Lacey, Melanie; (2024) The relationship between alcohol consumption, selected serum metabolites and CHD. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Background Alcohol consumption is associated with CHD risk and the mechanisms underlying this relationship are poorly understood. Serum DHA, omega-6 FA, phenylalanine and %MUFA have been associated with CHD risk but whether alcohol consumption affects these metabolites or they mediate the relationship between alcohol and CHD has not been established. This study investigates the relationship between alcohol consumption and these metabolites and CHD. Methods Data from the Whitehall II study (10,308 British civil servants aged 35-55 yrs at baseline) between 1985 and 2015 were used. Serum metabolites were measured by quantitative NMR. Data on alcohol consumption, confounders and CHD were collected via questionnaires, research clinics and by linkage to HES and mortality data. 5689 to 6081 participants met the inclusion criteria for different analyses. Missing data were imputed using multiple imputation by chained equations. Associations between recent and long term alcohol consumption and the metabolites were analysed using multivariable linear regression and mediation of the association between long-term alcohol consumption and CHD was investigated using difference-in-estimates in Cox regression. Results After adjustment for confounding recent alcohol consumption was positively associated with serum DHA and %MUFA and weakly associated with omega-6 FA. Long term alcohol consumption was more strongly associated with DHA and %MUFA, but not with n-6 FA. There was weak evidence that drinking trajectories were associated with serum phenylalanine. Drinking alcohol was associated with increased risk of CHD in males, but decreased risk in females. Mediation analyses suggested serum DHA and %MUFA may be partial mediators of the association between alcohol consumption and CHD. Conclusion This study suggests that changes in serum DHA and %MUFA are two possible mechanisms by which alcohol consumption alters risk of CHD. There was little evidence that serum n-6 FA or phenylalanine could be significant mediators of the relationship between alcohol consumption and CHD.

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