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Associations of Dietary Cholesterol or Egg Consumption With Incident Cardiovascular Disease and Mortality

Educational Objective
To understand the relationship of dietary cholesterol and egg consumption to the risk of developing cardiovascular disease.
1 Credit CME
Key Points

Question  Is consuming dietary cholesterol or eggs associated with incident cardiovascular disease (CVD) and all-cause mortality?

Findings  Among 29 615 adults pooled from 6 prospective cohort studies in the United States with a median follow-up of 17.5 years, each additional 300 mg of dietary cholesterol consumed per day was significantly associated with higher risk of incident CVD (adjusted hazard ratio [HR], 1.17; adjusted absolute risk difference [ARD], 3.24%) and all-cause mortality (adjusted HR, 1.18; adjusted ARD, 4.43%), and each additional half an egg consumed per day was significantly associated with higher risk of incident CVD (adjusted HR, 1.06; adjusted ARD, 1.11%) and all-cause mortality (adjusted HR, 1.08; adjusted ARD, 1.93%).

Meaning  Among US adults, higher consumption of dietary cholesterol or eggs was significantly associated with higher risk of incident CVD and all-cause mortality in a dose-response manner.

Abstract

Importance  Cholesterol is a common nutrient in the human diet and eggs are a major source of dietary cholesterol. Whether dietary cholesterol or egg consumption is associated with cardiovascular disease (CVD) and mortality remains controversial.

Objective  To determine the associations of dietary cholesterol or egg consumption with incident CVD and all-cause mortality.

Design, Setting, and Participants  Individual participant data were pooled from 6 prospective US cohorts using data collected between March 25, 1985, and August 31, 2016. Self-reported diet data were harmonized using a standardized protocol.

Exposures  Dietary cholesterol (mg/day) or egg consumption (number/day).

Main Outcomes and Measures  Hazard ratio (HR) and absolute risk difference (ARD) over the entire follow-up for incident CVD (composite of fatal and nonfatal coronary heart disease, stroke, heart failure, and other CVD deaths) and all-cause mortality, adjusting for demographic, socioeconomic, and behavioral factors.

Results  This analysis included 29 615 participants (mean [SD] age, 51.6 [13.5] years at baseline) of whom 13 299 (44.9%) were men and 9204 (31.1%) were black. During a median follow-up of 17.5 years (interquartile range, 13.0-21.7; maximum, 31.3), there were 5400 incident CVD events and 6132 all-cause deaths. The associations of dietary cholesterol or egg consumption with incident CVD and all-cause mortality were monotonic (all P values for nonlinear terms, .19-.83). Each additional 300 mg of dietary cholesterol consumed per day was significantly associated with higher risk of incident CVD (adjusted HR, 1.17 [95% CI, 1.09-1.26]; adjusted ARD, 3.24% [95% CI, 1.39%-5.08%]) and all-cause mortality (adjusted HR, 1.18 [95% CI, 1.10-1.26]; adjusted ARD, 4.43% [95% CI, 2.51%-6.36%]). Each additional half an egg consumed per day was significantly associated with higher risk of incident CVD (adjusted HR, 1.06 [95% CI, 1.03-1.10]; adjusted ARD, 1.11% [95% CI, 0.32%-1.89%]) and all-cause mortality (adjusted HR, 1.08 [95% CI, 1.04-1.11]; adjusted ARD, 1.93% [95% CI, 1.10%-2.76%]). The associations between egg consumption and incident CVD (adjusted HR, 0.99 [95% CI, 0.93-1.05]; adjusted ARD, −0.47% [95% CI, −1.83% to 0.88%]) and all-cause mortality (adjusted HR, 1.03 [95% CI, 0.97-1.09]; adjusted ARD, 0.71% [95% CI, −0.85% to 2.28%]) were no longer significant after adjusting for dietary cholesterol consumption.

Conclusions and Relevance  Among US adults, higher consumption of dietary cholesterol or eggs was significantly associated with higher risk of incident CVD and all-cause mortality in a dose-response manner. These results should be considered in the development of dietary guidelines and updates.

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Article Information

Corresponding Authors: Victor W. Zhong, PhD (wenze.zhong@northwestern.edu), and Norrina B. Allen, PhD (norrina-allen@northwestern.edu), Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, 680 N Lake Shore Dr, Ste 1400, Chicago, IL 60611.

Accepted for Publication: February 7, 2019.

Author Contributions: Drs Zhong and Allen had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design:Zhong, Van Horn, Lloyd-Jones, Allen.

Acquisition, analysis, or interpretation of data:Zhong, Van Horn, Cornelis, Wilkins, Ning, Carnethon, Greenland, Mentz, Tucker, Zhao, Norwood, Lloyd-Jones, Allen.

Drafting of the manuscript:Zhong, Van Horn.

Critical revision of the manuscript for important intellectual content:Zhong, Van Horn, Cornelis, Wilkins, Ning, Carnethon, Greenland, Mentz, Tucker, Zhao, Norwood, Lloyd-Jones, Allen.

Statistical analysis:Zhong, Zhao, Ning.

Obtained funding:Greenland, Lloyd-Jones.

Administrative, technical, or material support:Van Horn, Wilkins, Greenland, Norwood, Lloyd-Jones.

Supervision:Van Horn, Wilkins, Carnethon, Greenland, Mentz, Allen.

Conflict of Interest Disclosures: Dr Wilkins reported receiving consulting fees from NGM Biopharmaceuticals (Modest). Dr Mentz reported receiving research support from Akros, Amgen, AstraZeneca, Bayer, GlaxoSmithKline, Gilead, Luitpold, Medtronic, Merck, Novartis, Otsuka, and ResMed; honoraria from Abbott, Amgen, AstraZeneca, Bayer, Janssen, Luitpold Pharmaceuticals, Medtronic, Merck, Novartis, and ResMed; and serving on an advisory board for Amgen, AstraZeneca, Luitpold, Merck, Novartis and Boehringer Ingelheim. No other disclosures were reported.

Funding/Support: This study was supported by a postdoctoral fellowship to Dr Zhong from the American Heart Association Strategically Focused Research Networks (14SFRN20480260; principal investigator, Greenland). The Lifetime Risk Pooling Project was supported by the National Institutes of Health/National Heart, Lung, and Blood Institute (R21 HL085375) and by the Northwestern University Feinberg School of Medicine. The Jackson Heart Study is supported and conducted in collaboration with Jackson State University (HHSN268201300049C and HHSN268201300050C), Tougaloo College (HHSN268201300048C), and the University of Mississippi Medical Center (HHSN268201300046C and HHSN268201300047C), contracts from the National Heart, Lung, and Blood Institute, and the National Institute for Minority Health and Health Disparities.

Role of the Funder/Sponsor: The funders of this study had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and the decision to submit the manuscript for publication.

Disclaimer: Dr Greenland, a JAMA senior editor, was not involved in the review of or decision to publish this article.

Meeting Presentation: Presented orally in the Robert Levy Memorial Lecture/Lifestyle Young Investigator Award Competition in the American Heart Association Scientific Sessions; November 10-12, 2018; Chicago, Illinois.

Additional Contributions: We thank the staffs and participants of the Jackson Heart Study.

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