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Plasma lycopene, other carotenoids, and retinol and the risk of cardiovascular disease in men^1,2,3

¹ From the Divisions of Preventive Medicine and Aging, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, MA (HDS, JEB, and JMG); the Massachusetts Veterans Epidemiology Research and Information Center, VA Boston Healthcare System, Boston, MA (HDS, JEB, and JMG); the Department of Epidemiology, Harvard School of Public Health, Boston, MA (JEB); the Department of Ambulatory Care and Prevention, Harvard Medical School, Boston, MA (JEB); the Departments of Medical Research, Our Lady of Mercy Medical Center and Community and Preventive Medicine, New York Medical College, Bronx, NY (EPN)

Background: Emerging evidence suggests a possible role of lycopene in the primary prevention of cardiovascular disease (CVD).

Objective: We examined whether plasma lycopene concentrations in the Physicians' Health Study were associated with CVD in a prospective, nested, case-control design.

Design: Baseline blood samples were collected starting in 1996. During a mean follow-up of 2.1 y, we identified 499 cases of CVD (confirmed myocardial infarction, stroke, CVD death, or revascularization procedures) and an equal number of men free of CVD and matched for age (: 69.7 y), follow-up time, and smoking status. We collected self-reported coronary disease risk factors and measured plasma carotenoids, retinol, lipids, and C-reactive protein.

Results: In matched analyses with additional adjustment for plasma total cholesterol and randomized treatment, the relative risks (RRs) of CVD for men in the lowest to highest quartiles of plasma lycopene were 1.00 (reference), 0.92, 1.04, and 0.95 (P for linear trend = 0.93). With multivariate adjustment, the RRs of total CVD were 1.00 (reference), 1.08, 0.94, and 1.03 (P for linear trend = 0.98). For important vascular events (241 cases), excluding revascularization procedures, the multivariate RRs remained nonsignificant (P for linear trend = 0.50). Adding plasma carotenoids, lipids, or C-reactive protein to multivariate models had a minimal effect on the RRs of total CVD for plasma lycopene. Compared with lycopene, higher concentrations of plasma lutein/zeaxanthin and retinol suggested a moderate increase in CVD risk, whereas no association was found for ß-cryptoxanthin, -carotene, and ß-carotene.

Conclusions: Higher plasma lycopene concentrations were not associated with the risk of CVD in this study of older men. Further evaluation in diverse populations is necessary.

Key Words: Lycopene • carotenoids • cardiovascular disease • prospective studies • nutrition • epidemiology