EAL

PDM: Metabolic Syndrome (2013)

Citation:

Casella-Filho A, Chagas AC, Maranhao RC, Trombetta IC, Cesena FH, Silva VM, Tanus-Santos JE, Negrao CE, da Luz PL. Effect of exercise training on plasma levels and functional properties of high-density lipoprotein cholesterol in the metabolic syndrome. Am J Cardiol. 2011; 107(8): 1,168-1,172.

PubMed ID: 21310370

Study Design:

Case Control Study

Class:

C - Click here for explanation of classification scheme.

Quality Rating:

NEUTRAL: See Quality Criteria Checklist below.

Research Purpose:

To analyze the early effects of short-term exercise training, without any specific diet, on the high-density lipoprotein (HDL) cholesterol plasma levels and HDL functional characteristics in patients with the metabolic syndrome (MS).

Inclusion Criteria:

Non-smokers and abstainers or only moderate alcohol consumers (less than 25g per day)
No cardiovascular, renal, liver, gastrointestinal, pulmonary, endocrine or oncologic diseases
Not receiving antioxidant vitamin supplementation or drugs known to affect lipoprotein metabolism
Subjects with MS must meet the criteria for the clinical diagnosis of the MS, defined according to the American Heart Association/National Heart, Lung, and Blood Institute scientific statement
Written informed consent.

Exclusion Criteria:

Smokers
Alcohol consumers of 25g per day or more
Had cardiovascular, renal, liver, gastrointestinal, pulmonary, endocrine or oncologic diseases
Receiving antioxidant vitamin supplementation or drugs known to affect lipoprotein metabolism.

Description of Study Protocol:

Recruitment

The study cohort was selected from the outpatient clinic of the Heart Institute, Hospital das Clínicas of the University of São Paulo Medical School. 30 sedentary subjects, 20 with and 10 without MS, met the inclusion criteria and were included in the study.

Design

Case-control study.

Blinding Used

Implied with measurements.

Intervention

The patients with MS underwent moderate intensity exercise training for three months, which consisted of a three times per week supervised and controlled training load (45 minutes per day) on a bicycle ergometer. The participants began their training at the heart rate corresponding to the anaerobic threshold. The exercise was then progressively intensified up to the heart rate corresponding to 10% less than the respiratory compensation point. The healthy controls did not receive any exercise training. Both groups did not receive any specific nutritional counseling. Blood was sampled before and after training for biochemical analysis for the MS group and at baseline for the controls.

Statistical Analysis

All values are expressed as the mean ±SD, unless otherwise indicated. An α probability of P<0.05 was required for statistical significance. Between-group differences in the continuous variables were analyzed using the Student T-test or Wilcoxon non-parametric test for dependent samples, as applicable. The chi-square test was used to compare the proportions between the controls and the MS group.

Data Collection Summary:

Timing of Measurements

Blood was sampled before and after the three-month training for the MS group and at baseline for the controls. Samples were obtained after the patient had fasted for 12 or more hours, always at the same point of the menstrual cycle in the women and 16 or more hours after the last exercise session.

Dependent Variables

Anthropometrics/physical parameters: Body mass index (BMI), waist circumference, blood pressure
Serum levels of total cholesterol (TC), HDL cholesterol, triglycerides (TG) and apolipoprotein A-1 were measured; low-density lipoprotein (LDL) was calculated using the Friedewald formula
Paraoxonase-1 (PON1) activity
HDL subfraction composition (HDL2a, HDL2b, HDL3a, HDL3b, and HDL3c) and antioxidative capacity
Lipid transfer to HDL (assayed in vitro using a labeled nanoemulsion as the lipid donor): Transfer of ³H-triglycerides (³H-TG), ¹⁴C-cholesterol (¹⁴C-C), ³H-cholesteryl ester (³H-CE), and ¹⁴C-phospholipid (¹⁴C-PL).

Independent Variables

The patients with MS underwent moderate intensity exercise training for three months, which consisted of a three times per week supervised and controlled training load (45 minutes per day) on a bicycle ergometer. The participants began their training at the heart rate corresponding to the anaerobic threshold. The exercise was then progressively intensified up to the heart rate corresponding to 10% less than the respiratory compensation point.
The healthy controls did not receive any exercise training
Both groups did not receive any specific nutritional counseling.

Control Variables

Age
Sex.

Description of Actual Data Sample:

Initial N: 30
- MS group: 10 females, 10 males
- Control group: Four females, six males
Attrition (final N): 30
Age: 21 to 70 years (50±10 years in MS group, 45±7 years in controls)
Anthropometrics: Compared to the controls, the MS group had a greater BMI, waist circumference, blood pressure, TC, LDL cholesterol and plasma glucose.

	MS Group	Control Group	P Value
BMI (kg/m²)	32.4±3.3	24.3±2.6	<0.05
Waist circumference (cm)	110±10	88±7	<0.05
Blood pressure (mm Hg)	141±10/92±4	120±6/75±5	<0.05
TC (mg per dL)	203±20	192±25	<0.05
LDL cholesterol (mg per dL)	123±21	116±22	<0.05
Plasma glucose (mg per dL)	112±19	81±6	<0.05

Location: The Heart Institute, Hospital das Clínicas of the University of São Paulo Medical School, São Paulo, Brazil.

Summary of Results:

Key Findings

At baseline, the MS group had greater TG levels and a lower HDL cholesterol concentration and lower paraoxonase-1 activity than did the controls. Exercise decreased the plasma TG but did not change the LDL or HDL cholesterol levels (see table below).
Exercise did not affect the BMI but did reduce the waist circumference (from 110±10 to 107±9cm, P<0.05) and blood pressure (from 141±10/92±4 to 135 ±7/89±5mm Hg, P<0.05)
Exercise increased the HDL subfractions' antioxidative capacity and PON1 activity in patients with MS, although the final values of PON1 activity remained lower than those in the healthy controls
At baseline, the MS group had a lower transfer of ³H-TG, ¹⁴C-C, and ³H-CE than did controls, with similar ¹⁴C-PL transfer between the two groups. After training, the MS group had compositional changes in the smallest HDL subfractions associated with increased free cholesterol and cholesterol ester transfers to HDL, reaching normal values (see table below).

Lipid Concentration (mg per dL)

Transfer of Labeled Lipids to HDL (%)

HDL Cholesterol

¹⁴C-PL

³H-TG

¹⁴C-C

³H-CE

Before

After

Before

After

Before

After

Before

After

Before

After

Before

After

36±5^♦

37±6^♦

217±64^♦

184±68^♦^Δ

26.9±3.2^*

25.5±1.2^*

3.8±0.6^♦

4.1±1.2^♦

7.9±0.9^♦

8.3±0.8^*^Δ

3.3±1.1^♦

3.8±0.6^*^Δ

Controls

52±8

120±33

26.7±2.3

6.7±1.1

8.9±1.4

4.4±0.8

* P>0.05 vs. control; ♦ P<0.05 vs. control; Δ P<0.05 vs. before training.

Author Conclusion:

Functional change in HDL seemed to occur earlier than, and independent from, the increase in HDL cholesterol levels when MS patients started an aerobic exercise program. Serum concentration of HDL cholesterol only partially depicts the cardiovascular risk of this lipoprotein.
The present study has added relevant information about the dissociation between the quantitative and qualitative aspects of HDL after short-term exercise training without any specific diet in those with the MS, highlighting the importance of evaluating the functional aspects of the lipoproteins, in addition to their plasma levels.

Funding Source:

Government:

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, São Paulo, Brazil) -- Foundation for Research Support of the State of São Paulo

Reviewer Comments:

Small numbers of subjects in groups
Some lifestyle factors not measured and monitored during study period for possible confounding factors as people might have made other changes along with physical activity
No statistical analysis used to evaluate effects of possible confounding factors.

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.)	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?	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?	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?	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?	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?	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?		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)?	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?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes