EAL

MNT: Comparative Effectiveness of MNT Services (2009)

Citation:

Luepker RV, Smith LK, Rothchild SS, Gillis A, Kochman L, Warbasse JR. Management of hypercholesterolemia: evaluation of practical clinical approaches in healthy young adults. Am J Cardiol. 1978; 41: 590-596.

PubMed ID: 204183

Study Design:

Randomized controlled trial

Class:

A - Click here for explanation of classification scheme.

Quality Rating:

POSITIVE: See Quality Criteria Checklist below.

Research Purpose:

To determine how a sizable healthy working population with hypercholesterolemia can be most effectively identified and treated.

Inclusion Criteria:

All subjects identified as having type II hyperlipoproteinemia
Subjects with familial type II hyperlipidemia were also included.

Exclusion Criteria:

Subjects with hyperlipoproteinemia on a special diet
Subjects with normal cholesterol at the second screening or historical evidence of cardiovascular disease
Subjects presumed to have secondary hyperlipidemia.

Description of Study Protocol:

Recruitment

Over a two-year period at a work-site clinic, 6,000 employees participated in a cardiovascular screening program. 200 of these employees were selected by the department and invited to an orientation meeting. A media campaign with pamphlets and posters resulted in a voluntary participation rate of 91%. 152 of the 200 were identified from the two-stage screening process.

Design

Randomized controlled trial. Volunteers participated in a 24-week intervention study. They were randomly assigned (without stratification) to one of four study groups: A, B, C, D.

Intervention
Treatment in Four Subgroups

Group	Intervention
Group	Diet	Drug
A	Lipid Clinic	Lipid Clinic
B	Lipid Clinic	Private Physician
C	Private Physician	Private Physician
D	None	None

Group A: Treated at a Lipid Intervention Clinic conveniently located at the work-site of employment and staffed by one nutritionist and one physician. All treatment of the type II lipid abnormality was handled at the clinic. Throughout the study, nutrition education was emphasized in helping to change dietary habits. Dietary recommendations were for type II hyperlipoproteinemia (restriction of dietary cholesterol, saturated fat and increased intake of polyunsaturated fat). Drug therapy (clofibrate 500mg orally four times a day) was added after six weeks of dietary treatment and continued the remaining 18 weeks.
Group B: Received the same counseling at the clinic as Group A, but access to the clinic physician was limited to the initial visit. Subjects were encouraged to visit their private physician for drug therapy or other management. The physicians were asked to follow the study protocol of six weeks of diet therapy supplemented with orally administered clofibrate, 500mg four times a day, from the sixth to 24th week.
Group C: All subjects were referred to their private physician for treatment. Each physician was mailed the participant's lipid values, normal range according to the study, a description of the 24-week project and appropriate information about dietary and drug management of type II hyperlipoproteinemia.
Group D: Control subjects were told that initial tests had revealed elevated serum lipid levels and that these levels would be monitored.

Data Collection Summary:

Timing of Measurements

A 24-week study with measurements at six, 12 and 24 weeks.

Dependent Variables

Cholesterol Level: Blood drawn after 12 to 14 hours fasting
Triglycerides Level: Blood drawn after 12 to 14 hours fasting.

Independent Variables
Treatment in Four Subgroups

Group	Intervention
Group	Diet	Drug
A	Lipid Clinic	Lipid Clinic
B	Lipid Clinic	Private Physician
C	Private Physician	Private Physician
D	None	None

Group A: Treated at a Lipid Intervention Clinic conveniently located at the work-site of employment and staffed by one nutritionist and one physician. All treatment of the type II lipid abnormality was handled at the clinic. Throughout the study, nutrition education was emphasized in helping to change dietary habits. Dietary recommendations were for type II hyperlipoproteinemia (restriction of dietary cholesterol, saturated fat and increase intake of polyunsaturated fat). Drug therapy (clofibrate 500mg orally four times a day) was added after six weeks of dietary treatment and continued the remaining 18 weeks.
Group B: Received the same counseling at the clinic as Group A, but access to the clinic physician was limited to the initial visit. Subjects were encouraged to visit their private physician for drug therapy or other management. The physicians were asked to follow the study protocol of six weeks of diet therapy supplemented with orally administered clofibrate, 500mg four times a day from the sixth to 24th week.
Group C: All subjects were referred to their private physician for treatment. Each physician was mailed the participant's lipid values, normal range according to the study, a description of the 24-week project and appropriate information about dietary and drug management of type II hyperlipoproteinemia.
Group D: Control subjects were told that initial tests had revealed elevated serum lipid levels and that these levels would be monitored.

Description of Actual Data Sample:

Initial N: 146 (80 male) hypercholeterolemic participants
Attrition (final N): 128 participants. Baseline characteristics of the 18 subjects who left the study did not differ significantly from those subjects who completed the study.
Age: 32.8 years, range 20 to 50 years
Ethnicity: 20% to 30% African-American
Other relevant demographics: Lipid type
- 88 type IIa
- 58 type IIb.

Anthropometrics

Subjects did not differ significantly at baseline in age, sex distribution, race, body weight, lipid type distribution, cigarette smoking history and cholesterol level or triglyceride level.
Weight (kg)
- Group A: 72.7±3.2
- Group B: 72.5±1.7
- Group C: 77.3±2.9
- Group D: 74.7±2.9.

Location

Baltimore, Maryland, US.

Summary of Results:

Mean (± Standard Error of the Mean) Fasting Serum Triglyceride and Cholesterol Levels and Relative Body Weights for Baseline, Six, 12, and 24 Weeks

		Group
		A	P-value	B	P-value	C	P-value	D	P-value
Baseline Values	Relative weight	1.10±0.04		1.07±0.02		1.16±0.04		1.15±0.04
	Cholesterol (mg per 100ml)	291±7		296±9		299±6		292±7
	Triglycerides (mg per 100ml)	137±14		145±16		138±13		140±13
Six-Week Values	Relative weight	1.07±0.03 (-3%)	0.001	1.05±0.02 (-2%)	0.001	1.12±0.03 (-3%)	0.001
	Cholesterol (mg per 100ml)	252±9 (-13%)	0.001	268±8 (-9%)	0.001	267±7 (-11%)	0.001
	Triglycerides (mg per 100ml)	119±10 (-13%)	NS	120±11 (-17%)	0.05	130±12 (-6%)	NS
12-Week Values	Cholesterol (mg per 100ml)	237±10 (-19%)	0.001	252±8 (-15%)	0.001	260±7 (-14%)	0.001
12-Week Values	Triglycerides (mg per 100ml)	93 9 (-32%)	0.005	108±13 (-26%)	0.001	99±7 (-29%)	0.001
24-Week Values	Relative weight	1.07±0.03 (-3%)	0.005	1.04±0.02 (-3%)	0.005	1.13±0.04 (-3%)	0.05	1.14±0.04 (-1%)	NS
	Cholesterol (mg per 100ml)	256±11 (-12%)	0.001	252±9 (-15%)	0.001	251±8 (-16%)	0.001	280±7 (-4%)	0.05
	Triglycerides (mg per 100ml)	108±11 (-21%)	0.05	106±14 (-27%	0.005	106±11 (-23%)	0.005	125±12 (-10%)	0.05

Other Findings

At 24 weeks, all intervention groups had decreases in serum cholesterol (Group A: 12%, Group B: 15%, Group C: 17%, P<0.001)
The control Group D had a small decrease in cholesterol (4%)
Decreases in cholesterol were correlated with weight loss and decrease in fasting serum triglycerides but not with the use of clofibrate.

Author Conclusion:

Most type II hyperlipoproteinemic subjects in a working population can be identified and effectively treated. Specific treatment by lipid clinic or by private physician can effectively decrease fasting cholesterol levels in apparently healthy subjects, aged 20 to 50 years, for a period of at least 24 weeks.

Funding Source:

Government:

US Public Health Service, NIH, NHLBI

Reviewer Comments:

Statistical analysis was not discussed.

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?	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?	Yes
	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?	Yes
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?		???
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	No
	8.2.	Were correct statistical tests used and assumptions of test not violated?	???
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	???
	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)?	???
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	???
	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?	???
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