Table 3.
Association between randomized multivitamin assignment and risk of major cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death) according to baseline characteristics and treatment assignment in the Physicians' Health Study II.a
| Group | Multivitamin | |||
|---|---|---|---|---|
| No. of Men (No. of Major Cardiovascular Events) | ||||
| Active | Placebo | Hazard Ratiob (95% CI) | P Interaction | |
| Age, years | 0.041 | |||
| 50–59 | 2,944 (136) | 2,947 (109) | 1.27 (0.99–1.63) | |
| 60–69 | 2,348 (244) | 2,348 (225) | 1.09 (0.91–1.31) | |
| ≥70 | 2,025 (496) | 2,029 (522) | 0.91 (0.81–1.03) | |
| Body mass index, kg/m2 | 0.72 | |||
| <255 | 3,039 (347) | 3,021 (355) | 0.98 (0.84–1.13) | |
| 25–29 | 3,463 (417) | 3,474 (400) | 1.01 (0.88–1.16) | |
| ≥30 | 815 (112) | 826 (100) | 1.11 (0.85–1.45) | |
| Smoking status | 0.49 | |||
| Never | 4,145 (412) | 4,107 (414) | 0.95 (0.83–1.09) | |
| Former | 2,908 (419) | 1.06 (0.92–1.21) | ||
| Current | 255 (45) | 269 (41) | 1.11 (0.72–1.70) | |
| Exercise ≥1 time/week | 0.29 | |||
| No | 2,699 (398) | 2,806 (362) | 1.07 (0.93–1.24) | |
| Yes | 4,444 (454) | 4,328 (460) | 0.97 (0.85–1.10) | |
| Alcohol consumption | 0.32 | |||
| Rarely/never | 1,391 (194) | 1,339 (189) | 0.92 (0.75–1.12) | |
| ≥1 drink/month | 5,874 (671) | 5,942 (660) | 1.02 (0.92–1.14) | |
| Current aspirin use | 0.07 | |||
| No | 1,625 (199) | 1,636 (169) | 1.20 (0.98–1.48) | |
| Yes | 5,602 (654) | 5,565 (663) | 0.96 (0.86–1.07) | |
| History of hypertensionc | 0.95 | |||
| No | 4,229 (320) | 4,477 (316) | 1.00 (0.86–1.17) | |
| Yes | 3,039 (553) | 3,117 (539) | 1.01 (0.90–1.14) | |
| History of high cholesterold | 0.65 | |||
| No | 4,534 (511) | 4,432 (472) | 1.03 (0.91–1.16) | |
| Yes | 2,549 (353) | 2,641(369) | 0.98 (0.85–1.13) | |
| History of diabetes | 0.33 | |||
| No | 6,838 (765) | 6,883 (740) | 1.02 (0.92–1.13) | |
| Yes | 472 (109) | 433 (116) | 0.89 (0.68–1.16) | |
| Parental history of MI <60 yearse | 0.17 | |||
| No | 5,941 (700) | 5,928 (660) | 1.04 (0.94–1.16) | |
| Yes | 661 (75) | 701 (94) | 0.86 (0.63–1.17) | |
| MstoryofCVDf | 0.59 | |||
| No | 6,941 (745) | 6,946 (728) | 1.02 (0.92–1.13) | |
| Yes | 376 (131) | 378 (128) | 0.96 (0.75–1.22) | |
| Total cholesterol ≥240 mg/dLg | 0.77 | |||
| No | 3,694 (457) | 3,648 (443) | 1.02 (0.89–1.16) | |
| Yes | 622 (83) | 645 (82) | 1.07 (0.79–1.46) | |
| HDL cholesterol ≥50 mg/dLg | 0.66 | |||
| No | 3,029 (397) | 3,043 (412) | 0.97 (0.84–1.11) | |
| Yes | 1,294 (145) | 1,249 (113) | 1.27 (0.99–1.62) | |
| Fruit and vegetable intakeh | 032 | |||
| <4 servings/d | 2,994 (330) | 3,075 (308) | 1.09 (0.93–1.27) | |
| 4–<7 servings/d | 2,729 (318) | 2,615 (300) | 0.99 (0.85–1.17) | |
| ≥7 servings/d | 935 (107) | 962 (120) | 0.87 (0.67–1.13) | |
| Whole grain intakeh | 0.60 | |||
| <2 servings/day | 4,952 (547) | 4,999 (543) | 0.99 (0.88–1.12) | |
| ≥2 servings/day | 1,685 (202) | 1,644 (184) | 1.05 (0.86–1.29) | |
| Red meat intakeh | 0.59 | |||
| <1 serving/day | 4,900 (511) | 4,928 (504) | 0.99 (0.88–1.12) | |
| ≥1 serving/day | 1,736 (237) | 1,704 (220) | 1.05 (0.87–1.26) | |
| Randomized to vitamin C | 0.54 | |||
| Placebo | 3,653 (424) | 3,659 (432) | 0.98 (0.85–1.11) | |
| Active | 3,664 (452) | 3,665 (424) | 1.04 (0.91–1.19) | |
| Randomized to vitamin E | 0.46 | |||
| Placebo | 3,667 (430) | 3,659 (430) | 0.97 (0.85–1.11) | |
| Active | 3,650 (446) | 3,665 (426) | 1.04 (0.91–1.19) | |
| Randomized to beta-carotene | 0.97 | |||
| Placebo | 3,632 (441) | 3,645 (427) | 1.00 (0.88–1.15) | |
| Active | 3,685 (435) | 3,679 (429) | 1.01 (0.88–1.15) | |
Abbreviation: CI, confidence interval
Mean follow-up of 11.2 years for all 14,641 men through June 1, 2011.
Adjusted for age, PHS cohort (original PHS I participant, new PHS participant), randomized beta-carotene assignment, randomized vitamin E assignment, and randomized vitamin C assignment.
History of hypertension was defined as self-reported systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, or past/current treatment for hypertension.
History of high cholesterol was defined as self-reported total cholesterol ≥240 mg/dL or past/current treatment for high cholesterol.
Excludes 1,410 men with missing information on parental history of MI <60 years.
History of cardiovascular disease (CVD) included nonfatal myocardial infarction or nonfatal stroke.
Among 8,609 and 8,615 men with available biomarker data for plasma total cholesterol and HDL cholesterol, respectively.
Among 13,310, 13,280, and 13,268 men with available dietary data on fruit and vegetable intake, whole grain intake, and red meat intake, respectively.