Serum alkaline phosphatase and the risk of coronary heart disease, stroke and all-cause mortality: Tehran Lipid and Glucose Study

Abstract

Objectives To investigate the association of alkaline phosphatase (ALP) levels with the risk of the composite end point of cardiovascular disease (CVD), and all-cause mortality as well as each of them separately. Design Prospective cohort study. Setting Within the framework of the Tehran Lipid and Glucose Study (TLGS) cohort, participants were followed from baseline examination (1999-2001) until March 2014. Participants A total of 2578 participants, aged ≥30 years free of prevalent CVD at baseline examination. Primary outcome The main outcome measures were composite end point of coronary heart disease (CHD), stroke, all-cause mortality and each per se. Results During a median follow-up of 11.3 years, 369, 68, 420, 170 and 495 participants experienced CHD, stroke, CVD, all-cause mortality and the composite outcome, respectively. In the multivariable Cox regression models, the adjusted HRs (95% CI) for mentioned events per one SD increase in ALP level after full adjustment were 1.11 (1.01 to 1.22), 1.20 (0.97 to 1.49, p=0.058), 1.10 (1.01 to 1.21), 1.16 (1.01 to 1.33) and 1.11 (1.02 to 1.21), respectively. Furthermore, participants with ALP levels in the highest tertile had significant adjusted HRs (95% CI) for stroke (1.88 (1.00 to 3.61)), CVD (1.30 (1.01 to 1.68)) and composite outcome (1.27 (1.00 to 1.61)). The cut-off value of ALP ≥199 IU/L for predicting composite outcome was derived using Youden's index, based on which this cut-off point was associated with significant risk of 80%, 26%, 43% and 26% for incident stroke, CVD, all-cause mortality and composite outcome. Additionally, no improvement was seen in the predictive ability of traditional risk factors models after adding ALP values, considering the levels of Akaike information criterion, C-index and Net Reclassification Index. Conclusion Independent associations between ALP levels and the risks of CVD and mortality events were shown, despite the fact that adding the data of ALP to known risk factors did not improve the prediction of these events.