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

Author
item Onufrak, Stephen
item BELLASI, ANTONIO - EMORY UNIVERSITY
item CARDARELLI, FRANCESCA - EMORY UNIVERSITY
item VACCARINO, VIOLA - EMORY UNIVERSITY
item MUNTNER, PAUL - MT SINAI SCHOOL OF MED
item HERZOG, CHARLES - UNIV OF MINNESOTA
item SHAW, LESLEE - EMORY UNIVERSITY
item RAGGI, PAOLA - EMORY UNIVERSITY

Submitted to: American Journal of Epidemiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/31/2008
Publication Date: 1/1/2009
Citation: Onufrak, S.J., Bellasi, A., Cardarelli, F., Vaccarino, V., Muntner, P., Herzog, C., Shaw, L.J., Raggi, P. 2009. Investigation of Gender Heterogeneity in the Associations of Serum Phosphorus with Incident Coronary Artery Disease and All-Cause Mortality. American Journal of Epidemiology. 169(1):67-77.

Interpretive Summary: Serum phosphorus has been associated with increased risk of death and vascular disease among persons with kidney disease. There is also some evidence that elevated phosphorus is associated with cardiovascular disease in patients with normal kidney function. However, normal serum phosphorus levels differ greatly by gender. Our study found for the first time that elevated serum phosphorus levels increase risk of cardiovascular disease and death among men but not women.

Technical Abstract: Serum phosphorus levels are associated with increased morbidity and mortality in patients with chronic kidney disease. We examined whether serum phosphorus is associated with all-cause mortality and incident myocardial infarction in the general population using 13,998 middle age subjects from the Atherosclerosis Risk in Communities (ARIC) study. Patients with an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m2 were excluded. After a follow-up of 12.5 years there were 922 fatal or non-fatal myocardial infarctions and 1546 deaths. Baseline serum phosphorus was higher in women than in men and was associated with several traditional atherosclerosis risk factors. In multivariable adjusted models, including eGFR, men demonstrated a J-shaped relationship between serum phosphorus and myocardial infarction (lowest phosphorus quintile hazard ratio [HR]: 1.35, 95% CI: 1.05, 1.74; highest quintile HR: 1.79, 95% CI: 1.29, 2.48), as well as an increased risk of all-cause mortality across all quintiles of serum phosphorus (p<0.0001 for trend; highest phosphorus quintile HR: 1.49; 95% CI: 1.15, 1.93) while women did not. Serum phosphorus levels are associated with all-cause death and incident myocardial infarction in men from the community. These results suggest the need for further investigation into the contribution of mineral metabolism to cardiovascular outcome in the general population.