EAL

HTN: Medical Nutrition Therapy (2015)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To determine whether weight loss or reduced sodium intake is effective in the treatment of older persons with hypertension (HTN).

Inclusion Criteria:

Men and women 60 to 80 years old with an average systolic blood pressure (SBP) <145mmHg and diastolic blood pressure (DBP)<85mmHg (mean of nine measurements; three at each of three visits) while taking a single anti-hypertensive medication or a single combination regimen consisting of a diuretic agent and a non-diureticagent
Individuals taking two anti-hypertensive medications were enrolled if they could be successfully weaned to one anti-hypertensive medication during the screening phase
Willingness of an enrollee and his or her physician to participate
Stable health
Independence in activities of daily living
Presumed capacity to alter diet
Physical activity in accordance with the requirements of any TONE intervention.

Exclusion Criteria:

History of a heart attack or stroke within the preceding six months
Current angina pectoris
Congestive heart failure
Insulin dependent diabetes mellitus
Serious mental or physical illness
Unexplained or involuntary weight loss of 4.5kg or greater during the previous year
Body mass index (BMI) <21kg/m² in men or women or >33kg/m² in men or greater than 37kg/m² in women
Presumed inability to comply with the protocol
Hypercreatinemia (greater than 152umol/L {greater than 2.0mg/dL})
Hyperkalemia (greater than 5.5mmol/L)
Hyperglycemia (non-fasting level greater than 14.4mmol/L {greater than 260mg/dL})
Anemia (hemoglobin level less than 110g/L).

Description of Study Protocol:

Recruitment

The study was conducted as a multicenter, controlled clinical trial in which participants were randomly assigned to one of six treatment cells across two strata of body weight
Details of the recruitment experience have been published. (see reference 15).

Design

The trial was designed to test the following two hypotheses:

Prescribing a sodium reduction program for obese and non-obese older patients with HTN reduces the rate of primary end points following the withdrawal of BP-lowering medications
Prescribing a weight loss program for obese individuals reduces the rate of primary end points following the withdrawal of BP-lowering medications.

Blinding Used

Outcome information was obtained by staff members who were blind to the participants's intervention assignment.

Intervention

Small group and individual meetings with nutritionists and exercise counselors in which participants were advised on ways to change eating patterns and increase physical activity (for weight loss with or without sodium reduction)
Adapt the TONE lifestyle recommendations to their individual circumstances.

Statistical Analysis

Analysis of variance tests for continuous variables and X2 tests for discrete variables to highlight comparisons for which the randomization algorithm yielded a chance imbalance
Outcome analyses were conducted on an intentiona-to-treat basis using two-sided significance levels of 0.05
Kaplan-Meier curves were used to compare times to end points and each hypothesis was tested using Cox proportional hazards regression models
Relative hazard ratios (HR) were used to summarize the impact of treatment assignment on the rate of end points over time
Intervention related BP changes from baseline to follow-up were assessed using Laird-Ware models to average BPs after intervention assignment and prior to drug withdrawal
Likelihood ratio statistics and SEs were used to perform inference testing (SAS/STAT software, release 6.06, SAS Institute Inc. Cary, North Carolina)
Contrasts among the proportions of participants experiencing one or more events were evaluated using the Fisher exact test.

Data Collection Summary:

Timing of Measurements

Baseline and quarterly from August 1992 until December 1995 medical history including medication information and symptoms, measurements of body weight and BP
24 urine collections were obtained twice during the enrollment period and at the nine-month, 18-month and final closeout visits for measurement of sodium content
A 24-hour dietary recall history was obtained by a trained technician twice during enrollment and at the nine- and 12-month follow-up visits and every six months thereafter.

Dependent Variables

Body weight
Blood pressure
Anti-hypertensive medication use.

Independent Variables

Dietary sodium intake
Eating patterns and physical activity
Knowledge and behavior skills necessary to achieve and maintain their desired reductions in sodium intake and body weight.

Description of Actual Data Sample:

Initial N: 975 ( 585 obese,390 non-obese)
Attrition (final N): N=975
Age: 60 to 80 years; 78% between 60 to 69 years
Ethnicity: White and African American
Anthropometrics: Baseline characteristics similar in each group except that there were slightly more men in the sodium reduction and weight loss combined group than in the three other groups in the obese stratum
Location:
- Wake-Forest University School of Medicine, Winston-Salem, North Carolina
- Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland
- University of Tennessee-Memphis
- Robert Wood Johnson Medical School, New Brunswick.

Summary of Results:

BP Results

SBP and DBP did not differ across treatment groups at baseline, but at the last visit before medication withdrawal was attempted the mean SBP and DBP values were significantly lower in all the intervention groups than in the usual care group
The percentages for BP control at the goal of <140/90mmHg were 71% for those assigned to sodium reduction, 63% for weight loss, 73% for sodium reduction and weight loss combined and 65% for usual care.

Body Weight

The average reduction in weight for the participants assigned to weight loss was approximately 3.5 to 4.5kg resulting in net reductions of 3.8 (95% CI, 3.1-4.5), 3.6 (95% CI, 2.8-4.3) and 3.9 (95% CI, 2.7-5.1) kg at the nine, 18 and 30-month follow-up visits, respectively (P<0.01 for all), vs. an average 0.9kg reduction (95% CI, 0.4-1.3) for those not assigned to weight loss.

Withdrawal of Anti-hypertensive Medication

Anti-hypertensive medication could be stopped in 86.8% of those assigned to usual care in 92.6% assigned to sodium reduction alone, in 93.2% assigned to weight loss alone and in 93.2% assigned to weight loss and sodium reduction combined.

Author Conclusion:

The Tone study is the first trial of sufficient size and duration to provide convincing evidence regarding the feasibility, efficicacy and safety of dietary lifestyle interventions as a means to control high BP and decrease the need for anti-hypertensive medication in older patients with hypertension.

Funding Source:

Government:

National Institutes of Health

Reviewer Comments:

The positive study results should encourage more clinical trials.

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
	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
	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
	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
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
	1.	Was the research question clearly stated?	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
	1.1.	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
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
	1.3.	Were the target population and setting specified?	Yes
	2.	Was the selection of study subjects/patients free from bias?	???
2.	Was the selection of study subjects/patients free from bias?		???
	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
	2.1.	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
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	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?	???
	2.4.	Were the subjects/patients a representative sample of the relevant population?	???
	3.	Were study groups comparable?	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)	???
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	???
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	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
	3.3.	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
	3.4.	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
	3.5.	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
	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?	N/A
4.	Was method of handling withdrawals described?		N/A
	4.1.	Were follow-up methods described and the same for all groups?	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%.)	N/A
	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%.)	N/A
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	N/A
	4.4.	Were reasons for withdrawals similar across groups?	N/A
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
	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.	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?	No
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	No
	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
	5.2.	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
	5.3.	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
	5.4.	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
	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.	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
	6.1.	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
	6.2.	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
	6.3.	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
	6.4.	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?	No
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	No
	6.6.	Were extra or unplanned treatments described?	No
	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
	6.7.	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
	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.	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
	7.1.	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
	7.2.	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
	7.3.	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
	7.4.	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
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	No
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	No
	7.7.	Were the measurements conducted consistently across groups?	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.	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
	8.1.	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
	8.2.	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
	8.3.	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)?	???
	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)?	???
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	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
	8.6.	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
	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.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	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.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes