EAL

DLM: Plant Stanols and Sterols (2010)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To investigate relationships of cholesterol metabolism and plasma plant sterols with CAD

Inclusion Criteria:

Participant in the Ludwigshafen Risk and Cardiovascular health cohort study
- Caucasian
- Of German ancestry
- Living in southwest of Germany
Stable clinical condition (no concomitant acute illness such as infection or recent accident/surgery)
Availability of coronary angiogram (indications in patients with clinically stable condition were chest pain or non-invasive test results consistent with myocardial ischemia)
With or without statin treatment.

Exclusion Criteria:

Non-participant in Ludwigshafen Risk and Cardiovascular health study
Suffering from any acute illness other than acute coronary syndrome (other acute cardiac disease such as decompensated heart failure or decompensated valvular disease)
Acute non-cardiac disease (infection, endocrine disease any surgery within previous three months)
Chronic polymorbid disease in which non-cardiac disease predominant (chronic renal failure and hemodialysis, severe rheumatoid arthritis, persistent incapacitation after accident or trauma)
History of malignant disease in previous five years
Incapable of understanding purpose of study
Type 1 diabetes.

Description of Study Protocol:

Recruitment

From participants of Ludwigshafen Risk and Cardiovascular health study (recruited between July 1997 and January 2000)

Design

Cohort (divided by Friesinger Score which quantified severity of CAD)

Intervention

None

Statistical Analysis

Friesinger Score (FS) broken down to four categories of severity of CAD
Clinical and biochemical characteristics expressed as numbers and percentages of subjects
Categorical variables expressed as means ± standard deviations
Continuous variables expressed as means with interquartile ranges
X² test or univariate analysis of variance (ANOVA) for comparisons among the four groups
Logistic regression or general linear models with covariates used to calculate adjusted P-values
Ratios of non-cholesterol sterols to lathosterol
Pearson correlations between non-cholesterol sterols and cholesterol
Pearson correlations among non-cholesterol sterol to cholesterol ratios
Multivariate general linear models to examine relationships of the Friesinger Scores with uncorrected non-cholesterol sterols, non-cholesterol sterol to cholesterol rations and absorption marker to lathosterol ratios
Performed analyses by the whole group and by sub-groups of patients based on statin treatment
Two-sided statistical tests and P<0.05 considered significant.

Data Collection Summary:

Timing of Measurements

Baseline blood sample collected before angiography and frozen for analysis of:

Plasma total cholesterol and triglycerides
Plasma cholestanol campesterol, sitosterol and lathosterol.

Dependent Variables

Plasma triglycerides
Total plasma cholesterol
Plasma non-cholesterol sterol concentrations
- Campesterol
- Sitosterol
- Cholestanol
- Lathosterol.

Independent Variables (Exposure)

Friesinger Score (measure of severity of CAD)

Description of Actual Data Sample:

Initial N: 2,449 (1,676 males, 773 females)
Attrition (final N): Not applicable
Age by Friesinger Score Group:
- Zero to one (58.1±11.6 years)
- Two to four (64.1±9.8 years)
- Five to eight (63.6±10.1 years)
- Nine to 15 (64.9±9.3 years)
Ethnicity: German (Caucasian)
Other relevant demographics:
- Study participants with FS more than one significantly older and more predominantly male than female than those with FS of zero to one
- APOE 2X genotype associated with low FS
- Percentage of subjects receiving statins increased with higher FS
- Current or past smoking, type 2 DM and HTN more prevalent in subjects with higher FS
Anthropometrics:
- Elevated C-reactive protein and triglycerides and decreased HDL-cholesterol associated with increased severity of CAD
- Subjects with high FS had lower total and LDL-cholesterol due to increased use of statins
- Modest differences in BMI among four FS categories
Location: Germany.

Summary of Results:

Key Findings

Increase in ratio of cholestanol to cholesterol associated with high Friesinger Score (P=0.006); not significant in groups with Friesinger Scores of 8 or less
High ratio of latherosterol to cholesterol in parallel with low Friesinger Score (P<0.001)
Campesterol to cholesterol ratio significantly correlated with Friesinger Score (P=0.026)
Relationship of sitosterol to cholesterol ratio with Friesinger Score not significant in whole group
Modest association of high cholesterol absorption and low cholesterol synthesis with an increased severity of CAD
Atherogenic role of plant sterols unlikely in subjects who do not have sitosterolemia
There is an association of non-cholesterol sterols: Cholesterol ratio with the use of statins and type 2 diabetes (P<0.001).

Note: Plasma concentrations of non-cholesterol sterols were tested in patients before functional foods containing plant sterol or stanol ester (margarines) were brought to market in Germany.

Author Conclusion:

Atherogenic role of plasma plant sterols seems unlikely in subjects without sitosteroemia.

Funding Source:

Other:

Project GOLD (Genomics of Lipid-associated Disorders)

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?	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)	N/A
	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?	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?		N/A
	4.1.	Were follow-up methods described and the same for all groups?	N/A
	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%.)	N/A
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	N/A
	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?		Yes
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	N/A
	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?	Yes
	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?	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?	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?	N/A
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	N/A
	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)?	N/A
	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?	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?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes