Cardiovascular Disease and Micronutrients

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:

To investigate the effect of vitamin E on lipids and peroxidation during statin treatment.

Inclusion Criteria:
  • Diagnosis of type 1 diabetes
  • Total cholesterol higher than 4.9mmol per L
  • LDL-cholesterol higher than 3.0mmol per L
  • Triglycerides less than 4.5mmol per L
  • Normal blood levels of thyroxin and TSH.
Exclusion Criteria:

Did not meet inclusion criteria.

Description of Study Protocol:

Recruitment

Patients with history of high cholesterol recruited from outpatient diabetes clinic of Antwerp University hospital.

Design

  • RCT
  • Patients randomized in blocks of four, matched for age and sex
  • Divided into two groups.

Blinding Used

Patients blinded to treatment.

Intervention

After a lipid-lowering free washout period of four to six weeks, patients were randomized to receive 20mg Atorvastatin daily with either:

  • 250 IU (168mg) d-alpha-tocopherol three times daily
  • Placebo of 280mg soybean oil with 0.25mg tocopherol per capsule that was identical in appearance and taste to treatment capsule.

Statistical Analysis

  • Results expressed as means ±SD
  • Two-tailed P-values of 0.05 were considered significant
  • Between-group comparisons by T-test or Mann-Whitney test for non-Gaussian variables
  • Effect of medication versus placebo during the course of three visits analyzed by ANOVA
  • Data analyzed for change over time within the groups and for differences in the two groups.
Data Collection Summary:

Timing of Measurements

Lipids measured after four to six washout period without cholesterol-lowering medicine (baseline), after three months and after six months of treatment.

Dependent Variables

  • Blood lipids by standard hospital laboratory:
    • Total cholesterol
    • HDL-cholesterol
    • Triglycerides
    • LDL-cholesterol (calculated according to Friedewald equation).
  • Glycated hemoglobin (HPLC cation exchange column)
  • Oxidant-antioxidant balance (measured concentrations of vitamins E and A in serum using HPLC)
  • Susceptibility of LDL and VLDL to copper-catalyzed oxidation (measured by fluorescence method)
  • Composition of non-HDL fraction
  • Composition of LDL fraction.

Independent Variables

  • 20mg Atorvastatin and 250 IU d-alpha-tocopherol (three capsules daily)
  • 20mg Atorvastatin plus 280mg soybean oil (three capsules daily).

Control Variables

Standard diet for diabetes (7.5 to 8.5mJ per kg per day) with nutrient distribution as 50% carbohydrate, 20% protein, 30% fat.

Description of Actual Data Sample:

Initial N

24.

Attrition (Final N)

22:

  • 10 males and one female in Experimental Group
  • 10 males and two females in Placebo Group.

Age

  • Experimental Group: Median, 43 (range, 21 to 69)
  • Placebo Group: Median, 59 (range, 23 to 66).

Anthropometrics

No significant differences between groups at baseline for BMI (25.2 vs. 26.0kg/m2), blood lipid levels, HbA1C, insulin dosage, median years duration of diabetes or blood pressure.

Location

Antwerp, Belgium.

Summary of Results:

Between-group comparison of the change in serum lipids was not significant. Atorvastain treatment decreased serum lipids the same amount for both groups:

  • Cholesterol by 29%: From 6.08±0.68mmol before treatment to 4.34±0.77mmol after three months of treatment and 4.41±0.71mmol after six months of treatment; P<0.0001
  • LDL-cholesterol by 41%: From 3.91±0.52mmol before treatment to 2.32±0.58mmol after three months and 2.33±0.56mmol after six months on the drug; P<0.0001
  • Triglycerides decreased by 21%: From 1.17±0.57 to 0.93±0.39mmol per L after three months and 0.93±0.43mmol per L after six months; P=0.005.

There were no significant changes in HgA1C or HDL in either group.

Variables

Atorvastatin + Vitamin E

Atorvastatin + Placebo

Statistical Significance of Group Difference

Total Thiobarbituric Reactive Substances (TBARS)

4,654±1,110

6,527±1,696

P=0.020

Composition Non-HDL Fraction Content in Alpha-Tocopherol (mmol per L)

24.8±12.6

16.6±5.8

P=0.022

 

Author Conclusion:

Vitamin E does not affect lowering of plasma lipids achieved by Atovastatin. However, the antioxidant effect of vitamin E is attenuated when given with the statin.

Funding Source:
Other: Omega-Pharma NV furnished alpha tocopherol and placebo
Reviewer Comments:
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? N/A
  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")? 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? 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? 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
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? Yes
  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)? No
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? No
  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