Association Of Alkaline Phosphatase Research Articles

Association of Alkaline Phosphatase with Cardiovascular Disease in Patients with Dyslipidemia: A 6-Year Retrospective Study.

Serum alkaline phosphatase (ALP) activity has been associated with atherosclerotic cardiovascular disease (ASCVD). We aimed to investigate the association of ALP with ASCVD in patients with dyslipidemia. We conducted a retrospective cohort study including consecutive adults with dyslipidemia followed-up for ≥3 years (from 1999 to 2022) in the outpatient Lipid Clinic of Ioannina University General Hospital, Greece. The primary endpoint was the association between baseline ALP and incident ASCVD after adjusting for traditional risk factors (i.e., sex, age, hypertension, diabetes, smoking, and dyslipidemia), baseline ASCVD, and lipid-lowering treatment. ALP levels were stratified by tertiles as follows: low: <67 U/L, middle: 67-79 U/L, high: ≥79 U/L. Overall, 1178 subjects were included; 44% were males, and their median age was 57 years (range: 49-65). During a 6-year median follow-up (interquartile range: IQR: 4-9), 78 new ASCVD events (6.6%) occurred. A statistically significant association between baseline ALP levels and incident ASCVD was demonstrated (Odds Ratio, OR: 6.99; 95% Confidence Interval, CI: 2.29-21.03, p = 0.001). Subjects in the highest ALP tertile had the highest odds for ASCVD when compared with those in the lowest tertile (OR: 2.35; 95% CI: 1.24-4.41, p = 0.008). The present study indicates an association between ALP and the development of ASCVD in patients with dyslipidemia, which underscores the potential of ALP as a predictive tool or a therapeutic target in the realm of ASCVD prevention within this population.

Pediatric reference values of alkaline phosphatase: Analysis from a German population-based cohort and influence of anthropometric and blood parameters

BackgroundDue to different growth and metabolic processes, reference values of alkaline phosphatase (AP) for children aged 3 month to 18 years are dependent on age and sex. They are not constant and differ from those of adults due to the growth processes taking place. Accordingly, reference levels of AP continuous across these ages were generated for boys and girls based on of a large German health- and population-based study, LIFE Child. We considered AP at different growth and Tanner stages and additionally its association with other anthropometric parameters. The association between AP and BMI was of particulary great interest due to controversial literature on this topic. The role of AP in liver metabolism was investigated by examining ALAT, ASAT, and GGT. Methods3976 healthy children (12,093 visits) were included from the LIFE Child study from 2011 to 2020. The subjects´ age ranged from 3 months to 18 years. Serum samples from 3704 subjects (10,272 cases, 1952 boys and 1753 girls) were analysed for AP after applying specific exclusion criteria. After calculating of reference percentiles, associations between AP and height-SDS, growth velocity, BMI-SDS, Tanner stage and the liver enzymes ALAT, ASAT and GGT were examined via linear regression models. ResultsIn the continuous reference levels, AP showed a first peak during the first year of life, followed by a plateau at a lower level until the start of puberty. In girls, AP increased beginning at the age 8, with a peak around 11 years, in boys beginning at the age 9, with a peak around age 13. Afterwards, AP values decreased continuously until age 18. In Tanner stages 1 and 2, AP levels did not differ between the two sexes. We found a strong positive association between AP-SDS and BMI-SDS. We also observed a significantly positive association between AP-SDS and height-SDS, which was stronger in boys than in girls. We found different intensities in the associations of AP with growth velocity depending on age group and sex. Furthermore, we found a significantly positive association between ALAT and AP in girls but not in boys, whereas ASAT-SDS and GGT-SDS were significantly positively associated with AP-SDS in both sexes. ConclusionSex and age, but also BMI may act as confounding factors for AP reference ranges. Our data confirm the remarkable association between AP and growth velocity (or height-SDS, respectively) during infancy and puberty. In addition, we were able to specify the associations between AP and ALAT, ASAT, and GGT and their differences in both sexes. These relations should be considered when evaluating liver and bone metabolism markers, especially in infancy.

Prognostic values of serum alkaline phosphatase and globulin levels in patients undergoing intravenous thrombolysis.

BackgroundIn previous studies, alkaline phosphatase (ALP) level was a prognostic factor for patients with ischemic stroke, and globulin level was associated with hemorrhagic transformation (HT) after intravenous thrombolysis (IVT). However, the association between these serum biomarkers and prognosis in patients with acute ischemic stroke (AIS) who undergo IVT remains unclear. This study aimed to investigate the characteristics of serum ALP and globulin levels after IVT and to assess the relationship between these serum biomarkers and prognosis.Materials and methodsThis retrospective study used a prospectively collected database. We included patients with AIS who received recombinant tissue plasminogen activator (rt-PA) IVT. Demographic information, vascular risk factors, laboratory test results, and other stroke-related data were collected for analysis. Clinical outcomes included HT and 3-month poor outcome (modified Rankin Scale scores ≥ 2) after IVT. The association of ALP and globulin levels with HT and poor outcome was investigated using multivariate logistic regression analysis. An individualized prediction model based on ALP and globulin levels for functional outcomes was established.ResultsWe enrolled 750 patients in this study; 452 patients (60.3%) had poor outcome, and 117 patients (15.6%) had HT after IVT. After adjusting for all confounders, serum globulin level [OR = 1.055; 95% confidence intervals (CI): 1.006–1.107; P = 0.028] was independently associated with HT in patients with IVT. Serum ALP (OR = 1.009; 95% CI: 1.002–1.016; P = 0.010) and globulin levels (OR = 1.062; 95% CI: 1.020–1.107; P = 0.004) were associated with 3-month poor outcome in these patients. The constructed individualized prediction model for the 3-month poor outcome comprised the National Institutes of Health Stroke Scale (NIHSS) score, Trial of Org 10172 in Acute Stroke Treatment (TOAST), history of antihypertensive therapy, ALP and globulin levels. The area under the curve of the training and validation sets were 0.726 and 0.706, respectively, revealing that the model had good discriminating power. The P-values for the Hosmer-Lemeshow test in the training and validation sets were 0.978 and 0.148, respectively, indicating the model had good calibration.ConclusionThis study found that higher serum globulin levels were independently associated with HT. Additionally, higher serum ALP and globulin levels were independently associated with a poor outcome in patients after IVT.

Increased Serum Alkaline Phosphatase and Functional Outcome in Patients with Acute Ischemic Stroke Presenting a Low Ankle-Brachial Index.

Aims: Elevated serum alkaline phosphatase (ALP) levels are associated with an increased risk of cerebrocardiovascular diseases. However, the associations of ALP with peripheral arterial disease (PAD) and outcomes in patients with acute ischemic stroke (AIS) are not well-known. Methods: We examined the association between ALP levels and the ankle–brachial index (ABI) in 2111 consecutive patients with AIS. A poor functional outcome was defined as a modified Rankin Scale (mRS) score of 3–6 at 3 months after stroke. A low ABI was defined as a value of ≤ 0.9. Results: Of the total cohort, 482 patients (22.8%) had a low ABI. ALP levels were higher in patients with a low ABI than in those without (p＜0.001). The multivariable logistic analysis revealed that quartiles of ALP levels were significantly associated with a low ABI (odds ratio [OR]: 1.20, 95% confidence interval [CI]: 1.08–1.33). Of the 1322 patients with a premorbid mRS score of 0–2, 434 patients (32.8%) had a poor outcome. The multivariable analysis revealed that elevated serum ALP levels and a low ABI were independently associated with poor stroke outcomes after adjustment for baseline characteristics (OR: 1.21, 95% CI: 1.07–1.38, and OR: 2.00, 95% CI: 1.40–2.84, respectively). Conclusions: Increased serum ALP levels are significantly associated with a low ABI. These indicators are independent prognostic factors for poor stroke outcomes at 3 months.

Serum alkaline phosphatase level is correlated with the incidence of cerebral small vessel disease.

Vascular calcification is one of the mechanisms underlying the pathogenesis of cerebral small vessel disease (CSVD). Whether higher levels of serum alkaline phosphatase (ALP), a predictor of vascular calcification, are independently associated with CSVD remains inconclusive. The present study explored the link between levels of circulating ALP and CSVD in a Chinese population. A total of 568 participants were recruited from the healthcare center at the affiliated Zhongshan Hospital of Dalian University and the Fifth People Hospital of Dalian between January 2010 and December 2016. The subjects were divided into three groups based on the infarct and severity of white matter hyper-intensities (WMH) as categorized by brain magnetic resonance imaging (MRI) analysis and Fazekas rating scales: no/mild cerebral WMH (nm-WMH); moderate-to-severe WMH (MS-WMH); and silent lacunar infarct (SLI). The subjects were also divided into three tertiles based on circulating levels of ALP: ≤64, 65-105 and ≥106 (IU/L). Information regarding the risk factors, such as coronary artery disease, diabetes mellitus, hypertension and serum ALP level, C-reactive protein, homocysteine (HCY), and other laboratory results, were collected. The associations of ALP with WMH and SLI were evaluated using logistic regression analysis. After adjustment for vascular risk factors, subjects with MS-WMH and SLI were more likely to have ALP levels ≥106 IU/L than ≤64 IU/L. The mean circulating level of ALP was substantially increased in patients with MS-WMH or SLI compared with patients with nm-WMH. The multivariate model revealed that this significant difference remained when MS-WMH or SLI was added to the model, after adjustment for confounding factors. The circulating level of ALP was positively correlated with a high risk of silent lacunar infarct and white matter hyperintensity; important indicators of small vessel disease.

Alkaline phosphatase at diagnosis of primary sclerosing cholangitis and 1 year later: evaluation of prognostic value.

Primary sclerosing cholangitis (PSC) is a slowly progressive liver disease. Reliable biomarkers to predict outcome are urgently needed to serve as surrogate endpoints and/or stratifiers in clinical trials. Reduction in serum alkaline phosphatase (ALP) has been proposed as prognostic surrogate marker in PSC. The aim of this study was to asses if ALP at diagnosis (T0), 1 year later (T1), and percentage change between both time points hold prognostic value, and to determine the optimal threshold. We retrospectively collected ALP levels at T0 and T1 for patients included in a large PSC cohort. The association of ALP at T0, T1, and percentage change with the combined endpoint (PSC-related death, liver transplantation) was analysed. Predictive value was determined using C-statistics. A total of 366 patients were included, of whom 66 (18%) reached an endpoint: 26 (7%) PSC-related death, 40 (11%) liver transplantation. At T0 and T1, 84% used ursodeoxycholic acid. A positive association was observed between level of ALP at T0 and T1 and the hazard of reaching an endpoint, up to values around 2.5 times upper limit of normal (xULN). A larger decrease in ALP between T0 and T1 decreased the event rate. A range of thresholds (0.5-3×ULN) with about similar C-statistics was found. In this cohort, the optimal threshold was 1.3×ULN at T1. ALP can be used to discriminate between PSC patients with a good and a poor prognosis. These findings indicate that ALP can serve as stratifier, and potentially as surrogate endpoint for clinical trials in PSC.

Association of alkaline phosphatase with isolated coronary artery ectasia

Background. It has been shown that alkaline phosphatase (ALP) is a reliable marker for cardiovascular events and mortality. However, there is no data available regarding the association of ALP with isolated coronary artery ectasia (CAE). The aim of the present study was to assess the serum ALP activity in isolated CAE. Methods. Seventy-nine patients with isolated CAE (59 males; mean age, 52 ± 12 years) and 88 age- and gender-matched normal subjects (73 males; mean age, 52 ± 7 years) were enrolled. Baseline characteristics were recorded in both groups and serum ALP activity were compared between the two groups. Results. Patients with angiography-proved isolated CAE had significantly higher serum ALP activity compared with angiographic normal controls (72.41 ± 29.97 vs. 59.27 ± 14.46, p < 0.001). In the multivariate analysis, increased ALP (OR = 1.037, 95% CI 1.017–1.057, p < 0.001) were independent predictors for the presence of isolated CAE. A cut-off of ≥ 66.5 U/L of ALP activity measured on admission had a 60.8% sensitivity and 75.0% specificity in predicting isolated CAE by receiver operating characteristic (ROC) curve analysis. Conclusion. Our data firstly demonstrated that serum ALP activity, a readily available clinical laboratory value, was associated with the presence of isolated CAE.

Association of serum alkaline phosphatase with mortality in non-selected European patients with CKD5D: an observational, three-centre survival analysis

ObjectivesFor characterisation of mineral bone disease in chronic kidney disease (CKD), laboratory surrogates have been suggested. This observational should investigate the association of total and skeletal alkaline phosphatase (AP) with...

Association of alkaline phosphatase (ALP) with clinical outcomes in chemotherapy-naive patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): Results from COU-AA-302.

27 Background: Prognostic models have been developed for men with mCRPC. In this analysis we undertook a pragmatic approach to focus on commonly obtained markers. Baseline ALP and normalization of elevated ALP post-docetaxel have prognostic value for overall survival (OS). We examined the association between ALP and prostate-specific antigen (PSA) elevation at baseline and after 4 cycles of therapy (C5D1), when both markers were assessed, with long-term clinical outcomes in COU-AA-302, a randomized phase 3 study of abiraterone acetate (AA) in chemotherapy-naive mCRPC pts. Methods: 1,088 pts were randomized 1:1 to AA (1 g) + prednisone (P) (5 mg BID) or placebo + P. Radiographic progression-free survival (rPFS) and OS were co-primary end points. The study design, as well as primary and secondary end point results obtained at the time of a prespecified interim analysis at 55% OS events, have been described in detail previously. The effect of elevated ALP (above upper limit of normal) and PSA (above 106.2 µg/mL, baseline third quartile) status on rPFS and OS was assessed retrospectively using a stratified Cox regression model that included treatment and baseline factors log (lactate dehydrogenase), hemoglobin, whether patient had only bone metastasis, and age. Results: Elevated status of ALP and PSA were independent significant predictors of increased risk for outcomes at baseline as well as after 4 cycles of therapy (Table). Conclusions: These post hoc analyses of data from COU-AA-302 suggest that elevated ALP and PSA at baseline and during treatment confers individual and additive risk for adverse clinical outcomes in chemotherapy-naive mCRPC. Clinical trial information: NCT00887198. [Table: see text]

Association of alkaline phosphatase with acute myocardial infarction in a population with high prevalence of hypovitaminosis D

BackgroundSince Pakistanis have high prevalence of hypovitaminosis-D as well as acute myocardial infarction (AMI), the objective of the study was to investigate the relationship between vitamin-D deficiency and risk of AMI in a hospital-based population and to identify major risk factors for this disease. MethodsFasting serum samples from 66 consecutive AMI patients [age 30–70y] and 132 gender and age-matched (within 5y) healthy controls were analyzed for concentrations of glucose, total-cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, calcium, inorganic phosphate, alkaline phosphatase (ALP), bone-ALP, parathyroid hormone (PTH), 25(OH) vitamin-D (25(OH)D) and alanine aminotransferase. ResultsMean concentrations of serum 25(OH)D, PTH, total-ALP, bone-ALP, LDL-cholesterol, HDL-cholesterol and glucose were significantly different compared to healthy controls (p<0.05). Percent vitamin-D deficiency/insufficiency (levels<30ng/ml) was significantly greater in AMI patients compared to controls (93.9% vs.75.8%; p=0.001). Multiple conditional logistic regression analysis revealed that increased levels of 25(OH)D were associated with decreased risk of AMI [MAOR (95% CI)=0.821 (0.718, 0.940); p=0.004]. Hypertension and smoking were positively associated with AMI. ConclusionsIncreased vitamin-D levels were associated with decreased risk of AMI, while serum glucose, bone-ALP, hypertension and smoking were positively associated with it. Association of bone-ALP with AMI in hypovitaminosis-D is a novel finding of this study.

Associations of Serum Skeletal Alkaline Phosphatase with Elevated C-Reactive Protein and Mortality

Higher serum total alkaline phosphatase (AP) levels are associated with increased serum C-reactive protein (CRP) levels and mortality in the general and CKD populations. It is unclear to what extent these associations are related to bone disease. In a nationally representative sample of 10,707 adult participants from the 1999-2004 National Health and Nutrition Examination Survey, serum nonskeletal AP levels were estimated from the measured serum skeletal and total AP levels. The associations of serum skeletal AP and nonskeletal AP levels with elevated serum CRP concentrations (>3 mg/L) and mortality were examined in multivariable models. Skeletal AP was not associated with elevated CRP (for each doubling in non-CKD: odds ratio [OR], 1.00; 95% confidence interval [95% CI], 0.90-1.11; in CKD: OR, 1.19; 95% CI, 0.83-1.70) or mortality (for each doubling in non-CKD: hazard ratio [HR], 1.10; 95% CI, 0.94-1.29; in CKD: HR, 0.98; 95% CI, 0.75-1.28). In contrast, nonskeletal AP was associated with elevated CRP (for each doubling in non-CKD: OR, 4.51; 95% CI, 3.80-5.35; in CKD: OR, 5.98; 95% CI, 3.40-10.51). Nonskeletal AP was associated with mortality in non-CKD (for each doubling: HR, 1.96; 95% CI, 1.37-2.80) but not in CKD (for each doubling: HR, 0.92; 95% CI, 0.51-1.67) (interaction P=0.03). Bone disease is unlikely to account for the known associations of serum total AP with increased inflammation and mortality.

Mineral and bone disorders and survival in hemodialysis patients with and without polycystic kidney disease

Maintenance hemodialysis (MHD) patients with polycystic kidney disease (PKD) have better survival than non-PKD patients. Mineral and bone disorders (MBD) are associated with accelerated atherosclerosis and cardiovascular death in MHD patients. It is unknown whether the different MBD mortality association between MHD populations with and without PKD can explain the survival differential. Survival models were examined to assess the association between different laboratory markers of MBD [such as serum phosphorous, parathyroid hormone (PTH), calcium and alkaline phosphatase] and mortality in a 6-year cohort of 60,089 non-PKD and 1501 PKD MHD patients. PKD and non-PKD patients were 57±13 and 62±15 years old and included 46 and 45% women and 14 and 32% Blacks, respectively. Whereas PKD individuals with PTH 150 to <300 pg/mL (reference) had the lowest risk for mortality, the death risk was higher in patients with PTH<150 [hazard ratio (HR): 2.16 (95% confidence interval 1.53-3.06)], 300 to <600 [HR: 1.30 (0.97-1.74)] and ≥600 pg/mL [HR: 1.46 (1.02-2.08)], respectively. Similar patterns were found in non-PKD patients. Fully adjusted death HRs of time-averaged serum phosphorous increments<3.5, 5.5 to <7.5 and ≥7.5 mg/dL (reference: 3.5 to <5.5 mg/dL) for PKD patients were 2.82 (1.50-5.29), 1.40 (1.12-1.75) and 2.25 (1.57-3.22). The associations of alkaline phosphatase and calcium with mortality were similar in PKD and non-PKD patients. Bone-mineral disorder markers exhibit similar mortality trends between PKD and non-PKD MHD patients, although some differences are observed in particular in low PTH and phosphorus ranges.

Translocation of alkaline phosphatase during the activation of B cells

The association of alkaline phosphatase (ALPase) with the cytoskeleton in lymphoid cells was investigated. Extracting cells with non-ionic detergents such as Triton, we determined that ALPase is present in the cytoskeletal fraction in fully differentiated B lymphocytes, X63 myeloma cells and Sp2/O hybridoma cells. During the course of B-lymphocyte activation, the ALPase shifted from a soluble to a Triton-Insoluble form. Changes in the phosphorylation of Triton-insoluble proteins with molecular weights of 120, 100, 90, 75, 34 and 31 kDa were detected, coinciding with the appearance of the ALPase in this fraction. The possible role of ALPase in the differentiation of B cells is discussed.

Electron micrographic study of precipitates formed by interaction of silicic acid and alkaline phosphatase: Contribution to a study of silica urolithiasis in cattle

Association of alkaline phosphatase with silicic acid in precipitates formed in dilute solution was studied as a model for the nonspecific reaction between silicic acid and protein. Precipitates contained 68-83% of the silicic acid and 52-83% of the enzyme in the original mixture and were in the form of aggregates of roundish particles 150-800 nm in diameter. Enzyme protein formed a tightly bound layer on the surface of particles formed in solutions of freshly prepared silicic acid. The similarity between the ultrastructural features of precipitates from solutions of silicic acid and of internal portions of siliceous urinary calculi from cattle suggests that deposition of silica during development of such calculi is due, at least in part, to the interaction of protein with silicic acid in urine.