EAL

H/A: Hyperlipidemia (2009)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

The purpose of the study was to determine if interventions based on the NCEP guidelines effectively lowered lipids without disrupting the effectiveness of the protease inhibitor-based HIV therapy regimen
Secondary objective was to document the development of hyperlipidemia-associated events such as CAD and pancreatitis.

Inclusion Criteria:

Study participants were receiving treatment with one of the following PI-based regimen (indinavir, ritonavir/saquinavir or nelfinavir)
Participants were included if cholesterol level was greater than 200mg per dL and TG level greater than 400mg per dL.

Exclusion Criteria:

None reported; however, as stated from inclusion list, can infer cholesterol below 200mg per dL and TG lower than 400mg per dL.

Description of Study Protocol:

Recruitment

None reported, a group of convenience selected from the HIV clinic.

Design

Non-randomized trial.

Intervention

Diet, exercise and prescription of gemfibrozil alone or in combination with atorvastatin.

Statistical Analysis

Not described in methods; however, results show means, SD, and T-tests.

Data Collection Summary:

Timing of Measurements

Baseline, monthly and every three months.

Dependent Variables

Lipid levels (participants were asked to fast for 10 hours and labs taken)
CAD (measurements not reported)
Pancreatitis.

Independent Variables

Diet (counsel on reduction of fat, sugar in diet)
Exercise (encouraged to increase, decrease or eliminate smoking and alcohol)
Drugs.

Description of Actual Data Sample:

Initial N: N=45 (39 males, six females)
Attrition (final N): 45 subjects, ongoing study. Currently, a total of 27 persons continue to be followed for intervention of protease inhibitor-associated hyperlipidemia. 16 participants have discontinued their protease inhibitor and two have been lost to follow-up.
Age: Mean age, 41 years.

Ethnicity

African American: Seven
Caucasian: 34
Hispanic: Two
Southeast Asian: One
Native American: One.

Other Relevant Demographics

Cardiac risk: 19 had zero; 18 had one; five had two; two had three; and one was classified as unlikely risk
CDC classification.

Anthropometrics

Mean CD4+ cell count at study entry was 340 cells per uL and the HIV RNA level was 3,686 copies per ml.

Location

HIV Clinic at Regions Hospital, St. Paul, Minnesota.

Summary of Results:

Lipid Profile (N)	Mean (SD)	P-value	T-value
Average cholesterol Before PI (N=39) Start of study (N=45) Stop PI or Current (N=45)	172 (28.8) 289 (115.6) 201 (34.2)	0.001 0.001	-6.62 4.87
Average Triglyceride Before PI Start Study (N=45) Stop PI or Current (N=45)	NA 879 (1,160.7) 440 (3,83.9)	0.01	2.41

21 participants were on diet and exercise regimen to reduce hyperlipidemia; mean cholesterol, 243mg per dL and 342mg per dL for TG; 15 participants failed intervention and were placed on lipid-lowering drugs
Six participants continued diet and exercise regimen for 10 months; overall diet and exercise regimen did not significantly reduce lipids for this group
13 participants were treated with diet, exercise, atorvastatin or gemfibrozil. Mean cholesterol and TG at baseline was 251mg per dL and 408mg per dL respectively for patients on atorvastatin; mean cholesterol and TG after eight months was 189mg per dL and 307mg per dL (P<0.0001).
17 participants were on combination atorvastatin and gemfibrozil; four changed to atorvastatin alone. 13 remained and had cholesterol and TG levels of 271mg and 1,054mg at baseline; after eight months, cholesterol was 209mg per dL and 629mg per dL for TG (P<0.05).
Overall, 45 patients received a PI and placed on lipid-lowering agents; average cholesterol and TG levels at baseline were 289mg and 879mg and after 20 months, intervention reduction was 201mg per dL (cholesterol) and 440mg per dL for TG (P<0.001).

Other Findings

Medical events related to hyperlipidemia that were attributed to PI and was reported: Cardiac and pancreatitis
Three participants developed cardiac problems and were reported as cases
Two reported pancreatitis and were reported as cases.

Author Conclusion:

Intervention with atorvastatin alone or in combination with gemfibrozil was effective in significantly reducing hyperlipidemia
The initial intent of the study was to follow the NCEP guidelines in treatment of the hyperlipidemia, which rely on HDL and LDL to guide treatment; however, due to elevated TG, the laboratory was unable to calculate the HDL and LDL in a significant number of the participants (N=18)
The study investigated a small cohort and although the intervention was determined to be effective, further investigation is imperative
A limitation of the study was the reliance on the cholesterol and triglyceride in the determination of treatment intervention.

Funding Source:

University/Hospital:

Regions Hospital

Reviewer Comments:

This study is nine years old and omitted a number of details that are considered relevant for publications today
It started out saying the document will review; however, it was describing an intervention so it was a bit difficult to follow in the beginning
The other concern is that only total cholesterol and triglyceride were the focus for inclusion (eligibility) as well as analysis; other relevant fractions and other confounding factors such as weight were omitted
Diet and exercise did not seem to play a big role in lipid reduction according to the findings in the article, but I think more investigation is needed for that conclusion
The application of drugs was the main focus, and as a result it may not be as helpful to dietetic practice.

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?		No
	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?	N/A
	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?	No
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)	No
	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?	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?		No
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	No
	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.)	No
	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?	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?	N/A
7.	Were outcomes clearly defined and the measurements valid and reliable?		No
	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?	???
	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?	???
	7.5.	Was the measurement of effect at an appropriate level of precision?	???
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	No
	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?		No
	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?	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?	No
	10.2.	Was the study free from apparent conflict of interest?	Yes