EAL

VN: Cardiovascular Disease (2008)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To evaluate mortality in the vegetarian subjects, particularly in relation to cardiovascular mortality and comparing this to non-vegetarian controls.

Inclusion Criteria:

United Kingdom residents between September 1980 and January 1984
Subjects separated into groups based on diet habits (vegetarian vs. meat and fish eater)
Vegetarian subjects recruited through the Vegetarian Society of the United Kingdom, national and local media
Non-vegetarian subjects were recruited by the vegetarian subjects; nominated for similar lifestyles and social class.

Exclusion Criteria:

Not a resident of the United Kingdom
Children
Over age 70.

Description of Study Protocol:

Recruitment

Vegetarian subjects recruited through the Vegetarian Society of the United Kingdom, national and local media (N=6,000)
Non-vegetarian subjects were recruited by the vegetarian subjects; nominated for similar lifestyles and social class (N=5,000).

Design

Four-day diet record between September 1985 and July 1986
Food frequency questionnaire and lifestyle factors and family history related to health questionnaire completed upon recruitment
Between April 1984 and January 1986, blood samples were taken to test plasma lipid levels (total cholesterol directly measured; LDL-cholesterol and HDL-cholesterol indirectly).

Blinding Used

NA.

Intervention

NA.

Data Collection Summary:

Timing of Measurements

Upon entry into the study (September 1980 and January 1984)
Survey and blood sampling of smaller N done within first six years of initiation of study
Diet survey sent out between September 1985 and July 1986.

Dependent Variables

Lipid profile (total cholesterol, LDL-cholesterol, HDL-cholesterol)
Nutrient intake
Mortality
Emergency appendectomy
Sex hormone concentration in males
Thyroid-stimulating hormone in males.

Independent Variables

Diet
Divided into four groups: Vegans, ovolactovegetarians, pesco-vegetarians and meat eaters.

Control Variables

Weight
Height
Smoking
Social class.

Description of Actual Data Sample:

Initial N

Vegetarian: 6,000
Non-vegetarian: 5,000.

Attrition (Final N)

Plasma lipid samples from 3,773 subjects: Data on 3,277 reported (others not accounted for).

Vegans: 114
Vegetarians: 1,550
Fish eaters: 415
Meat eaters: 1,198.

Age

NA.

Ethnicity

NA.

Other Relevant Demographics

Residents of the United Kingdom.

Anthropometrics

NA (assume similarities within the groups).

Location

United Kingdom (Oxford Vegetarian Study).

Summary of Results:

Plasma Lipids and Diet Groups

Both total and LDL-cholesterol concentrations were significantly lower in vegans than in meat-eaters (P<0.001)
HDL-cholesterol concentrations were highest in fish-eaters, but did not differ among the groups
Based on the mean cholesterol levels among the groups, the incidence of ischemic heart disease might be 24% lower in lifelong vegetarians and 57% lower in lifelong vegans than in meat eaters.

Plasma Lipids and Nutrient Intakes

Protein carbohydrate, total fat, saturated fat, dietary cholesterol, dietary fiber and ratio of PUFA:SFA each showed significant differences among diet groups (P<0.045 or lower)
No significant differences in total energy intake
In general, vegans consumed more carbohydrate and fiber, less SFA, negligible amounts of cholesterol and had a higher PUFA:SFA
The nature rather than the quantity of dietary fat is an important determinant of the plasma cholesterol concentration.

Plasma Lipids, Foods and Lifestyle

Smoking (for men) and use of saturated spreading fats in women were positively associated with total cholesterol levels
Meat and cheese consumption were positively associated and dietary fiber was inversely associated with total cholesterol
Results provided further evidence of the hypocholesterolemic effect of diets with high fiber contents and limited use of meat and cheese and exclusion of meat from the diet might result in a 15% to 25% reduction in risk for ischemic heart disease.

Mortality by Diet Group

Within the cohort, death rates were lower among the non-meat-eaters than in the meat-eaters for all three endpoints (ischemic heart disease, malignant neoplasms and all causes of death)
There was a positive strong correlation between increasing consumption of animal fats and ischemic heart disease mortality
After adjusting for differences in smoking habits, BMI and social class, the death rate ratios (and 95% CIs) for the non-meat-eaters, compared with the meat-eaters, were 0.80 (0.65, 0.99) for all causes of death, 0.72 (0.47, 1.10) for ischemic heart disease and 0.61 (0.44, 0.84) for all malignant neoplasms. These results were similar for both men and women and also after restricting the analysis to subjects who had never smoked.

Mortality in Relation to Foods, Animal Fats and Dietary Fiber

Based on initial questionnaire, subjects were grouped to diet as well as total fat, cholesterol, fiber and alcohol amounts. The analysis included a total of 525 deaths before the age of 80 years, during an average of 13.3 years follow-up: 392 of the deaths were in subjects without history of heart disease or DM at recruitment. Vegetarians and vegans had lower mortality than meat-eaters.
There was a positive association between increasing consumption of animal fats and ischemic heart disease mortality
However, there was no protective effect noted for dietary fiber, fish or alcohol consumption
Consumption of eggs and cheese were both positively associated with ischemic heart disease mortality.

Other Aspects of Health and Disease

The proportion of subjects that reported an emergency appendectomy was higher in life-long meat-eaters (10.7%) than in either life-long non-meat-eaters (7.8%) or those who had stopped eating meat (8.0%). Unfortunately, the data did not allow for reliable testing of other hypotheses and therefore meat consumption may simply be a marker for another dietary, lifestyle or socioeconomic factor.
There were no significant differences in mean concentration of testosterone (total or free) or estradiol between vegans and omnivores, but the sex hormone-binding globulin (SHBG) was 23% higher in the vegans (P=0.001). There were statistically significant correlations between total testosterone and polyunsaturated fatty acid intake (partial R=0.37); and between SHBG and each of total fat, saturated fatty acids, polyunsaturated fatty acids and alcohol (partial R=0.43, 0.46, 0.33 and -0.39 respectively).
The geometric mean TSH concentration was 47% higher in the vegans than in the omnivores (P=0.001)
Thyroid function tests in association with hypercholesterolemia were performed on vegetarians and meat-eaters. It was concluded that hypothyroidism is relatively common in apparently healthy people with raised plasma cholesterol concentrations, but is no more common in vegetarians than in meat-eaters.
There was no significant association between reported cardiovascular-related disease and alcohol consumption for either men or women. However, there was an association between diet group and cardiovascular-related disease in women, with a 15% excess in the observed number of meat-eating women with previous disease, compared with the expected number after adjustment for age, smoking, drinking and social class. In male meat-eaters, a similar 8% excess of cardiovascular-related disease was observed.

Author Conclusion:

The Oxford Vegetarian Study has achieved its aims: Mortality in the vegetarian subjects has been evealuated and compared with that of the non-vegetarian control subjects for major causes of death
The plasma lipid concentrations of different diet groups have been compared and the study examined the effects of different foods and nutrients on these concentrations
Sub-studies have compared hormone concentrations in male vegans and omnivores, investigated the prevalence of hypothyroidism in hyperlipidemic subjects, compared emergency appendectomy rates of meat-eaters and non-meat-eaters and studied the relationship between previous cardiovascular-related disease and alcohol.

Funding Source:

Not-for-profit

Foundation associated with industry:

Reviewer Comments:

Difficult to assess diet, as years of the study continue
Food frequency questionnaire has improved since initiation of the study, suggesting that the data may be somewhat questionable.

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)	No
	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?	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?		No
	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%.)	???
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	???
	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?		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.)	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?		N/A
	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?	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