Alkaline phosphatase variability predicts new onset heart failure, cardiovascular mortality, and all-cause mortality in patients with type-2 diabetes mellitus: a population-based study

ObjectiveTo investigate the associations of alkaline phosphatase (ALP) variability measures with new onset heart failure, cardiovascular mortality, and all-cause mortality in type 2 diabetes mellitus patients with a populational-cohort study. MethodThis study included patients with type 2 diabetes mellitus who presented to ambulatory, outpatient and inpatient facilities managed by the public sector in Hong Kong between January 1st, 2000 to December 31st, 2019. Comprehensive clinical and medical data including demographics, past comorbidities, medications, and laboratory examinations of complete blood, lipid/glycemic profile and their variability were collected. ALP and its variability measures were extracted. Univariable and multiple multivariable Cox regression were used to identify the associations of alkaline phosphatase variability with new onset heart failure and mortality risks. Patients were stratified into three subgroups based on the tertiles of baseline ALP level. ResultsThe study cohort consisted of 14289 patients (52.52% males, mean age at initial drug exposure: 74.55 years old [standard deviation (SD): 12.7]). Over a mean follow up of 2513 days [interquartile range (IQR): 1151-4173]), 10182 patients suffered from all-cause mortality (incidence rate [IR]: 71.25%), 1966 patients (IR: 13.75%) died from cardiovascular causes, and 1171 patients (IR: 8.19%) developed with new onset heart failure. Higher cumulative incidences of all three outcomes were observed for the highest tertile of ALP compared to medium/low tertiles. ALP baseline and variability level predicted new onset heart failure, cardiovascular and all-cause mortality before adjusting for subclinical biomarkers (p < 0.01). Amongst the measures of ALP variability, the hazard ratio (HR) of coefficient of variation (CV) was markedly raised in particular (new onset heart failure: HR=2.73, 95% confidence interval [CI]= [1.71-4.37], p <0.0001; all-cause mortality: HR= 5.83, 95% CI= [5.01-6.79], p <0.0001; cardiovascular mortality: HR= 4.81, 95% CI= [3.36-6.88], p <0.0001). ConclusionsRaised ALP level and variability are associated with increased risks of all-cause mortality, cardiovascular mortality and new onset heart failure amongst patients with type 2 diabetes mellitus.