TABLE 3.
RRs and 95% CIs for cardiovascular disease mortality by quintile of energy-adjusted flavonoid intake in men and women in the CPS II Nutrition Cohort, 1999–20061
| Men (n = 38,180) |
Women (n = 60,289) |
Men and women (n = 98,469)2 |
||||||||
| Quintile | Median intake (range) | Deaths | Age-adjusted RR3 | Multivariate-adjusted RR (95% CI)4 | Deaths | Age-adjusted RR3 | Multivariate-adjusted RR (95% CI)4 | Deaths | Age-adjusted RR3 | Multivariate-adjusted RR (95% CI)4 |
| mg/d | no. | no. | no. | |||||||
| Total flavonoids | ||||||||||
| 1 | 94.5 (<121.5) | 322 | 1.00 (—) | 1.00 (—) | 293 | 1.00 (—) | 1.00 (—) | 615 | 1.00 (—) | 1.00 (—) |
| 2 | 146.5 (121.5–172.3) | 305 | 0.76 (0.65, 0.89) | 0.84 (0.72, 0.98) | 233 | 0.79 (0.67, 0.94) | 0.86 (0.72, 1.02) | 538 | 0.77 (0.69, 0.87) | 0.84 (0.75, 0.95) |
| 3 | 201.9 (172.4–238.0) | 330 | 0.79 (0.68, 0.92) | 0.91 (0.78, 1.06) | 222 | 0.73 (0.62, 0.88) | 0.82 (0.69, 0.98) | 552 | 0.77 (0.68, 0.86) | 0.87 (0.77, 0.98) |
| 4 | 286.0 (238.1–359.6) | 343 | 0.80 (0.69, 0.93) | 0.95 (0.81, 1.10) | 208 | 0.67 (0.56, 0.80) | 0.76 (0.63, 0.91) | 551 | 0.74 (0.66, 0.83) | 0.86 (0.76, 0.96) |
| 5 | 512.5 (≥359.7) | 289 | 0.72 (0.61, 0.84) | 0.83 (0.71, 0.98) | 226 | 0.72 (0.61, 0.86) | 0.81 (0.68, 0.97) | 515 | 0.72 (0.64, 0.80) | 0.82 (0.73, 0.92) |
| P-trend5 | 0.003 | 0.2 | 0.002 | 0.05 | <0.0001 | 0.01 | ||||
| Anthocyanidin | ||||||||||
| 1 | 3.8 (<5.5) | 323 | 1.00 (—) | 1.00 (—) | 313 | 1.00 (—) | 1.00 (—) | 636 | 1.00 (—) | 1.00 (—) |
| 2 | 6.8 (5.5–8.1) | 284 | 0.83 (0.70, 0.97) | 0.92 (0.79, 1.09) | 244 | 0.74 (0.62, 0.87) | 0.81 (0.68, 0.95) | 528 | 0.78 (0.70, 0.88) | 0.87 (0.77, 0.98) |
| 3 | 9.8 (8.2–11.4) | 318 | 0.82 (0.71, 0.96) | 0.94 (0.81, 1.11) | 230 | 0.71 (0.60, 0.84) | 0.80 (0.68, 0.96) | 548 | 0.77 (0.68, 0.86) | 0.87 (0.78, 0.98) |
| 4 | 13.7 (11.5–16.6) | 339 | 0.78 (0.67, 0.91) | 0.95 (0.82, 1.11) | 199 | 0.63 (0.53, 0.76) | 0.74 (0.62, 0.88) | 538 | 0.72 (0.64, 0.80) | 0.86 (0.76, 0.96) |
| 5 | 22.2 (≥16.7) | 325 | 0.72 (0.62, 0.84) | 0.91 (0.77, 1.06) | 196 | 0.70 (0.58, 0.84) | 0.82 (0.69, 0.99) | 521 | 0.70 (0.62, 0.79) | 0.86 (0.76, 0.97) |
| P-trend5 | 0.0002 | 0.3 | 0.0002 | 0.06 | <0.0001 | 0.04 | ||||
| Flavan-3-ols | ||||||||||
| 1 | 7.0 (<9.5) | 305 | 1.00 (—) | 1.00 (—) | 316 | 1.00 (—) | 1.00 (—) | 621 | 1.00 (—) | 1.00 (—) |
| 2 | 11.8 (9.5–14.0) | 295 | 0.84 (0.71, 0.98) | 0.92 (0.78, 1.08) | 239 | 0.76 (0.64, 0.90) | 0.83 (0.70, 0.99) | 534 | 0.79 (0.71, 0.89) | 0.88 (0.78, 0.98) |
| 3 | 16.8 (14.1–20.3) | 333 | 0.81 (0.69, 0.94) | 0.95 (0.81, 1.11) | 215 | 0.73 (0.61, 0.87) | 0.82 (0.69, 0.98) | 548 | 0.77 (0.69, 0.86) | 0.88 (0.79, 0.99) |
| 4 | 26.3 (20.4–37.1) | 354 | 0.81 (0.69, 0.94) | 0.98 (0.84, 1.15) | 194 | 0.70 (0.58, 0.84) | 0.79 (0.66, 0.95) | 548 | 0.76 (0.68, 0.85) | 0.89 (0.79, 1.01) |
| 5 | 63.7 (≥37.2) | 302 | 0.74 (0.63, 0.87) | 0.87 (0.74, 1.02) | 218 | 0.70 (0.59, 0.84) | 0.79 (0.66, 0.94) | 520 | 0.72 (0.64, 0.81) | 0.83 (0.74, 0.93) |
| P-trend5 | 0.004 | 0.1 | 0.005 | 0.05 | <0.0001 | 0.02 | ||||
| Flavanones | ||||||||||
| 1 | 3.5 (<7.0) | 317 | 1.00 (—) | 1.00 (—) | 289 | 1.00 (—) | 1.00 (—) | 606 | 1.00 (—) | 1.00 (—) |
| 2 | 10.4 (7.0–13.7) | 258 | 0.81 (0.68, 0.95) | 0.90 (0.76, 1.06) | 201 | 0.67 (0.56, 0.81) | 0.74 (0.62, 0.89) | 459 | 0.74 (0.66, 0.84) | 0.82 (0.73, 0.93) |
| 3 | 17.4 (13.8–21.6) | 301 | 0.81 (0.69, 0.95) | 0.95 (0.81, 1.12) | 231 | 0.75 (0.63, 0.90) | 0.86 (0.72, 1.03) | 532 | 0.78 (0.70, 0.88) | 0.91 (0.81, 1.02) |
| 4 | 27.3 (21.7–35.3) | 331 | 0.84 (0.72, 0.98) | 0.98 (0.84, 1.15) | 228 | 0.72 (0.61, 0.86) | 0.85 (0.71, 1.01) | 559 | 0.78 (0.70, 0.88) | 0.92 (0.82, 1.03) |
| 5 | 49.9 (≥35.4) | 382 | 0.82 (0.71, 0.96) | 0.99 (0.85, 1.15) | 233 | 0.70 (0.59, 0.83) | 0.80 (0.67, 0.96) | 615 | 0.77 (0.68, 0.86) | 0.90 (0.80, 1.01) |
| P-trend5 | 0.1 | 0.7 | 0.005 | 0.1 | 0.002 | 0.5 | ||||
| Flavones | ||||||||||
| 1 | 0.4 (<0.5) | 401 | 1.00 (—) | 1.00 (—) | 292 | 1.00 (—) | 1.00 (—) | 693 | 1.00 (—) | 1.00 (—) |
| 2 | 0.7 (0.5–0.8) | 306 | 0.84 (0.72, 0.97) | 0.92 (0.79, 1.07) | 264 | 0.90 (0.76, 1.06) | 0.98 (0.83, 1.16) | 570 | 0.86 (0.77, 0.96) | 0.94 (0.84, 1.05) |
| 3 | 1.1 (0.9–1.2) | 301 | 0.79 (0.68, 0.92) | 0.92 (0.79, 1.07) | 238 | 0.82 (0.69, 0.97) | 0.93 (0.78, 1.11) | 539 | 0.79 (0.71, 0.89) | 0.91 (0.81, 1.02) |
| 4 | 1.6 (1.3–2.0) | 290 | 0.76 (0.65, 0.88) | 0.90 (0.78, 1.05) | 227 | 0.79 (0.66, 0.94) | 0.92 (0.77, 1.10) | 517 | 0.77 (0.68, 0.86) | 0.91 (0.81, 1.02) |
| 5 | 3.0 (≥2.1) | 291 | 0.73 (0.63, 0.85) | 0.89 (0.76, 1.04) | 161 | 0.62 (0.51, 0.75) | 0.74 (0.61, 0.90) | 452 | 0.68 (0.60, 0.77) | 0.82 (0.72, 0.92) |
| P-trend5 | 0.0002 | 0.2 | <0.0001 | 0.001 | <0.0001 | 0.001 | ||||
| Flavonols | ||||||||||
| 1 | 6.9 (<8.5) | 333 | 1.00 (—) | 1.00 (—) | 324 | 1.00 (—) | 1.00 (-) | 657 | 1.00 (—) | 1.00 (—) |
| 2 | 9.9 (8.5–11.3) | 316 | 0.80 (0.68, 0.93) | 0.88 (0.75, 1.03) | 226 | 0.73 (0.62, 0.87) | 0.79 (0.67, 0.94) | 542 | 0.76 (0.68, 0.86) | 0.83 (0.74, 0.93) |
| 3 | 13.0 (11.4–14.7) | 341 | 0.82 (0.71, 0.96) | 0.95 (0.81, 1.11) | 214 | 0.72 (0.61, 0.86) | 0.79 (0.67, 0.94) | 555 | 0.77 (0.69, 0.87) | 0.87 (0.78, 0.98) |
| 4 | 17.2 (14.8–20.5) | 317 | 0.78 (0.67, 0.91) | 0.92 (0.79, 1.08) | 199 | 0.66 (0.55, 0.79) | 0.74 (0.62, 0.89) | 516 | 0.72 (0.64, 0.81) | 0.84 (0.74, 0.94) |
| 5 | 27.2 (≥20.6) | 282 | 0.76 (0.65, 0.89) | 0.88 (0.74, 1.03) | 219 | 0.72 (0.61, 0.86) | 0.82 (0.69, 0.97) | 501 | 0.74 (0.66, 0.83) | 0.84 (0.75, 0.94) |
| P-trend5 | 0.006 | 0.2 | 0.002 | 0.07 | <0.0001 | 0.03 | ||||
| Proanthocyanidins | ||||||||||
| 1 | 53.1 (<71.6) | 307 | 1.00 (-) | 1.00 (—) | 283 | 1.00 (—) | 1.00 (—) | 590 | 1.00 (—) | 1.00 (—) |
| 2 | 90.0 (71.6–109.2) | 327 | 0.93 (0.80, 1.09) | 1.02 (0.87, 1.20) | 246 | 0.86 (0.72, 1.02) | 0.92 (0.77, 1.09) | 573 | 0.89 (0.80, 1.00) | 0.97 (0.86, 1.09) |
| 3 | 132.0 (109.3–160.2) | 358 | 0.96 (0.83, 1.12) | 1.07 (0.92, 1.26) | 199 | 0.68 (0.57, 0.82) | 0.75 (0.63, 0.91) | 557 | 0.83 (0.74, 0.94) | 0.92 (0.82, 1.04) |
| 4 | 196.8 (160.3–253.5) | 317 | 0.86 (0.74, 1.01) | 0.99 (0.84, 1.16) | 223 | 0.74 (0.62, 0.88) | 0.81 (0.68, 0.97) | 540 | 0.80 (0.71, 0.90) | 0.90 (0.80, 1.01) |
| 5 | 379.4 (≥253.6) | 280 | 0.81 (0.69, 0.95) | 0.91 (0.77, 1.08) | 231 | 0.75 (0.63, 0.89) | 0.83 (0.70, 0.99) | 511 | 0.78 (0.69, 0.88) | 0.87 (0.77, 0.98) |
| P-trend5 | 0.006 | 0.1 | 0.01 | 0.09 | 0.0001 | 0.02 | ||||
| Isoflavones | ||||||||||
| 1 | 0.024 (<0.027) | 249 | 1.00 (—) | 1.00 (—) | 290 | 1.00 (-) | 1.00 (-) | 539 | 1.00 (-) | 1.00 (-) |
| 2 | 0.029 (0.027–0.031) | 291 | 0.90 (0.76, 1.07) | 0.94 (0.79, 1.11) | 254 | 0.99 (0.84, 1.18) | 1.02 (0.86, 1.21) | 545 | 0.96 (0.85, 1.08) | 0.99 (0.88, 1.12) |
| 3 | 0.036 (0.032–0.041) | 353 | 0.86 (0.73, 1.01) | 0.91 (0.77, 1.08) | 277 | 1.18 (1.00, 1.40) | 1.24 (1.05, 1.46) | 630 | 1.01 (0.90, 1.13) | 1.06 (0.94, 1.19) |
| 4 | 0.055 (0.042–0.141) | 433 | 0.80 (0.68, 0.93) | 0.83 (0.71, 0.98) | 186 | 1.02 (0.85, 1.23) | 1.04 (0.86, 1.25) | 619 | 0.90 (0.80, 1.01) | 0.93 (0.82, 1.05) |
| 5 | 0.713 (≥0.142) | 263 | 0.72 (0.60, 0.86) | 0.84 (0.71, 1.01) | 175 | 0.85 (0.71, 1.03) | 0.99 (0.82, 1.20) | 438 | 0.79 (0.70, 0.90) | 0.92 (0.81, 1.05) |
| P-trend5 | 0.004 | 0.3 | 0.02 | 0.4 | 0.0001 | 0.1 | ||||
1
(—), referent; CPS II, Cancer Prevention Study II.
2
There was no heterogeneity in RRs by sex, tested by using likelihood ratio tests of models with and without an interaction term of flavonoid (quintiles) and sex.
3
Age-adjusted models for men and women combined were additionally adjusted for sex.
4
Multivariate model was adjusted for age, smoking, beer and liquor intake, history of hypertension, history of cholesterol, family history of myocardial infarction, BMI, physical activity, energy intake, aspirin use, hormone replacement therapy (in women only), and sex (in combined model only) by using Cox proportional hazards regression.
5
Test for trend by using median values for each quintile and modeling as a continuous variable.