Table 3.
Associations between flavonoid intakes, incidence of coronary heart disease, stroke, and total cardiovascular disease mortality and incidence by cohort and country (multivariate adjusted ptrend <.05 in bold face)*
| Cohort | Study | Flavonoid classes studied |
Population | Follow up yrs |
Covariate measures |
CHD mortality (deaths) |
Stroke mortality (deaths) |
CVD mortality (deaths) |
CHD incidence (events) |
Stroke incidence (events) |
CVD incidence (events) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Finland | |||||||||||
| Finnish Mobile Clinic Health Examination Survey | Knekt 199673 | Flavones & flavonols | 2,748 M & 2,385 F | 26 | age, BMI, BP, chol, smoking BC, energy, FA, fiber, vit C, vit E |
Flavones & flavonols 0.67 RR (0.44, 1.00) CI ptrend 0.12 [4.8 vs 2.1 mg/d]b (n 324 men) Flavones & flavonols 0.73 RR (0.41, 1.32) CI ptrend 0.21 [5.5 vs 2.4 mg/d]b (n 149 women) |
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| Knekt 200072 | Flavonol (Quercetin) | 9,208 M & F | 28 | age, BMI, BP, chol, diabetes, region, SE, smoking BC, energy, FA, fiber, quercetin, vit C, vit E, |
Flavonols 0.99 RR (0.71, 1.38) CI ptrend 0.80 [4.6 vs 2.0 mg/d]b (n 445 men) Flavonols 0.85 RR (0.60, 1.21) CI ptrend 0.62 [5.2 vs 2.3 mg/d]b (n 378 women) |
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| Knekt 200274 | Flavanones, flavones, flavonols | 9,131 M & F | 28 | age, BMI, BP, chol, diabetes, region, SE, sex, smoking |
Flavonol (Quercetin) 0.79 RR (0.63, 0.99) CI ptrend 0.02 [M 3.9 vs 1.5, F 4.7 vs 1.8 mg/d]b (n 681) (Kaempferol) 0.82 RR (0.66, 1.02) CI ptrend 0.06 [M 0.8 vs 0.1, F 0.9 vs 0.2 mg/d]b (n 681) |
Flavonol (Kaempferol) 0.70 RR (0.56, 0.86) CI ptrend 0.003 [M 0.8 vs 0.1, F 0.9 vs 0.2 mg/d]b (n 806) Flavanones (Hesperetin) 0.80 RR (0.64, 0.99) CI ptrend 0.008 [M 15.4 vs 0, F 26.8 vs 3.2 mg/d]b (n 806) (Naringenin) 0.79 RR (0.64, 0.98) CI ptrend 0.006 [M 4.7 vs 0, F 7.7 vs 0.9 mg/d]b (n 806) Flavanones & flavones & flavonols 0.79 RR (0.64, 0.98) CI ptrend 0.006 [M 26.9 vs 4.3, F 39.5 vs 8.5 mg/d]b (n 806) |
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|
alpha-tocopherol, beta-carotene Cancer Prevention Study (ATBC) |
Hirvonen 200070 | Flavones & flavonols | 26,497 M | 6.1 | age, BMI, BP, chol, diabetes, hist CHD, SE, smoking alcohol, suppl |
Flavones & flavonols 0.98 RR (0.80, 1.21) CI ptrend 0.81 [16.4 vs 4.2 mg/d (medians)]b (n 736) |
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| Hirvonen 200169 | Flavones & flavonols | 25,372 M | 6.1 | age, BMI, BP, chol, diabetes, hist CHD, MS, PA, SE, smoking suppl, |
Flavones & flavonols 0.89 RR (0.71, 1.11) CI trend not given [17.8 vs 3.94 mg/d (medians)]c (n 815) |
Flavones & flavonols 0.77 RR (0.64, 0.93) CI trend not given [17.8 vs 3.94 mg/d (medians)]c (n 1,122, nonfatal) |
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| Turku and Environs Health Survey | Marniemi 200576 | Flavones & flavonols | 361 M & 394 F elderly | 10 | age, FC, sex, smoking energy |
Flavone (Luteolin) 0.53 RR (0.33, 0.86) CI p = 0.0096a (n 130, fatal & nonfatal) |
Flavones & flavonols 0.65 RR (0.34, 1.23) CIa p not given (n 70) |
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| Kuopio Ischemic Heart Disease Risk Factor study | Mursu 200878 |
5 classes (flavonols, flavones, flavanones, flavan-3-ols, anthocyanidins) |
1,950 M | 15.2 | age, BMI, BP, BP meds, chol, diabetes, exam, fam CHD, O2, smoking, TAG alcohol, FA, folate, vit E |
5 classes 1.25 RR (0.74, 2.11) CI ptrend 0.73 [435 vs 9.5 mg/d]b (n 153) Flavanones 0.54 RR (0.32, 0.92) CI ptrend 0.27 [3.1 mg/d]b (n 153) |
Flavonols 0.55 RR (0.31, 0.99) CI ptrend 0.027 [10.0 mg/d]b (n 102) 5 classes 0.71 RR (0.37, 1.37) CI ptrend 0.137 [435 vs 9.5 mg/d]b (n 102) |
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| Netherlands | |||||||||||
| Zutphen Elderly Study | Hertog 199366 | Flavones & flavonols | 805 M | 5 | BMI, BP, chol, PA, smoking energy, FA |
Flavones & flavonols 0.32 RR (0.15, 0.71) CI ptrend 0.003 [29.9 vs 19.0 mg/d]a (n 43) |
Flavones & flavonols 0.52 RR (0.22,1.23) CI ptrend 0.15 [29.9 vs 19.0 mg/d]a (n 38, fatal & nonfatal) |
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| Keli 199671 | Flavones & flavonols | 552 M | 15 | age, BP, chol, smoking alcohol, energy, fish |
Flavones & flavonols 0.27 RR (0.11, 0.70) CI ptrend 0.004 [28.6 vs 18.3 mg/d]a (n 42) |
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| Hertog 199767 | Flavones & flavonols | 804 (mortality) 692 (incidence) | 10 | BMI, BP, chol, PA, smoking energy, FA, |
Flavones & flavonols 0.47 RR (0.27, 0.82) CI ptrend 0.006 [29.9 vs 19.0 mg/d]a (n 90) |
Flavones & flavonols 0.62 RR (0.24,1.05) CI ptrend 0.078 [29.9 vs 19.0 mg/d]a (n 92, fatal & nonfatal) |
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| Arts 200163 | Flavan-3-ols | 806 M | 15 | age, BMI, PA, smoking alcohol, BC, coffee, diet, energy, FA, fiber, fish, vit C, vit E |
Flavan-3-ols 0.49 RR (0.27, 0.88) CI ptrend 0.017 [85.9 vs 49.0 mg/d]a (n 90) |
Flavan-3-ols 0.81 RR (0.36, 1.83) CI ptrend 0.61 [85.9 vs 49.0 mg/d]a (n 47) |
Flavan-3-ols 0.70 RR (0.39, 1.26) CI ptrend 0.23 [85.9 vs 49.0 mg/d]a (n 90, fatal & nonfatal) |
Flavan-3-ols 0.921 RR (0.51, 1.68) CI ptrend 0.606 [85.9 vs 49.0 mg/d]a (n 88) |
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| Rotterdam Study | Geleijnse 200265 | Flavonols | 1836 M & 2971 F | 5.6 | age, BMI, SE, sex, smoking alcohol, coffee, energy, FA, fiber, vit E |
Flavonols 0.35 RR (0.13, 0.98) CI trend not given [32.9 vs 22.8 mg/d]a (n 30) |
Flavonols 0.93 RR (0.57, 1.52) CI nsd [32.9 vs 22.8 mg/d]a (n 116, nonfatal) Flavonols 0.76 RR (0.49, 1.18) CI nsd [32.9 vs 22.8 mg/d]a (n 146, fatal & nonfatal) |
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| Dutch Prospect-EPIC (European Prospective Study Into Cancer and Nutrition) Cohort | Van der Schouw 200581 | Isoflavones | 16,165 F | 6.25 median | age, BMI, BP, chol, diabetes, HRT, OC, PA, smoking alcohol, energy, F&V, FA, fiber, protein, |
Isoflavones 0.94 HR (0.68, 1.30) CI nsd [0.54 vs 0.26 mg/d]b,d (n 372, fatal & nonfatal) |
Isoflavones 1.05 HR (0.64, 1.70) CI nsd [0.54 vs 0.26 mg/d]b,d (n 147) |
Isoflavones 0.97 HR (0.74, 1.27) CI nsd [0.54 vs 0.26 mg/d]b,d (n 519) |
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| Wales, UK | |||||||||||
| Caerphilly Study | Hertog 199768 | Flavonols | 1,900 M | 10 incidence 14 mortality |
age, BMI, BP, chol, hist CHD, SE, smoking alcohol, BC, energy, FA, vit C, vit E, |
Flavonols 1.6 RR (0.9, 2.9) CI ptrend 0.119 [34 vs 19 mg/d]b (n 131) |
Flavonols 1.1 RR (0.6, 1.6) CI ptrend 1.00 [34 vs 19 mg/d]b (n 186, fatal & nonfatal) |
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| US | |||||||||||
|
Health Professionals Follow-up Study (HPFS) |
Rimm 199679 | Flavones & flavonols | 34,789 M | 2 or 6 | age, BMI, BP, chol, diabetes, fam CHD, SE, smoking alcohol, vit E, |
Flavones & flavonols 0.77 RR (0.45, 1.35) CI nsd [40.0 vs 7.1 mg/d (medians)]c (n 140, 2 yr FU, N 38,036) Flavones & flavonols 0.63 RR (0.33, 1.20) CI nsd [40.0 vs 7.1 mg/d (medians)]c (n 105, 2 yr FU, N 4838 CHD prevalent) |
Flavones & flavonols 1.08 RR (0.81, 1.43) CI nsd [40.0 vs 7.1 mg/d (medians)]c (n 486 6 yr FU nonfatal) Flavones & flavonols 0.94 RR (0.68 – 1.31) CI nsd [40.0 vs 7.1 mg/d (medians)]c (n 373, 2 yr FU, fatal & nonfatal) |
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| Iowa Women's Health Study | Yochum 199982 | Flavones & flavonols | 34,492 F post | 10 | BP, chol, diabetes, HRT, MS, PA, SE, smoking, WH alcohol, energy, FA, fiber, grains, vit E, |
Flavones & flavonols 0.62 RR (0.44, 0.87) CI ptrend 0.11 [32.3 vs 4.3 mg/d]c (n 438) |
Flavones & flavonols 1.18 RR (0.70, 2.00) CI ptrend 0.83 [18.7 vs 5.7 mg/d]c (n 131) |
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| Arts 200164 | Flavan-3-ols | 32,857 F post | 13 | age, BMI, BP, diabetes, HRT, MS, PA, SE, smoking, WH alcohol, BC, energy, FA, folate, grains, vit C, vit E, vit suppl, |
Flavan-3-ols 0.85 RR (0.67, 1.07) CI nsd [36.8 vs 6.3 mg/d]c (n 767) |
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| Mink 200777 |
7 classes (flavonols, flavones, flavanones, flavan-3-ols, anthocyanidins, isoflavones, proanthocyanidins) |
34,492 F post | 16 | age, BMI, BP, diabetes, HRT, MS, PA, SE, smoking, WH energy |
Flavanones 0.78 RR (0.65, 0.94) CI ptrend 0.010 [72.8 vs 16.1 mg/d]c (n 1329) Anthocyanidins 0.88 RR (0.78, 0.99) CI ptrend 0.031 [0.01 vs 0 mg/d] (n 1329) |
7 classes 0.94 RR (0.69, 1.29) CI ptrend 0.80 [425.3 vs 133.2 mg/d] c (n 469) |
Flavanones 0.88 RR (0.77, 1.01) CI ptrend 0.054 [72.8 vs 16.1 mg/d]c (n 2316) Anthocyanidins 0.91 RR (0.83, 0.99) CI ptrend 0.032 [0.1 vs 0 mg/d]c (n 2316) |
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|
Women's Health Study (WHS) |
Sesso 200380 | Flavones & flavonols | 38,445 F | 6.9 | age, aspirin, BMI, BP, chol, diabetes, fam CHD, HRT, PA, smoking alcohol, BC, F&V, FA, fiber, folate, vit E |
Flavones & flavonols 1.05 RR (0.62, 1.78) CI nsd [47.4 vs 8.9 mg/d (medians)]c (n not given) |
Flavones & flavonols 0.82 RR (0.51, 1.30) CI nsd [47.4 vs 8.9 mg/d (medians)]c (n not given, fatal & nonfatal) |
Flavones & flavonols 0.70 RR (0.46, 1.07) CI nsd [47.4 vs 8.9 mg/d (medians)]c (n not given) |
Flavones & flavonols 0.80 RR (0.59, 1.09) CI ptrend 0.80 [47.4 vs 8.88 mg/d (medians)]c (n 519 events) |
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|
Nurses' Health Study (NHS) |
Lin 200775 | Flavones & flavonols | 66,360 F | 12 | age, aspirin, BMI, BP, chol, diabetes, fam CHD, HRT, meno, PA, smoking alcohol, energy, vit E, vit suppl |
Flavonol (Kaempferol) 0.66 RR (0.48, 0.93) CI ptrend 0.04 [4.7 mg/d mean]c (n 324) |
Flavones & flavonols 1.05 RR (0.85, 1.29) CI ptrend 0.55 [30.9 vs 9.6 mg/d]c (n 938, nonfatal) |
*
Blank cells – outcome not studied
Bold font indicates the class(es) significant for inverse association with the given event at multivariate adjusted ptrend<.05 or less.
nsd – association not significant at ptrend<.05 for compounds or classes studied.
F – females, HR – Hazard ratios, M – males, Post – postmenopausal, RR – Risk ratios
General covariate measures: age; aspirin – aspirin use; BMI – body mass index; BP – blood pressure (diastolic, hypertension, systolic); BP meds – blood pressure medication; chol – cholesterol (HDL, high, LDL, total cholesterol); diabetes; exam - examination years; fam CHD – history of family CHD; FC - functional capacity; hist CHD - history of CHD; HRT – hormone replacement therapy; meno - menopausal; MS - marital status; O2 - oxygen uptake; OC - oral contraceptive; PA - physical activity; region - geographic region; SE – socioeconomic demographic (education, occupation, profession, social class); sex; smoking; TAG - triglycerides; WH - waist to hip ratio
Intake covariate measures: alcohol; BC – beta-carotene; coffee; diet - prescribed diet; energy - total energy; F&V - fruit & vegetable; FA – fat (cholesterol, fat, monounsaturated fatty acids, polyunsaturated fatty acids, saturated fatty acids); fiber; fish; folate; grains - whole grains; protein - animal protein; quercetin; suppl - supplementation group; vit C - vitamin C; vit E - vitamin E; vit suppl - multivitamin supplement
a
tertiles
b
quartiles
c
quintiles
d
Intake from FFQ but food items scored for isoflavones, analytical values were not used.