Phosphorus levels are associated with subclinical atherosclerosis in the

general population.

Stephen Onufrak, PhD, Antonio Bellasi, MD, Francesca Cardarelli, MD, Viola Vaccarino, MD, PhD, Paolo Raggi, MD

Emory University School of Medicine, Atlanta, GA

What is Phosphorus?

• Mineral

• Makes up 1% of the total body weight

• 85% found in bones and teeth

• Critically important in every cell

Biologic Functions of Phosphorus

• Component of phospholipids in plasma membranes

• Energy production and storage (ATP)

• Component of virtually all enzymes and cellular messengers

• Acid-base regulation

Phosphorus and Vascular Disease

• Calcification of coronary arteries and aorta observed in hyperphosphatemia (abnormally elevated phosphorus levels)

– Most common in persons with renal disease

• One study demonstrated increased risk of MI, CHF, and all-cause mortality with increasing phosphorus levels in patients with history of acute MI

Copyright ©2005 American Heart Association

Tonelli, M. et al. Circulation 2005;112:2627-2633

Fully adjusted risk of clinical outcomes by baseline serum phosphate

Objective

To determine whether serum phosphorus levels are associated with carotid IMT in the general population

Study Population• Atherosclerosis Risk in Communities (ARIC) study-

Prospective study of the etiology of atherosclerotic cardiovascular disease

• Subjects from four communities in North Carolina, Mississippi, Minnesota, and Maryland.

• 15,792 men and women ages 45 to 64 years, both black and white.

• Baseline clinic visit during 1987 to 1989.

Study Design

• Cross Sectional

• Examine mean carotid intima medial thickness according to quintile of serum phosphorus

Carotid Intima Medial Thickness

• Noninvasive measurement of systemic atherosclerosis

• Performed using ultrasound

• Validated as indicator of stroke and coronary heart disease risk

• Average of mean far wall measurements for up to six different sites for each subject:

– (left and right) common bifurcation, internal carotid, and common carotid

Statistical Analysis

• Explore heterogeneity of effect according to sex, age, race, kidney function, serum calcium, diabetes, total cholesterol, and current smoking status.

• Compare crude and adjusted mean IMT for phosphorus quintiles using generalized linear model.

Subject Characteristics According to Serum Phosphorus Level

<0.01306.3304.1299.5297.8297.4Fibrinogen

0.5992.692.692.092.692.0Est. GFR

<0.01222.1216.2215.5210.8209.5T. Cholesterol

<0.0133.027.825.722.921.4Current Smoke%

0.0432.331.931.531.034.6Hypertension %

0.0211.59.69.09.210.6Diabetes %

0.0726.225.225.623.823.3Black Race %

<0.0179.968.557.847.233.4Female %

0.0254.354.1 53.953.953.9Age

>3.83.6-3.83.4-3.53.1-3.3<3.0

p-valueSerum Phosphorus (mg/dL)

Evaluation of Heterogeneity of Effect

0.18Diabetes

0.24Serum Calcium

0.60Current Smoking

0.31Total Cholesterol

0.70Age

0.39Kidney Function

0.04Race

0.0007Gender

Interactionp-value

Stratification Variable

Age-Adjusted Carotid IMT According to Serum Phosphate Among Men

0.7630.759

0.772

0.794 0.794

0.710

0.730

0.750

0.770

0.790

0.810

<3.0 3.1-3.3 3.4-3.5 3.6-3.8 >3.8

Serum Phosphorus Level

Carotid IMT

Trend Test: p<0.0001

Age-Adjusted Carotid IMT According to Serum Phosphate Among Women

0.6770.67

0.6770.681

0.686

0.640

0.660

0.680

0.700

0.720

0.740

<3.0 3.1-3.3 3.4-3.5 3.6-3.8 >3.8

Serum Phosphorus Level

Carotid IMT

Trend Test: p=0.009

Multivariate Adjusted Carotid IMT According to Serum Phosphate Among Men

0.763 0.762

0.775

0.7910.784

0.710

0.730

0.750

0.770

0.790

0.810

<3.0 3.1-3.3 3.4-3.5 3.6-3.8 >3.8

Serum Phosphorus Level

Carotid IMT

Adjusted for age, race, diabetes, hypertension, total cholesterol, HDL, eGFR, and smoking status

Trend Test: p<0.0001

Multivariate Adjusted Carotid IMT According to Serum Phosphate Among Women

0.6870.683 0.685

0.691 0.69

0.640

0.660

0.680

0.700

0.720

0.740

<3.0 3.1-3.3 3.4-3.5 3.6-3.8 >3.8

Serum Phosphorus Level

Carotid IMT

Adjusted for age, race, diabetes, hypertension, total cholesterol, HDL, eGFR, and smoking status

Trend Test: p=0.19

Conclusions

• Elevated serum phosphorus levels are associated with increased carotid intima medial thickness in a healthy population among men but not women

• The association is independent of standard atherosclerotic risk factors and estimated GFR (renal function)