EAL

DF: Cardiovascular Disease (2008)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To examine the hypothesis that serum cholesterol reduction occurs as a result of addition of dietary fiber, separate from, and perhaps in addition to, the reduction of dietary fat.

Inclusion Criteria:

30 to 50 years
80% to 120% of ideal body weight by the Metropolitan tables
Caucasian
After a 12-hour fast on two screenings:
- Serum cholesterol 5.18 to 7.76mmol per L (200 to 300mg per dL)
- Serum triglycerides less than 5.65mmol per L (500mg per dL).

Exclusion Criteria:

Types III and IV hyperlipoproteinemia
History of lipid-modifying diets
Hypertension (blood pressure higher than 160/90mm Hg)
Diabetes (fasting glucose lower than 140mg per dL)
Coronary, renal, COPD, malignant tumors and other potentially life-shortening diseases
On steroids, birth-control, estrogen or cholesterol-lowering medication.

Description of Study Protocol:

Recruitment

Participants recruited from major employers, churches, and shopping centers in the Central Kentucky area between March and October of 1987.

Design

Randomized crossover trial.

Blinding Used

Because of the nature of the educational program, subjects were not blinded to their group assignment, nor were their teaching or coordinating dietitians. Technicians who analyzed blood samples were blinded to group assignment.

Intervention

Participants were randomized to one of three groups:
- AHA: The American Heart Association Phase II diet
- HCF: The high-carbohydrate fiber (a similar low-fat diet with a generous amount of fiber added)
- CG (control group): Directed to maintain current dietary behaviors
AHA and HCF groups received a 10-week, diet-education seminar series, with periodic contacts with teaching dietitians for the balance of the first year. CG participants received no diet education.

Statistical Analysis

One-way analysis of variance (ANOVA)
Pairwise contrasts among the three study groups followed, using the Protected LSD (alpha=0.05)
Repeated measures ANOVA was used to compare the two diet groups at four, eight and 12 months with respect to changes from baseline on blood lipid variables
Triglycerides were log-transformed
Changes from baseline to 12 months were analyzed using ANCOVA using a backward selection procedure.

Data Collection Summary:

Timing of Measurements

Participants were followed for 12 months, with diet and blood lipid data collected at baseline, four, eight and 12 months from diet groups, and at baseline and 12 months from the control group.

Dependent Variables

Serum cholesterol and blood lipid samples were collected after a 12-hour fast:

Serum cholesterol, triglyceride and high-density lipoprotein (HDL) cholesterol concentrations were determined in the Lipid Analysis Resource Unit of the Lexington Veterans’ Affairs Medical Center, Lexington, KY, by enzymatic methods,using the Abbott VP Analyzer (Abbott Laboratories, North Chicago, IL)
Serum total cholesterol was measured by using a cholesterol-esterase, cholesterol oxidase assay
Serum HDL-cholesterol was measured by the same method as total cholesterol after removing low-density lipoprotein (LDL) cholesterol and very-low-density lipoprotein (VLDL) cholesterol with magnesium dextran sulfate
Serum triglyceride concentrations were determined by hydrolyzing the triglycerides and measuring the released glycerol.

Independent Variables

Energy and nutrient intake at baseline, four, eight and 12 months from diet groups and zero and 12 months from the control group was measured with three-day food records (including one weekend day) tabulated using Nutritionist III.

Control Variables

Body weight was measured with calibrated balance scales
Smoking behavior was measured with a self-administered questionnaire on which participants were asked to report whether or not they currently smoked, and if so, how many cigarettes per day
Exercise was measured with an interview, by the method of Sallis et al,which estimates total energy expended daily in all activities.

Description of Actual Data Sample:

Initial N: 177 randomized
Attrition (final N): 31 (146; 51 in CG, 47 AHA, 48 HCF); 16 dropped out due to lack of time (N-8), illness (N=2), initiating drug tx (N=4), personal matters (N=2); 11 dropped for taking medication that might interfere with cholesterol (N=10); one was pregnant and four moved out of the area.
Age: Mean±SD; 40±5 years
Ethnicity: Caucasian, not otherwise specified
Anthropometrics: Weights similar at baseline, but the two intervention groups lost approximately 0.5kg more than the control group during follow-up
Location: Central Kentucky, US.

Summary of Results:

Change (12-month Baseline)	Control Group Mean±SE (N=51)	AHA Group Mean±SE (N=47)	HCF Group Mean±SE (N=48)	Statistical Significance of Group Difference
Cholesterol (mmol per L)	-0.42±0.08	-0.59±0.09	-0.79±0.09	0.009
LDL	-0.40±0.06	-0.56±0.08	-0.75±0.08	0.005
HDL	0.01±0.02	0.01±0.02	-0.04±0.02	NS

Other Findings

At 12 months, the HCF reported consuming more total and soluble fiber than the AHA group (P=0.011 and P=0.006), but only consumed approximately 50% of prescribed amounts (25g per day vs. approximately 50g per day)
Changes from baseline
- Diet: Saturated fat reduced in AHA (mean 6.4g per day, SE 0.42) and HCF groups (mean 6.6g per day, SE 0.48) compared to the control group
- Control group: Only significant change was cholesterol intake, which decreased by 48 mmol per L.

Author Conclusion:

This study indicates that including information about soluble fiber and educating hypercholesterolemic individuals about the hypocholesterolemic effects of soluble fiber might enhance the effectiveness of the AHA diet.

Funding Source:

Government:

NHLBI

Reviewer Comments:

Analysis was not ITT: Excluded individuals post-randomization, creating imbalance in the treatment groups by gender
Control group outcomes were not assessed as often as intervention groups.

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?		No
	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?	No
	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?	Yes
	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?	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
	5.3.	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?	No
	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?	No
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		No
	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)?	No
	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