EAL

H/A: Physical Activity (2009)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To determine if the arteriovenous oxygen difference and cardiac output responses to maximum exercise treadmill testing differed between individuals with asymptomatic HIV infection and sedentary but otherwise healthy controls.

Inclusion Criteria:

None of the participants had participated in an exercise program during the past six months or routinely engaged in employment or other activity that would cause perspiration on the average of once weekly, discounting the effects of ambiance
None of the participants had any known neurological, orthopedic, pulmonary, hematologic or cardiorespiratory limitations or were taking any medications that would contraindicate treadmill testing or alter the cardiorespiratory response to exercise
All HIV-infected participants were asymptomatic and never had a CD4 count below 200 or an opportunistic infection
All HIV-infected participants were taking at least one nucleoside analog or a protease inhibitor for a period of six months and reported good adherence with therapy.

Exclusion Criteria:

Participants not reaching one of two accepted criteria for maximal physiologic exertion of attaining at least 90% of the predicted maximal heart rate (220 - age) or a respiratory exchange ratio of at least 1.10.

Description of Study Protocol:

Recruitment

Recruitment methods not described

Design

Case-Control Study; Quasi-Experimental Cross-Sectional Study

Blinding used (if applicable)

Intervention (if applicable)

Participants performed an incremental maximal exercise treadmill test to exhaustion. Electrocardiogram, metabolic and non-invasive cardiac output measurements were evaluated at rest and throughout the tests.

Statistical Analysis

Power analysis was performed to determine the number of subjects
ANOVA were used to determine if age, height, weight and BMI differed significantly between the group with HIV infection and controls
Data were analyzed by using analysis of covariance
Differences in adjusted independent group means were examined post-hoc by least squares means analyses
Pearson product-moment correlation coefficients were calculated to identify expected relationships among the variables.

Data Collection Summary:

Timing of Measurements

Dependent Variables

Peak oxygen consumption (V0₂) measured through indirect calorimetry
Cardiac output
Stroke volume
Arteriovenous oxygen difference determined indirectly using Fick Equation.

Independent Variables

HIV infection or healthy controls

Control Variables

Age

Description of Actual Data Sample:

Initial N

15 subjects with HIV (10 men, five women) and 15 healthy controls (10 men, five women)

Attrition (final N)

12 subjects with HIV and 14 controls. Four were excluded because they did not meet one of the criteria for maximal physiologic exertion.

Age

Mean age 41.9±1.7 years in HIV group, 36.1±1.8 years in controls

Ethnicity

Not mentioned

Other relevant demographics:

Mean CD4 count in HIV group: 429.8±56.4cells/mm³
Mean viral load in HIV group: 6,012.8±5,817.4copies/cm³

Anthropometrics

Subjects were matched for gender and activity level, but the HIV group was significantly older (P<0.02). Four of the HIV-infected participants were smokers (27%) and there were no smokers in the control group.

Location

Baltimore, Maryland

Summary of Results:

Peak Cardiorespiratory and Exercise Test Variables Adjusted for Age Differences

Variables	HIV+Group	Control Group	Statistical Significance of Group Difference
VO₂ peak (mL/kg per minute)	24.6±1.2	32.0±1.2	P<0.001
Cardiac output (Liter per minute)	17.8±1.3	19.7±1.3	NS
Stroke volume (mL per beat)	107.0±7.2	107.5±7.2	NS
a-VO₂ (vol percentage)	10.8±0.5	12.4±0.5	P<0.05
Respiratory exchange ratio	1.2±0.02	1.3±0.02	P<0.005
Heart rate (bpm)	167.8±3.5	180.1±3.5	P<0.05
VE peak (Liter per minute)	77.7±6.9	103.2±6.9	P<0.05
VT (mL/kg per minute)	13.1±0.7	14.7±0.7	NS
Test duration (minute)	16.4±0.9	19.3±0.8	P<0.001
Power output (W)	207.1±22.0	278.4±22.0	P<0.001

Other Findings

Peak VO₂ was significantly lower (P<0.0005) in participants with HIV (24.6±1.2mL/kg per minute) compared with controls (32.0±1.2mL/kg per minute)
There were no significant intergroup differences in cardiac output or stroke volume at peak exercise
Peak arteriovenous oxygen difference was significantly lower (P<0.04) in those infected with HIV (10.8±0.5 volume percentage) than in controls (12.4±0.5 volume percentage)
Viral load, CD4 count, white blood cell count, duration of HIV infection and antiretroviral therapy, hematocrit, and hemoglobin levels were not significantly related to peak VO₂, heart rate, cardiac output, stroke volume or arteriovenous oxygen difference.

Author Conclusion:

Peak aerobic capacity was diminished in HIV-infected participants compared with controls. Aerobic capacity in HIV-infected participants was decreased to levels associated with functional aerobic impairment and therefore may have been as a result of pathologic processes. The current findings of similarity in age-adjusted peak cardiac output and stroke volume among those with HIV and controls and the observation of diminished arteriovenous oxygen difference supported the hypothesis that aerobic capacity in asymptomatic HIV-infected participants was limited by muscle tissue oxygen extraction and utilization abnormalities rather than by central circulatory oxygen delivery deficits. Potential mechanisms for the observed attenuation of oxygen extraction and utilization may have included HIV infection and inflammation, HAART medication regimens or a combination of these factors. Further studies aiming to determine specific mechanisms for attenuated arteriovenous oxygen difference and aerobic capacity are warranted.

Funding Source:

Other:

Not described

Reviewer Comments:

Recruitment methods not described. Small numbers of subjects in groups. Groups were significantly different regarding age and smoking status.

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?		???
	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?		No
	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?	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?	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.)	No
	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?	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?	N/A
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	Yes
	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?	N/A
	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?	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?	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?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	Yes
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?	No
	10.2.	Was the study free from apparent conflict of interest?	Yes