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      Apolipoprotein B/Apolipoprotein A-I Ratio Is a Better Predictor of Cancer Mortality Compared with C-Reactive Protein: Results from Two Multi-Ethnic US Populations

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          Abstract

          Background: There is a lack of evidence regarding the link between apolipoproteins and cancer mortality. By using two nationally representative samples of US adults, we prospectively evaluated the associations between apolipoprotein B (apoB) levels and apoB/apoA-I ratio with cancer mortality. We also examined the role of C-reactive protein (CRP) in these associations. Materials and Methods: Adults aged ≥20 years, enrolled in the 3rd National Health and Nutrition Examination Survey (NHANES III, 1988–1994) and continuous NHANES (2005–2010), and followed up to 31 December 2011, were included in the analysis. Multiple Cox regressions were applied to evaluate the associations between the variables of interest and cancer mortality. Results: Overall, 7695 participants were included (mean age: 49.2 years; 50.4% men, median follow-up: 19.1 years). In the fully adjusted model, participants in the highest quartile (Q4) of apoB/apoA-I had a significantly greater risk for cancer mortality (hazard ratio (HR): 1.40; 95% confidence interval (CI): 1.25–1.93) compared with those in the first quartile (Q1). In the same model, a positive and significant association between apoB levels and cancer mortality was observed for individuals in Q3 (HR: 1.12; 95% CI: 1.09–1.16) and Q4 (HR: 1.17; 95% CI: 1.09–1.25) compared with those in Q1. When CRP levels were added in the analysis, the apoB/apoA-I ratio, but not apoB levels, remained significantly related to cancer mortality (Q4 = HR: 1.17; 95% CI: 1.09–1.25). In contrast, CRP levels were not able to predict cancer death after correction for apoB/apoA-I ratio. Conclusions: In a large representative sample of the US adult population, the apoB/apoA-I ratio and apoB levels significantly predicted cancer mortality, independently of several cardiometabolic risk factors. The predictive value of apoB/apoA-I, but not apoB levels, remained significant after taking into account CRP, whereas CRP was not associated with cancer mortality after adjustment for apoB/apoA-I ratio. If further evidence supports our findings, apoA-I and apoB measurements could be considered in general healthcare policies.

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          Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: a systematic analysis for the Global Burden of Disease Study 2017

          Summary Background Global development goals increasingly rely on country-specific estimates for benchmarking a nation's progress. To meet this need, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 estimated global, regional, national, and, for selected locations, subnational cause-specific mortality beginning in the year 1980. Here we report an update to that study, making use of newly available data and improved methods. GBD 2017 provides a comprehensive assessment of cause-specific mortality for 282 causes in 195 countries and territories from 1980 to 2017. Methods The causes of death database is composed of vital registration (VR), verbal autopsy (VA), registry, survey, police, and surveillance data. GBD 2017 added ten VA studies, 127 country-years of VR data, 502 cancer-registry country-years, and an additional surveillance country-year. Expansions of the GBD cause of death hierarchy resulted in 18 additional causes estimated for GBD 2017. Newly available data led to subnational estimates for five additional countries—Ethiopia, Iran, New Zealand, Norway, and Russia. Deaths assigned International Classification of Diseases (ICD) codes for non-specific, implausible, or intermediate causes of death were reassigned to underlying causes by redistribution algorithms that were incorporated into uncertainty estimation. We used statistical modelling tools developed for GBD, including the Cause of Death Ensemble model (CODEm), to generate cause fractions and cause-specific death rates for each location, year, age, and sex. Instead of using UN estimates as in previous versions, GBD 2017 independently estimated population size and fertility rate for all locations. Years of life lost (YLLs) were then calculated as the sum of each death multiplied by the standard life expectancy at each age. All rates reported here are age-standardised. Findings At the broadest grouping of causes of death (Level 1), non-communicable diseases (NCDs) comprised the greatest fraction of deaths, contributing to 73·4% (95% uncertainty interval [UI] 72·5–74·1) of total deaths in 2017, while communicable, maternal, neonatal, and nutritional (CMNN) causes accounted for 18·6% (17·9–19·6), and injuries 8·0% (7·7–8·2). Total numbers of deaths from NCD causes increased from 2007 to 2017 by 22·7% (21·5–23·9), representing an additional 7·61 million (7·20–8·01) deaths estimated in 2017 versus 2007. The death rate from NCDs decreased globally by 7·9% (7·0–8·8). The number of deaths for CMNN causes decreased by 22·2% (20·0–24·0) and the death rate by 31·8% (30·1–33·3). Total deaths from injuries increased by 2·3% (0·5–4·0) between 2007 and 2017, and the death rate from injuries decreased by 13·7% (12·2–15·1) to 57·9 deaths (55·9–59·2) per 100 000 in 2017. Deaths from substance use disorders also increased, rising from 284 000 deaths (268 000–289 000) globally in 2007 to 352 000 (334 000–363 000) in 2017. Between 2007 and 2017, total deaths from conflict and terrorism increased by 118·0% (88·8–148·6). A greater reduction in total deaths and death rates was observed for some CMNN causes among children younger than 5 years than for older adults, such as a 36·4% (32·2–40·6) reduction in deaths from lower respiratory infections for children younger than 5 years compared with a 33·6% (31·2–36·1) increase in adults older than 70 years. Globally, the number of deaths was greater for men than for women at most ages in 2017, except at ages older than 85 years. Trends in global YLLs reflect an epidemiological transition, with decreases in total YLLs from enteric infections, respiratory infections and tuberculosis, and maternal and neonatal disorders between 1990 and 2017; these were generally greater in magnitude at the lowest levels of the Socio-demographic Index (SDI). At the same time, there were large increases in YLLs from neoplasms and cardiovascular diseases. YLL rates decreased across the five leading Level 2 causes in all SDI quintiles. The leading causes of YLLs in 1990—neonatal disorders, lower respiratory infections, and diarrhoeal diseases—were ranked second, fourth, and fifth, in 2017. Meanwhile, estimated YLLs increased for ischaemic heart disease (ranked first in 2017) and stroke (ranked third), even though YLL rates decreased. Population growth contributed to increased total deaths across the 20 leading Level 2 causes of mortality between 2007 and 2017. Decreases in the cause-specific mortality rate reduced the effect of population growth for all but three causes: substance use disorders, neurological disorders, and skin and subcutaneous diseases. Interpretation Improvements in global health have been unevenly distributed among populations. Deaths due to injuries, substance use disorders, armed conflict and terrorism, neoplasms, and cardiovascular disease are expanding threats to global health. For causes of death such as lower respiratory and enteric infections, more rapid progress occurred for children than for the oldest adults, and there is continuing disparity in mortality rates by sex across age groups. Reductions in the death rate of some common diseases are themselves slowing or have ceased, primarily for NCDs, and the death rate for selected causes has increased in the past decade. Funding Bill & Melinda Gates Foundation.
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            Inflammation and cancer.

            Recent data have expanded the concept that inflammation is a critical component of tumour progression. Many cancers arise from sites of infection, chronic irritation and inflammation. It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival and migration. In addition, tumour cells have co-opted some of the signalling molecules of the innate immune system, such as selectins, chemokines and their receptors for invasion, migration and metastasis. These insights are fostering new anti-inflammatory therapeutic approaches to cancer development.
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              The central role of arterial retention of cholesterol-rich apolipoprotein-B-containing lipoproteins in the pathogenesis of atherosclerosis: a triumph of simplicity.

              Today, it is no longer a hypothesis, but an established fact, that increased plasma concentrations of cholesterol-rich apolipoprotein-B (apoB)-containing lipoproteins are causatively linked to atherosclerotic cardiovascular disease (ASCVD) and that lowering plasma LDL concentrations reduces cardiovascular events in humans. Here, we review evidence behind this assertion, with an emphasis on recent studies supporting the 'response-to-retention' model - namely, that the key initiating event in atherogenesis is the retention, or trapping, of cholesterol-rich apoB-containing lipoproteins within the arterial wall.
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                Author and article information

                Contributors
                On behalf of : on behalf of the International Lipid Expert Panel (ILEP)
                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                08 January 2020
                January 2020
                : 9
                : 1
                : 170
                Affiliations
                [1 ]Department of Twin Research and Genetic Epidemiology, King’s College London, St Thomas’ Hospital, Strand, London SE1 7EH, UK
                [2 ]First Department of Internal Medicine, Center for Diabetes, Metabolism and Endocrinology, AHEPA University Hospital, 546 36 Thessaloniki, Greece; nikikatsiki@ 123456hotmail.com
                [3 ]Department of Clinical Biochemistry, Royal Free Campus, University College London Medical School, University College London (UCL), London NW3 2QG, UK; MIKHAILIDIS@ 123456aol.com
                [4 ]Guy’s & St Thomas’ NHS Foundation Trust, London SE1 7EH, UK; dina.radenkovic@ 123456gmail.com
                [5 ]2nd Cardiology Clinic East Slovak Institute for CV Disease and Faculty of Medicine PJ Safarik University, 04011 Kosice, Slovakia; daniel.pella@ 123456upjs.sk
                [6 ]Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, 93-338 Lodz, Poland
                [7 ]Polish Mother’s Memorial Hospital Research Institute (PMMHRI), 93-338 Lodz, Poland
                [8 ]Cardiovascular Research Centre, University of Zielona Gora, 65-046 Zielona Gora, Poland
                Author notes
                [* ]Correspondence: mohsen.mazidi@ 123456kcl.ac.uk (M.M.); maciejbanach@ 123456aol.co.uk (M.B.); Tel.: +46-729-414-259 (M.M.); Tel./Fax: +48-42-639-37-71 (M.B.)
                [†]

                Membership of the International Lipid Expert Panel (ILEP) is provided in the Acknowledgments.

                Author information
                https://orcid.org/0000-0003-1355-6967
                https://orcid.org/0000-0001-6690-6874
                Article
                jcm-09-00170
                10.3390/jcm9010170
                7019626
                31936330
                f6693654-0bce-4a13-a3e9-eeff773b80b5
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 23 December 2019
                : 03 January 2020
                Categories
                Article

                apolipoprotein b,apolipoprotein a-i,c-reactive protein,cancer mortality,nhanes

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