Protective effect of homovanillyl alcohol on cardiovascular disease and total mortality: virgin olive oil, wine, and catechol-methylathion
De la Torre, R.; Corella, D.; Castaner, O.; Martínez González, Miguel Ángel
; Salas-Salvador, J.; Vila, J.; Estruch, R. ; Sorli, J. V. ; Aros, F.; Fiol, M. ; Ros, E.; Serra-Majem, L.; Pinto, X.; Gomez-Gracia, E.; Lapetra, J. ; Ruiz-Canela, Miguel
; Basora, J.; Asensio, E. M.; Covas, M. I.; Fito, M.
Background: Hydroxytyrosol is a phenolic compound that is present in virgin olive oil (VOO) and wine. Hydroxytyrosol-related foods have been shown to protect against cardiovascular disease (CVD). Objective: We investigated the associations between hydroxytyrosol and its biological metabolite, 3-O-methyl-hydroxytyrosol, also known as homovanillyl alcohol (HVAL), with CVD and total mortality. Design: We included 1851 men and women with a mean +/- SD age of 66.8 +/- 6 y at high risk of CVD from prospective cohort data. The primary endpoint was a composite of myocardial infarction, stroke, and death from cardiovascular causes; the secondary endpoint was all-cause mortality. Twenty-four-hour urinary hydroxytyrosol and HVAL and catechol-O-methyltransferase (COMT) rs4680 genotypes were measured. Results: After multivariable adjustment, all biomarkers were associated, as a continuous variable, with lower CVD risk, but only HVAL showed a strong inverse association (HR: 0.44; 95% CI: 0.25, 0.80) for the comparison between quintiles. Only HVAL, as a continuous variable, was associated with total mortality (HR: 0.81; 95% CI: 0.70, 0.95). Individuals in the highest quintile of HVAL compared with the lowest had 9.2 (95% CI: 3.5, 20.8) and 6.3 (95% CI: 2.3, 12.1) additional years of life or years free of CVD, respectively, after 65 y. Individuals with the rs4680GG genotype had the highest HVAL concentrations (P = 0.05). There was no association between COMT genotypes and events or interaction between COMT genotypes and HVAL concentrations. Conclusions: We report, for the first time to our knowledge, an independent association between high urinary HVAL concentrations and a lower risk of CVD and total mortality in elderly individuals. VOO and wine consumption and a high metabolic COMT capacity for methylation are key factors for high HVAL concentrations. The association that stems from our results reinforces the benefits of 2 key components of the Mediterranean diet (wine and VOO).