Efecto de la ingesta de polifenoles en biomarcadores y riesgo cardiovascular

Resum

Introduction Cardiovascular disease is the leading cause of death worldwide and, despite preventive strategies, continues to be a public health problem. The Mediterranean diet has demonstrated numerous benefits in this regard given its richness in antioxidant and anti-inflammatory molecules, and most especially, in polyphenols. These bioactive compounds have shown cardiovascular benefits due to their antithrombotic, anti-inflammatory and antiplatelet properties. However, the study of their potential in humans is limited. Given the large number of compounds that exist and, therefore, their varied bioavailability and mechanisms of action, there are still many points that need to be clarified. For this reason, the main objective of this doctoral thesis is to evaluate the association between polyphenol intake and cardiovascular risk (CVR) and biomarkers. Methods The information available from 6,633 participants in the PREDIMED-Plus study was used, it is a multicenter randomized clinical trial, which collected information on dietary habits and lifestyles, as well as blood samples for biochemical analysis. Polyphenol intakes were estimated using food consumption data from the 143-item semi-quantitative food frequency questionnaire and the polyphenol content of each food contained in the Phenol-Explorer database. Estimated intakes were adjusted for total energy intake according to the residuals method. The association between polyphenol intake and CVR (estimated using risk equations) was evaluated using multivariate linear regression models. In addition, the association between polyphenol intake and uric acid was evaluated (using multivariate linear regression) and, using Cox regression models with a constant follow-up time (t=1), the prevalence ratio of hyperuricemia was estimated. On the other hand, polyphenol consumption patterns were established by factor analysis and cluster analysis, comparing both methods and relating adherence to each pattern with the estimated CVR. All analyses were performed for men and women separately, as well as in the total population. Results Total polyphenol (βQ5vs.Q1= 0.10, 95% CI: 0.04 to 0.17) and flavonoid (βQ5vs.Q1= 0.17, 95% CI: 0.10 to 0.24) intakes were directly and significantly associated with improved optimal cardiovascular health (Life's Simple 7). Inverse associations were found between other polyphenols class intake and, CVR estimated by Framingham (βQ5vs.Q1= -1.22%, 95% CI: -2.37 to -0.07) and SCORE (βQ5vs.Q1=-0.32, 95% CI: -2.37 to -0.07). In women, the associations between polyphenol intake and all risk equations tended to be protective. The intake of phenolic acids (βQ5vs.Q1= -0.17, 95% CI: -0.27 to -0.06), hydroxycinnamic acids (βQ5vs.Q1= -0.19, 95% CI: -0.3 to -0.09), alkylmethoxyphenols (βQ5vs.Q1= 0.2, 95% CI: -0.31 to -0. 1) and methoxyphenols (βQ5vs.Q1= -0.24, 95% CI -0.34 to -0.13) showed an inverse association with serum uric acid levels and, hyperuricemia (PRQ5vs.Q1=0.82, 95% CI:0.71-0.95; PRQ5vs.Q1=0.82, 95% CI:0.71-0.95; PRQ5vs.Q1=0.80, 95% CI:0.70-0.92 and PRQ5vs.Q1=0.79, 95% CI:0.69-0.91, respectively). The polyphenol patterns revealed differences between men and women, as well as, in their association with CVR. Regarding those derived from the factorial analysis: for the total sample and the men, pattern 3 (olives and olive oil poyphenols) was positively associated with CVR, they also had a higher prevalence of diabetes and higher sodium intake. Pattern 4, formed by coffee polyphenols in all groups, was also associated with higher CVR. As for the cluster analysis, cluster 2 in the total and in men, characterized by consumption of coffee polyphenols and olives and olive oil, also showed higher CVR. Conclusions The other polyphenols class showed inverse associations with estimated cardiovascular risk, finding similar results with the Framingham, Framingham-REGICOR and Life's Simple 7 equations (after eliminating the diet component), and different with the SCORE, but predictors included in this scale are scarce. Higher intakes of polyphenols present in coffee: hydroxycinnamic acids, alkylmethoxyphenols, and methoxyphenols, were inversely associated with serum uric acid levels and hyperuricemia. We found differences in polyphenol intake patterns between men and women, and in their associations with CVR. These sex differences may be explained by the fact that they lead different lifestyles, since a pattern does not refer only to dietary habits. Moreover, subjects who were at higher risk at baseline might be more motivated to improve their dietary habit (reverse causality). Our findings add new insights in the study of phenolic compounds, highlighting the importance of analyzing them by sex and studying the determinants of food choices and dietary patterns in relation to risk perception and specific lifestyles.