Abstract
BackgroundIt is demonstrated that elevated serum levels of alkaline phosphatase (ALP) and phosphate indicate a higher risks of cardiovascular disease (CVD) and total mortality in population with chronic kidney disease (CKD), but it remains unclear whether this association exists in people with normal or preserved renal function.MethodClinical trials were searched from Embase and PubMed from inception to 2013 December using the keywords “ALP”, “phosphate”, “CVD”, “mortality” and so on, and finally 24 trials with a total of 147634 patients were included in this study. Dose-response and semi-parametric meta-analyses were performed.ResultsA linear association of serum levels of ALP and phosphate with risks of coronary heart disease (CHD) events, CVD events and deaths was identified. The relative risk(RR)of ALP for CVD deaths was 1.02 (95% confidence interval [CI], 1.01–1.04). The RR of phosphate for CVD deaths and events was 1.05 (95% CI, 1.02–1.09) and 1.04 (95% CI: 1.03–1.06), respectively. A non-linear association of ALP and phosphate with total mortality was identified. Compared with the reference category of ALP and phosphate, the pooled RR of ALP for total mortality was 1.57 (95% CI, 1.27–1.95) for the high ALP group, while the RR of phosphate for total mortality was 1.33 (95% CI, 1.21–1.46) for the high phosphate group. It was observed in subgroup analysis that higher levels of serum ALP and phosphate seemed to indicate a higher mortality rate in diabetic patients and those having previous CVD. The higher total mortality rate was more obvious in the men and Asians with high ALP.ConclusionA non-linear relationship exists between serum levels of ALP and phosphate and risk of total mortality. There appears to be a positive association of serum levels of ALP/phosphate with total mortality in people with normal or preserved renal function, while the relationship between ALP and CVD is still ambiguous.
Highlights
Alkaline phosphatase (ALP) is an enzyme responsible for hydrolyzing phosphate esters and liberating inorganic phosphate
Some researchers have recently found that higher levels of serum alkaline phosphatase (ALP) and phosphate indicate a higher risk of cardiovascular diseases (CVDs) and total mortality in people without chronic kidney disease (CKD)
Key words used for search included ‘‘alkaline phosphatase’’, ‘‘phosphate’’, ‘‘hypophosphatemia’’, ‘‘hyperphosphatemia’’, ‘‘cardiovascular diseases’’ and ‘‘mortality’’
Summary
Alkaline phosphatase (ALP) is an enzyme responsible for hydrolyzing phosphate esters and liberating inorganic phosphate. Serum ALP activity is elevated in hepatobiliary and bone diseases such as obstructive jaundice and bone cancer Phosphorus exists in both organic and inorganic forms in our body. Previous meta-analyses show that elevated serum levels of phosphorus indicate a higher risk of mortality in population with chronic kidney disease (CKD) [3,4], with the premise that the relation between the exposure and outcome being linear. We conduct a dose-response meta-analysis to quantify the association between serum levels of ALP and phosphate and the risk of CVDs and total mortality in these individuals. It is demonstrated that elevated serum levels of alkaline phosphatase (ALP) and phosphate indicate a higher risks of cardiovascular disease (CVD) and total mortality in population with chronic kidney disease (CKD), but it remains unclear whether this association exists in people with normal or preserved renal function
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