EAL

FNOA: Assessment of Overweight/Obesity (2012)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To evaluate whether low muscle mass, when occurring in association both with and without obesity, might predict mortality.

Inclusion Criteria:

Participant in the "Invecchiare in Chianti" Study (InCHIANTI, Aging in the Chianti area) aged 65 years or older
Those whose data was complete
Those who were not lost to follow-up.

Exclusion Criteria:

Participants in the InCHIANTI study who had missing data or were lost to follow-up.

Description of Study Protocol:

Recruitment: Participants were randomly-selected in two towns in the Chianti area of Tuscany, Italy. Sampling procedure was outlined elsewhere and information was not provided in this paper.
Design: Prospective cohort study
Blinding used: Implied with measurements
Intervention: Not applicable.

Statistical Analysis

Chi-square analysis was used to assess differences in proportions and means of variables, according to the vital status as the end of the follow-up
Median values with inter-quartile ranges and P-values based on Mann-Whitney U statistics were calculated and reported for non-normally-distributed variables
For non-normally-distributed variables, log transformation was used
Pearson's correlation analyses were performed among the independent variables of interest
Cox proportional hazard models were used to evaluate the relationship of calf pQCT measures with survival
Kaplan-Meier survival curves stratified for BMI were analyzed according to sarcopenia groups
BMI-stratified adjusted Cox proportional hazard models were performed to estimate the risk of sarcopenia on time of death.

Data Collection Summary:

Timing of Measurements

Data was collected at baseline (September 1998 to March 2000), at three years (2001 to 2003) and at six years (2004 to 2006) after baseline.

Dependent Variables

Mortality, as measured by data obtained from the Mortality General Registry maintained by the Tuscany Region and from death certificates filed upon death at the registry office of the municipality of interest.

Independent Variables

Skeletal muscle mass, as measured by peripheral quantitative computerized tomography (pQCT)
Obesity, as measured by BMI, using height and weight and defined as BMI 30kg/m² or greater.

Control Variables

Socio-demographic information (age, gender), smoking habit, Mini-Mental exam, Center for Epidemiological Studies Depression Scale, comorbidity and physical activity level information were collected
Inflammatory markers (Interleukin-6, C-reactive protein and tumor necrosis factor) were obtained
Disease diagnosis was based on self-reported history, clinical documentation and medication use as well as pre-standardized criteria derived from the Women's Health and Aging Study Protocol
Physical activity was assessed using an interviewer-administered questionnaire.

Description of Actual Data Sample:

Initial N: 934 participants in the InCHIANTI study met inclusion criteria, so initial N was 934. 54.9% of the sample population were women.
Attrition (final N): All participants were accounted for
Age: Mean at baseline was 74.5±7.0 years
Ethnicity: Not specified
Other relevant demographics: Data on education level was collected but not reported for the entire group at baseline. It was reported that those who survived had a higher education level (5.8±3.3 years) than those who died (4.9±2.9 years) at follow-up.
Anthropometrics: Data was collected at baseline, reported in quintiles as those who survived vs. those who died
Location: Greve, in Chianti and Bagno a Ripoli, Tuscany, Italy.

Summary of Results:

Key Findings

Unadjusted analyses showed significant associations of muscle density (hazard ratio, 0.78; 95% confidence interval, 0.69 to 0.88), muscle area (hazard ratio, 0.75; 95% confidence interval, 0.66 to 0.86) and fat area (hazard ratio, 0.82; 95% confidence interval, 0.73 to 0.92) with mortality
After adjustment for potential confounders, no body composition parameter was significantly associated with mortality
Participants who died during follow-up were older, more likely to be men and had lower education and cognitive function than those who survived. They also had a higher prevalence of many chronic diseases and higher levels of inflammatory markers.
Participants who died during follow-up had significantly lower muscle density, muscle and fat areas and walking speed, compared with those who survived
No significant association with mortality was found for body composition parameters. No significant interaction was found for frailty or high inflammatory profiles in the relationship between sarcopenia and mortality.
Walking speed was significantly associated with mortality and muscle area (hazard ratio, 0.73; 95% confidence interval, 0.60 to 0.88)
These results did not change after the analyses were stratified according to sarcopenia and body mass index groups and restricted to participants with frailty or a high inflammatory profile.

Results from Separate Cox Proportional Hazard Analyses Exploring the Relationship of Body Composition Parameters and Physical Performance (per Standard Deviation Increments) with Mortality

	Model 1, HR (95% CI)	Model 2, HR (95% CI)	Model 3, HR (95% CI)	Model 4, HR (95% CI)
Muscle Density (mg/cm³)	0.75 (0.65-0.86)*	0.90 (0.78-1.04)	0.94 (0.80-1.10)	0.94 (0.80-1.11)
Muscle Area (cm²)	0.83 (0.69-0.98)*	0.82 (0.66-1.00)	0.84 (0.67-1.05)	0.86 (0.68-1.08)
Fat Area (log value of cm²)	0.74 (0.64-0.84)*	1.00 (0.84-1.19)	0.99 (0.82-1.19)	0.96 (0.78-1.18)
Walking Speed (m/s)	0.55 (0.48-0.62)*	0.69 (0.59-0.81)*	0.72 (0.60-0.87)*	0.73 (0.60-0.88)*

Model 1: Adjusted for height and weight
Model 2: Adjusted for model 1 + age and gender
Model 3: Adjusted for model 2 = site, education, Mini-Mental State Exam score, height, weight, Center for Epidemiological Studies Depression Scale Score, physical activity, congestive heart failure, coronary artery disease, hypertension. peripheral artery disease, respiratory disease, osteoarthritis and stroke
Model 4: Adjusted for Model 3 + interleukin-6, C-reactive protein and tumor necrosis factor
*P<0.05.

Results from Adjusted Cox Proportional Hazard Models [Expressed as Hazard Ratio (95% Confidence Interval) Exploring the Relationship of Sarcopenia and Low Walking Speed With Mortality, According to Body Mass Index (BMI, in kg/m²) Groups]

	No Sarcopenia	Sarcopenia
BMI<25	1 (reference group) n/N-18/81	1.25 (90.69-2.25), n/N=66/168
BMI 25-29	1.17 (0.65-2.09) n/N=63/307	1.24 (0.65-2.37), n/N=30/94
BMI ≥30	0.99 (0.53-1.84), n/N=27/163	1.18 (0.46-3.02), n/N =10/25
	No Low Walking Speed	Low Walking Speed
BMI<25	1 (reference group), n/N=27/163	2.29 (1.36-3.88)*, n/N = 52/85)
BMI 25-29	1.33 (0.77-2.27), n/N=37/289	1.98 (1.17-3.35)*, n/N = 52/85
BMI ≥30	1.09 (0.58-2.07), n/N=20/146	2.15 (1.22-3.78)*, n/N=36/79

n/N=number of participants. Analyses adjusted for age, gender, site, education, Mini-Mental State Examination score, Center for Epidemiological Studies Depression scale score, physical activity, congestive heart failure, coronary artery disease, hypertension, peripheral artery disease, respiratory disease, osteoarthritis, stroke, interleukin-6, C-reactive protein and tumor necrosis factor.
*P<0.05.

Author Conclusion:

The authors conclude that skeletal muscle measures and sarcopenia are not associated with a significantly higher risk of mortality in community-dwelling older persons
They also conclude that physical performance (as measured by walking speed) is a powerful predictor of health-related events, independent of sociodemographics, clinical conditions and inflammation.

Funding Source:

Government:	Italian Ministry of Health, US National Institute on Aging
University/Hospital:	Catholic University, Rome, Italy, University of Florida, Tuscany Regional Health Agency, Health Agency of Florence, Italy

Reviewer Comments:

Authors note the following limitations:

The InCHIANTI study allows for the adjustment of our analyses for many health- and disease-related characteristics, but there could be unmeasured factors potentially explaining the observed relationships
Muscle and fat measurements were obtained from pQCT scans and may not be applicable to the entire body composition.

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?	???
	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?	Yes
	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?		N/A
	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?	N/A
	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?	Yes
	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?	N/A
	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?	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?	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)?	Yes
	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?	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