EAL

FNOA: Assessment of Overweight/Obesity (2012)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To analyze all-cause mortality and its determinants in three national groups relating the cohorts to the lifestyle-related risk factor measurements.

Inclusion Criteria:

Enrolled in the FINE Study (Finland, Italy and Netherlands Elderly Study)
Male
Aged 65 to 84 years
Residing in one of five geographic areas studied:
- Two rural cohorts from Finland described as east Finland and west Finland
- A Dutch cohort from the small town of Zutphen
- Two Italian cohorts from rural areas in the villages of Crevalcore and Montegiorgio.

Exclusion Criteria:

Not enrolled in the FINE Study
Female
Age less than 65 years or greater than 84 years.

Description of Study Protocol:

Recruitment

Subjects from the Seven Countries Study on Cardiovascular Diseases cohort who had completed the 25 years of follow-up were asked to participate in the FINE Study if the participant resided in one of the five areas chosen as a FINE center. Additional subjects were recruited for the Dutch cohort in the town of Zutphen to ensure that a statistical sample of two- thirds of the male population of the town was sampled.

Design

Prospective cohort study with preliminary follow-up at five years and conclusion at 10 years.

Statistical Analysis

Univariate analysis was performed by computing age-adjusted death rates in tertile classes or in arbitrary classes of risk factors
Multivariate analysis was run using the proportional hazards model for the prediction of five-year all-cause mortality as a function of risk factors
Covariates were controlled for, including age, systolic blood pressure, HDL-cholesterol, non-HDL cholesterol, BMI and smoking habits.

Data Collection Summary:

Timing of Measurements

Several measurements were taken during an entry examination at the beginning of the FINE Study. These measurements included:

Age
Blood pressure
Total and HDL serum cholesterol after fast
Measured height and weight
Calculated BMI
Smoking habits by questionnaire
Heart rate measured on a resting ECG
Diagnosed coronary heart disease prevalence by medical history.

Dependent Variables

All-cause mortality. Mortality data were collected during the first five years of follow-up by linking participants and filed death certificates.

Independent Variables

Age
Serum HDL and non-HDL-cholesterol
Smoking prevalence
BMI
Systolic blood pressure
Diastolic blood pressure
Heart rate
Coronary heart disease prevalence.

Description of Actual Data Sample:

Initial N: 2,226 men
Attrition (final N): All subjects accounted for in final analysis
Age: 65 to 84 years
Ethnicity: Finnish, Dutch, Italian
Other relevant demographics: All subjects resided in rural areas
Location: Finland, the Netherlands and Italy.

Summary of Results:

Key Findings

The univariate relationship of some risk factors to five-year all-cause mortality shows that on many occasions, the lowest risk was located in the intermediate or even on the highest levels of risk factors, suggesting a curvilinear or U-shaped relationship
In multivariate analysis, when all subjects were considered in the same model, the coefficients of most risk factors were significant for five-year all-cause mortality. Non-HDL-cholesterol, HDL-cholesterol, systolic blood pressure and BMI all suggested a parabolic shaped model. Age, heavy smoking (10 to 19 cigarettes per day) and prevalence of coronary heart disease were directly related to five-year all-cause mortality risk in a linear fashion.

Levels of Risk Factors Corresponding to Minimum Risk as Derived from Multivariate Models

	All Subjects	Finland	Netherlands	Italy
Non-HDL-cholesterol (mg per dL)	183.3	196.0	178.0	174.3
HDL-cholesterol (mg per dL)	59.8	63.7	53.6	--
Systolic blood pressure (mm Hg)	177.5	156.7	--	--
Body mass index (kg/m²)	30.2	28.3	32.1	--

Other Findings

Finnish subjects: Minimum risk for five-year all-cause mortality was seen with intermediate levels of systolic blood pressure and highest levels of diastolic blood pressure, non-HDL-cholesterol, HDL-cholesterol and BMI
Dutch subjects: Minimum risk for five-year all-cause mortality was seen with intermediate levels of systolic and diastolic blood pressure, HDL-cholesterol and heart rate and with highest levels of non-HDL-cholesterol and body mass index
Italian subjects: Minimum risk of five-year all-cause mortality was seen with intermediate levels of systolic and diastolic blood pressure and HDL-cholesterol and with lowest levels of heart rate and in relatively heavy smokers.

Author Conclusion:

In these elderly men, the association of traditional risk factors with all-cause mortality is reduced, U-shaped or even inverted. This is probably due to selection due to previous mortality, to comorbidity, and to changes in homeostatic mechanisms.

Funding Source:

Government:

National Aging Institute (US)

Reviewer Comments:

Population studied was elderly men from rural areas in central Europe. The results may not be applicable outside of this demographic.
The variable studied was five-year all-cause mortality based on risk factors measured during the elderly years. Data regarding the history of the subjects with regard to the risk factors studied (i.e., weight gain/loss, lab values and blood pressure) over the course of the life cycle is unknown (with the exception of smoking status and previously diagnosed history of CHD). The authors did note that desirable levels of risk factors may be modified in the elderly years and that the levels noted in this study can not be generalized for recommendations targeting a younger demographic.
Risk factors between the different national groups studied differed at baseline, which may play a role in the differences noted between nationalities when looking at which risk factors demonstrated a significant association with all-cause mortality. This difference is mitigated in the pooled analysis looking at all subjects together.

Authors note the following:

Predictive models provided uncertain results influenced by small numbers despite significant mortality rates
Apart from age, the predictive power of the other risk factors studied was not consistent
The short-term all-cause mortality in the elderly population belonging to different cultures is associated with some recently measured cardiovascular risk factors. The relationship is different from the relationship seen traditionally in younger people when a monotonic increasing (or decreasing) risk is associated with increasing (or decreasing) levels of individual measurements.
Measurements were taken in advanced age which may indicate why short-term mortality was often high at low levels of the risk factor. Higher mortality associated with low levels of some factors may be due to the existence of comorbidity which could not be controlled for in this analysis. Older people may develop homeostatic regulation of lipid metabolism and circulatory patterns, perhaps requiring higher levels of some risk factors compared with those best protecting at younger ages.

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)	N/A
	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)	N/A

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.)	No
	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?	No
	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?	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.)	No
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	No
	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?	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?	No
	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?	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?	N/A
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	???
	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?	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