EAL

DLM: Fiber (2001)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To evaluate whether high whole-grain intake reduces risk of coronary heart disease (CHD) in women
Specifically:
- Dose-response relations of intake of total whole grain and its major source foods to CHD risk
- Whether the relationship of whole-grain intake to CHD risk can be attributed to its constituents such as vitamin E, vitamin B₆, fiber and folate, which have individually been associated with lower risk of CHD in other studies.

Inclusion Criteria:

Nurses Health Study cohort
Baseline was the 1984 assessment
Women age 38 to 63 years.

Exclusion Criteria:

Respondents who did not satisfy the a priori criteria of reported daily energy intake between 600kcal and 3,500kcal
Women with previously diagnosed diabetes, angina, myocardial infarction (MI), stroke or other cardiovascular diseases.

Description of Study Protocol:

The cohort was followed for 10 years starting in 1984 (baseline)
Every two years, women filled out semi-quantitative food-frequency questionnaires (SFFQ)
Cases of CHD were collected
As part of the larger study, women completed other surveys and some of this information was used as controls in the pooled logistic regression.

Data Collection Summary:

Instruments

SFFQ: 126-item; collected in 1984, 1986, and 1990; food and portion sizes were specified
- How often, on average, during the previous year did you consume that amount?
- Nine responses were possible, ranging from "Never" to "Six or more times per day"
- Type and brand of breakfast cereal (considered whole grain if at least 25% whole grain or bran by content weight)
- Used procedure by Jacobs et al to classify foods as whole or refined grains
Medical record: Biennual request starting in 1984
- Reviewed if the woman had reported having a nonfatal myocardial infarction
  - Diagnosis confirmed by physician unaware of questionnaire data and using World Health Organization (WHO) criteria
  - If no medical record was available, incident was listed as probable if confirmed by interview or letter
- Reviewed if fatal CHD reported
  - Confirmed by hospital records, autopsy or if CHD was listed as a cause of death on certificate.

Dependent Variables

Incident CHD, including fatal CHD and nonfatal MI during the 10-year period (confirmed and probable)
Intermediate endpoints: Angina, hypercholesterolemia, diabetes, hypertension.

Independent Variables

Whole grain consumption and quintiles (included dar bread, whole-grain breakfast cereal, popcorn, cooked oatmeal, wheat grem, brown rice, bran and othe grains like bulgar, kasha, and couscous)
Refined-grain consumption (included sweet rolls, cake desserts, white bread, pasta, English muffins, muffins or biscuits, refined-grain breakfast cereal, white rice, pancakes or waffles and pizza).

Statistical Analysis

Person-time for each participant was calculated from the date of return of the 1984 questionnaire to the date of tfirst coronary event, death, or June 1, 1994
Distributions of individual foods were used to create categories of consumption with adequate person-time at risk in each category (pre-analysis)
Incidence rates were calculated by dividing the number of events by person-time in each category
Relative risks (RR) were estimated as the rate of coronary events in a specific category of intake of whole grain or reined grain divided by the rate in the lowest category
Pooled logistic regression with two-year intervals assessed incidence of CHD in relation to the cumulative average diet from all three cycles of SFFQs
- If intermediate enpoints occured during follow-up, further information on diet was not used
Multivariate analyses to determine if specific dietary components found in whole grains may explain any association observed between whole grains and CHD. All components were included with whole grain in the same model.
Alternative analyses conducted to minimize confounding factors: Women who never smoked, less active, and did not receive HRT or use multivitamin or vitamin E supplements.

Description of Actual Data Sample:

N=75,521 female US nurses aged 38 to 63 years old in 1984

Subject Characteristics (% of Group) by Quintile (With Quintile Median) of Whole-grain Intake

	1 (0.13)	2 (0.43)	3 (0.85)	4 (1.31)	5 (2.70)
Parental MI before age 60	15	15	14	14	14
Vigorous activity at least 1 time/wk	36	41	44	47	50
Current smoker	35	28	23	18	16
Multivitamin use	30	34	37	40	44
Current HRT postmenopause	20	22	23	26	27
Hypertension	22	22	22	20	19
Hypercholesterolemia	7	8	8	8	9
BMI	25±5	25±5	25±4	25±5	25±4
Carbohydrate (g/d)	178±35	180±35	185±3	190±28	195±30
Saturated Fat (g/d)	23±5	25±5	22±4	21±4	20±4
Trans fat (g/d)	4±1	4±1	3±1	3±1	3±1
Protein (g/day)	69±14	70±12	72±12	72±12	73±12
Fiber (g/day)	14±4	15±4	16±4	18±4	20±5

Summary of Results:

Baseline Dietary Intake

In 1984, mean daily intake of whole grain foods was 1.12 servings per day, with dark bread contributing 55% of the servings and whole-grain breakfast cereal the second largest proportion (16%)
Women with high intakes of whole-grain foods smoked less, exercised more and were more likely to receive post-menopausal HRT or use supplements of multivitamins or vitamin E
Greater whole grain intake was associated with higher intakes of carbohydrates, proteins, dietary fiber, cereal fiber, and folate but lower intakes of fat, cholesterol and alcohol; no differences in BMI and history of parental MI.

Dietary Intake from 1984 to 1990

Mean intakes of whole grain increased from 1.12 servings per day to 1.43 servings per day.

Whole Grain Intake and Risk of CHD

Age-adjusted RR of CHD was 0.51 (95% CI: 0.41, 0.64, P<0.0001 for trend) for women in the highest compared with the lowest quintiles
- inverse relationship observed in fatal (RR=0.51, 95% CI: 0.33, 0.80; P<0.001) and nonfatal (RR=0.51, 95% CI: 0.39, 0.66; P<0.0001)
- 729,472 person-years of follow-up
- 761 cases of CHD
  - 208 fatal CHD
  - 553 nonfatal CHD
After adjustment for age and smoking, the inverse association was maintained. Relative risks by quartiles was 1.0 (reference), 0.86, 0.82, 0.72 and 0.67 (95% CI: 0.54, 0.84; P for trend <0.001).
After additional adjustment for BMI, post-menopausal hormone use, alcohol intake, multivitamin use, vitamin E supplement use, aspirin use, physical activity, and types of fat intake, RRs were 1.0, 0.92, 0.93, 0.83 and 0.74 (95% CI; 0.59, 0.95; P for trend=0.01)
- RR of 0.91 (95% CI: 0.85, 0.97) for CHD risk for each additional daily serving of whole-grain foods
The inverse relation between whole-grain intake and CHD was even stronger in the subgroup of never smokers (RR=0.49; 95% CI, 0.30, 0.79; P for trend=0.003).

Constituents

Intakes of whole grains was positively associated with intakes of its constituents, such as dietary fiber (Spearman r = 0.55), folate (0.32), vitamin B₆ (0.29) and vitamin E (0.34)
The risk associated with whole-grain intake was not fully explained by its contribution to intakes of dietary fiber, folate, vitamin B₆ and vitamin E
No association between refined-grain intake and risk of CHD.

Author Conclusion:

Higher intakes of whole-grain foods were associated with lower risks of both fatal and nofatal CHD in this large population of women
The inverse association was independent of known coronary risk factors and components of whole-grain foods currently believed to be beneficial.

Funding Source:

Government:

NIH

Reviewer Comments:

Strengths:

Large, representative sample
Valid and reliable instrumentation (including relatively high accuracy for whole grain, r=0.70 compared with a dietary record)
Three measures over 10 years of diet
Alternative explanations considered: Other healthy lifestyle factors in women in the highest quintile of whole-grain intake that were not accounted for in this study.

Weaknesses:

Observational (not causal)
Self-administered questionnaire for response bias and for misclassification of intake
Some comments after the publication of this study, suggested researchers should have looked at copper and its association to CHD risk
Dark bread may have included refined grain products, such as pumpernickel.

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?	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.)	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?		No
	4.1.	Were follow-up methods described and the same for all groups?	No
	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%.)	No
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	No
	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.)	N/A
	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?		No
	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?	No
	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?	No
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