium alone
    2. Usual lifestyle control group.
  • This article only evaluated the random assignment to reduced sodium intervention or control group
  • TONE interventions: Introductory individual session for those in reduced sodium group within one month,  “Intensive” phase with weekly group meetings for four months, “Extended” phase with biweekly group meetings for next three months and “Maintenance” phase. Every fourth contact was individual session.
  • Three months: Medication was withdrawn. Participants had three additional biweekly visits to confirm BP within defined limits.
  • Primary trial endpoint was defined as an occurrence of an average systolic BP of 150mm Hg or more, an average diastolic BP of 90mm Hg or more, the resumption of medication or a cardiovascular event during follow-up
  • Nine months: 24-hour urine collection, 24-hour dietary recalls
  • 12 months: 24-hour dietary recalls
  • 18 months: 24-hour urine collection, 24-hour dietary recalls
  • 24 months: 24-hour dietary recalls
  • 30 months: 24-hour urine collection.
Data Collection Summary:

Data Collection

  • All BP measurements obtained by trained and certified observers, who were masked to intervention assignment
  • At each visit, three BP measurements obtained while participant rested in seated position
  • Random-zero sphygmomanometer was used to minimize observer bias
  • 24-hour dietary recalls obtained by trained, certified technicians who were masked to intervention assignment.
Description of Actual Data Sample:
  • 681 patients with HTN
  • Aged 60 to 80 years from the TONE trial
  • There was no evidence of a substantial imbalance between the reduced sodium and usual lifestyle groups.
Summary of Results:
  • Analyses were conducted on an intention-to-treat basis. In primary analyses, the distributions of time until first occurrence of an endpoint were compared in participants assigned to the reduced sodium and usual lifestyle groups. Times were measured from the end of the drug withdrawal process until the occurrence of the endpoint.
  • At the nine-month follow-up visit, attendance was 91% in the reduced sodium group and 88% in the usual lifestyle group. At the 18-month follow-up visit, corresponding attendance was 85% and 83%.
  • Compared with control, mean urinary sodium excretion was 40mmol per day less in the reduced sodium intervention group (P < 0.001). Significant reductions in sodium excretion occurred in subgroups defined by sex, race, age and obesity. Prior to medication withdrawal, mean reductions in systolic and diastolic BPs from the reduced sodium intervention, net of control, were 4.3mm Hg (P<0.0001) and 2.0mm Hg (P=0.001). During follow-up, an end point occurred in 59% of reduced sodium and 73% of control group participants (relative hazard ratio=0.68, P<0.001). In African-Americans, the corresponding relative hazard ratio was 0.56 (P=0.005); results were similar in other subgroups. In dose-response analyses, end points were progressively less frequent with greater sodium reduction (P for trend =0.002).
Author Conclusion:
  • This large RCT demonstrated that free-living older people with HTN can reduce their sodium intake and that a reduced sodium intake can lower BP and the need for antihypertensive drug therapy
  • In summary, a reduced sodium intake is a broadly effective, non-pharmacologic therapy that lowers BP and controls HTN in older individuals
  • Our results in combination with the high prevalence of HTN and its treatment with medication in the elderly, argue for substantial efforts to reduce sodium intake in older persons.


Funding Source:
Government: NIH,NHLBI
Reviewer Comments:
  • A second data analysis of the original TONE trial data
  • The effects of the intervention on BP and endpoints in the age group 70 to 80 years did not achieve statistical significance, perhaps as a result of small sample size.
Quality Criteria Checklist: Primary Research
Relevance Questions
  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
Validity Questions
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")? Yes
4. Was method of handling withdrawals described? Yes
  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%.) Yes
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? Yes
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? Yes
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? No
  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