In this prospective cohort, we demonstrated that infrequent consumption of eggs (up to 6 per week) was not associated with HF, whereas consumption of 7 or more eggs per week was associated with an increased risk of HF among male physicians. Furthermore, similar association was observed for HF without antecedent myocardial infarction, and we did not find evidence for effect measure modification by hypercholesterolemia, diabetes mellitus, smoking, or hypertension on the observed associations.
Because eggs are rich in dietary cholesterol, researchers have been interested in the effects of egg consumption on serum cholesterol or other intermediate phenotypes. However, limited and inconsistent data have been reported on egg consumption and incident cardiovascular disease (CVD) and mortality. Data from 514 Western Australian Aborigines showed a 2.6-fold increased risk of CHD comparing egg consumption of 2+ vs. < 2/week after ~14 years of follow up14
. Compared with egg consumption of less than 1/week, the incidence rate ratio for total mortality was 1.23 and 2.68 among subjects consuming 1-5 and 6+ eggs/week, respectively, after adjustment for age, sex, smoking, and social class17
. Qureshi et al.18
reported a 2-fold increased risk of CHD among people reporting an intake of 6+ eggs/week compared with intakes of < 1 per week. In addition, compared to egg intake of < 1 per week, Hu et al.19
reported a 2-fold increased risk of CHD for egg consumption of >1 per day among 37,851 diabetic men from the Health Professionals Follow-up Study after adjustment for potential confounders; these data suggest that the observed increased risk of HF with egg consumption could be mediated through CHD. Unfortunately, we did not have enough cases of HF with antecedent myocardial infarction to further examine this hypothesis. The fact that we observed elevated risk of HF without antecedent myocardial infarction suggests that alternative physiologic mechanisms could be responsible for the observed association. Alternatively, additional lifestyle/dietary factors associated with frequent egg consumption could be responsible for the observed relationship. Given the observational nature of our design, we cannot exclude chance or residual confounding by measured and unmeasured factors as a
possible explanation of our findings. In particular, the lack of details on the dietary questionnaire prevented us from controlling for energy intake and other major nutrients. The hypothesis of chance finding or residual confounding is supported by the lack of association between egg consumption and CHD in other studies20,21
. Changes in dietary patterns may lead to a spurious association between baseline exposure and incident outcome. In our data, we used time-dependent Cox regression models to update reported egg consumption at 24, 48, 72, 96, and 120 months after randomization. Such exposure update over time led to similar conclusions, suggesting that our findings are robust and not sensitive to possible changes in egg consumption over time. In addition, adjustment for interim cases if myocardial infarction had a little effect on the results.
A wide variability in individual response to dietary cholesterol (hyper-responders vs. hypo-responders) has been reported. It has been suggest that among hyper-responders, dietary cholesterol from eggs leads to a modest increase in
serum LDL- and HDL-cholesterol and no effect on LDL/HDL ratio 8,22-25
. Thus, it is possible that the observed increased risk of HF with egg consumption might be limited to hyper-responders. However, the fact that we did not observe an association between egg consumption and baseline cholesterol in our study does not lend support to this theory. The lack of a relationship between egg consumption and serum cholesterol is consistent with other reported findings showing no effect of egg consumption on the LDL subfraction22
Our study has additional limitations. Our participants are male physicians who may have different behaviors than the general population, thereby limiting the generalizability of our findings. Furthermore, we did not have data on protein intake, serum albumin, and creatinine to explore the influence of protein load on the observed association, especially in the presence of kidney dysfunction and/or type 2 diabetes. Egg consumption was assessed using an abbreviated food questionnaire. This might have led to under-reporting of usual egg consumption and a bias toward the null. However, if such a bias were present, we would anticipate the true effect measure to be even larger between frequent egg consumption and HF. In this study, we did no directly validate the abbreviated food questionnaire used to assess egg consumption. However, validation of full food frequency questionnaires (including egg consumption questionnaire used in this study) has been published elsewhere26,27
. Lastly, measured plasma total- and HDL-cholesterol were available at baseline only in a limited number of subjects. On the other hand, the large sample size, the longer duration of follow up, and the robustness of our findings in sensitivity analyses are strengths of the present study.
In conclusion, our data suggest that egg consumption up to 6/week is not associated with HF whereas consumption of 7+/week is related to an increased risk of HF. Confirmation of these findings is warranted along with exploration of underlying biologic mechanisms.