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

Published on Nov 1, 2018in BMJ Open2.496
· DOI :10.1136/BMJOPEN-2018-023735
Maryam Kabootari4
Estimated H-index: 4
,
Mohammad Reza Raee1
Estimated H-index: 1
(Shahid Beheshti University of Medical Sciences and Health Services)
+ 3 AuthorsFarzad Hadaegh42
Estimated H-index: 42
(Shahid Beheshti University of Medical Sciences and Health Services)
Sources
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. © Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Figures & Tables
Download
📖 Papers frequently viewed together
11 Citations
20137.19Stroke
17 Authors (Masato Nagai, ..., Hirotsugu Ueshima)
73 Citations
References43
Newest
#1Gjin NdrepepaH-Index: 1
Alkaline phosphatase (AP) is a plasma membrane-anchored enzyme that is widely distributed in nature from bacteria to humans. AP has a broad specificity and catalyzes the hydrolysis of phosphate monoesters from a wide range of substrates. The best known physiological function of AP is participation in the bone mineralization by increasing the availability of phosphate that is used for hydroxyapatite synthesis. Measurement of AP activity in plasma is widely used for the diagnosis of bone and liver...
3 CitationsSource
#1Mathias Haarhaus (Linköping University)H-Index: 12
#2Vincent Brandenburg (RWTH Aachen University)H-Index: 59
Last. Per Magnusson (Linköping University)H-Index: 24
view all 5 authors...
Cardiovascular disease is the main cause of early death in the settings of chronic kidney disease (CKD), type 2 diabetes mellitus (T2DM), and ageing. Cardiovascular events can be caused by an imbal ...
78 CitationsSource
#1Rashmee Patil (BCM: Baylor College of Medicine)H-Index: 7
#2Gagan Sood (BCM: Baylor College of Medicine)H-Index: 21
: Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease associated with insulin resistance and metabolic syndrome. The spectrum of disease ranges from simple steatosis to steatohepatitis and progression to cirrhosis. Compelling evidence over the past several years has substantiated a significant link between NAFLD and cardiovascular disease ranging from coronary artery disease to subclinical carotid atherosclerosis. Close follow up, treatment of risk factors for NAFLD, and cardiov...
63 CitationsSource
#1Keiichi Sumida (University of Tsukuba)H-Index: 24
#2Miklos Z. Molnar (Semmelweis University)H-Index: 64
Last. Csaba P. Kovesdy (UTHSC: University of Tennessee Health Science Center)H-Index: 102
view all 11 authors...
Author(s): Sumida, K; Molnar, MZ; Potukuchi, PK; Thomas, F; Lu, JL; Obi, Y; Rhee, CM; Streja, E; Yamagata, K; Kalantar-Zadeh, K; Kovesdy, CP | Abstract: Higher serum alkaline phosphatase (ALP) levels have been associated with excess mortality in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) and end-stage renal disease (ESRD). However, little is known about the impact of late-stage NDD-CKD ALP levels on outcomes after dialysis initiation.Among 17 732 US veterans who transi...
19 CitationsSource
#1Mahsa Sardarinia (Shahid Beheshti University of Medical Sciences and Health Services)H-Index: 5
#2Samaneh Akbarpour (Shahid Beheshti University of Medical Sciences and Health Services)H-Index: 8
Last. Farzad Hadaegh (Shahid Beheshti University of Medical Sciences and Health Services)H-Index: 42
view all 8 authors...
Background To examine the association between potentially modifiable risk factors with cardiovascular disease (CVD) and all-cause mortality and to quantify their population attributable fractions (PAFs) among a sample of Tehran residents. Methods Overall, 8108 participants (3686 men) aged≥30 years, were investigated. To examine the association between risk factors and outcomes, multivariate sex-adjusted Cox proportional hazard regression analysis were conducted, using age as time-scale in two mo...
50 CitationsSource
#1Iman Moghaddasifar (Mazandaran University of Medical Sciences)H-Index: 4
#2Kamran Bagheri Lankarani (Shiraz University of Medical Sciences)H-Index: 36
Last. Mina Malary (Mazandaran University of Medical Sciences)H-Index: 5
view all 8 authors...
Background: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease in developing and developed countries. Estimating the total prevalence of NAFLD by means of appropriate statistical methods can provide reliable evidence for health policy makers. Objective: To determine the prevalence of NAFLD in Iran using a systematic review and meta-analysis. Methods: We identified relevant studies by searching national and international databases. Standard error of the prevalen...
37 Citations
#1Kenneth D. KochanekH-Index: 35
#2Sherry L MurphyH-Index: 29
Last. Betzaida Tejada-VeraH-Index: 8
view all 4 authors...
Objectives-This report presents final 2014 data on U.S. deaths, death rates, life expectancy, infant mortality, and trends, by selected characteristics such as age, sex, Hispanic origin, race, state of residence, and cause of death.
287 Citations
#1Setor K Kunutsor (University of Cambridge)H-Index: 44
#2Stephan J. L. Bakker (UMCG: University Medical Center Groningen)H-Index: 92
Last. Robin P. F. Dullaart (UMCG: University Medical Center Groningen)H-Index: 69
view all 6 authors...
Alkaline phosphatase (ALP) has been suggested to be associated with cardiovascular disease (CVD) risk, however, important aspects of the association, such as shape and independence from established risk factors, have yet to be characterized in detail. We assessed the association of ALP with CVD risk and determined its utility for CVD risk prediction. Alkaline phosphatase activity was measured at baseline in the PREVEND prospective cohort involving 6,974 participants aged 28-75 years without pre-...
25 CitationsSource
#1Setor K Kunutsor (University of Cambridge)H-Index: 44
#2Tanefa A. Apekey (University of Leeds)H-Index: 13
Last. Hassan Khan (University of Cambridge)H-Index: 32
view all 3 authors...
Abstract Background Gamma glutamyltransferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP), commonly used markers of liver dysfunction, have been implicated with risk of cardiovascular disease (CVD). However, the strength and consistency of their associations in the general population have not been reliably quantified. Methods We synthesized available prospective epidemiological data on the associations of baseline levels of GGT, ALT, AST...
109 CitationsSource
#1Davood Khalili (Shahid Beheshti University of Medical Sciences and Health Services)H-Index: 30
#2Farhad Sheikholeslami (Shahid Beheshti University of Medical Sciences and Health Services)H-Index: 14
Last. Farzad Hadaegh (Shahid Beheshti University of Medical Sciences and Health Services)H-Index: 42
view all 6 authors...
Background Data on incidence of coronary heart disease (CHD) is scarce in the Middle East and little is known about the contribution of known risk factors in this area. Methods The incidence of CHD and the effect of modifiable risk factors were explored in 2889 men and 3803 women aged 30–74 years in the population based cohort of the Tehran Lipid and Glucose Study, during 1999–2010. Average population attributable fraction (aPAF) was calculated for any risk factor using direct method based on re...
45 CitationsSource
Cited By7
Newest
#1Wen Guo (Nanjing Medical University)H-Index: 5
#2Xiaona Li (Nanjing Medical University)H-Index: 2
Last. Qun Zhang (Nanjing Medical University)H-Index: 9
view all 9 authors...
BACKGROUND Serum alkaline phosphatase (ALP) has been recognized as a biomarker of cardiovascular disease (CVD) risk, recently. This study aimed to explore the association of ALP with arterial stiffness and 10-year CVD risk. METHODS A total of 12 539 participants without CVD who underwent health examinations including serum ALP level were retrospectively analysed. Arterial stiffness was measured by brachial-ankle pulse wave velocity (baPWV), and 10-year CVD risk was evaluated by Framingham risk s...
Source
#1Hiroyuki Naito (Hiroshima University)H-Index: 5
#2Tomohisa Nezu (Hiroshima University)H-Index: 14
Last. Hirofumi Maruyama (Hiroshima University)H-Index: 32
view all 13 authors...
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 month...
Source
#1Irene Ruderman (Royal Melbourne Hospital)H-Index: 5
#2Nigel D Toussaint (Royal Melbourne Hospital)H-Index: 15
Last. Grahame J Elder (Garvan Institute of Medical Research)H-Index: 22
view all 7 authors...
BACKGROUND: Calciphylaxis is a rare disease, predominantly affecting patients with chronic kidney disease (CKD) and associated with significant morbidity and mortality due to progressive cutaneous calcification, necrotic ulceration and infection. Clinical registries have been established to better understand the risk factors, optimal treatments and disease outcomes of calciphylaxis. METHODS: We established a prospective, Internet-based clinical registry for the online notification of calciphylax...
3 CitationsSource
Last. Tanvir AlamH-Index: 10
view all 6 authors...
Cardiovascular disease (CVD) is reported to be the leading cause of mortality in the middle eastern countries, including Qatar. But no comprehensive study has been conducted on the Qatar specific CVD risk factors identification. The objective of this case-control study was to develop machine learning (ML) model distinguishing healthy individuals from people having CVD, which could ultimately reveal the list of potential risk factors associated to CVD in Qatar. To the best of our knowledge, this ...
Source
#1Almudena Veiga-Lopez (UIC: University of Illinois at Chicago)H-Index: 28
#2Visalakshi Sethuraman (MSU: Michigan State University)
Last. Flóra Szeri (Semmelweis University)H-Index: 12
view all 10 authors...
Epidemiological studies indicate that elevated alkaline phosphatase activity is associated with increased cardiovascular disease risk. Other epidemiological data demonstrate that mothers giving multiple childbirths (multipara) are also at increased risk of developing late-onset cardiovascular disease. We hypothesized that these two associations stem from a common cause, the insufficient plasma level of the ectopic mineralization inhibitor inorganic pyrophosphate, which is a substrate of alkaline...
Source
#1Yuya Yokota (Okayama University)
#2Yoshito Nishimura (Okayama University)H-Index: 5
Last. Fumio Otsuka (Okayama University)H-Index: 35
view all 10 authors...
Alkaline phosphatase (ALP) is an enzyme that is expressed in a variety of tissues. Among the isoforms of ALP, bone-specific alkaline phosphatase (BAP) is used as a marker for evaluating bone metabolism. We investigated the clinical usefulness of the ratio of serum BAP to total ALP for the diagnosis of various disorders in general practice. We retrospectively analyzed the cases of 107 Japanese patients whose serum BAP levels were exam-ined, focusing on clinical characteristics. We observed that t...
Source
#1Ilia Beberashvili (TAU: Tel Aviv University)H-Index: 16
#2Oleksandra Samogalska (TAU: Tel Aviv University)H-Index: 1
Last. Shai Efrati (TAU: Tel Aviv University)H-Index: 26
view all 5 authors...
Objective Higher serum alkaline phosphatase (sALP) levels associate with a poor prognosis in maintenance hemodialysis patients. However, little is known about the meaning of lower sALP in this population. We hypothesized that lower sALP concentrations may express nutritional status and survival accordingly. Methods A retrospective, longitudinal cohort study of a clinical database containing the medical records of 554 patients (367 men and 187 women, mean age 67.6 ± 14.2 years) receiving maintena...
2 CitationsSource