Cover of Evidence review for dietary cholesterol strategies

Evidence review for dietary cholesterol strategies

Cardiovascular disease: risk assessment and reduction, including lipid modification

Evidence review B

NICE Guideline, No. 238

London: National Institute for Health and Care Excellence (NICE); .
ISBN-13: 978-1-4731-5204-5
Copyright © NICE 2023.

1. Dietary cholesterol

1.1. Review question

What is the clinical and cost effectiveness of dietary cholesterol strategies compared with usual diet for adults without established CVD and with established CVD?

1.1.1. Introduction

The 2014 update of CG181 includes recommendations for lifestyle interventions for reducing risk of CVD. This update focusses only on dietary cholesterol strategies. It was previously recommended that reductions in dietary cholesterol intake were made to reduce cardiovascular risk, based on the understanding at that time that changes in dietary cholesterol modify blood lipids and other risk factors and that these changes were associated with reductions in morbidity and mortality from cardiovascular events. However, it has been suggested that the evidence and understanding on how this relates to cardiovascular risk has changed since the last update of the guideline. The updated review will therefore look at the recent evidence for this area to inform up-to-date recommendations on the topic.

1.1.2. Summary of the protocol

For full details see the review protocol in Appendix A.

Table 1. PICO characteristics of review question.

Table 1

PICO characteristics of review question.

1.1.3. Methods and process

This evidence review was developed using the methods and process described in Developing NICE guidelines: the manual. Methods specific to this review question are described in the review protocol in appendix A and the methods document.

Declarations of interest were recorded according to NICE’s conflicts of interest policy.

1.1.4. Effectiveness evidence

1.1.4.1. Included studies

No relevant clinical studies comparing dietary cholesterol with no dietary cholesterol were identified.

See also the study selection flow chart in Appendix C.

1.1.4.2. Excluded studies

No evidence from RCTs or interventional cohort studies was identified that matched the review protocol. A number of prospective prognostic studies were found which examined the association of egg consumption with CVD outcomes, and there were systematic reviews of these studies. Prognostic studies examine selected predictive variables or risk factors and assess their influence on patient outcomes, in this case dietary cholesterol consumption would be the prognostic factor or predictor variable. RCTs are considered the best evidence to inform effectiveness of interventions or treatment strategies as they enable control for between group variables, including known and unknown prognostic factors. Therefore, prognostic studies are not usually considered for review questions about interventions, and these were not included in the CG181 on cardioprotective diets.

Some RCTs were identified that examined egg consumption versus no egg consumption, but the follow-ups were less than 1 year and the outcomes were clinical biochemistry tests or tests for atherosclerosis. Some older RCTs identified in this review looked at dietary cholesterol but the actual interventions included other advice such as increasing polyunsaturated fat, decreasing saturated fat, and stopping smoking and so these interventions did not match the review protocol.

See the excluded studies list in Appendix G.

1.1.5. Summary of studies included in the effectiveness evidence

There was no effectiveness evidence.

1.1.6. Economic evidence

1.1.6.1. Included studies

No health economic studies were included.

1.1.6.2. Excluded studies

No relevant health economic studies were excluded due to assessment of limited applicability or methodological limitations.

See also the health economic study selection flow chart in Appendix D.

1.1.7. Summary of included economic evidence

No health economic studies were included.

1.1.8. Economic model

This area was not prioritised for new cost-effectiveness analysis.

1.1.9. Evidence statements

1.1.9.1. Effectiveness/Qualitative
  • No relevant published evidence was identified.
1.1.9.2. Economic
  • No relevant economic evaluations were identified.

1.1.10. The committee's discussion and interpretation of the evidence

1.1.10.1. The outcomes that matter most

The committee agreed that the following outcomes were the most important to inform recommendations:

  • All-cause mortality
  • CVD mortality
  • Stroke
  • Combined major CVD events (incl. CVD death, myocardial infarction, and stroke).

The committee agreed that evidence that changes in dietary cholesterol can impact the risk of major cardiovascular events were essential to forming recommendations. They also agreed that clinical biochemistry tests or tests for atherosclerosis were not appropriate surrogates for the impact of dietary cholesterol strategies on cardiovascular health. However, there was no relevant evidence identified for this review question.

1.1.10.2. The quality of the evidence

The evidence review found no RCTs or interventional cohort studies that matched the review protocol.

The committee agreed to discuss any revisions to the existing recommendation based on informal consensus and their expert opinion and knowledge of other relevant guidance.

1.1.10.3. Benefits and harms

Since there was no new clinical evidence to review, the committee discussed the benefits and harms of the existing recommendation on a cardioprotective diet for the management of dietary cholesterol. The previous recommendation from the 2014 update of CG181 was:

1.2.1 Advise people at high risk of or with CVD to eat a diet in which total fat intake is 30% or less of total energy intake, saturated fats are 7% or less of total energy intake, intake of dietary cholesterol is less than 300 mg/day and where possible saturated fats are replaced by mono-unsaturated and polyunsaturated fats. Further information and advice can be found on the NHS Eat well webpage.

The committee noted that this recommendation was adopted based on the Joint British Societies' guidance (JBS2, 2005), rather than being based on any evidence directly reviewed by the committee. They also noted that the subsequent update to the Joint British Societies’ guidance, JBS3 (2014), had removed this recommendation, based on a systematic review showing little evidence to support an association between dietary cholesterol and coronary heart disease risk in the general population, with the caveat that it may have a detrimental effect in people who react to dietary cholesterol with a large increase in plasma cholesterol (hyper-responders). The committee were aware of this systematic review, but it did not meet the protocol criteria for the guideline review as it included prognostic association data rather than intervention studies with an RCT or comparative cohort design. The committee agreed that the definition of ‘hyper-responders’ was unclear. They agreed it wasn’t necessary to make a statement similar to that in JBS3 about hyper-responders in the updated recommendation.

Based on this information and the lack of new comparative clinical evidence from intervention studies, the committee agreed that there was no evidence to support a limit of 300mg per day of dietary cholesterol. They also noted that organisations like the American Heart Association have acknowledged that it is impractical to set limits on dietary cholesterol intake as a method of reducing the risk of CVD events. Additionally, the committee agreed that saturated fat intake has a greater impact on a person’s cholesterol profile and corresponding risk of CVD events.

1.1.10.4. Cost effectiveness and resource use

The committee agreed that not advising people to restrict cholesterol intake would have no implications for resource use. The updated recommendation was considered to be in line with current practice.

1.1.10.5. Other factors the committee took into account

The committee agreed that the guidance on limits on macronutrients as a proportion of a person’s daily diet in the recommendation (e.g. total fat less than 30%, saturated fat less than 7%) would be difficult to interpret and implement for most people. The committee agreed that it may be more effective to provide broader guidance advising people to increase their intake of fruits and vegetables rather than provide percentage limits on fat consumption. However, this was beyond the remit of this update and this evidence had not been reviewed.

1.1.11. Recommendations supported by this evidence review

This evidence review supports recommendation 1.3.2.

1.1.12. References

1.
National Institute for Health and Care Excellence. Developing NICE guidelines: the manual [updated January 2022], London. National Institute for Health and Care Excellence, 2014. Available from: http://www​.nice.org.uk​/article/PMG20/chapter​/1%20Introduction%20and%20overview

Appendices

Appendix A. Review protocols

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Appendix B. Literature search strategies

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Appendix C. Effectiveness evidence study selection

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Appendix D. Economic evidence study selection

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Appendix E. Economic evidence tables

None.

Appendix F. Health economic model

This area was not prioritised for new cost-effectiveness analysis.

Appendix G. Excluded studies

G.1. Clinical studies

Table 4. Studies excluded from the clinical review.

Table 4

Studies excluded from the clinical review.

G.2. Health Economic studies

Published health economic studies that met the inclusion criteria (relevant population, comparators, economic study design, published 2007 or later and not from non-OECD country or USA) but that were excluded following appraisal of applicability and methodological quality are listed below. See the health economic protocol for more details.

Table 5. Studies excluded from the health economic review.

Table 5

Studies excluded from the health economic review.