EAL

PDM: Metabolic Syndrome (2013)

Citation:

Cicero AF, Derosa G, Bove M, Di Gregori V, Gaddi AV, Borghi C. Effect of a sequential training programme on inflammatory, prothrombotic and vascular remodelling biomarkers in hypertensive overweight patients with or without metabolic syndrome. Eur J Cardiovasc Prev Rehabil. 2009; 16(6): 698-704.

PubMed ID: 19741540

Study Design:

Non-Randomized Controlled Trial

Class:

C - Click here for explanation of classification scheme.

Quality Rating:

NEUTRAL: See Quality Criteria Checklist below.

Research Purpose:

To evaluate the short-term effect of sequential physical activity programs on pharmacologically untreated hypertensive overweight patients with or without metabolic syndrome on non-conventional cardiovascular disease risk factors, such as inflammatory, prothrombotic and vascular remodeling biomarkers
To evaluate the feasibility of a physical activity intervention program from a specialist setting as a training center.

Inclusion Criteria:

Overweight
Newly diagnosed mild hypertension, defined as systolic blood pressure of 140 to 149 mm Hg and diastolic blood pressure of 90 to 99 mm Hg.

Exclusion Criteria:

Treated with anti-hypertensive or anti-hyperlipidaemic drugs
Under stabilized treatment for hypertension for more than six months.

Description of Study Protocol:

Recruitment

Patients were consecutively enrolled.

Design

Non-randomized trial.

Blinding Used

Implied with measurements.

Intervention

All subjects were assigned to:

Diet: For three months, participants were asked to follow the American Heart Association Step Two diet:
- Reduced energy intake (mean, 600kcal per day)
- 30% of calories as fat (6% saturated), 50% as carbohydrates and 20% as protein
- Cholesterol 300mg per day or less
- Fiber 35g per day or more
- Salt less than 2.3g per day (100mmol per day)
Physical activity (five days per week) following diet intervention:
- 56 days of three metabolic equivalent tasks per week (i.e., 30-minute brisk walking at 5km per hour)
- 56 days of six metabolic equivalent tasks per week (i.e., 30-minute slow jogging at 7km per hour).

Statistical Analysis

ANOVA
ANCOVA
One-sample T-test (before and after intervention)
Two-sample T-test (between-group comparison).

Data Collection Summary:

Timing of Measurements

Diet, anthropometric measurements, BP measurement, insulin-resistance profile and plasma lipids measured at each study step.

Dependent Variables

Blood pressure measurements: Three consecutive measurements were obtained using a standard mercury sphygmomanometer at one-minute intervals after the patient had rested in a quiet room for more than 10 minutes. The average value of these measurements was calculated.
Fasting (12-hour) plasma measures:
- Glucose
- Lipids
- Homocysteine: HPLC and fluorescent detection
- Plasminogen activator inhibitor 1 (PAI-1): Commercial two-stage indirect enzymatic assay
- Fibrinogen
- High-sensitivity C-reactive protein (HsCRP): Latex-enhanced immunonephelometric assays on a BN II analyzer
- MMP-2 and MMP-9 levels: Two-site ELISA methods using commercial reagents.

Independent Variables

Overweight hypertensive patients with or without the metabolic syndrome
All subjects were assigned to:
- Diet: For three months, participants were asked to follow the American Heart Association Step Two diet:
  - Reduced energy intake (mean, 600kcal per day)
  - 30% of calories as fat (6% saturated), 50% as carbohydrates and 20% as protein
  - Cholesterol 300mg per day or less
  - Fiber 35g per day or more
  - Salt less than 2.3g per day (100mmol per day)
- Physical activity (five days per week) following diet intervention:
  - 56 days of three metabolic equivalent tasks per week (i.e., 30-minute brisk walking at 5km per hour)
  - 56 days of six metabolic equivalent tasks per week (i.e., 30-minute slow jogging at 7km per hour)
- Baseline physical activity measured by the Minnesota questionnaire, but no description of follow-up measures; method for monitoring diet was not described.

Description of Actual Data Sample:

Initial N: 80 (36 male, 44 female)
Attrition (final N): Zero (all 80 completed)
Age: Mean 62.9±8.3 years
Ethnicity: Italian
Other relevant demographics: Mean BMI 29.4±2.3kg/m²
Anthropometrics: Subjects with or without metabolic syndrome
Location: Italy.

Summary of Results:

Key Findings

Modification of Anthropometric, Hemodynamic and Laboratory Parameters After Moderate and Intensive Training Phases in the Whole Sample of Enrolled Patients

Variable	Pre-Diet Data	Baseline	After Moderate Training	After Intensive Training
Body weight (kg)	86.9±10.7*	85.3±10.4	84.4±10.2*	83.3±10.0^, *
Body mass index (kg/m²)	29.7±2.4*	29.4±2.3	29.0±2.2*	28.4±2.3^, *
Waist circumference (cm)	109.8±13.0*	107.7±12.0	105.9±12.0*	104.3±2.±11.6^, *
Systolic BP (mm Hg)	147.7±3.1*	145.2±2.8	137.3±5.7*	136.4±2.4*
Diastolic BP (mm Hg)	95.7±3.3*	93.5±3.1	89.7±4.2*	86.9±3.1^, *
Fasting plasma glucose (mg per dL)	101.9±10.3*	97.8±9.7	99.6±8.8	92.2±7.8^, *
Plasminogen activator inhibitor - 1 (ng per ml)	NA	21.3±4.9	18.2±2.9*	19.9±4.5
Basal homocysteine (μmol per L)	NA	6.9±1.7	6.9±1.6	7.2±1.7
Fibrinogen (mg per dL)	NA	340.1±50.1	311.8±32.4*	336.6±49.9^, *
Metalloproteinase 2 (pg per ml)	NA	1,330.9±177.7	725.3±210.2*	659.6±319.9^, *
Activated metalloproteinase 2 (pg per ml)	NA	140.8±9.1	107.4±6.9*	94.4±4.1^, *
Metalloproteinase 9 (pg per ml)	NA	499.9±58.4	122.3±11.6*	53.3±16.7
Activated metalloproteinase 9 (pg per ml)	NA	97.3±6.9	64.4±7.1*	52.2±10.1^, *

NA, not applicable. *P<0.05 when compared with the baseline. **P<0.05 when compared with the moderate training phase.

Other Findings

All patients experienced a significant decrease in body mass index, waist circumference and blood pressure after both the training phases
Prevalence of metabolic syndrome was 35% in women and 34% in men (Pearson χ²=0.788, 1 d.f., P>0.05)
Patients with metabolic syndrome had significantly lower high-density lipoprotein cholesterol (HDL-C) (T=3.439, 79 d.f., P=0.001), higher triglycerides (TG) (T=–5.148, 79 d.f., P>0.001) and fasting plasma glucose (FPG) (T=–3.803, 79 d.f., P=0.001)
HDL-C (T=–2.7, 79 d.f., P=0.10), TG (T=2.5, 79 d.f., P=0.01) and FPG (T=10.8, 79 d.f., P>0.001) significantly improved only after the intensive training phase compared with the baseline
High-sensitivity C-reactive protein P level significantly decreased towards baseline and towards the previous phase, after exercise intensification, but only in MetS patients.

Author Conclusion:

A sequential physical training program has significant anti-inflammatory action and an improving effect on circulating biomarkers of vascular remodeling in hypertensive overweight patients.

Funding Source:

University/Hospital:

Department of Internal Medicine, University of Bologna, Italy

Reviewer Comments:

Unclear whether participants completed informed consent. The authors stated there was no loss to follow-up throughout the intervention period. This is highly unusual for a study of this duration and intensity.
Adherence was not described
The statistical analysis approach is unclear, as well as the confounding variables.

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?	N/A
	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?	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.)	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?		No
	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?	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?	N/A
	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?	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?	No
	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)?	???
	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