Original Investigation
Pathogenesis and Treatment of Kidney Disease
Association of Serum Phosphorus With Left Ventricular Mass in Men and Women With Stable Cardiovascular Disease: Data From the Heart and Soul Study

https://doi.org/10.1053/j.ajkd.2010.03.030Get rights and content

Background

Higher serum phosphorus levels are associated with cardiovascular disease (CVD) events in the general population, an association that may be stronger in men. Estradiol has phosphaturic properties. Whether higher serum phosphorus levels are associated with left ventricular (LV) mass in persons without end-stage renal disease and whether the association is modified by sex is unknown.

Study Design

Cross-sectional observational study.

Setting & Participants

978 outpatients with stable CVD.

Predictor

The primary predictor variable was serum phosphorus level. Sex was evaluated as an effect modifier.

Outcome & Measurements

LV mass using transthoracic echocardiography.

Results

The association of serum phosphorus level with LV mass differed by sex (interaction P = 0.04). In models adjusted for age, race, kidney function, smoking, diabetes, blood pressure, cholesterol level, C-reactive protein level, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use, each 1-mg/dL higher serum phosphorus level was associated with 4.52-g/m2 greater LV mass (95% CI, 1.04-8.01; P = 0.01) in men. Conversely, in women, no statistically significant association was found between serum phosphorus level and LV mass.

Limitations

Older adult population with stable CVD; 19% were women.

Conclusions

In outpatients with stable CVD, higher serum phosphorus levels are associated with greater LV mass in men, but not women. Whether sex hormones may account for these differences requires future study.

Section snippets

Participants

The Heart and Soul Study is an observational study designed to evaluate the association of psychological factors and CVD. Methods have been described previously.20 Briefly, participants with prevalent CVD, defined as history of myocardial infarction, angiographic evidence of >50% stenosis in 1 or more coronary vessels, evidence of exercise-induced ischemia using treadmill or nuclear stress testing, or history of coronary revascularization, were recruited from outpatient clinics in the San

Results

Mean age of the 978 study participants was 67 years. The study recruited heavily from a Veterans Affairs medical center; therefore, 19% (n = 181) were women. Thirty percent had moderate CKD (eGFRCysC <60 mL/min/1.73 m2). Mean serum phosphorus level was 3.7 ± 0.6 mg/dL overall; however, this differed by sex (3.6 ± 0.5 mg/dL in men and 4.0 ± 0.7 mg/dL in women; P < 0.001). Baseline characteristics by phosphorus tertiles are listed separately for men and women (Table 1, Table 2, respectively). In

Discussion

In this study of outpatients with stable CVD, higher serum phosphorus levels were associated with greater LV mass in men, but not women. Two prior studies conducted in the ARIC cohort showed that associations of phosphorus levels with carotid intima media thickness and CVD events were limited to men.4, 15 The sex difference in the association of phosphorus level with LV mass shown here provides additional evidence supporting unique relationships of phosphorus levels with CVD in men and women in

Acknowledgements

Dr Saab acknowledges the Harry S. Truman VA Hospital for providing the facility space for the design of this analysis and drafting of the manuscript. Results of this study were presented as a poster in abstract form at the 2009 ASN Renal Week, October 31, 2009, San Diego, CA.

Support: Dr Ix is funded by a grant from the American Heart Association Fellow-to-Faculty Transition Award. The Heart and Soul Study was funded by the Department of Veterans Affairs, American Federation for Aging Research,

References (38)

  • M. Smebye et al.

    Effect of hemoglobin levels on cardiovascular outcomes in patients with isolated systolic hypertension and left ventricular hypertrophy (from the LIFE Study)

    Am J Cardiol

    (2007)
  • C. Castelo-Branco et al.

    The effect of hormone replacement therapy on postmenopausal bone loss

    Eur J Obstet Gynecol Reprod Biol

    (1992)
  • G.A. Block et al.

    Mineral metabolism, mortality, and morbidity in maintenance hemodialysis

    J Am Soc Nephrol

    (2004)
  • R. Dhingra et al.

    Relations of serum phosphorus and calcium levels to the incidence of cardiovascular disease in the community

    Arch Intern Med

    (2007)
  • S.J. Onufrak et al.

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

    Am J Epidemiol

    (2009)
  • M. Tonelli et al.

    Relation between serum phosphate level and cardiovascular event rate in people with coronary disease

    Circulation

    (2005)
  • S. Jono et al.

    Phosphate regulation of vascular smooth muscle cell calcification

    Circ Res

    (2000)
  • K.L. Adeney et al.

    Association of serum phosphate concentrations with vascular and valvular calcification in moderate chronic kidney disease: the Multi-Ethnic Study of Atherosclerosis

    J Am Soc Nephrol

    (2009)
  • W.G. Goodman et al.

    Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis

    N Engl J Med

    (2000)
  • Cited by (36)

    • Update on Chronic Kidney Disease Mineral and Bone Disorder in Cardiovascular Disease

      2018, Seminars in Nephrology
      Citation Excerpt :

      In many human studies, abnormalities of MBD components including phosphorus, vitamin D, PTH, and FGF23 associate with adverse changes in cardiac structure or function that are independent of static blood pressure.16,18,53,110 Relationships of higher FGF23 with left ventricular hypertrophy, concentric and eccentric remodeling, and diastolic dysfunction are some of the most widely reported, with independent associations found in adults and children with and without kidney disease.31,111-117 Experiments in preclinical models have suggested that these associations may be the result of direct effects of FGF23 on the myocardium,113,118,119 owing to biased signaling via FGF receptor 4 without klotho as a co-receptor.120,121

    • Serum phosphorus is related to left ventricular remodeling independent of renal function in hospitalized patients with chronic kidney disease

      2016, International Journal of Cardiology
      Citation Excerpt :

      In another community-dwelling study with young adults (mean age 25 years), serum phosphorus 5 years earlier was also associated with LVMI (7.1 g/m2 for each 1 mmol/L increment in serum phosphorus) and the prevalence of LVH, with the significance mainly presented in the fifth quintile phosphorus levels (> 4.0 mg/dl) [18]. In a study with stable CVD outpatients, higher serum phosphorus was associated with greater LVMI in men (4.5 g/m2 increase for each 1 mmol/L increment in serum phosphorus), but not in women [19]. The association between serum phosphorus and left ventricular mass was greatly strengthened in CKD outpatients with stage 2 to stage 4 using cardiac magnetic resonance (16.7 g/m2 increase for each 1 mmol/L increment in serum phosphorus) [20].

    • Determinants of phosphorus mobilization during hemodialysis

      2013, Kidney International
      Citation Excerpt :

      In addition, Saab et al.28 have recently demonstrated in outpatients with stable cardiovascular disease that higher serum phosphorus concentrations are associated with greater left ventricular mass in men, but not in women. These previous studies suggest that serum phosphorus concentrations and their relationship with cardiovascular disease are influenced by patient sex, perhaps by the influence of hormonal differences.28,29 Thus, the sex differences we observed in phosphorus mobilization clearance are not incompatible with other findings related to serum phosphorus concentration in other patient groups.

    • Phosphate homeostasis in CKD: Report of a scientific symposium sponsored by the national kidney foundation

      2013, American Journal of Kidney Diseases
      Citation Excerpt :

      Whether higher phosphate level is linked to CVD and death in geographic regions with different indigenous dietary patterns is uncertain. Third, several studies have suggested that the relationships between serum phosphate concentrations with subclinical and clinical CVD outcomes may differ by sex and menopausal status.92-94 Race/ethnic differences have not been fully explored.27,51,95

    View all citing articles on Scopus

    Originally published online as doi:10.1053/j.ajkd.2010.03.030 on June 28, 2010.

    View full text