Associations between flavan-3-ol intake and CVD risk in the Norfolk cohort of the European Prospective Investigation into Cancer (EPIC-Norfolk)

Abstract

Dietary intervention studies suggest that flavan-3-ol intake can improve vascular function and reduce the risk of cardiovascular diseases (CVD). However, results from prospective studies failed to show a consistent beneficial effect. Associations between flavan-3-ol intake and CVD risk in the Norfolk arm of the European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk) were investigated. Data were available from 24,885 (11,252 men; 13,633 women) participants, recruited between 1993 and 1997 into the EPIC-Norfolk study. Flavan-3-ol intake was assessed using 7-day food diaries and the FLAVIOLA Flavanol Food Composition database. Missing data for plasma cholesterol and vitamin C were imputed using multiple imputation. Associations between flavan-3-ol intake and blood pressure at baseline were determined using linear regression models. Associations with CVD risk were estimated using Cox regression analyses. Median intake of total flavan-3-ols was 1034mg/d (range: 0-8531mg/d) for men and 970mg/d (0-6695mg/d) for women, median intake of flavan-3-ol monomers was 233mg/d (0-3248mg/d) for men and 217 (0-2712mg/d) for women. There were no consistent associations between flavan-3-ol monomer intake and baseline systolic and diastolic blood pressure (BP). After 286,147 person-years of follow-up, there were 8463 cardiovascular events and 1987 CVD related deaths; no consistent association between flavan-3-ol intake and CVD risk (HR 0.93, 95% CI: 0.87; 1.00; Q1 vs Q5) or mortality was observed (HR 0.93, 95% CI: 0.84; 1.04). Flavan-3-ol intake in EPIC-Norfolk is not sufficient to achieve a statistically significant reduction in CVD risk.

Keywords: Cardio-vascular diseases; EPIC Norfolk; Flavan-3-ols; Nutritional epidemiology.

Graphical abstract

Fig. 1

Study population and exclusion criteria.

Fig. 2

Relative composition of total dietary flavan-3-ols by flavan-3-ol monomer intake in male participants of EPIC-Norfolk (results for women and postmenopausal women are similar). (−)-Epicatechin and (+)-catechin were the main contributors of total monomer intake in the bottom quintile, while gallated compounds were the main contributor to monomer intake in the top four quintiles. For concomitantly consumed nonmonomeric flavanols, similar differences were observed. In the bottom quintile, proanthocyanidins were the dominant class of compounds, while in the other quintiles, theaflavins were more important.

Fig. 3

Association between flavan-3-ol intake and risk of CVD in 11,253 men (a) and 13634 women (b) of EPIC-Norfolk. This figure shows HR (95% CI) estimated using the parsimonious model and quintiles of intake of each respective flavan-3-ol group.

Fig. 4

Association between flavan-3-ol intake and incidence of CVD in observational epidemiological studies conducted previously. Data show the estimated HR (95% CI) comparing the bottom and top quintile of intake. Studies included: Zutphen Elderly Study ; EPIC-Norfolk (this study); HPFS: Health-Professional Follow-Up Study ; CPS: Cancer Prevention Study II ; IWH: Iowa Women׳s Health Study ; NHS I and II: Nurses Health Study . Data for IHD and CHD were combined.

Fig. 5

Dietary intervention studies investigating the effect of dietary flavan-3-ols on systolic blood pressure (see Supplemental Table 4 for details) based on (−)-epicatechin intake. Circles indicate studies, which were blinded, conducted for at least 28 days and provided information on (−)-epicatechin based on analyses. All other studies with a duration of 14 days or more are indicated by an X. (−)-Epicatechin intake was estimated as 10% of cocoa flavanol intake for studies where no analytical data were available. The histogram shows the distribution of intake in EPIC-Norfolk. Error bars were omitted to improve clarity.

Fig. 6

Mean (−)-epicatechin intake and age-standardized CHD mortality (per 100,000, data for 2005) in European countries. (−)-epicatechin intake in EPIC-Norfolk is shown for the relevant quintiles.