O-43 - Higher egg intake tracks an unhealthier diet-lifestyle pattern (more red-processed meat, smoking, BMI, T2D) in Harvard cohorts
The confounder-correlation structure: in the US diet, eggs co-occur with an unhealthier dietary and lifestyle pattern. This is what the multivariable models adjust away and the basis for the residual-confounding concern.
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Two components. (1) Cohort analysis pooling three Harvard prospective cohorts — NHS (83,349 women, 1980-2012), NHS II (90,214 women, 1991-2013), HPFS (42,055 men, 1986-2012), free of CVD/T2D/cancer at baseline; 5,540,314 person-years, 14,806 incident CVD events. Whole-egg intake assessed every 2-4 years by validated semiquantitative FFQ (deattenuated validity r≈0.77-0.80 vs weighed records); repeated measures modeled as cumulative average, allowing baseline-only and simple-update sensitivity analyses. Endpoints (nonfatal/fatal MI, fatal CHD, fatal/nonfatal stroke) physician-adjudicated from medical records, blinded to exposure. Cox models with sequential adjustment (model 1 age; model 2 +lifestyle; model 3 +co-consumed foods). E-value sensitivity analysis. Substitution modeling swaps 1 egg/day for 1 serving/day of alternative foods. (2) Updated systematic review and random-effects meta-analysis of 33 prospective-cohort risk estimates (screened from 763 studies), with prespecified subgroup meta-regression by region, sex, follow-up, cohort size, risk of bias, and diet-assessment type. The cohort observations rest on the Harvard cohorts (D-7); the meta-analytic observations rest on the pooled 33-cohort corpus (D-26).
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Why this is evidence
Higher egg eaters cluster with established CVD risk factors (more red/processed meat, smoking, higher BMI, more T2D). This confounding structure is exactly what H-21 (null) needs to explain away the modest crude positive egg-CVD association as non-causal, and it is the mechanism by which an apparent harm signal (H-27) could be manufactured without any causal effect. Under H-6 (protection) one would not expect a positive crude association at all. The observation thus discriminates the null from the harmful reading by supplying the confounding pathway; it is agnostic between them only on residual (unmeasured) confounding.