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Original Investigation
April 5, 2017

Effect of Baseline Nutritional Status on Long-term Multivitamin Use and Cardiovascular Disease RiskA Secondary Analysis of the Physicians’ Health Study II Randomized Clinical Trial

Author Affiliations
  • 1Division of Preventive Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
  • 2Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
  • 3Division of Aging, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
  • 4Veterans Affairs Boston Healthcare System, Boston, Massachusetts
  • 5Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
JAMA Cardiol. Published online April 5, 2017. doi:10.1001/jamacardio.2017.0176
Key Points

Question  Does baseline nutritional status explain the lack of an effect of multivitamin use on risk of cardiovascular disease in the Physicians’ Health Study II?

Findings  In this randomized clinical trial of 13 316 male physicians observed for a mean (SD) follow-up of 11.4 (2.3) years, there was no consistent evidence of effect modification by various foods, nutrients, dietary patterns, or baseline supplement use on the effect of multivitamin use on cardiovascular disease end points.

Meaning  Long-term multivitamin use does not prevent major cardiovascular disease events in men, regardless of baseline nutritional status.

Abstract

Importance  Long-term multivitamin use had no effect on risk of cardiovascular disease (CVD) in the Physicians’ Health Study II. Baseline nutritional status may have modified the lack of effect.

Objective  To investigate effect modification by various baseline dietary factors on CVD risk in the Physicians’ Health Study II.

Design, Setting, and Participants  The Physicians’ Health Study II was a randomized, double-blind, placebo-controlled trial testing multivitamin use (multivitamin [Centrum Silver] or placebo daily) among US male physicians. The Physicians’ Health Study II included 14 641 male physicians 50 years or older, 13 316 of whom (91.0%) completed a baseline 116-item semiquantitative food frequency questionnaire and were included in the analyses. This study examined effect modification by baseline intake of key foods, individual nutrients, dietary patterns (Alternate Healthy Eating Index and Alternate Mediterranean Diet Score), and dietary supplement use. The study began in 1997, with continued treatment and follow-up through June 1, 2011.

Interventions  Multivitamin or placebo daily.

Main Outcomes and Measures  Major cardiovascular events, including nonfatal myocardial infarction, nonfatal stroke, and CVD mortality. Secondary outcomes included myocardial infarction, total stroke, CVD mortality, and total mortality individually.

Results  In total, 13 316 male physicians (mean [SD] age at randomization, 64.0 [9.0] years in those receiving the active multivitamin and 64.0 [9.1] years in those receiving the placebo) were observed for a mean (SD) follow-up of 11.4 (2.3) years. There was no consistent evidence of effect modification by various foods, nutrients, dietary patterns, or baseline supplement use on the effect of multivitamin use on CVD end points. Statistically significant interaction effects were observed between multivitamin use and vitamin B6 intake on myocardial infarction, between multivitamin use and vitamin D intake on CVD mortality, and between multivitamin use and vitamin B12 intake on CVD mortality and total mortality. However, there were inconsistent patterns in hazard ratios across tertiles of each dietary factor that are likely explained by multiple testing.

Conclusions and Relevance  The results suggest that baseline nutritional status does not influence the effect of randomized long-term multivitamin use on major CVD events. Future studies are needed to investigate the role of baseline nutritional biomarkers on the effect of multivitamin use on CVD and other outcomes.

Trial Registration  clinicaltrials.gov Identifier: NCT00270647

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