Skip to main content

Main menu

  • Home
  • Content
    • Published Ahead of Print
    • Current Issue
    • JASN Podcasts
    • Article Collections
    • Archives
    • Kidney Week Abstracts
    • Saved Searches
  • Authors
    • Submit a Manuscript
    • Author Resources
  • Editorial Team
  • Editorial Fellowship
    • Editorial Fellowship Team
    • Editorial Fellowship Application Process
  • More
    • About JASN
    • Advertising
    • Alerts
    • Feedback
    • Impact Factor
    • Reprints
    • Subscriptions
  • ASN Kidney News
  • Other
    • ASN Publications
    • CJASN
    • Kidney360
    • Kidney News Online
    • American Society of Nephrology

User menu

  • Subscribe
  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
American Society of Nephrology
  • Other
    • ASN Publications
    • CJASN
    • Kidney360
    • Kidney News Online
    • American Society of Nephrology
  • Subscribe
  • My alerts
  • Log in
  • My Cart
Advertisement
American Society of Nephrology

Advanced Search

  • Home
  • Content
    • Published Ahead of Print
    • Current Issue
    • JASN Podcasts
    • Article Collections
    • Archives
    • Kidney Week Abstracts
    • Saved Searches
  • Authors
    • Submit a Manuscript
    • Author Resources
  • Editorial Team
  • Editorial Fellowship
    • Editorial Fellowship Team
    • Editorial Fellowship Application Process
  • More
    • About JASN
    • Advertising
    • Alerts
    • Feedback
    • Impact Factor
    • Reprints
    • Subscriptions
  • ASN Kidney News
  • Follow JASN on Twitter
  • Visit ASN on Facebook
  • Follow JASN on RSS
  • Community Forum
CLINICAL EPIDEMIOLOGY
You have accessRestricted Access

Serum Phosphorus Levels Associate with Coronary Atherosclerosis in Young Adults

Robert N. Foley, Allan J. Collins, Charles A. Herzog, Areef Ishani and Philip A. Kalra
JASN February 2009, 20 (2) 397-404; DOI: https://doi.org/10.1681/ASN.2008020141
Robert N. Foley
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Allan J. Collins
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Charles A. Herzog
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Areef Ishani
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Philip A. Kalra
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data Supps
  • Info & Metrics
  • View PDF
Loading

Abstract

Phosphorus levels correlate with atherosclerosis in both animal models and humans with advanced chronic kidney disease, but whether this relationship exists among individuals with normal kidney function is unknown. This study aimed to determine whether an association exists between phosphorus levels and coronary artery calcium levels in a community-based cohort of 3015 healthy young adults in the prospective Coronary Artery Risk Development in Young Adults (CARDIA) study. Phosphorus levels were measured at baseline, and presence of coronary artery calcium was assessed by computed tomography 15 yr later. Mean age at study inception was 25.2 yr, and the mean levels of phosphorus and calcium were 3.6 and 9.5 mg/dl, respectively. Only 0.2% of participants had estimated GFR <60 ml/min per 1.73 m2. Phosphorus levels were associated with coronary artery calcium in unadjusted models. In multivariate models, however, phosphorus levels were significantly associated with the category of coronary artery calcium level. In conclusion, higher serum phosphorus levels, even within the normal range, may be a risk factor for coronary artery atherosclerosis in healthy young adults.

Experimental studies have suggested that higher phosphorus levels can cause vascular disease. For example, hyperphosphatemia, arteriosclerosis, and vascular calcification are cardinal features of fibroblast growth factor 23 gene 2 and Klotho gene 3 knockout models, phenotypic characteristics that can be altered in Klotho null mice with a low-phosphorus diet.1–3 Current knowledge remains incomplete, but, clearly, prevention of vascular calcification is a dynamic, multifaceted process. Endogenous inhibitors of crystal formation and of osteogenic differentiation of vascular smooth muscle cells have been identified, including matrix Gla protein and fetuin-A; experimental studies have shown that exposure of experimental animals to high ambient phosphorus is followed by expression of an osteogenic phenotype in vascular smooth muscle cells and by vascular calcification.4–8 Other potential mechanisms linking rising phosphorus levels to vascular disease include inhibition of 1,25-dihydroxyvitamin D synthesis and increased parathyroid hormone (PTH) production.9–11

Several observational studies of dialysis populations have shown that high serum phosphorus levels are antecedent associations of mortality and cardiovascular events, independent of calcium and PTH levels.12–15 If high phosphorus levels truly cause vascular disease, then it seems natural to hypothesize that this relationship also applies within the normal range of phosphorus levels, even in the presence of normal kidney function. Coronary artery calcium levels are believed to reflect accurately the overall burden of atherosclerosis and to exhibit dosage–response relationships with the incidence of future cardiovascular events.16–26 Studying phosphorous levels and coronary artery calcification can potentially reveal the mechanisms by which serum phosphorous may lead to cardiovascular disease and, perhaps, suggest the existence of novel mechanisms for developing atherosclerosis. The major objective of this study was to determine whether an association exists between phosphorus levels and coronary artery calcium levels in community-dwelling young adults.

RESULTS

The Coronary Artery Risk Development in Young Adults (CARDIA) study is a prospective, multicenter, observational study of cardiovascular disease in young adults.27 Initially, 5115 participants, aged 18 to 30 yr, were studied in 1985 and 1986 in Birmingham, AL; Chicago, IL; Minneapolis, MN; and Oakland, CA. Of these, 3671 (71.8%) returned for the year 15 examination; 3042 (of 3671) participants had coronary artery calcium estimated by computer tomography (CT), and serum phosphorus levels were available for 3015 (of 3042) participants. Table 1 shows the baseline characteristics of these 3015 participants at the first study visit. The mean age of the population was 25.2 yr, 54.4% were women, and 45.0% were black. Mean phosphorus level was 3.6 mg/dl, calcium level was 9.5 mg/dl, and calcium-phosphorus product was 26.3 mg2/dl2. Mean estimated GFR (eGFR) was 116.6 ml/min per 1.73 m2, and values for 0.2% of participants were <60 ml/min per 1.73 m2.

View this table:
  • View inline
  • View popup
Table 1.

Baseline characteristics at study inception (n = 3015)a

Multivariate associations of serum phosphorus, calcium, and calcium-phosphorus product are shown in Table 2. The associations of serum phosphorus included younger age, female gender, black race, family history of myocardial infarction (MI), lower body mass index (BMI), HDL cholesterol, triglycerides, lower systolic BP (SBP), diastolic BP (DBP), exercise intensity score, lower carbohydrate intake, and use of cardiac medications. Calcium levels were associated with younger age, male gender, black race, <12 yr of education, self-reported hypertension, lower BMI, LDL cholesterol, HDL cholesterol, triglycerides, glucose, DBP, and lower eGFR values. Calcium-phosphorus product levels were associated with younger age, black race, lower SBP, and higher DBP.

View this table:
  • View inline
  • View popup
Table 2.

Associations of phosphorus, calcium, and calcium-phosphorus product levels at study inceptiona

At year 15, 3.2% of the study population had minimal coronary artery calcification, 4.8% had mild calcification, 1.1% had moderate calcification, and 0.5% had severe calcification (Figure 1). Table 3 summarizes associations between phosphorus levels at baseline and coronary artery calcium categorized as 0, >0 to <10, 10 to 100, 101 to 300, or >300 units. In unadjusted models, higher phosphorus levels, as a continuous variable, were associated with lower likelihood of coronary artery calcification (odds ratio [OR] 0.87 per 0.5 mg/dl; P = 0.0332). In multivariate models, higher phosphorus levels were associated with greater likelihood of higher calcium level categories (adjusted OR 1.17 per 0.5 mg/dl; P = 0.0331); considered as quartiles, phosphorus values in the fourth quartile (>3.9 mg/dl) were associated with an adjusted OR of 1.52 (95% confidence interval 1.04 to 2.22) compared with values in the first quartile (≤3.3 mg/dl). Table 3 shows that findings were broadly similar when coronary artery calcium was analyzed as binary variables, defined by calcium scores >0, 10, and 100 units.

Figure 1.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 1.

Coronary calcification scores by computer tomography at year 15 (n = 3015).

View this table:
  • View inline
  • View popup
Table 3.

Associations between serum phosphorus at baseline and coronary artery calcium at year 15a

Multivariate P-spline plot analysis (Figure 2) suggested that phosphorus levels >3.9 mg/dl were associated with greater likelihood of coronary artery calcium ≥100. As shown in Figure 3, serum calcium and calcium-phosphorus product levels had no association with coronary artery calcification. Figure 3 also shows that associations between coronary artery calcium and phosphorus, calcium, and calcium-phosphorus product were very similar when individual with eGFR <60 ml/min per 1.73 m2 were excluded.

Figure 2.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 2.

Spline plot relating adjusted OR (with 95% confidence intervals) of coronary artery calcium ≥100 and serum phosphorus levels. Adjusted for age, gender, race, hypertension, diabetes, education, smoking, family history of MI, BMI, LDL cholesterol, HDL cholesterol, triglycerides, glucose, SBP, and eGFR.

Figure 3.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 3.

Multivariate associations of coronary artery calcification severity and quartiles of phosphorus, calcium, and calcium-phosphorus product. (Top) Overall population. (Bottom) Population with eGFR ≥60 ml/min per 1.73 m2. Adjusted for age, gender, race, hypertension, diabetes, education, smoking, family history of MI, BMI, LDL cholesterol, HDL cholesterol, triglycerides, glucose, SBP, and eGFR.

DISCUSSION

We found that serum phosphorus levels in young adults showed a complex relationship with classic cardiovascular risk factors, including associations with younger age, female gender, black race, family history of MI, low BMI, HDL cholesterol, triglycerides, and lower SBP. Although phosphorus levels, especially levels >3.9 mg/dl, were associated with coronary artery calcium levels, this association was evident only in multivariate models.

To date, most observational data examining the association between phosphorus levels and cardiovascular disease have come from populations with advanced chronic kidney disease (CKD). These studies have shown consistent associations between abnormal phosphorus levels and cardiovascular outcomes; in contrast, associations with calcium levels and PTH levels have been inconsistent in the same studies.12–15 These findings have been extended to phosphorus levels within the normal range by a retrospective analysis of the Cholesterol and Recurrent Events (CARE) trial among individuals with previous MI.28

Few studies have examined associations between phosphorus levels and cardiovascular disease in community-dwelling adults without overt kidney disease. In this regard, a recent report from participants in the Framingham Offspring Study was noteworthy. In this prospective, observational study, the average age of the study population was approximately 20 yr older than in the CARDIA study. Several associations of higher phosphorus levels mirrored the findings in our study. For example, associations of higher phosphorus levels included female gender, lower BP, and lower BMI. During a mean follow-up of 16.1 yr, 524 incident cardiovascular events were observed; when adjustment was made for classic cardiovascular risk factors, GFR, hemoglobin, serum albumin, proteinuria, and C-reactive protein levels, serum phosphorus was associated with these events in a continuous manner, and phosphorus levels ≥3.5 mg/dl were associated with an adjusted hazard ratio 1.55 times levels <2.9 mg/dl.29

Because ours was a nonexperimental study, determining whether the association between phosphorus levels and coronary calcification is a true phenomenon or the magnitude of residual confounding is impossible. Similarly, the relative contributions of genetic and environmental factors to the associations remain speculative. The associations between phosphorus levels and other cardiovascular risk factors were notable and seemed to be qualitatively different from classical cardiovascular risk factors, in the sense that higher phosphorus levels were associated with some seemingly protective factors (younger age, female gender, lower BMI, higher HDL cholesterol, and lower SBP) and other factors that might be considered to increase cardiovascular risk (black race, family history of MI, and higher triglycerides). This duality may account for the observation that associations between phosphorus levels and coronary artery calcification were more apparent in adjusted than unadjusted analyses. Interestingly, a report from the Framingham Offspring Study showed a similar pattern of risk factor duality; this unusual risk factor profile suggests novel mechanisms for cardiovascular disease that may be worth exploring using experimental methods.29

Our study has several strengths. The study population was relatively large, and the interval between putative risk factor and outcome assessments was long. A population of young adults was studied, which should be useful for identifying earlier stage, subclinical coronary artery disease. The candidate risk factor seems to be novel, has little overlap with classic treatable risk factors, and should be modifiable. Intervention trials targeting phosphorus, vitamin D metabolism, and PTH levels are already under way among patients with CKD.30

Unlike many cardiovascular risk factors uncovered in observational studies, potential interventions that can address some of the hypotheses suggested by this study may already exist. Our findings suggest that extending these trials to high-risk individuals without CKD in the general population has the potential to improve public health. Quite apart from the underlying determinants, the associations seen in this study suggest that high phosphorus levels might help to identify young adults for whom modifiable risk factors might be screened and managed more aggressively.

The limitations of our study include its nonexperimental design. In addition, PTH and vitamin D levels were not available, so the hypothesis that our findings reflect phosphorus-induced abnormalities of these axes cannot be refuted. Although inflammatory markers and urinary albumin-creatinine ratios were not available at baseline, adjusting for C-reactive protein and urinary albumin-creatinine ratios at year 15 had no effect on the associations between serum phosphorus and coronary calcium levels. Sample size issues may also be relevant. Approximately 10% of the study population had coronary calcification. To detect a 20% difference between two groups with α of 0.05 and power of 0.90, the total sample size requirement would exceed 10,468. Finally, whereas the design of CARDIA enables enrollment of young adults representative of the overall population, our study was somewhat self-selected, because it was limited to participants who attended the year 15 examination.

CONCISE METHODS

Study Population

The CARDIA study used a random sampling scheme to ensure that population-based samples were balanced within centers by age, race, gender, and education level. The Chicago and Minneapolis centers used census tract information to achieve the population balance mandated in the original request for proposals, which required that the study should have approximately equal proportions of men, women, and black and white Americans. The Oakland center selected study participants from the Kaiser-Permanente health plan membership, and the Birmingham center used telephone exchanges to sample the entire city population. One household member per household was randomly selected and assessed for the study eligibility criteria: Aged between 18 and 30 yr with a permanent address in the target area. Follow-up examinations were performed at years 2, 5, 7, 10, and 15.

Measurements

Gender, race, education, cigarette smoking, previous hypertension and diabetes, and parental history of MI were ascertained by structured interviews and self-administered questionnaires. Participants were instructed to fast for 12 h and to avoid heavy physical activity and smoking for 2 h before the examination. Sitting BP was measured in the right arm after 5 min of rest. First- and fifth-phase Korotkoff sounds were recorded three times at 1-min intervals with a random zero sphygmomanometer (WA Baum Company, Copiague, NY), and the average of the second and third measurements was used in the analyses presented here. Phosphorus, calcium, albumin, and creatinine levels were measured with a SMAC 12 continuous-flow analyzer (Technicon Instruments Corp., Tarrytown, NY) at American BioScience Laboratories (now SmithKline Beecham, King of Prussia, PA).

Data from the Third National Health and Nutrition Examination Survey (1988 to 1992) were used to align creatinine levels from the first CARDIA examination to those expected on the basis of the age, gender, and racial characteristics of the CARDIA participants. Thus, 0.23 mg/dl was subtracted from creatinine levels for CARDIA participants, and the reexpressed Modification of Diet in Renal Disease formula was used to estimate GFR. Calcium levels were corrected for the presence of serum albumin levels <4 g/dl with the following formula: Corrected calcium (mg/dl) = observed calcium (mg/dl) + 0.8 (4 − serum albumin [mg/dl]).31 Enzymatic methods were used to measure HDL cholesterol and triglycerides (University of Washington Northwest Lipid Research Clinical Laboratory, Seattle, WA), and the Friedewald equation was used to calculate LDL cholesterol levels. Glucose levels were measured by the hexokinase-ultraviolet method at Linco (now Millipore, Billerica, MA).

The CARDIA diet history was an interviewer-administered instrument based on 24-h recall.32,33 The CARDIA activity instrument was an interviewer-administered self-report that assessed frequency of participation over the previous 12 mo in eight vigorous-intensity and five moderate-intensity leisure activities; a score of 200 exercise units was equivalent to exercise performed at six metabolic equivalents for 2 h/wk for 11 mo of the year.34,35 Both instruments have been found to have good validity and reliability.

An Imatron (South San Francisco, CA) C-150 electron beam scanner, a GE (Fairfield, CT) Lightspeed multidetector scanner, or a Siemens (Berlin, Germany) VZ multidetector scanner was used for CT scanning. Two scans were performed on each participant, with a hydroxyapatite phantom used to standardize image brightness. Scans were electrocardiogram gated at 80% (Imatron) or 50% (GE and Siemens) of the R-R interval, with a slice thickness of 3 mm (Imatron) or 2.5 mm (GE and Siemens), and completed within 100 (Imatron), 520 (GE), or 360 ms (Siemens). Image processing software was used to identify potential calcific foci with at least two adjacent pixels of area ≥1.87 mm2 and density >130 Hounsfield units (HU). Total coronary calcium scores were calculated by multiplying focus area by a coefficient ranging between 1 and 4, based on the peak density in the focus (1 = 131 to 200 HU, 2 = 201 to 300 HU, 3 = 301 to 400 HU, and 4 = ≥401 HU).36 Scan readers were blinded to participant characteristics and to image data from the other CT scan performed on each participant. Reproducibility rates within and between scan readers were high.37

Statistical Analysis

The analysis was restricted to individuals with CT scans at year 15. Participants with CT scans were older than those without scans (25.2 versus 24.3 yr), more likely to be white (54.8 versus 39.1%), and more likely to have completed a high school education (92.8 versus 86.1%). P < 0.05 was considered statistically significant. Linear regression was used to quantify associations of phosphorus, calcium, and calcium-phosphorus product levels. To address the hypothesis that serum phosphorus levels at baseline were associated with coronary artery calcium burden 15 yr later, we treated coronary artery calcium level as an ordinal variable defined by the categories 0 (no calcification), 1 to <10 (minimal calcification), 10 to 100 (mild calcification), 101 to 300 (moderate calcification), and >300 (severe calcification),17,38–40 and we used ordinal logistic regression to quantify parameter estimates. We checked for statistical interactions between phosphorus and age, gender, and race in the multivariate analysis of coronary calcification category and found none (P > 0.1 for all interactions tested). Binary logistic regression models were used to examine associations between phosphorus levels and coronary artery calcium >0 (versus 0), ≥10 (versus <10), and ≥100 (versus <100).40 Penalized smoothing splines (P-splines) were used for graphical depiction of the adjusted association between scores of ≥100 and the range of phosphorus levels observed in this study.41,42 We performed several sensitivity analyses. Thus, phosphorus-related findings were similar when coronary artery calcium was treated as a linear variable and when urinary albumin-creatinine ratios measured at year 15 were included as covariates (C-reactive protein levels and urinary albumin-creatinine ratios were not measured at baseline).

SAS 9.1 (SAS Institute, Cary, NC) was used for all analyses with the following exceptions: We adjusted national parameter estimates from the Third National Health and Nutrition Examination Survey for the sampling weights implicit in complex survey designs using SUDAAN software (Research Triangle Institute, Research Triangle Park, NC) for complex sample surveys, and we used S-PLUS 6.1 (Insightful Corp., Seattle, WA) for P-spline analysis.

DISCLOSURES

R.N.F. has received consulting fees from Amgen and Genzyme. A.J.C. has received consulting fees from Amgen. C.A.H. has received consulting fees as a member of the Executive Committee of the EVOLVE trial, an Amgen-sponsored clinical trial of cinacalcet HCl therapy in dialysis patients.

Acknowledgments

This study was performed as a deliverable under contracts HHSN267200715002C and HHSN267200715003C (National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD).

We thank United States Renal Data System colleagues Beth Forrest for regulatory assistance, Shane Nygaard for manuscript preparation, and Nan Booth, MSW, MPH, for manuscript editing.

Footnotes

  • Published online ahead of print. Publication date available at www.jasn.org.

  • Copyright © 2009 by the American Society of Nephrology

REFERENCES

  1. ↵
    Sitara D, Razzzaque MS, Hesse M, Yoganathan S, Taguchi T, Erben RG, Juppner H, Lanske B: Homozygous ablation of fibroblast growth factor-23 results in hyperphosphatemia and impaired skeletogenesis, and reverses hypophosphatemia in Phex-deficient mice. Matrix Biol 23 : 421– 432, 2004
    OpenUrlCrossRefPubMed
  2. Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, Ohyama Y, Kurabayashi M, Kaname T, Kume E, Iwasaki H, Iida A, Shiraki-Iida T, Nishikawa S, Nagai R, Nabeshima YI: Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 390 : 45– 51, 1997
    OpenUrlCrossRefPubMed
  3. ↵
    Morishita K, Shirai A, Kubota M, Katakura Y, Nabeshima Y, Takeshige K, Kamiya T: The progression of aging in klotho mutant mice can be modified by dietary phosphorus and zinc. J Nutr 131 : 3182– 3188, 2001
    OpenUrlAbstract/FREE Full Text
  4. ↵
    Jono S, McKee MD, Murry CE, Shioi A, Nishizawa Y, Mori K, Morii H, Giachelli CM: Phosphate regulation of vascular smooth muscle cell calcification. Circ Res 87 : E10– E17, 2000
    OpenUrlCrossRefPubMed
  5. Steitz SA, Speer MY, Curinga G, Yang HY, Haynes P, Aebersold R, Schinke T, Karsenty G, Giachelli CM: Smooth muscle cell phenotypic transition associated with calcification: upregulation of Cbfa1 and downregulation of smooth muscle lineage markers. Circ Res 89 : 1147– 1154, 2001
    OpenUrlAbstract/FREE Full Text
  6. Wada T, McKee MD, Steitz S, Giachelli CM: Calcification of vascular smooth muscle cell cultures: Inhibition by osteopontin. Circ Res 84 : 166– 178, 1999
    OpenUrlAbstract/FREE Full Text
  7. Chen NX, O’Neill KD, Duan D, Moe SM: Phosphorus and uremic serum up-regulate osteopontin expression in vascular smooth muscle cells. Kidney Int 62 : 1724– 1731, 2002
    OpenUrlCrossRefPubMed
  8. ↵
    Luo G, Ducy P, McKee MD, Pinero GJ, Loyer E, Behringer RR, Karsenty G: Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature 386 : 78– 81, 1997
    OpenUrlCrossRefPubMed
  9. ↵
    Portale AA, Halloran BP, Morris RC Jr: Physiologic regulation of the serum concentration of 1,25-dihydroxyvitamin D by phosphorus in normal men. J Clin Invest 83 : 1494– 1499, 1989
    OpenUrlCrossRefPubMed
  10. Zittermann A, Schleithoff SS, Tenderich G, Berthold HK, Korfer R, Stehle P: Low vitamin D status: A contributing factor in the pathogenesis of congestive heart failure? J Am Coll Cardiol 41 : 105– 112, 2003
    OpenUrlPubMed
  11. ↵
    Smogorzewski M, Zayed M, Zhang YB, Roe J, Massry SG: Parathyroid hormone increases cytosolic calcium concentration in adult rat cardiac myocytes. Am J Physiol 264 : H1998– H2006, 1993
    OpenUrlPubMed
  12. ↵
    Block GA, Hulbert-Shearon TE, Levin NW, Port FK: Association of serum phosphorus and calcium x phosphate product with mortality risk in chronic hemodialysis patients: A national study. Am J Kidney Dis 31 : 607– 617, 1998
    OpenUrlCrossRefPubMed
  13. Ganesh SK, Stack AG, Levin NW, Hulbert-Shearon T, Port FK: Association of elevated serum PO(4), Ca x PO(4) product, and parathyroid hormone with cardiac mortality risk in chronic hemodialysis patients. J Am Soc Nephrol 12 : 2131– 2138, 2001
    OpenUrlAbstract/FREE Full Text
  14. Stevens LA, Djurdjev O, Cardew S, Cameron EC, Levin A: Calcium, phosphate, and parathyroid hormone levels in combination and as a function of dialysis duration predict mortality: Evidence for the complexity of the association between mineral metabolism and outcomes. J Am Soc Nephrol 15 : 770– 779, 2004
    OpenUrlAbstract/FREE Full Text
  15. ↵
    Slinin Y, Foley RN, Collins AJ: Calcium, phosphorus, parathyroid hormone, and cardiovascular disease in hemodialysis patients: The USRDS waves 1, 3, and 4 study. J Am Soc Nephrol 16 : 1788– 1793, 2005
    OpenUrlAbstract/FREE Full Text
  16. ↵
    Mautner GC, Mautner SL, Froehlich J, Feuerstein IM, Proschan MA, Roberts WC, Doppman JL: Coronary artery calcification: Assessment with electron beam CT and histomorphometric correlation. Radiology 192 : 619– 623, 1994
    OpenUrlCrossRefPubMed
  17. ↵
    Budoff MJ, Achenbach S, Blumenthal RS, Carr JJ, Goldin JG, Greenland P, Guerci AD, Lima JA, Rader DJ, Rubin GD, Shaw LJ, Wiegers SE: Assessment of coronary artery disease by cardiac computed tomography: A scientific statement from the American Heart Association Committee on Cardiovascular Imaging and Intervention, Council on Cardiovascular Radiology and Intervention, and Committee on Cardiac Imaging, Council on Clinical Cardiology. Circulation 114 : 1761– 1791, 2006
    OpenUrlFREE Full Text
  18. McNamara JJ, Molot MA, Stremple JF, Cutting RT: Coronary artery disease in combat casualties in Vietnam. JAMA 216 : 1185– 1187, 1971
    OpenUrlCrossRefPubMed
  19. Detrano R, Hsiai T, Wang S, Puentes G, Fallavollita J, Shields P, Stanford W, Wolfkiel C, Georgiou D, Budoff M, Reed J: Prognostic value of coronary calcification and angiographic stenoses in patients undergoing coronary angiography. J Am Coll Cardiol 27 : 285– 290, 1996
    OpenUrlPubMed
  20. Guerci AD, Arad Y, Agatston A: Predictive value of EBCT scanning. Circulation 97 : 2583– 2584, 1998
    OpenUrlFREE Full Text
  21. Schmermund A, Denktas AE, Rumberger JA, Christian TF, Sheedy PF, Bailey KR, Schwartz RS: Independent and incremental value of coronary artery calcium for predicting the extent of angiographic coronary artery disease: Comparison with cardiac risk factors and radionuclide perfusion imaging. J Am Coll Cardiol 34 : 777– 786, 1999
    OpenUrlCrossRefPubMed
  22. Bielak LF, Rumberger JA, Sheedy PF, Schwartz RS, Peyser PA: Probabilistic model for prediction of angiographically defined obstructive coronary artery disease using electron beam computed tomography calcium score strata. Circulation 102 : 380– 385, 2000
    OpenUrlAbstract/FREE Full Text
  23. Arad Y, Spadaro LA, Goodman K, Newstein D, Guerci AD: Prediction of coronary events with electron beam computed tomography. J Am Coll Cardiol 36 : 1253– 1260, 2000
    OpenUrlCrossRefPubMed
  24. O’Malley PG, Taylor AJ, Jackson JL, Doherty TM, Detrano RC: Prognostic value of coronary electron-beam computed tomography for coronary heart disease events in asymptomatic populations. Am J Cardiol 85 : 945– 948, 2000
    OpenUrlCrossRefPubMed
  25. Wong ND, Hsu JC, Detrano RC, Diamond G, Eisenberg H, Gardin JM: Coronary artery calcium evaluation by electron beam computed tomography and its relation to new cardiovascular events. Am J Cardiol 86 : 495– 498, 2000
    OpenUrlCrossRefPubMed
  26. ↵
    Detrano R, Guerci AD, Carr JJ, Bild DE, Burke G, Folsom AR, Liu K, Shea S, Szklo M, Bluemke DA, O’Leary DH, Tracy R, Watson K, Wong ND, Kronmal RA: Coronary calcium as a predictor of coronary events in four racial or ethnic groups. N Engl J Med 358 : 1336– 1345, 2008
    OpenUrlCrossRefPubMed
  27. ↵
    Friedman GD, Cutter GR, Donahue RP, Hughes GH, Hulley SB, Jacobs DR Jr, Liu K, Savage PJ: CARDIA: Study design, recruitment, and some characteristics of the examined subjects. J Clin Epidemiol 41 : 1105– 1116, 1988
    OpenUrlCrossRefPubMed
  28. ↵
    Tonelli M, Sacks F, Pfeffer M, Gao Z, Curhan G: Relation between serum phosphate level and cardiovascular event rate in people with coronary disease. Circulation 112 : 2627– 2633, 2005
    OpenUrlAbstract/FREE Full Text
  29. ↵
    Dhingra R, Sullivan LM, Fox CS, Wang TJ, D’Agostino RB Sr, Gaziano JM, Vasan RS: Relations of serum phosphorus and calcium levels to the incidence of cardiovascular disease in the community. Arch Intern Med 167 : 879– 885, 2007
    OpenUrlCrossRefPubMed
  30. ↵
    Qunibi WY: Reducing the burden of cardiovascular calcification in patients with chronic kidney disease. J Am Soc Nephrol 16[ Suppl 2]: S95– S102, 2005
    OpenUrlAbstract/FREE Full Text
  31. ↵
    Payne RB, Little AJ, Williams RB, Milner JR: Interpretation of serum calcium in patients with abnormal serum proteins. BMJ 4 : 643– 646, 1973
    OpenUrlAbstract/FREE Full Text
  32. ↵
    McDonald A, Van HL, Slattery M, Hilner J, Bragg C, Caan B, Jacobs D Jr, Liu K, Hubert H, Gernhofer N: The CARDIA dietary history: Development, implementation, and evaluation. J Am Diet Assoc 91 : 1104– 1112, 1991
    OpenUrlPubMed
  33. ↵
    Liu K, Slattery M, Jacobs D Jr, Cutter G, McDonald A, Van HL, Hilner JE, Caan B, Bragg C, Dyer A: A study of the reliability and comparative validity of the cardia dietary history. Ethn Dis 4 : 15– 27, 1994
    OpenUrlPubMed
  34. ↵
    Jacobs D, Hahn L, Haskell W, Pirie P, Sideny S: Validity and reliability of short physical activity history: Cardia and the Minnesota Heart Health Program. J Cardiopulm Rehabil 9 : 448– 459, 1989
    OpenUrlCrossRefPubMed
  35. ↵
    Sidney S, Jacobs DR Jr, Haskell WL, Armstrong MA, Dimicco A, Oberman A, Savage PJ, Slattery ML, Sternfeld B, Van Horn L: Comparison of two methods of assessing physical activity in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Am J Epidemiol 133 : 1231– 1245, 1991
    OpenUrlPubMed
  36. ↵
    Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M Jr, Detrano R: Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 15 : 827– 832, 1990
    OpenUrlCrossRefPubMed
  37. ↵
    Carr JJ, Nelson JC, Wong ND, McNitt-Gray M, Arad Y, Jacobs DR Jr, Sidney S, Bild DE, Williams OD, Detrano RC: Calcified coronary artery plaque measurement with cardiac CT in population-based studies: Standardized protocol of Multi-Ethnic Study of Atherosclerosis (MESA) and Coronary Artery Risk Development in Young Adults (CARDIA) study. Radiology 234 : 35– 43, 2005
    OpenUrlCrossRefPubMed
  38. ↵
    Rumberger JA, Sheedy PF, Breen JF, Fitzpatrick LA, Schwartz RS: Electron beam computed tomography and coronary artery disease: scanning for coronary artery calcification. Mayo Clin Proc 71 : 369– 377, 1996
    OpenUrlCrossRefPubMed
  39. Cheng YJ, Church TS, Kimball TE, Nichaman MZ, Levine BD, McGuire DK, Blair SN: Comparison of coronary artery calcium detected by electron beam tomography in patients with to those without symptomatic coronary heart disease. Am J Cardiol 92 : 498– 503, 2003
    OpenUrlCrossRefPubMed
  40. ↵
    Manson JE, Allison MA, Rossouw JE, Carr JJ, Langer RD, Hsia J, Kuller LH, Cochrane BB, Hunt JR, Ludlam SE, Pettinger MB, Gass M, Margolis KL, Nathan L, Ockene JK, Prentice RL, Robbins J, Stefanick ML: Estrogen therapy and coronary-artery calcification. N Engl J Med 356 : 2591– 2602, 2007
    OpenUrlCrossRefPubMed
  41. ↵
    Eilers P, Marx B: Flexible smoothing with B-splines and penalties. Stat Sci 11 : 89– 121, 1996
    OpenUrlCrossRef
  42. ↵
    Eisen EA, Agalliu I, Thurston SW, Coull BA, Checkoway H: Smoothing in occupational cohort studies: an illustration based on penalised splines. Occup Environ Med 61 : 854– 860, 2004
    OpenUrlAbstract/FREE Full Text
PreviousNext
Back to top

In this issue

Journal of the American Society of Nephrology: 20 (2)
Journal of the American Society of Nephrology
Vol. 20, Issue 2
February 2009
  • Table of Contents
  • Table of Contents (PDF)
  • Index by author
View Selected Citations (0)
Print
Download PDF
Sign up for Alerts
Email Article
Thank you for your help in sharing the high-quality science in JASN.
Enter multiple addresses on separate lines or separate them with commas.
Serum Phosphorus Levels Associate with Coronary Atherosclerosis in Young Adults
(Your Name) has sent you a message from American Society of Nephrology
(Your Name) thought you would like to see the American Society of Nephrology web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Serum Phosphorus Levels Associate with Coronary Atherosclerosis in Young Adults
Robert N. Foley, Allan J. Collins, Charles A. Herzog, Areef Ishani, Philip A. Kalra
JASN Feb 2009, 20 (2) 397-404; DOI: 10.1681/ASN.2008020141

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
Serum Phosphorus Levels Associate with Coronary Atherosclerosis in Young Adults
Robert N. Foley, Allan J. Collins, Charles A. Herzog, Areef Ishani, Philip A. Kalra
JASN Feb 2009, 20 (2) 397-404; DOI: 10.1681/ASN.2008020141
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like

Jump to section

  • Article
    • Abstract
    • RESULTS
    • DISCUSSION
    • CONCISE METHODS
    • DISCLOSURES
    • Acknowledgments
    • Footnotes
    • REFERENCES
  • Figures & Data Supps
  • Info & Metrics
  • View PDF

More in this TOC Section

  • Sex Differences in the Recognition, Monitoring, and Management of CKD in Health Care: An Observational Cohort Study
  • Association of Rosuvastatin Use with Risk of Hematuria and Proteinuria
  • Hurricanes and Mortality among Patients Receiving Dialysis
Show more Clinical Epidemiology

Cited By...

  • A Randomized Trial on the Effect of Phosphate Reduction on Vascular End Points in CKD (IMPROVE-CKD)
  • Serum Phosphate and Microvascular Function in a Population-Based Cohort
  • Effects of Nicotinamide and Lanthanum Carbonate on Serum Phosphate and Fibroblast Growth Factor-23 in CKD: The COMBINE Trial
  • Lack of Awareness of Dietary Sources of Phosphorus Is a Clinical Concern
  • CT-Detected Growth of Coronary Artery Calcification in Asymptomatic Middle-Aged Subjects and Association With 15 Biomarkers
  • Circulating MicroRNA-125b Predicts the Presence and Progression of Uremic Vascular Calcification
  • Association of Serum Phosphorus Concentration with Mortality and Graft Failure among Kidney Transplant Recipients
  • Ferric Citrate Controls Phosphorus and Delivers Iron in Patients on Dialysis
  • Hyperphosphatemia: The hidden killer in chronic kidney disease
  • Serum magnesium, phosphorus, and calcium are associated with risk of incident heart failure: the Atherosclerosis Risk in Communities (ARIC) Study
  • Dietary Intake of Calcium and Phosphorus and Serum Concentration in Relation to the Risk of Coronary Artery Calcification in Asymptomatic Adults
  • Fibroblast Growth Factor-23 and Incident Coronary Heart Disease, Heart Failure, and Cardiovascular Mortality: The Atherosclerosis Risk In Communities Study
  • Assessing the Health Impact of Phosphorus in the Food Supply: Issues and Considerations
  • The Connection between Dietary Phosphorus, Cardiovascular Disease, and Mortality: Where We Stand and What We Need to Know
  • Serum 25-Hydroxyvitamin D Level Is Associated With Arterial Stiffness, Left Ventricle Hypertrophy, and Inflammation in Newly Diagnosed Hypertension
  • 24-Hour Urine Phosphorus Excretion and Mortality and Cardiovascular Events
  • Public health impact of dietary phosphorus excess on bone and cardiovascular health in the general population
  • Lanthanum Carbonate for Hyperphosphatemia in Patients on Peritoneal Dialysis
  • Cardiovascular Effects of Sevelamer in Stage 3 CKD
  • Chronic kidney disease and vascular remodelling: molecular mechanisms and clinical implications
  • Lower concentrations of serum phosphorus within the normal range could be associated with less calcification of the coronary artery in Koreans with normal renal function
  • Phosphate and CVD: It's All in What's on the Table
  • Dietary Phosphate Modulates Atherogenesis and Insulin Resistance in Apolipoprotein E Knockout Mice--Brief Report
  • Association of Serum Phosphate Levels With Aortic Valve Sclerosis and Annular Calcification: The Cardiovascular Health Study
  • Donor Phosphorus Levels and Recipient Outcomes in Living-Donor Kidney Transplantation
  • Chronic Kidney Disease Progression and Outcome According to Serum Phosphorus in Mild-to-Moderate Kidney Dysfunction
  • FGF-23 as a Predictor of Renal Outcome in Diabetic Nephropathy
  • Serum Phosphate and Mortality in Patients with Chronic Kidney Disease
  • Optimising care at the cardio-renal interface
  • Risk Factor Differences for Aortic Versus Coronary Calcified Atherosclerosis: The Multiethnic Study of Atherosclerosis
  • Low Socioeconomic Status Associates with Higher Serum Phosphate Irrespective of Race
  • Fibroblast Growth Factor-23 in Early Chronic Kidney Disease: Additional Support in Favor of a Phosphate-Centric Paradigm for the Pathogenesis of Secondary Hyperparathyroidism
  • Serum Alkaline Phosphatase and Phosphate and Risk of Mortality and Hospitalization
  • Hypophosphatemic Effect of Niacin in Patients without Renal Failure: A Randomized Trial
  • Understanding Sources of Dietary Phosphorus in the Treatment of Patients with Chronic Kidney Disease
  • Longitudinal Relationships among Coronary Artery Calcification, Serum Phosphorus, and Kidney Function
  • Coronary Calcification in Chronic Kidney Disease: Morphology, Mechanisms and Mortality
  • Phosphate Levels and Cardiovascular Disease in the General Population
  • Google Scholar

Similar Articles

Related Articles

  • No related articles found.
  • PubMed
  • Google Scholar

Articles

  • Current Issue
  • Early Access
  • Subject Collections
  • Article Archive
  • ASN Annual Meeting Abstracts

Information for Authors

  • Submit a Manuscript
  • Author Resources
  • Editorial Fellowship Program
  • ASN Journal Policies
  • Reuse/Reprint Policy

About

  • JASN
  • ASN
  • ASN Journals
  • ASN Kidney News

Journal Information

  • About JASN
  • JASN Email Alerts
  • JASN Key Impact Information
  • JASN Podcasts
  • JASN RSS Feeds
  • Editorial Board

More Information

  • Advertise
  • ASN Podcasts
  • ASN Publications
  • Become an ASN Member
  • Feedback
  • Follow on Twitter
  • Password/Email Address Changes
  • Subscribe to ASN Journals
  • Wolters Kluwer Partnership

© 2022 American Society of Nephrology

Print ISSN - 1046-6673 Online ISSN - 1533-3450

Powered by HighWire