To begin, it’s worth noting the complexity of trying to extrapolate from observational studies. As noted in a recent review of the evidence published in Current Atherosclerosis Reports (which found mixed evidence regarding eggs and CVD risk), it is difficult to isolate one dietary component from a larger pattern, including other lifestyle factors. For example, the authors of this review point out that in Asian cultures, higher egg consumption tracks with a higher socioeconomic status, a healthier dietary pattern, and more physical activity, as well as a lower likelihood of smoking, while nearly the opposite associations are observed in the United States (and generally greater risk with eggs is observed in the U.S. vs Asian cohorts). Thus, any study requires multivariate adjustments to even attempt to overcome these types of associations, and the true effect of egg consumption may be obscured.
Among the studies that have found adverse effects associated with egg consumption, one of the larger ones with multivariate adjustment was published in JAMA in 2019. This analysis of 6 prospective cohort studies had a median follow-up of 17.5 years and included nearly 30,000 adults. It concluded that each ½ egg per day above the median (which was 0.14 eggs per day) was associated with a 6% and 8% higher risk for incident CVD and all-cause mortality, respectively. This was a monotonic dose-dependent association, i.e., an entire egg above the median would be associated with a 12% and 16% higher risk for CVD and death, respectively. These results suggest that consuming a large number of eggs per day would potentially carry clinically meaningful risks. This link remained after adjusting for multiple CVD risk factors, dietary fats, animal protein, fiber, sodium, etc., but did not persist after adjusting for dietary cholesterol, strongly suggesting that it is the cholesterol content of eggs that drives the increase in risk (depicting a suggestion that red meat, processed meat, and eggs may have a special role).
The connection between dietary cholesterol and CVD risk remains a controversial topic, but this analysis supports the findings of a more recent systematic review of 40 studies published in Circulation, which also included data from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study (which alone included 27,000 participants, with 3 decades of follow-up). This meta-analysis captured data from 3.6 million participants and found that 1 additional egg per day was associated with a significant 4% increase in CVD risk (8% among U.S. cohorts), and this increase in risk diminished after adjusting for dietary cholesterol intake. The authors of this review point out that there were regional differences, with the largest risk observed in U.S. cohorts, marginal risk in European cohorts, and no additional risk observed among Asian cohorts, which they also suggest may explain why other analyses have not observed a heightened CVD risk with egg consumption. Egg consumption has also been linked specifically to heart failure in men, as well as stroke risk and higher blood glucose among those with diabetes or impaired glucose tolerance in some but not all studies.
Despite these studies which suggest eggs may be an important contributor to CVD, there are others (in addition to the update mentioned above) that find no such associated risk. For example, an umbrella review of meta-analyses and systemic reviews published in Public Health Nutrition found no increase in risk for CVD in the general population, though there may be a link between eggs and type 2 diabetes in U.S. cohorts only, as well as a possible risk for heart failure. A large meta-analysis of 39 studies published in the European Journal of Nutrition included nearly 2 million individuals and concluded that there was no strong association between CVD outcomes when comparing 1 egg per day to none, though men did appear to have an increase in risk for heart failure in U.S. cohorts. Instead, they found that moderate intake (4 eggs per week) may carry a lower risk for CVD than no intake. This finding parallels one published in the American Journal of Medicine, that >1 egg per day reduced the risk of coronary artery disease compared to 1 or no eggs per day.
It's difficult to know how to interpret these mixed findings, and the type of high-quality studies that would sharpen this picture may never come. It seems clear that a limited number of eggs is not likely to substantially increase the risk of disease, though genetic background and/or other dietary/lifestyle patterns may modify this risk, and men with a particularly high risk for heart failure may want to be cautious. Regarding genetic factors, a recent study published in the American Journal of Clinical Nutrition offers insight. In this study based in China, a polygenic risk score (based on 540 genetic variants) made a large impact on risk. With over 34,000 participants, a small increase in risk for coronary artery disease was observed with egg consumption for everyone, but people genetically predisposed had roughly a tripling in their risk for CAD over a 10-year period when consuming 10 or more eggs per week. Perhaps this type of genetic predictor may play a role in identifying individuals most at risk with more precision than observational studies.