25-hydroxyvitamin D concentration is inversely associated with serum MMP-9 in a cross-sectional study of African American ESRD patients.

BACKGROUND: Circulating 25-hydroxyvitamin D [25(OH)D] concentration is inversely associated with peripheral arterial disease and hypertension. Vascular remodeling may play a role in this association, however, data relating vitamin D level to specific remodeling biomarkers among ESRD patients is sparse. We tested whether 25(OH)D concentration is associated with markers of vascular remodeling and inflammation in African American ESRD patients. METHODS: We conducted a cross-sectional study among ESRD patients receiving maintenance hemodialysis within Emory University-affiliated outpatient hemodialysis units. Demographic, clinical and dialysis treatment data were collected via direct patient interview and review of patients records at the time of enrollment, and each patient gave blood samples. Associations between 25(OH)D and biomarker concentrations were estimated in univariate analyses using Pearson's correlation coefficients and in multivariate analyses using linear regression models. 25(OH) D concentration was entered in multivariate linear regression models as a continuous variable and binary variable (<15 ng/ml and ≥15 ng/ml). Adjusted estimate concentrations of biomarkers were compared between 25(OH) D groups using analysis of variance (ANOVA). Finally, results were stratified by vascular access type. RESULTS: Among 91 patients, mean (standard deviation) 25(OH)D concentration was 18.8 (9.6) ng/ml, and was low (<15 ng/ml) in 43% of patients. In univariate analyses, low 25(OH) D was associated with lower serum calcium, higher serum phosphorus, and higher LDL concentrations. 25(OH) D concentration was inversely correlated with MMP-9 concentration (r = -0.29, p = 0.004). In multivariate analyses, MMP-9 concentration remained negatively associated with 25(OH) D concentration (P = 0.03) and anti-inflammatory IL-10 concentration positively correlated with 25(OH) D concentration (P = 0.04). CONCLUSIONS: Plasma MMP-9 and circulating 25(OH) D concentrations are significantly and inversely associated among ESRD patients. This finding may suggest a potential mechanism by which low circulating 25(OH) D functions as a cardiovascular risk factor.

Investigation of gender heterogeneity in the associations of serum phosphorus with incident coronary artery disease and all-cause mortality.

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.

Phosphorus levels are associated with subclinical atherosclerosis in the general population.

BACKGROUND: Elevated serum phosphorus has been linked to mortality among patients with renal failure and in one study in the general population. The aim of our study was to examine the association of serum phosphorus level with carotid atherosclerosis in the general population. METHODS: We determined the association of serum phosphorus levels with carotid intima-media thickness (cIMT) in 13,340 subjects 45-64 years old without known coronary heart disease, stroke, or renal disease from the Atherosclerosis Risk in Communities (ARIC) study. RESULTS: Phosphorus levels were significantly associated with age, female gender, diabetes mellitus, hypertension, hypercholesterolemia and fibrinogen levels (p < 0.0001 for each), but not with estimated glomerular filtration rate (eGFR). Age- and sex-adjusted mean cIMT ranged from 0.718 to 0.736 mm for the lowest to the highest quintile of serum phosphorus (p-value for trend < 0.0001). This relationship was attenuated but remained statistically significant after adjustment for atherosclerotic risk factors and eGFR (trend p < 0.0001) in men but not in women. In a multivariable model, a one standard deviation increase in baseline serum phosphorus (0.48 mg/dL) was associated with a 0.012 mm increase in mean cIMT (p < 0.007) in men. CONCLUSION: In a population-based cohort of subjects free of overt cardiovascular and renal disease serum phosphorus was positively associated with cIMT independent of traditional risk factors for atherosclerosis and eGFR in men but not in women.