EAL

UWL: Food, Appetite and Environment (2009)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To assess changes in various lipid concentrations over about 20 years from 1972 to 1992 and correlate them with all-cause mortality in a large cohort of Japanese-American men who were followed up in the Honolulu Heart Program.

Inclusion Criteria:

Subjects were participants of the Honolulu Heart Program cohort
Details of the selection process for the cohort have been published elsewhere.

Exclusion Criteria:

Published elsewhere.

Description of Study Protocol:

Recruitment

Subjects were participants of Honolulu Heart Program, a longitudinal epidemiological study of cardiovascular disease which began with 8,006 Japanese-American men, living on the island of Oahu, Hawaii in 1965.

Design

Cohort study.

Statistical Analysis

Participants were divided into quartiles of serum cholesterol concentrations (2.09 to 4.32, 4.33 to 4.86, 4.87 to 5.43, 5.44 to 9.88mmol per L)
Means of variables were compared with linear regression
Age-adjusted mortality rates were calculated according to quartiles of cholesterol
Changes in lipid and serum cholesterol concentrations over 20 years were compared with all-cause mortality using three different Cox proportional hazards models.

Data Collection Summary:

Timing of Measurements

Lipid and serum cholesterol concentrations assessed over 20 years (1972 to 1992). Report is based on the fourth examination of the cohort, which was done in 1991 to 1993, and the ascertainment of mortality, which was done between the fourth examination and December 31, 1996.

Dependent Variables

All-cause mortality assessed through monitoring of hospital discharge records and death certificates.

Independent Variables

Lipid and serum cholesterol concentrations measured through fasting blood tests.

Control Variables

Age
Medical and psychosocial questionnaires
Cognitive function testing
Two-hour glucose tolerance test
Blood pressure
Anthropometry: Weight and BMI
Physical activity index
Spirometry
Electrocardiogram.

Description of Actual Data Sample:

Initial N: Originally 8,006 men. 3,741 men at the fourth examination of the cohort.
Attrition (final N): 3,572 Japanese-American men
Age: Aged 71 to 93 years
Ethnicity: Japanese-American
Location: Honolulu, Hawaii.

Summary of Results:

Mortality rates by quartiles of cholesterol

Variables: All Deaths	Quartile One	Quartile Two	Quartile Three	Quartile Four
Participants	904	858	902	908
Deaths	259	173	147	148
Unadjusted mortality rate	72.3	48.2	37.9	37.9
Age-adjusted mortality rate	68.3	48.9	41.1	43.4
Age-adjusted relative risk for mortality (95% CI)	1	0.72 (0.60 to 0.87), P=0.0012	0.60 (0.49 to 0.74), P=0.0012	0.65 (0.53 to 0.80), P=0.0012

Other Findings

Mean cholesterol fell significantly with increasing age, from 5.00mmol per L in those aged 71 to 74, to 4.93mmol per L in those aged 75 to 79, to 4.85mmol per L in those aged 80 to 84 and 4.61mmol per L in those aged older than 85 years (test for trend, P<0.0001).

For increasing quartiles of cholesterol concentration, there were significant positive associations with BMI, HDL cholesterol, hypertension, fibrinogen, hemoglobin, hand-grip strength and cholesterol concentration at the third examination.

There were no significant associations with physical activity index, smoking, alcohol intake, diabetes, forced expiratory volume after 1 second (FEV1), cirrhosis, congestive heart disease, stroke and cancer.

Age-adjusted mortality rates were 68.3, 48.9, 41.1 and 43.3 for the first to fourth quartiles of cholesterol concentrations, respectively.

Relative risks for mortality were 0.72 (95% confidence interval: 0.60 to 0.87), 0.60 (0.49 to 0.74) and 0.65 (0.53 to 0.80) in the second, third and fourth quartiles, respectively, with quartile one as reference.

A Cox proportional hazard model assessed changes in cholesterol concentrations between examinations three and four. Only the group with low cholesterol concentrations at both examinations had a significant association with mortality (risk ratio, 1.64; 95% confidence interval, 1.13 to 2.36).

Author Conclusion:

We have been unable to explain our results. These data cast doubt on the scientific justification for lowering cholesterol to very low concentrations (less than 4.65mmol per L) in elderly people.

Funding Source:

Reviewer Comments:

Large cohort spanning 20 years.

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?		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?	N/A
	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)	N/A
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	N/A
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	N/A
	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?		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?	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?	N/A
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	N/A
	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?		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