Submitted to: British Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/21/2015
Publication Date: 9/3/2015
Citation: Jacques, P.F., Cassidy, A., Rogers, G., Peterson, J.J., Dwyer, J.T. 2015. Dietary flavonoid intakes and cardiovascular disease incidence in the Framingham Offspring Cohort. British Journal of Nutrition. 114:1496-1503. doi: 10.1017/S0007114515003141. Interpretive Summary: Cardiovascular disease (CVD) remains the leading cause of death in the United States. Worldwide, it is estimated that there are more than 17 million deaths each year from CVD, and CVD incidence continues to increase in low and middle income countries. Diet has been shown to be a critical factor in CVD prevention, and fruits and vegetables are an important part of diets associated with lower CVD risk. However, the mechanism of how vegetable and fruit intake lowers CVD risk is not known. Dietary flavonoids, a class of polyphenols found in a large array of plant foods, have been examined as one potential component responsible for lowering CVD risk. Previous studies have examined the relationship between flavonoid intakes and CVD, but many of these studies have had limitations. Some studies have examined only a few flavonoid classes. Other studies had short follow-up periods or only used one point in time to determine an individual’s flavonoid intake. Also, many studies did not account for the fact that diets higher in flavonoids tend to be generally better in diet quality meaning that a lower risk of CVD could be due to the better overall diet rather than the flavonoids specifically. Therefore, we examined the relationship between incident CVD, coronary heart disease (CHD) and cerebrovascular disease and long-term flavonoid intake using a complete flavonoid database, measuring flavonoid intake at multiple time-points, and accounting for the fact that diets high in flavonoids may have better overall quality. We examined intake of 6 flavonoid classes (flavonols, flavones, flavanones, flavan-3-ols, anthocyanins, polymeric flavonoids) among over 2,800 participants from the Framingham Offspring Study. Flavonol intake was significantly associated with lower risk of CVD. However, once we accounted for fruit and vegetable intake, as well as overall diet quality, we no longer saw this association between flavonols, or any of the other five flavonoid classes, with CVD or CHD. These results suggest that there may be a modest benefit of flavonols in reducing CVD risk; however, this benefit may be due to better overall diet quality. Future research on this topic is warranted.
Technical Abstract: This study examines the relationship between long-term intake of six flavonoid classes and incidence of CVD and CHD, using a comprehensive flavonoid database and repeated measures of intake, while accounting for possible confounding by components of a healthy dietary pattern. Flavonoid intakes were assessed using a FFQ among the Framingham Offspring Cohort at baseline and three times during follow-up. Cox proportional hazards regression was used to characterise prospective associations between the natural logarithms of flavonoid intakes and CVD incidence using a time-dependent approach, in which intake data were updated at each examination to represent average intakes from previous examinations. Mean baseline age was 54 years, and 45% of the population was male. Over an average 14.9 years of follow-up among 2880 participants, there were 518 CVD events and 261 CHD events. After multivariable adjustment, only flavonol intake was significantly associated with lower risk of CVD incidence (hazard ratios (HR) per 2.5-fold flavonol increase=0.86, P trend=0.05). Additional adjustment for total fruit and vegetable intake and overall diet quality attenuated this observation (HR=0.89, P trend=0.20 and HR=0.92, P trend=0.33, respectively). There were no significant associations between flavonoids and CHD incidence after multivariable adjustment. Our findings suggest that the observed association between flavonol intake and CVD risk may be a consequence of better overall diet. However, the strength of this non-significant association was also consistent with relative risks observed in previous meta-analyses, and therefore a modest benefit of flavonol intake on CVD risk cannot be ruled out.