EAL

DLM: Stanols/Sterols (2001)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

The purpose of the study was to "investigate how often optimal LDL cholesterol level can be reached with dietary measures by using only sitostanol ester margarine, alone or in combination with statins, in women with a previous myocardial infarction, and to which extent cholesterol metabolism is altered".

Inclusion Criteria:

-postmenopausal female

-documented coronary disease with history of angiography, coronary artery bypass surgery, or percutaneous transluminal angioplasty in the past 3 months

Exclusion Criteria:

-history of estrogen replacement therapy

-live outside study area

-Thyroid, liver, renal disease, diabetes

. On lipid medications (except second group of 10 women that had been treated with simvastatin >1 yr)

Description of Study Protocol:

2 studies with 2 groups of women described: Group 1: women who had received angiography, 8 had CABG, 11 had angioplasty a. Women randomly assigned to 21 g rapeseed oil margarine without (n=11) or with sitostanol ester (3 g)(n=11) for 7 weeks, then switched to the other margarine for 7 weeks. 2. Group 2: 10 women receiving 10-20 mg/d of simvastatin over 1 year. a. Women replaced 21 g of daily fat intake with sitostanol ester margarine for 12 weeks.

Data Collection Summary:

Outcome measures: 1. Total cholesterol 2. LDL cholesterol 3. HDL cholesterol 4. TG 5. Serum sterols 6. Dietary cholesterol absorption

Description of Actual Data Sample:

Group 1: n=22

Variables	Mean±SE	Range

Age, y	51 ±1	48-56
Body mass index, kg/m²	26.0±0.7	21-33
Dietary cholesterol, mg/d	247 ±17	96-431

Summary of Results:

Group 1: no lipid lowering meds

- Sistanol ester margarine lowered serum total cholesterol 13% (P<0.05)

- LDL cholesterol 20% (P<0.01) Sistanol ester margarine serum total cholesterol in all women, LDL cholesterol (<100 mg/dl) in 32% and (<133 mg/dl) in 73% vs. none and 27% during the basal diet (P<0.01).

Table 2. Serum Total and Lipoprotein Lipids (mmol/L) in Women With Previous Myocardial Infarction Without Previous Hypolipidemic Treatment (n=22) on Different Diets

Variables	Home Diet	Rapeseed Oil Margarine	Rapeseed Oil Margarine+ Sitostanol Ester

	Total
Cholesterol¹	6.26 ±0.20	6.01±0.22¹	5.46±0.21¹ ²
Phospholipids¹	3.17±0.09	3.07±0.09	2.96 ±0.10
Triglycerides¹	1.36 ±0.11	1.40±0.16	1.28±0.10
	LDL
Cholesterol, total	3.85±0.17	3.66 ±0.19¹	3.13±0.17¹ ²
Cholesterol, free	1.07 ±0.05	1.01±0.05	0.86±0.04¹ ²
Cholesterol, esterified	2.78±0.12	2.64±0.14	2.27±0.13¹ ²
Phospholipids	1.27±0.05	1.20±0.05	1.05±0.05¹ ²
Triglyceride	0.29±0.01	0.26±0.01	0.25 ±0.02²
	HDL
Cholesterol, total¹	1.28±0.06	1.26±0.06	1.23±0.05
Cholesterol, free	0.20±0.01	0.20±0.01	0.20 ±0.01
Cholesterol, esterified	1.08±0.05	1.06 ±0.05	1.03±0.04
Phospholipids	1.26±0.05	1.21 ±0.05	1.22±0.06
Triglyceride	0.16 ±0.01	0.14±0.01¹	0.14±0.01¹

¹ P<.05 from home values,

² P<.05 from margarine values. To get mg/dL, multiply cholesterol values by 38.7 and triglyceride values by 88.2.

Group 2: on 10 mg to 20 mg simvastatin Sistanol ester margarine

Table 5. Serum Lipids (mmol/L) (mean±SE) Before and at the End of 3-Month Sitostanol Ester Margarine Period of Women With Previous Myocardial Infarction (n=10) Receiving Simvastatin

Serum Lipid	Before	End	% Change

Cholesterol, total	4.94±0.43	4.38±0.35	-11.1 ±3.2¹
LDL cholesterol	2.86±0.44	2.37 ±0.35	-16.3±5.0¹
HDL cholesterol	1.35 ±0.08	1.37±0.05	+2.5±5.8
Triglycerides	1.63±0.15	1.43±0.15	-12.1 ±7.8

¹ P<.05 from before.

Total cholesterol 11+3% (P<0.01) LDL cholesterol 16+5% (P<0.01) The effects of sitostanol on cholesterol metabolism:

- Absorption (- 45%)

- Fecal elimination (+45% as neutral sterols) - Synthesis (+39%)absorption (- 45%) - Fecal elimination (+45% as neutral sterols) - Synthesis (+39%) Dietary use of sitastanol ester margarine normalizes LDL cholesterol in ~1/3 of women with previous MI, especially in those with baseline absorption and synthesis of cholesterol and when combined with statins the needed drug dose. High cholestanol and plant sterol ( cholesterol absorption) and low baseline precursor sterol proportions (low cholesterol synthesis) predicted high in serum cholesterol.

Author Conclusion:

Use of sitostanol ester margarine effectively inhibited cholesterol absorption wheic then reduced the LDL levels in 32% of the patients to <100 mg/dL compared with none during home diet in postmenopausal women with coronary heart disease.

Funding Source:

Government:

Finnish Academy of Medical Sciences

University/Hospital:

Helsinki University Hospital

Not-for-profit

Foundation associated with industry:

Reviewer Comments:

Randomization approach not explicitly stated

No dropouts mentioned

No mention of compliance/blinding

Unclear how "home diet" was measured

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?	???
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)	???
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	N/A
	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%.)	N/A
	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?		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?	No
	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?	N/A
	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)?	N/A
	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?	No
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