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American Journal of Epidemiology Advance Access originally published online on November 2, 2008
American Journal of Epidemiology 2009 169(1):67-77; doi:10.1093/aje/kwn285
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American Journal of Epidemiology © The Author 2008. Published by the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

ORIGINAL CONTRIBUTIONS

Investigation of Gender Heterogeneity in the Associations of Serum Phosphorus With Incident Coronary Artery Disease and All-Cause Mortality

Stephen J. Onufrak, Antonio Bellasi, Francesca Cardarelli, Viola Vaccarino, Paul Muntner, Leslee J. Shaw and Paolo Raggi

Correspondence to Dr. Paolo Raggi, Emory University School of Medicine, 1365 Clifton Road NE, AT-504, Atlanta, GA 30322 (e-mail: praggi{at}emory.edu).

Received for publication November 30, 2007. Accepted for publication August 14, 2008.

Serum phosphorus levels in the general population have been reported to be associated with cardiovascular morbidity and mortality and increased carotid intima-media thickness. The authors examined gender heterogeneity in the association of phosphorus with all-cause mortality and incident coronary artery disease using data from the Atherosclerosis Risk in Communities Study (1987–2001). Baseline phosphorus levels were higher in women and were associated differently among men and women with traditional atherosclerosis risk factors such as age, low density lipoprotein cholesterol, diabetes mellitus, and hypertension. In a multivariable-adjusted model, men in the highest quintile of serum phosphorus level (>3.8 mg/dL) had an increased mortality rate (hazard ratio = 1.45, 95% confidence interval: 1.12, 1.88), while women did not (hazard ratio = 1.18, 95% confidence interval: 0.89, 1.57). The multivariable likelihood ratio test of effect modification by gender was significant at {alpha} = 0.1 (P = 0.085) for all-cause mortality. Although the associations of phosphorus with coronary artery disease also appeared to differ substantially by gender, the multivariable test for effect modification suggested that the difference was consistent with random variation (P = 0.195). These results suggest the need for further investigation into gender differences in the contribution of mineral metabolism to cardiovascular disease in the general population.

cardiovascular diseases; coronary artery disease; mortality; phosphorus; risk; sex factors

Abbreviations: ARIC, Atherosclerosis Risk in Communities; CAD, coronary artery disease; CI, confidence interval; HDL, high density lipoprotein


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