Risks of ischaemic heart disease and stroke in meat eaters, fish eaters, and vegetarians over 18 years of follow-up: results from the prospective EPIC-Oxford study

Abstract Objective To examine the associations of vegetarianism with risks of ischaemic heart disease and stroke. Design Prospective cohort study. Setting The EPIC-Oxford study, a cohort in the United Kingdom with a large proportion of non-meat eaters, recruited across the country between 1993 and 2001. Participants 48 188 participants with no history of ischaemic heart disease, stroke, or angina (or cardiovascular disease) were classified into three distinct diet groups: meat eaters (participants who consumed meat, regardless of whether they consumed fish, dairy, or eggs; n=24 428), fish eaters (consumed fish but no meat; n=7506), and vegetarians including vegans (n=16 254), based on dietary information collected at baseline, and subsequently around 2010 (n=28 364). Main outcome measures Incident cases of ischaemic heart disease and stroke (including ischaemic and haemorrhagic types) identified through record linkage until 2016. Results Over 18.1 years of follow-up, 2820 cases of ischaemic heart disease and 1072 cases of total stroke (519 ischaemic stroke and 300 haemorrhagic stroke) were recorded. After adjusting for sociodemographic and lifestyle confounders, fish eaters and vegetarians had 13% (hazard ratio 0.87, 95% confidence interval 0.77 to 0.99) and 22% (0.78, 0.70 to 0.87) lower rates of ischaemic heart disease than meat eaters, respectively (P<0.001 for heterogeneity). This difference was equivalent to 10 fewer cases of ischaemic heart disease (95% confidence interval 6.7 to 13.1 fewer) in vegetarians than in meat eaters per 1000 population over 10 years. The associations for ischaemic heart disease were partly attenuated after adjustment for self reported high blood cholesterol, high blood pressure, diabetes, and body mass index (hazard ratio 0.90, 95% confidence interval 0.81 to 1.00 in vegetarians with all adjustments). By contrast, vegetarians had 20% higher rates of total stroke (hazard ratio 1.20, 95% confidence interval 1.02 to 1.40) than meat eaters, equivalent to three more cases of total stroke (95% confidence interval 0.8 to 5.4 more) per 1000 population over 10 years, mostly due to a higher rate of haemorrhagic stroke. The associations for stroke did not attenuate after further adjustment of disease risk factors. Conclusions In this prospective cohort in the UK, fish eaters and vegetarians had lower rates of ischaemic heart disease than meat eaters, although vegetarians had higher rates of haemorrhagic and total stroke.

2 P-heterogeneity represents significance of heterogeneity in risk between diet groups based on likelihood ratio tests. 3 Meat eaters were participants who reported eating meat, regardless of whether they ate fish, dairy, or eggs; fish eaters were participants who did not eat meat but did eat fish.

Supplementary table 4.
Prospective associations between diet groups and risk of cardiovascular diseases in EPIC-Oxford, further adjusted for potential mediators of the associations, and possible relevant dietary factors (n =48 188).
Hazard ratios (95% confidence intervals) with additional adjustment for 1 Outcome and diet groups 1 Self-reported prior high blood pressure Self-reported prior high blood cholesterol Meat eaters were participants who reported eating meat, regardless of whether they ate fish, dairy, or eggs; fish eaters were participants who did not eat meat but did eat fish; and vegetarians included vegans.

5
All potential mediators included self-reported prior high blood cholesterol, self-reported prior high blood pressure, self-reported prior diabetes, and body mass index. 6 Fruit and vegetable intake, total fibre, and total energy were adjusted for continuously. All analyses included age as the underlying time variable, and were stratified by sex, method of recruitment (general practice or postal), and region (7 categories), and adjusted for year of recruitment (per year), education (no qualifications, basic secondary [e.g. O level], higher secondary [e.g. A level], degree, unknown), Townsend deprivation index (quartiles, unknown), smoking (never, former, light, heavy, unknown), alcohol consumption(<1g, 1-7g, 8-15g, 16+ g/day), physical activity (inactive, low activity, moderately active, very active, unknown), dietary supplement use (no, yes, unknown), and oral contraceptive and hormone replacement therapy use in women. Total N reported for each sensitivity analysis was based on N in the analyses for ischaemic heart disease if numbers varied.

2
Meat eaters were participants who reported eating meat, regardless of whether they ate fish, dairy, or eggs; fish eaters were participants who did not eat meat but did eat fish; and vegetarians included vegans.
3 P-heterogeneity represents significance of heterogeneity in risk between diet groups based on Wald tests. Meat eaters were participants who reported eating meat, regardless of whether they ate fish, dairy, or eggs; fish eaters were participants who did not eat meat but did eat fish; and vegetarians included vegans.

Supplementary
3 P-heterogeneity represents significance of heterogeneity in risk between diet groups based on Wald tests. 4 Presence of one or more of self-reported prior high blood pressure, high blood cholesterol, or diabetes. 5 Based on responses to the question: "Are you receiving long-term treatment for any illness or condition?" 6 Test of interaction by sex, age at recruitment, body mass index, smoking, and presence of risk factors were performed by adding appropriate interaction terms to the Cox models, and testing for statistical significance of interaction across strata using likelihood ratio tests.