EAL

DLM: Hypertension (2001)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To test the effects of dietary patterns on blood pressure.

Inclusion Criteria:

More than 22 years of age
Average systolic blood pressure (SBP) less than 160mmHg
Average diastolic blood pressure (DBP) 80 to 95mmHg
Persons with medication-treated hypertension if above criteria for blood pressure met after supervised withdrawal of medication.

Exclusion Criteria:

Poorly controlled diabetes mellitus
Hyperlipidemia
Cardiovascular event within the past six months
Chronic disease that would interfere with participation
Pregnancy or lactation
BMI greater than 35kg per m²
Use of meds that affect blood pressure
Unwillingness to discontinue vitamin/mineral supplements or antacids containing magnesium or calcium
Renal insufficiency
More than 14 alcoholic drinks per week.

Description of Study Protocol:

Multicenter, randomized feeding study

Three screening visits
Run-in phase in which subjects received the control diet
Randomized to one of the following diets for an eight-week intervention
- Control diet
  - Potassium, magnesium and calcium levels close to the 25th percentile of US consumption
  - Macronutrients and fiber corresponded to average consumption
  - Sodium ~3g per day
- Diet rich in fruits/vegetables
  - Potassium and magnesium levels close to the 75th percentile of US consumption
  - High amounts of fiber
  - Fewer snacks and sweets
  - Sodium ~3g per day
- Combination diet rich in fruits, vegetables and low fat dairy products and reduced in saturated fat and total fat and cholesterol
  - Potassium, magnesium and calcium at levels close to the 75th percentile of US consumption
  - High amounts of fiber and protein
  - Sodium ~3g per day

Statistics

Hypotheses
- Change in blood pressure would differ between the combination and control diets
- The change in blood pressure would differ between the fruit/vegetable and control diets
- Change in blood pressure would differ between the combination and fruit/vegetable diets
For primary analyses and within each subgroup stratum, between diet differences in the change in blood pressure were tested by two way analysis of variance, with adjustment for clinical center
To adjust for multiple comparisons, a between diet difference was considered statistically significant at P<0.025 (two tailed); 97.5% CI are given for between diet differences
Outcome measurements
- Primary: Change in DBP at rest
- Secondary: Changes in SBP and changes in systolic and ambulatory DBP and SBP.

Data Collection Summary:

SV*1

SV2

SV3

R**1

I***1

Blood pressure measurement

Physical activity questionnaire

24 Hour urine

Symptom questionnaire

Randomization

*SV: Screening visit **R: Run-in Phase, weeks ***I: Intervention Diet, weeks

Description of Actual Data Sample:

Initial sample: N=459
Final sample: N=459

Characteristics of the Subjects According to Diet*

	Control Diet	F/V Diet	Combination Diet
	N=154	N=154	N=151
Characteristics
Age, yr	44±11	45±11	44±10
Female, %	47.4	48.7	51.0
Ethnicity, %
Nonminority	35.1	35.7	31.1
Black	59.7	58.4	61.6
Other minority	5.2	5.8	7.3
Household income, %
<$30,000	37.1	36.7	36.0
$30,000-$59,999	41.7	36.7	42.7
≥$60,000	21.2	26.7	21.3
Weight, kg
Men	87.7±13.7	86.6±13.9	88.0±15.7
Women	75.4±12.2	77.1±12.5	78.9±11.7
BMI
Men	27.7±3.6	27.5±3.6	28.1±4.0
Women	28.3±4.0	28.9±4.3	29.0±3.9
BP med discontinued, %	5.8	5.8	4.6
Ever received BP med, %	20.8	25.3	20.5
Alcohol, drinks per week	1.3±2.5	1.1±2.2	1.3±2.5
Blood pressure
Systolic, mmHg ≥140, %¥	132±10.7	132±2.2	131.2±10.0
Diastolic, mmHg ≥90, %¥	85.3±4.0	84.8±3.9	35.1±3.6
Ambulatory systolic, mm Hg§	130.9±11.3	132.0±10.8	131.9±10.7
Ambulatory diastolic, mm Hg§	83.3±7.4	83.9±8.0	83.6±6.8

* Plus-minus values are means±SD

¥ Means for three screening visits

§ Mean 24-hour blood pressures in subjects in enrollment groups 2 to 5 (control [N=118], F/V [N=121] and combination [N=115] diets)

Location of Clinical Centers
- Brigham and Women's Hospital and Harvard Medical School, Boston, MA
- Duke University Medical Center, Durham, NC
- Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA
- Johns Hopkins University, Baltimore, MD.

Summary of Results:

Comparison of Mean Changes in Blood Pressure (mmHg)

Category	N	Change in Combination Group minus Change in Control Group (97.5% CI)	P-Value	Change in Combination Group Minus Change in Fruit/Veg Group (97.5% CI)	P-Value	Change in Fruit/Veg Group Minus Change in Control Group (97.5% CI)	P-Value
Systolic Pressure
All subjects	459	-5.5 (-7.4 to -3.7)	<0.001	-2.7 (-4.6 to -0.9)	0.001	-2.8 (-4.7 to -0.9)	<0.001
Men	234	-4.9 (-7.3 to -2.5)	<0.001	-1.6 (-4.0 to 0.8)	0.13	-3.3 (-5.6 to -0.9)	0.002
Women	225	-6.2 (-9.2 to -3.3)	<0.001	-3.9 (-6.9 to -1.0)	0.003	-2.3 (-5.3 to 0.7)	0.08
Minority	303	-6.8 (-9.2 to -3.3)	<0.001	-3.2 (-5.6 to-0.8)	0.003	-3.6 (-6.1 to -1.2)	0.001
Nonminority	156	-3.0 (-5.9 to -0.1)	0.02	-1.9 (-4.8 to 1.0)	0.13	-1.1 (-3.9 to 1.7)	0.38
Nonhypertensive	326	-3.5 (-5.3 to -1.6)	<0.001	-2.7 (-4.5 to -0.8)	0.001	-0.8 (-2.7 to 1.1)	0.33
Hypertensive	133	-11.4 (-15.9 to -6.9)	<0.001	-4.1 (-8.6 to 0.3)	0.04	-7.2 (-11.4 to -3.0)	<0.001
Diastolic Pressure
All subjects	459	-3.0 (-4.3 to -1.6)	<0.001	-1.9 (-3.3 to -0.6)	0.002	-1.1 (-2.4 to 0.3)	0.07
Men	234	-3.3 (-5.1 to -1.5)	<0.001	-1.3 (-3.2 to 0.5)	0.10	-2.0 (-3.7 to -0.2)	0.01
Women	225	-2.7 (-4.8 to -0.7)	0.003	-2.5 (-4.6 to -0.5)	0.006	-0.2 (-2.3 to 1.9)	0.83
Minority	303	-3.5 (-5.2 to -1.8)	<0.001	-2.1 (-3.8 to -0.4)	0.007	-1.4 (-3.2 to 0.3)	0.07
Nonminority	156	-2.0 (-4.2 to 0.2)	0.04	-1.6 (-3.8 to 0.5)	0.09	-0.4 (-2.5 to 1.7)	0.70
Nonhypertensive	326	-2.1 (-3.6 to -0.5)	0.003	-1.8 (-3.4 to -0.3)	0.009	-0.3 (-1.9 to 1.3)	0.71
Hypertensive	133	-5.5 (-8.2 to -2.7)	<0.001	-2.6 (-5.4 to 0.1)	0.03	-2.8 (-5.4 to -0.3)	0.01

Combination diet reduced mean 24-hour ambulatory SBP by 4.5mmHg more than the control diet and DBP by 2.7mmHg more (P<0.001 for each)
Fruit and vegetable diet reduced mean 24-hour ambulatory SBP by 3.1mmHg more (P=0.001) than the control diet and DBP 2.1mmHg more (P=0.002).

Adverse Events

Occurrence of GI symptoms was infrequent and similar for all the diets
- During run in phase, moderate or severe constipation in the preceding month was reported by 9% of subjects
- At the end of intervention phase, constipation was reported by 10.1% (control diet), 5.4% (fruit/vegetable diet) and 4.0% (combination diet).

Adherence

Completion of intervention phase
- 95.5% (control diet)
- 97.4% (fruit/vegetable diet)
- 98.7% (combination diet)
Self-reported adherence to study diets (all study food, no non-study foods)
- Control diet: 94.6% of person-days
- Fruit/vegetable diet: 93.9% of person-days
- Combination diet: 93.2% of person-days

Urinary potassium increased from the run in phase to the intervention phase in the fruit/vegetable diet and combination group diets and magnesium excretion increased in the combination group
Urinary urea nitrogen increased withthe combination diet
Urinary calcium excretion decreased in the control and fruit/vegetable diet groups
Urinary phosphorus excretion increased in the combination group
Urinary sodium excretion changed little in each group between the run-in and intervention phases.

Other

Mean changes in weight from end of run in to end of intervention phase: -0.1kg (control diet), -0.3kg (fruit/vegetable diet), and -0.4kg (combination diet)
Mean changes in alcohol consumption and physical activity were small and similar in the three groups.

Author Conclusion:

A diet rich in fruits and vegetables and low-fat dairy foods and with reduced saturated fat and total fat can substantially lower blood pressure
This diet offers an additional nutritional approach to preventing and treating hypertension.

Funding Source:

Government:

NHLBI, Office of Research on Minority Healthy, NCRR

Reviewer Comments:

Well-controlled study
Combination diet contained: 25.6% fat, 151mg cholesterol, 4,415mg potassium, 480mg magnesium, 1,265mg calcium and 2,359mg sodium.

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)	No
	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?		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?	???
	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?	???
	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?	N/A
	6.6.	Were extra or unplanned treatments described?	N/A
	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?	Yes
9.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	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