EAL

Cardiovascular Disease and Micronutrients

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To test the effects of gemfribrozil and Vitamin E independently and combined on levels of serum lipids (total cholesterol, triglycerides, HDL, LDL), Vitamin E, malondialdehyde, glutathione, glutothione perioxidase, and superoxide dismutase in young and elderly hyperlipidemic subjects.

Inclusion Criteria:

Hyperlipidemic patient
Attending Internal Medicine Clinic of Osmangazi University Hospital between 2004 and 2005.

Exclusion Criteria:

Acute illness
Severe chronic disease
Diabetes
Hypertension
Angina pectoris
Previous myocardial infarction
Peripheral vascular disease
Thyroid dysfunction
Alcohol intake
Smoking
Hormonal supplementation within the last six months
Iron supplementation within the last six months.

Description of Study Protocol:

Recruitment

Subjects were recruited from the Internal Medicine Clinic of Osmangazi University Hospital.

Design

99 hyperlipidemic subjects divided into three total groups comprised of some elderly hyperlipidemic subjects and some young hyperlipidemic subjects
Each group received a different treatment (Vitamin E, gemfibrozil, and Vitamin E + gemfibrozil)
Treatments occurred over one month's time (four weeks)
Measurements were taken at the beginning and the end of one month of therapy
Measurements were compared to a control group (however, demographic and anthropometric characteristics were not described).

Intervention

One group received Vitamin E (600mg per day)
One group received gemfibrozil (600mg twice daily)
One group received both Vitamin E (600mg per day) and gemfibrozil (1,200mg per day).

Statistical Analysis

Student's T-test was used to establish significant differences
Findings were significant at P<0.05.

Data Collection Summary:

Timing of Measurements

Taken at the beginning and the end of one month of therapy.

Dependent Variables

Body mass index (measured height and weight before and after therapy)
Total cholesterol (measured in serum samples using Boehringer Mannheim Hitachi 742 autoanalyzer and kits/enzymatic methods)
Triglyceride (measured in serum samples using Boehringer Mannheim Hitachi 742 autoanalyzer and kits/enzymatic methods)
HDL (measured in serum samples using Boehringer Mannheim Hitachi 742 autoanalyzer and kits/enzymatic methods)
LDL (calculated according to LDL = Total Cholesterol - HDL cholesterol - triglyceride/5)
Plasma levels of Vitamin E (measured in serum samples using Hashim's method)
Malondialdehyde (MDA) (determined in plasma samples)
Glutathione (GSH) (measured in whole blood samples by centrifuge at 1500g for 5 minutes)
Glutathione peroxidase (GP_x)
Superoxide dismutase (SOD).

Independent Variables

Vitamin E intake (600mg per day)
Gemfibrozil intake (1,200mg per day)
Vitamin E (600mg per day) and Gemfibrozil (1,200mg per day) intake.

Control Variables

Not described in this article
There was a control group, and their data was compared against the data collected from all three intervention groups.

Description of Actual Data Sample:

Initial N: 99 hyperlipidemic patients, comprised of 54 males and 45 females
Age: Elderly group: 71±2.9 years (N=65); young group: 29±4.39 years (N=34)
Other relevant demographics: Differences in demographics of this population were not found to be statistically significant
Anthropometrics: Anthropometrics of this population were not found to be statistically significant (body mass index, body weight before and after treatment, systolic blood pressure before and after treatment, diastolic blood pressure before and after treatment)
Location: Osmangazi University, Eskisehir, Turkey.

Summary of Results:

Other Findings

Statistically no difference between groups for age, gender, body mass index, or blood pressure.

Results of serum cholesterol, lipoproteins, and Vitamin E per treatment group.

	Treatment
Elderly Hyperlipidemics	Vitamin E	Gemfribrozil	Vitamin E + Gemfribrozil
Total Cholesterol	NS	NS	NS
Triglyceride	NS	3.7±1.3 (before) 2.5±1.7 (after) (P<0.001)	3.6±0.18 (before) 2.23±0.07 (after) (P<0.001)
HDL	NS	0.47±0.3 (before) 0.82±0.04 (after) (P<0.05)	0.49±0.3 (before) 0.82±0.04 (after) (P<0.05)
LDL	NS	NS	NS
Vitamin E	19.4±1.7 (before) 27.8±2.3 (after) (P<0.05)	NS	19±0.006 (before) 26±0.1 (after) (P<0.05)
Young hyperlipidemics	Vitamin E	Gemfribrozil	Vitamin E + Gemfribrozil
Total Cholesterol	NS	NS	NS
Triglyceride	NS	3.11±0.05 (before) 1.97±0.18 (after) (P<0001)	3.15±0.04 (before) 1.88±0.07 (after) (P<0.001)
HDL	0.80±0.05 (before) 1.38±0.13 (after) (P<0.05)	0.75±0.04 (before) 1.41±0.08 (after) (P<0.05)	0.76±0.06 (before) 1.57±0.04 (after) (P<0.01)
LDL	5.82±0.06 (before) 4.70±0.08 (after) (P<0.05)	5.91±0.05 (before) 4.72±0.1 (after)	5.98±0.18 (before) 4.61±012 (after) (P<0.01)
Vitamin E	37.3±0.07 (before) 46.6±0.006 (after) (P<0.05)	NS	36±0.03 (before) 45.9±0.02 (after) (P<0.05)

NS = not signficicant.

Results of MDA, GSH, GPX, and SOD levels per treatment group.

	Treatment
Elderly hyperlipidemics	Vitamin E	Gemfribrozil	Vitamin E + Gemfribrozil
MDA	NS	NS	NS
GSH	NS	NS	NS
GPX	NS	NS	NS
SOD	NS	NS	NS
Young hyperlipidemics	Vitamin E	Gemfribrozil	Vitamin E + Gemfribrozil
MDA	3.31±0.05 (before) 1.96±0.02 (after) (P<0.05)	NS	3.29±0.02 (before) 1.92±0.04 (after) (P<0.05)
GSH	106±1.8 (before) 123±3.0 (after) (P<0.05)	NS	104±2.3 (before) 121±1.7 (after) (P<0.01)
GPX	5.0±0.5 (before) 7.9±0.4 (after) (P<0.01)	NS	5.3±0.2 (before) 8.1±0.4 (after) (P<0.05)
SOD	NS	NS	NS

NS = not significant.

Author Conclusion:

In conclusion, our results suggest that in order to prevent atherosclerosis in hyperlipidemic subjects, gemfibrozil plus Vitamin E therapy may be more effective than gemfibrozil therapy alone.

Funding Source:

University/Hospital:

Osmangazi University, Eskisehir, Turkey

Reviewer Comments:

All groups reduced their BMI during the intervention (although not statistically significant) as well as blood pressure decreased or remained the same

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)	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?	Yes
	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%.)	No
	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
	4.5.	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?		???
	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.)	???
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	???
	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?		???
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	N/A
	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?	???
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	???
	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?	???
	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?	???
	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)?	N/A
	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?	No
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?	No
	10.2.	Was the study free from apparent conflict of interest?	???