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Title: Flavonoid intake and cardiovascular disease mortality in a prospective cohort of US adults

Author
item Mccullough, Marjorie - American Cancer Society
item Peterson, Julia - Tufts University
item Patel, Roshni - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item Jacques, Paul - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item Shah, Roma - American Cancer Society
item Dwyer, Johanna - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/7/2011
Publication Date: 1/4/2012
Citation: Mccullough, M.L., Peterson, J.J., Patel, R., Jacques, P.F., Shah, R., Dwyer, J.T. 2012. Flavonoid intake and cardiovascular disease mortality in a prospective cohort of US adults. American Journal of Clinical Nutrition. 95(2):454-464.

Interpretive Summary: Despite declining rates over the past 2 decades, cardiovascular disease (CVD) remains the leading cause of death in adults over 65 years of age. Medical and pharmacologic interventions can reduce cardiovascular mortality among individuals at risk, but they are costly and sometimes have adverse side effects. Consumption of plant foods presents a more cost-effective and safe alternative to reducing CVD risk. Plant foods are associated with lower risk of both CVD and hypertension which may be due, in part, to the high fiber, potassium, and magnesium content of these foods. However, flavonoids may also be responsible for lowering risk of CVD in humans. Flavonoids are secondary metabolites in plants that cannot be synthesized by humans and are found primarily in fruits, vegetables, nuts, cocoa, and beverages such as tea and wine. They have many beneficial properties; for example, they can act as antioxidants, anti-inflammatory agents, and reduce LDL cholesterol. There are many classes of flavonoid compounds; however, comprehensive epidemiologic investigation of most classes in relation to CVD risk in Western populations has been limited. Thus, we examined the association between total flavonoids and 7 flavonoid classes and three health outcomes, fatal CVD, ischemic heart disease (IHD), and stroke, among the American Cancer Society’s CPS-II Nutrition Cohort. This is a large cohort study examining 38,180 men and 60,289 women in the United States. Our results indicated that five flavonoid classes—anthocyanidins, flavan-3-ols, flavones, flavonols, and proanthocyanidins—were individually associated with lower risk of fatal CVD. In men, total flavonoid intakes were more strongly associated with stroke mortality than with IHD. Flavonoid consumption was associated with lower risk of death from CVD. Our results additionally suggested that even relatively small amounts of flavonoid-rich foods may be beneficial to health.

Technical Abstract: Background: Flavonoids are plant-based phytochemicals with cardiovascular protective properties. Few studies have comprehensively examined flavonoid classes in relation to cardiovascular disease mortality. We examined the association between flavonoid intake and cardiovascular disease (CVD) mortality among participants in a large, prospective US cohort. In 1999, a total of 38,180 men and 60,289 women in the Cancer Prevention Study II Nutrition Cohort with a mean age of 70 and 69 y, respectively, completed questionnaires on medical history and lifestyle behaviors, including a 152-item food-frequency questionnaire. Cox proportional hazards modeling was used to calculate multivariate-adjusted hazard RRs and 95% CIs for associations between total flavonoids, 7 flavonoid classes, and CVD mortality. During 7 y of follow-up, 1589 CVD deaths in men and 1182 CVD deaths in women occurred. Men and women with total flavonoid intakes in the top (compared with the bottom) quintile had a lower risk of fatal CVD (RR: 0.82; 95% CI: 0.73, 0.92; P-trend =0.01). Five flavonoid classes—anthocyanidins, flavan-3-ols, flavones, flavonols, and proanthocyanidins—were individually associated with lower risk of fatal CVD (all P-trend , 0.05). In men, total flavonoid intakes were more strongly associated with stroke mortality (RR: 0.63; 95% CI: 0.44, 0.89; P-trend = 0.04) than with ischemic heart disease (RR: 0.90; 95% CI: 0.72, 1.13). Many associations appeared to be nonlinear, with lower risk at intakes above the referent category. Flavonoid consumption was associated with lower risk of death from CVD. Most inverse associations appeared with intermediate intakes, suggesting that even relatively small amounts of flavonoid-rich foods may be beneficial.