Serum phosphorus is related to left ventricular remodeling independent of renal function in hospitalized patients with chronic kidney disease☆,☆☆
Introduction
It is well established that chronic kidney disease (CKD) carries a high public health burden and cardiovascular diseases (CVD) are the leading causes of death in CKD [1], [2]. Indeed, mildly to moderately impaired renal function can convey a high risk of CVD [3]. Even CKD patients are more likely to die of CVD before they reach end stage renal disease [3]. Cardiac structural and functional changes are the most prevalent cardiovascular risks in CKD, accounting for a large number of cardiovascular mortality [4], [5]. Cardiac structural and functional changes start in the early stages of CKD and this association strengthens in patients with deteriorated renal function approaching or on dialysis [6], [7]. These cardiac changes observed in CKD patients are attributed to not only conventional risk factors but also CKD-related risk factors such as uremic toxins, anemia, mineral metabolism disorders and so on [8].
Recently, serum phosphorus emerged as an important cardiovascular risk factor. Increased serum phosphorus, which is prevalent in CKD patients due to impaired phosphorus excretion, was associated with adverse cardiovascular outcomes in both maintenance hemodialysis [9] and earlier stages of CKD patients [10]. Even serum phosphorus in normal range has been linked with cardiovascular events in coronary disease [11], type 2 diabetes [12], or the incidence of CVD in the community [13], [14]. However, the underlying mechanism between phosphorus and CVD has not yet been clarified.
Left ventricular remodeling may be the structural basis of heart failure, arrhythmias and sudden cardiac death, which are the most common causes of cardiac death [15]. Although blood pressure still plays a major role in the process inducing left ventricular remodeling in CKD, some other CKD-related factors may also be actively involved in the process. The fact that serum phosphorus is closely linked to vascular and valvar calcification may account for one important reason [16]. However, left ventricular remodeling may also serve as another potential mechanism of the cardiac toxicity of phosphorus. Some studies indicated the significant association between serum phosphorus and left ventricular mass in community-based population [17], [18], male stable CVD outpatients [19], and CKD outpatients [20]. However, few studies have characterized the association of serum phosphorus with left ventricular geometry remodeling.
In the present study, we conducted a cross-sectional analysis between serum phosphorus and left ventricular remodeling among hospitalized patients with pre-dialysis CKD, who did not have symptomatic heart failure or take phosphorus binders or calcitriol medications. We characterized the associations of serum phosphorus with left ventricular mass and morphology. Since CKD is closely associated with hypertension and left ventricular remodeling is a well recognized consequence of hypertension, we explored blood pressure and renal function in relation to left ventricular remodeling as compared to serum phosphorus.
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Study Population
From January to December 2014, we studied 405 consecutive patients with chronic kidney disease, who were hospitalized in the Department of Nephrology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine in Shanghai, China. We excluded 109 subjects from the present analysis, because of severe systolic dysfunction with left ventricular ejection fraction less than 50% (n = 19), moderate to severe cardiac valve diseases (n = 17), or taking phosphate binders or calcitriol
Characteristics of the Study Subjects
The 296 study subjects (mean age 56.4 years) included 169 (57.1%) men, 203 (68.6%) hypertensive patients, of whom 171 (58%) took antihypertensive drugs, and 64 (21.6%) diabetic patients. Table 1 shows the characteristics of the study subjects categoried by serum phosphorus in tertiles. Blood pressure and iPTH significantly increased, while serum corrected calcium, hemoglobin, and renal function decreased across increasing tertiles of serum phosphorus (P ≤ 0.002). Among echocardiographic indices,
Discussion
In this study, we found that serum phosphorus was significantly and independently associated with LVMI and the prevalence of LVH in hospitalized patients with CKD. To the best of our knowledge, our study was the first to demonstrate this association mainly due to the eccentric left ventricular remodeling. As compared, both SBP and eGFR were associated with LVMI and the prevalence of LVH, with SBP associated with both concentric and eccentric LVH, whereas eGFR, excluded the effect of serum
Conflicts of interest
The authors report no relationships that could be construed as a conflict of interest.
Acknowledgments
The authors gratefully acknowledge the voluntary participation of all study subjects.
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These authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.