EAL

DLM: Elevated Triglycerides, Carbohydrate and Fat (2007)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To compare in a 23-y follow-up, the mortality rate from ischemic heart disease (IHD) of men who had a normal triacylglycerol concentration at screening with that of men who had a high triacylglycerol concentration at screening in the Oslo Diet and Antismoking Trial.

Inclusion Criteria:

Healthy men between 40 and 49 years of age with an elevated serum cholesterol concentration or coronary risk score.

Normal electorcardiogram at rest and free of chest pain during exercise testing.

Exclusion Criteria:

Cardiovascular disease, hypertension, diabetes mellitus, cancer, disabling diseases, psychopathologic diseases, and alcoholism.

Men on lipid-lowering diets

Description of Study Protocol:

Recruitment

All men between 40 and 49 years of age in Oslo

Design

Determine the outcome status of all participants screened for the Oslo Diet and Antismoking Trial.

During the Trial the men were randomized to either the control group or the dietary intervention group.

Statistical Analysis

The subjects were classified according tothe median triacylglycerol concentration, and risk factors were compared between the normaml and high triacylglycerol groups according to intervention or control status. For continuous variables, a two-factor analysis of variance with terms for interaction between triacylglycerol concentration and treatment group was applied. For categorical variables, the Cochran and Mantel-Haenszel statistics tests was applied by using the Wolf test for interactions.

The subject's age on January 1, 1972, was used in all analyses. The inclusion period lasted 2 y; thus, the age range of subjects was 40-51 y. Person-time for each subject was calculated from the date of screening to the date of confirmation of death due to IHD or until December 31, 1996, whichever came first. The relative risk (RR) of IHD mortality for assignment to the intervention or the control group was estimated for men whose triacylglycerol concentration was below the median (0.69-2.00 mmol/L) or equal to or greater than the median (2.01-13.80 mmol/L). The Cox regression analysis was used to test the main hypothesis that the RRs of men with high triacylglycerol would differ from those of men with normal triacylglycerol. A Wald test was applied to test whether the product (interaction term) was statistically significant. The test was done by linear regression analysis using triacylglycerol concentration, treatment group, and triacylglycerol concentration x treatment group. Further analyses were based on 615 men men with triacylglycerol concentrations equal to or greater than the median. Comparison of univariate survival curves between the treatment groups within each of the triacylglycerol subgroups was performed by using log rank statistics.

The following variables were specified for inclusion in the multivariate model because of their potential relation with IHD mortality: age, body mass index, cigarette smoking, total cholesterol and triacylglycerol concentrations, glucose concentration, systolic and diastolic blood pressure, total dietary score (or score for each dietary item), alcohol intake, and activity at work or during leisure time. The relations between assignment to the intervention or the control group and IHD mortality were then analyzed with the multivariate Cox proportional hazards model, with initial adjustment for age followed by adjustment for potential confounders. All calculations were done with SPSS.

Data Collection Summary:

Timing of Measurements

Blood samples were drawn at initial screening (nonfasting), second screening (fasting), at half-yearly intervals, and after 3 and 5 y of follow-up. The screening dates were in 1972 and 1973. The outcome status for IHD mortality was set at December 31, 1996.

Dependent Variables

Variable 1: Fasting blood samples from the second screening were used for this study. These were taken after a 12-h fast and assayed for serum total cholesterol, triacylglycerol, and glucose concentrations. The same methods of analysis were used for samples taken at all visits. For missing values at 5 y, the last available value was used in the present analysis.
Variable 2: IHD mortality outcome was based on linkage to Statistics Norway which gives a unique 11-digit identification number to all Norwegian citizens. Codes were identified according to the International Classification of Diseases (ICD). For IHD mortality, the ICD 8th revision (codes 410-414 and 795), the ICD 9th revision (codes 410-414 and 798.1) and the ICD 10th revision (codes 121.0-121.9, 125.0-125.9 adn R96.0) were used.

Independent Variables

Subjects with elevated total cholesterol levels were advised to reduce saturated fat intake and to slightly increase polyunsaturated fat intake. Subjects with elevated triacylglycerol levels were asked to reduce total energy intake (mainly by reducing sugar, sweet drinks, chocolate, alcohol, and fat). For breakfast and evening meals, all subjects weere asked to consume fiber-rich bread with no or only a thin layer of highly polyunsaturated, low-fat margarine. Preferred bread filllings included fish, vegetables, fruit, low sugar jam, and low-fat meats and cheeses. Skim milk and 1 egg or less per week were recommended. For main meals, the use of lean meat, fish, and low-fat fish products, together with potatoes and vegetables, was advised. Cigarette smokers were urged to stop smoking. Each subject was monitored individually and given nutritional advice in groups. The results of the blood tests were used druing the nutrition sessions as a monitoring tool. These subjects visited the clinic every six months and were seen by the doctor and dietitian, both of whom gave dietary advice individually and during group sessions.

Control Variables

The control group was seen at 12-month intervals.

Description of Actual Data Sample:

Initial N: 1232 men

Attrition (final N):1232

Age: 40-51

Ethnicity: Not described

Anthropometrics There was a significant difference in BMI between those who had a normal triacylglcerol concentation vs. those with a high triacylglcerol concentration (p=0.01) at the start of the Trial.

Location: Oslo, Norway

Summary of Results:

Variables	Normal TG, Treatment Group (n=297)	Normal TG, Control Group (n=318)	High TG, Treatment Group (n=307)	High TG, Control group (n=310)
Follow-up time (person-years)	6772	7250	7000	7068
Number of IHD deaths	34	33	25	44
Rate ratio	1.10 (0.68,1.78)*		0.58(0.35,0.94)*
Relative risk, adjusted for age	1.09 (0.68,1.72)*		0.55 (0.33,0.89)*
Relative risk, multivariate model	1.10 (0.66,1.83)*		0.56 (0.34,0.93)*
Cigarette smoking (%) after 5 y**	55	65	64	67
BMI, after 5 y⁺	23.4±2.7	24.5±3.0	24.7±2.6	25.9±3.2
Total cholesterol (mmol/L), after 5 y⁺	6.7±1.0	7.4±1.0	7.0±1.0	7.6±0.9
Triaclylglycerols (mmol/L), after 5 y⁺	1.5±0.6	1.6±0.6	2.1±0.9	2.6±1.4

*95% CI

**Significant difference between intervention and controls, p<0.01

⁺Significant difference between intervention and controls, p<0.001

Other Findings

Survival curves show that, relative to the control group, the intervention group of the high triacylglycerol level group, had an early and persistent decrease in cumulative IHD mortality (log rank x² = 5.9, p=-.015). The survival curve was not different between the control and intervention subgroups of the normal triacylglycerol level group.

Author Conclusion:

Advice given to hypertriglyceridemic men to change dietary habits and stop smoking may be associated with a >40% reduction in IHD mortality relative to IHD mortality in the control group after 23 y of follow-up. There was no reduction in IHD mortality in men with normal triacylglycerol concentrations who were given the same advice, depite apparently similar changes in total cholesterol concentrations in both groups. Middle-aged men with hypertriglyceridemias may benefit more from changes in lifestyle than do their counterparts without hypertriglyceridemia.

Funding Source:

University/Hospital:

Ulleval University

Reviewer Comments:

no additional comments

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?	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?	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?	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?	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.)	N/A
	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?		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?	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