Clinical trial NCT05171283: Meta-analysis of Oat Fiber and Cardiovascular Risk Reduction
Official title: Oat Fiber and Cardiovascular Risk Reduction: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Cardiovascular Diseases
Coronary Heart Disease
Keywords: Oat
Oat fibre
beta-glucan
Avena sativa
Systematic reviews and meta-analysis
Clinical practice guidelines
Controlled trials
Cardiovascular disease
Coronary heart disease
10-year cardiovascular risk score
Lead sponsor: University of Toronto
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: Quaker Oats Centre of Excellence, Quaker
First posted: 2021-12-28
Enrollment: 1
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Any population type.

Brief summary: Oat fibre has been shown to lower cholesterol and may have cardioprotective effects. However, whether this translates to actual cardiovascular risk reduction is unclear, as there is a lack of controlled human trials. To address this uncertainty, the investigator proposes to use established cardiovascular disease risk scores, such as those recommended by the Canadian Cardiovascular Society and other clinical practice groups, to create composite risk scores in assessing future risk. The data on oat fibre will be collected through a systematic review of controlled trials, composite cardiovascular risk scores will be calculated for each eligible study, and meta-analyses will be conducted to assess the overall effect. The findings generated by this proposed knowledge synthesis will help improve the health of consumers through informing evidence-based guidelines and improving health outcomes by educating healthcare providers and patients, stimulating industry innovation, and guiding future research design.

Detailed description: Background: Although oat beta-glucan has an approved health claim for cholesterol-lowering in Canada, US, and Europe, it is unclear whether this effect translates into lower cardiovascular disease risk. There is a well-established causal link between LDL-C and cardiovascular disease based on the results of pharmacological interventions that target different LDL-C- lowering mechanisms and mendelian randomization studies. However, there are no randomized controlled trials of the effect of whole grain oats or oat beta-glucan on cardiovascular outcomes and the few prospective cohort studies that have assessed the relation of whole grain oats with cardiovascular outcomes have failed to show a reliable protective association.

One way to confirm the cardiovascular benefit of whole grain oats and oat beta-glucan would be to use an established 10-year cardiovascular disease risk score such as the modified Framingham Risk Score (FRS) (recommended by the Canadian Cardiovascular Society \[CCS\]), the American College of Cardiology/American Heart Association (ACC/AHA) ASCVD risk estimator (recommended by the ACC/AHA) or Systemic Coronary Risk Estimation (SCORE) (recommended by the European Society of Cardiology \[ESC\] and European Atherosclerosis Society \[EAS\]). These scores are composites of cardiovascular risk factors in which cholesterol and blood pressure carry important weight. There are numerous systematic reviews and meta-analyses of randomized trials showing a benefit of whole grain oats and oat beta-glucan for cholesterol and blood pressure. The investigators propose a novel approach to leverage these benefits to detect an overall reduction in 10-year cardiovascular disease by these scores.

Need for proposed research: High quality systematic reviews and meta-analyses of randomized controlled trials represent the highest level of evidence to support dietary guidelines and public health policy development. As dietary guidelines and public health policy have shifted toward food and dietary-pattern based recommendations, there is a need for systematic reviews and meta-analyses on the effect of oats and oat beta-glucan on cardiovascular risk.

Objective: To improve evidence-based guidance for clinical practice guidelines for nutrition therapy and public health policy development, the investigators will conduct a systematic review and meta-analysis of the effects of whole grain oats and oat beta-glucan on 10-year cardiovascular disease risk using (1) the modified Framingham Risk Score, (2) the ASCVD risk estimator, and (3) the SCORE.

Design: The systematic review and meta-analysis will be conducted according to the Cochrane Handbook for Systematic Reviews of Interventions and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).

Data sources: MEDLINE, EMBASE, and The Cochrane Central Register of Controlled Trials (Clinical Trials; CENTRAL) will be searched using appropriate search terms supplemented by manual searches of references of included studies.

Study selection: The investigators will include randomized controlled trials of ≥3-weeks in adults of all health backgrounds assessing the effect of oat beta-glucan compared with a suitable non-beta-glucan control on 10-year cardiovascular risk calculated by the 3 cardiovascular risk scores which will require data on a combination of blood lipids (total-cholesterol and HDL-cholesterol) and systolic blood pressure (for calculation of the 3 scores). Studies that are not conducted in humans, not randomized, have an acute feeding design (\<3 weeks), lack a suitable control (non-isocaloric, contain beta-glucan) and/or do not report viable endpoint data will not be included.

Data extraction: Two or more investigators will independently extract relevant data and assess risk of bias using the Cochrane Risk of Bias Tool. All disagreements will be resolved by consensus.. Authors will be contacted for additional information and standard computations and imputations will be used to derive missing variance data.

Outcomes: The primary outcome will be the between treatment change in the modified Framingham Risk Score (FRS) to estimate 10-year risk of cardiovascular disease (https://www.ccs.ca/images/Guidelines/Tools_and_Calculators_En/FRS_eng_2017_fnl1.pdf). Secondary outcomes include the between treatment change in the American College of Cardiology/American Heart Association (ACC/AHA) ASCVD risk estimator (https://tools.acc.org/ascvd-risk-estimator-plus/#!/calculate/estimate/) to estimate the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) and in the Systemic Coronary Risk Estimation (SCORE) (https://www.escardio.org/Education/Practice-Tools/CVD-prevention-toolbox/SCORE-Risk-Charts) derived by the European Society of Cardiology to estimate 10-year risk of cardiovascular disease. Additional outcomes include between treatment changes in the modifiable components of all the scores: total-cholesterol, HDL-cholesterol, and systolic blood pressure.

Data synthesis: Separate pooled analyses will be conducted for each cardiovascular risk score using the Generic Inverse Variance method. Random-effects models will be used even in the absence of statistically significant between-study heterogeneity, as this yield more conservative summary effect estimates in the presence of residual heterogeneity. Exceptions will be made for the use of fixed-effects models where there is \<5 included trials irrespective of heterogeneity or small trials are being pooled with larger more precise trials in the absence of statistically significant heterogeneity. Paired analyses will be applied to all crossover trials. Heterogeneity will be tested by Cochran's Q statistic and quantified by the I2 statistic. To explore sources of heterogeneity, the investigators will conduct sensitivity analyses, in which each study is systematically removed. If there are ≥10 studies, then the investigators will also explore sources of heterogeneity by a priori subgroup analyses by study design (parallel or crossover), follow-up duration (\<12 weeks or ≥12 weeks), comparator diet, baseline risk, risk of bias and background health status. Significant unexplained heterogeneity will be investigated by additional post hoc subgroup analyses by age (\<18y vs ≥18y), energy balance (neutral, negative or positive), feeding control (metabolic, supplemented, dietary advice, ad libitum), and funding. Meta-regression analyses will assess the significance of categorical and continuous subgroups analyses. Linear dose-response analyses will be assessed using continuous meta-regression analyses. Non-linear dose-response association will be assessed using a two-stage multivariate random-effects method with restricted cubic splines with three knots. When ≥10 studies are available, publication bias will be investigated by inspection of funnel plots and formal testing using the Egger's and Begg's tests. If publication bias is suspected, then the investigators will attempt to adjust for funnel plot asymmetry by imputing the missing study data using the Duval and Tweedie trim and fill method.

Evidence assessment: The strength of the evidence for each outcome will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE).

Knowledge translation plan: The results will be disseminated through interactive presentations at local, national, and international scientific meetings and publication in high impact factor journals. Target audiences will include the public health and scientific communities with interest in nutrition, diabetes, obesity, and cardiovascular disease. Feedback will be incorporated and used to improve the public health message and key areas for future research will be defined. Applicant/Co-applicant Decision Makers will network among opinion leaders to increase awareness and participate directly as committee members in the development of future guidelines.

SIGNIFICANCE The proposed project will aid in knowledge translation related to the role of oats in cardiovascular risk reduction strengthening the evidence-base for guidelines development in the U.S., Canada, Europe, and beyond and improving health outcomes, by educating healthcare providers and patients, stimulating industry innovation, and guiding future research design.

Eligibility criteria: Inclusion Criteria:

* Dietary trials in humans
* Randomized treatment allocation
* ≥3 weeks
* Intervention with oats or oat beta-glucan
* Suitable control (i.e. isocaloric diet that is not vegetarian or vegan)
* Ascertainment of viable outcome data for cardiovascular risk calculations

Exclusion Criteria:

* Non-human studies
* Non-randomized treatment allocation
* \<3 weeks
* No intervention of oats or oat beta-glucan
* Lack of a suitable control (i.e. non-isocaloric)
* No viable endpoint data

Primary outcomes:
measure: Framingham Risk Score (FRS)
timeFrame: >= 3-weeks
Secondary outcomes:
measure: ACC/AHA ASCVD risk estimator
timeFrame: >= 3-weeks
measure: Systematic COronary Risk Evaluation (SCORE)
timeFrame: >= 3-weeks
Other outcomes:
measure: Modifiable components of the risk scores - total-cholesterol
timeFrame: >= 3-weeks
measure: Modifiable components of the risk scores - HDL-cholesterol
timeFrame: >= 3-weeks
measure: Modifiable components of the risk scores - systolic blood pressure
timeFrame: >= 3-weeks
Locations:
city: Toronto
country: Canada
facility: The Toronto 3D (Diet, Digestive tract and Disease) Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital
state: Ontario
Study officials:
affiliation: University of Toronto
name: John L Sievenpiper, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References:
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