EAL

Cardiovascular Disease and Micronutrients

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To determine the efficacy of vitamins E, C and A, and fruit on the cholesterol lipoproteins and lipid peroxide levels in congestive heart disease (CHD).

Inclusion Criteria:

CHD by either history of documented angina or acute coronary syndrome more than 30 days previous to the trial.

Exclusion Criteria:

Unstable coronary syndrome, concomitant serious medical illness or acute conditions that increase the oxidant load.

Description of Study Protocol:

Recruitment: From successive patients with stable CHD presenting at the center
Design: Placebo RCT using a Latin-square design
Intervention: Placebo, 400 IU synthetic vitamin E, 1,000mg ascorbic acid, 25,000 IU vitamin A or 400g raw unpeeled apple or guava per day for 30 days. Supplemental vitamins were stopped one month prior to the study.
Statistical analysis: ANOVA or X² test to compare baseline values. Paired T-test for within-group comparisons and unpaired T-test for across-group comparisons in biochemical measures. P<0.05 was significant.

Data Collection Summary:

Timing of Measurements

Baseline and at one month.

Dependent Variables

T-cholesterol: Measured fasting and assayed by CHOD-PAP enzymatic method
TG and HDL: Measured fasting and assayed by GPOP method
LDL: Measured fasting and calculated using Freidewald's equation
FBG: Measured fasting, assayed per enzymatic method
Lipid peroxide: Measured fasting assayed by Slater's method.

Independent Variables

400 IU vitamin E
1,000mg vitamin C
25,000 IU vitamin A
400g fruit (compliance by telephone interview once per week)
Diet history: Standardized pre-coded FFQ
Current energy intake: Three-day 24-hour dietary recall
Nutrient intake calculation by Indian National Institute of Nutrition tables and other sources, specifically for vitamin E and flavonoids
Compliance with fruit and vitamin intake was done by telephone once per week.

Control Variables

American Heart Association Step II diet, promotion of physical activity, cessation of smoking and no change in medications.

Description of Actual Data Sample:

Initial N: 175
Attrition (final N): 157 (125 males, 32 females)
Age: Average age for the groups ranged from 53.7 to 55.9 years
Other relevant demographics: No difference in mean age, gender distribution, occupational or educational class
Anthropometrics: There was no difference in the presence of other coronary risk factors. Dietary intake of major nutrients, fats and antioxidants was similar. Calorie intake varied from 1,812±377 to 2,048±469.
Location: India.

Summary of Results:

Findings

There was no significant change in total, LDL and HDL cholesterol among the groups except for the Fruit Group, which had a significant (P<0.05) decrease in total cholesterol (-7.8±11.1%) and LDL (-11.2±25.4%) and an increase in HDL (+12.9±20.1%).
All of the intervention groups had a significant decrease (P<0.01) in lipid peroxide levels. The greatest decrease was in the Vitamin E Group (-36.4±17.7%). In the Vitamin C Group, it decreased -19.8±10.8%; in the Fruit Group, -13.1±12.0%; in the Vitamin A Group, -5.4±17.1%.
There was no significant change in the placebo group.

Author Conclusion:

All the antioxidant vitamins and fruits significantly decrease lipid peroxide levels and oxidant load in CHD patients
Fruits are the best choice as they also favorably modify the lipid profile.

Funding Source:

University/Hospital:

University of Rajasthan, Jaipur; Monilek Hospital and Research Center, Jaipur India

Reviewer Comments:

No documentation of compliance with AHA Step II diet, physical activity or smoking cessation.

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?		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?	???
	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?	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
	7.1.	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?	No
	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)?	N/A
	8.6.	Was clinical significance as well as statistical significance reported?	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
	9.1.	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?		???
	10.1.	Were sources of funding and investigators' affiliations described?	No
	10.2.	Was the study free from apparent conflict of interest?	???