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      Leukocyte telomere length and risk of coronary heart disease and stroke mortality: prospective evidence from a Russian cohort

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          Abstract

          Previous studies suggest that reduced leukocyte telomere length (LTL) is related to higher risk of mortality and several chronic conditions, including coronary heart disease (CHD) and stroke. However, the consistency of this association differs across populations. We investigated the relationship of LTL with CHD, stroke and all-cause mortality together with non-fatal CHD and stroke events in a Russian cohort with a mean age of 58 years at baseline. Data from 1,144 individuals in the Russian subset of the Health Alcohol and Psychosocial Factors in Eastern Europe (HAPIEE) cohort study were used. The associations between LTL at baseline and fatal/non-fatal outcomes during 12 years of follow-up were assessed using multivariable Cox regression models, which yielded adjusted hazard ratios (HR). Compared to individuals in the shortest tertile, those in the longest tertile of LTL had a 42% lower risk of death from all-causes (HR 0.58; 95% CI: 0.39–0.88) and 58% lower risk of death from CHD (HR 0.42; 95%CI: 0.19–0.97). Similar patterns of association were identified for non-fatal and combined fatal/non-fatal CHD and stroke events but the associations were weaker. Consistent with results of previous studies in Western populations, this cohort of elderly Russian adults found an inverse association between LTL and CHD and all-cause mortality. These findings reinforce the hypothesis that LTL may play (or be a marker of) an aetiological role in human health across diverse populations.

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          Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015

          Summary Background Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures. Methods We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography–year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Findings Globally, life expectancy from birth increased from 61·7 years (95% uncertainty interval 61·4–61·9) in 1980 to 71·8 years (71·5–72·2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11·3 years (3·7–17·4), to 62·6 years (56·5–70·2). Total deaths increased by 4·1% (2·6–5·6) from 2005 to 2015, rising to 55·8 million (54·9 million to 56·6 million) in 2015, but age-standardised death rates fell by 17·0% (15·8–18·1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14·1% (12·6–16·0) to 39·8 million (39·2 million to 40·5 million) in 2015, whereas age-standardised rates decreased by 13·1% (11·9–14·3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42·1%, 39·1–44·6), malaria (43·1%, 34·7–51·8), neonatal preterm birth complications (29·8%, 24·8–34·9), and maternal disorders (29·1%, 19·3–37·1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000–183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000–532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death. Interpretation At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems. Funding Bill & Melinda Gates Foundation.
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            Telomere measurement by quantitative PCR.

            R. Cawthon (2002)
            It has long been presumed impossible to measure telomeres in vertebrate DNA by PCR amplification with oligonucleotide primers designed to hybridize to the TTAGGG and CCCTAA repeats, because only primer dimer-derived products are expected. Here we present a primer pair that eliminates this problem, allowing simple and rapid measurement of telomeres in a closed tube, fluorescence-based assay. This assay will facilitate investigations of the biology of telomeres and the roles they play in the molecular pathophysiology of diseases and aging.
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              Associations of fats and carbohydrate intake with cardiovascular disease and mortality in 18 countries from five continents (PURE): a prospective cohort study

              The relationship between macronutrients and cardiovascular disease and mortality is controversial. Most available data are from European and North American populations where nutrition excess is more likely, so their applicability to other populations is unclear.
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                Author and article information

                Contributors
                denes.stefler@ucl.ac.uk
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                9 November 2018
                9 November 2018
                2018
                : 8
                : 16627
                Affiliations
                [1 ]ISNI 0000000121901201, GRID grid.83440.3b, Department of Epidemiology and Public Health, , University College London, ; London, United Kingdom
                [2 ]ISNI 0000 0001 2254 1834, GRID grid.415877.8, Research Institute of Internal and Preventive Medicine – Branch of IC&G SB RAS, ; Novosibirsk, Russia
                [3 ]ISNI 0000 0004 1936 8948, GRID grid.4991.5, Medical Research Council Population Health Research Unit at the University of Oxford, ; Oxford, UK
                [4 ]ISNI 0000 0004 1936 8948, GRID grid.4991.5, Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, , University of Oxford, Richard Doll Building, Old Road Campus, Roosevelt Drive, ; Oxford, OX3 7LF UK
                [5 ]ISNI 0000 0001 0440 1440, GRID grid.410556.3, National Institute for Health Research Oxford Biomedical Research Centre, , Oxford University Hospital, ; Oxford, UK
                Article
                35122
                10.1038/s41598-018-35122-y
                6226519
                30413768
                a544be86-a1ae-4760-8aef-4d2999451c5f
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 25 May 2018
                : 29 October 2018
                Funding
                Funded by: Russian Scientific Foundation (Grant Number: 14-45-00030)
                Funded by: FundRef https://doi.org/10.13039/100004440, Wellcome Trust;
                Award ID: WT064947
                Award ID: WT081081
                Award Recipient :
                Funded by: MacArthur Foundation Initiative on Social Upheaval and Health
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