Clinical research study
Serum Phosphorus and Cardiovascular Mortality in Type 2 Diabetes

https://doi.org/10.1016/j.amjmed.2008.09.039Get rights and content

Abstract

Background

Although serum phosphorus, calcium, and calcium-phosphorus product levels have been associated with cardiovascular events and mortality in patients with normal kidney function, most studies have not examined the association of these minerals with outcomes when collected repeatedly over time.

Methods

We evaluated the association of serum phosphorus, calcium, and calcium-phosphorus product levels with cardiovascular events and mortality in 950 participants of the Appropriate Blood Pressure Control in Diabetes trial by both time-dependent Cox regression models using the cumulative average of minerals measured over time and fixed covariate Cox regression models with only baseline values of these minerals.

Results

There were 42 deaths and 193 cardiovascular events among the participants, who were followed for an average of 4.8 years following randomization. A significant association was noted between baseline serum phosphorus >3.9 mg/dL and baseline calcium-phosphorus product >36.8 mg2/dL2 compared with the lowest referent category with the adjusted risk of cardiovascular death (hazard ratio [HR] 5.00; 95% confidence interval [CI], 1.70-14.72) and (HR 10.01; 95% CI, 2.55-39.31), respectively. However, in time-dependent models using mineral values repeated during the course of the study, only the average of serum phosphorus remains significant (HR 4.25; 95% CI, 1.15 to 16.65).

Conclusions

In the Appropriate Blood Pressure Control in Diabetes cohort, serum phosphorus, but not serum calcium or calcium-phosphorus product, was associated with cardiovascular mortality in time-dependent Cox regression models. Thus, serum phosphorus levels may be more reliable in predicting cardiovascular mortality in patients with type 2 diabetes.

Section snippets

Study Design and Participants

This is a post hoc analysis of the Appropriate Blood-pressure Control in Diabetes (ABCD) trial, which evaluated the effects of intensive versus moderate blood pressure control on diabetic microvascular and macrovascular complications.11, 12 In the ABCD trial, 950 patients with type 2 diabetes mellitus were assigned randomly to one of 2 treatment arms: intensive treatment with a diastolic blood pressure goal of 75 mm Hg or moderate treatment with a diastolic blood pressure goal of 80-89 mm Hg.

Results

Baseline characteristics for the entire group by phosphorus level are summarized in Table 1. Data show that there were higher non-HDL cholesterol and calcium levels, and lower estimated GFR in subjects in the higher quartiles of phosphorus. The lowest prevalence of overt albuminuria occurred in the subjects in the middle 2 quartiles of phosphorus. Of note, the mean serum phosphorus level was significantly lower (P <.01) in males (3.43 ± 0.47 mg/dL) than in females (3.76 ± 0.49).

The mean follow-up

Conclusions

In a study cohort of type 2 diabetic patients with normal or near-normal kidney function, higher baseline fasting serum phosphorus and calcium-phosphorus product were associated with cardiovascular mortality independent of other important confounders, whereas in time-dependent models, only serum phosphorus was independently related to the outcome. Although the findings obtained with baseline covariate Cox regression models are confirmatory of observations made by Tonelli et al5 and Dhingra et al

References (26)

  • G.A. Block et al.

    Mineral metabolism, mortality, and morbidity in maintenance hemodialysis

    J Am Soc Nephrol

    (2004)
  • Y. Slinin et al.

    Calcium, phosphorus, parathyroid hormone, and cardiovascular disease in hemodialysis patients: the USRDS waves 1, 3, and 4 study

    J Am Soc Nephrol

    (2005)
  • S. Savage et al.

    The ABCD (Appropriate Blood Pressure Control in Diabetes) trial: rationale and design of a trial of hypertension control (moderate or intensive) in type II diabetes

    Control Clin Trials

    (1996)
  • Cited by (53)

    • Serum phosphorus levels are associated with endothelial dysfunction in hypertensive patients

      2016, Nutrition, Metabolism and Cardiovascular Diseases
      Citation Excerpt :

      It is well known that the pathogenesis of endothelial dysfunction is multifactorial, involving many of the clinical conditions leading to an increased oxidative stress and subclinical inflammation [13,14]. Recent published data reported that elevated serum phosphorus concentrations, even if within the normal range, emerged as a non-traditional risk factor for CV events in patients with high CV risk conditions such as chronic kidney disease [15,16], coronary or peripheral artery diseases [17,18], diabetes [19] as well as in the general population [20,21]. Finally, recent data reported that acute postprandial phosphorus load is inversely correlated with endothelium-dependent vasodilation in young healthy men, evaluated by brachial flow-mediated vasodilation [22].

    • Bioavailable dietary phosphate, a mediator of cardiovascular disease, may be decreased with plant-based diets, phosphate binders, niacin, and avoidance of phosphate additives

      2014, Nutrition
      Citation Excerpt :

      In recent prospective epidemiologic analyses, serum phosphate within the normal physiological range has been found to correlate positively and monotonically with risk for cardiovascular events, new heart failure, and cardiovascular and all-cause mortality [1–8]; an excellent summary of these data in tabular form was provided previously [9].

    View all citing articles on Scopus

    Funding: Clinical revenues.

    Conflict of Interest: None.

    Authorship: All authors participated in the conception and design of the study, the interpretation of data, drafting and critical revision of the manuscript, and have read and approved the manuscript.

    View full text