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      Association of statin use in older people primary prevention group with risk of cardiovascular events and mortality: a systematic review and meta-analysis of observational studies

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      1 , , 1 , 1 , 2 , 3 , 4 , 5 , 4 , 6 , 7 , 8 , 9 , 10 , 11 , , on behalf of the Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group and the International Lipid Expert Panel (ILEP)
      BMC Medicine
      BioMed Central
      Statins, Older, Primary prevention, Myocardial infarction, Mortality, Stroke

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          Abstract

          Background

          Current evidence from randomized controlled trials on statins for primary prevention of cardiovascular disease (CVD) in older people, especially those aged > 75 years, is still lacking. We conducted a systematic review and meta-analysis of observational studies to extend the current evidence about the association of statin use in older people primary prevention group with risk of CVD and mortality.

          Methods

          PubMed, Scopus, and Embase were searched from inception until March 18, 2021. We included observational studies (cohort or nested case-control) that compared statin use vs non-use for primary prevention of CVD in older people aged ≥ 65 years; provided that each of them reported the risk estimate on at least one of the following primary outcomes: all cause-mortality, CVD death, myocardial infarction (MI), and stroke. Risk estimates of each relevant outcome were pooled as a hazard ratio (HR) with a 95% confidence interval (CI) using the random-effects meta-analysis model. The quality of the evidence was rated using the GRADE approach.

          Results

          Ten observational studies (9 cohorts and one case-control study; n = 815,667) fulfilled our criteria. The overall combined estimate suggested that statin therapy was associated with a significantly lower risk of all-cause mortality (HR: 0.86 [95% CI 0.79 to 0.93]), CVD death (HR: 0.80 [95% CI 0.78 to 0.81]), and stroke (HR: 0.85 [95% CI 0.76 to 0.94]) and a non-significant association with risk of MI (HR 0.74 [95% CI 0.53 to 1.02]). The beneficial association of statins with the risk of all-cause mortality remained significant even at higher ages (> 75 years old; HR 0.88 [95% CI 0.81 to 0.96]) and in both men (HR: 0.75 [95% CI: 0.74 to 0.76]) and women (HR 0.85 [95% CI 0.72 to 0.99]). However, this association with the risk of all-cause mortality remained significant only in those with diabetes mellitus (DM) (HR 0.82 [95% CI 0.68 to 0.98]) but not in those without DM. The level of evidence of all the primary outcomes was rated as “very low.”

          Conclusions

          Statin therapy in older people (aged ≥ 65 years) without CVD was associated with a 14%, 20%, and 15% lower risk of all-cause mortality, CVD death, and stroke, respectively. The beneficial association with the risk of all-cause mortality remained significant even at higher ages (> 75 years old), in both men and women, and in individuals with DM, but not in those without DM. These observational findings support the need for trials to test the benefits of statins in those above 75 years of age.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s12916-021-02009-1.

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          Most cited references82

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          Bias in meta-analysis detected by a simple, graphical test

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            GRADE: an emerging consensus on rating quality of evidence and strength of recommendations.

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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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                Author and article information

                Contributors
                kamal225244@medicine.zu.edu.eg
                maciejbanach77@gmail.com
                Journal
                BMC Med
                BMC Med
                BMC Medicine
                BioMed Central (London )
                1741-7015
                22 June 2021
                22 June 2021
                2021
                : 19
                : 139
                Affiliations
                [1 ]GRID grid.31451.32, ISNI 0000 0001 2158 2757, Faculty of Medicine, , Zagazig University, ; Zagazig, Egypt
                [2 ]GRID grid.239578.2, ISNI 0000 0001 0675 4725, Department of Cardiovascular Medicine, Heart and Vascular Institute, , Cleveland Clinic Foundation, ; Cleveland, OH USA
                [3 ]GRID grid.415992.2, ISNI 0000 0004 0398 7066, Liverpool Centre for Cardiovascular Science, , University of Liverpool and Liverpool Heart & Chest Hospital, ; Liverpool, UK
                [4 ]GRID grid.21107.35, ISNI 0000 0001 2171 9311, The Ciccarone Center for the Prevention of Cardiovascular Disease, , Johns Hopkins School of Medicine, ; Baltimore, MD USA
                [5 ]GRID grid.240416.5, ISNI 0000 0004 0608 1972, John Ochsner Heart and Vascular Institute, , Ochsner Clinical School-the University of Queensland School of Medicine, ; New Orleans, LA USA
                [6 ]GRID grid.419665.9, ISNI 0000 0004 0520 7668, Preventive Cardiology, , CGH Medical Center, ; Sterling, IL USA
                [7 ]GRID grid.10419.3d, ISNI 0000000089452978, Department of Cardiology, , Leiden University Medical Center, Leiden, the Netherlands and Netherlands Heart Institute, ; Utrecht, the Netherlands
                [8 ]GRID grid.8756.c, ISNI 0000 0001 2193 314X, Institute of Cardiovascular and Medical Sciences, , University of Glasgow, ; Glasgow, UK
                [9 ]GRID grid.8267.b, ISNI 0000 0001 2165 3025, Head Department of Hypertension, , WAM University Hospital in Lodz, Medical University of Lodz (MUL), ; Lodz, Poland
                [10 ]GRID grid.415071.6, ISNI 0000 0004 0575 4012, Polish Mother’s Memorial Hospital Research Institute (PMMHRI), ; Lodz, Poland
                [11 ]GRID grid.28048.36, ISNI 0000 0001 0711 4236, Cardiovascular Research Centre, , University of Zielona Gora, ; Zielona Gora, Poland
                Author information
                http://orcid.org/0000-0001-6707-1629
                Article
                2009
                10.1186/s12916-021-02009-1
                8218529
                34154589
                29c563ed-9600-47c6-826d-47aafa26e696
                © The Author(s) 2021

                Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 25 March 2021
                : 17 May 2021
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2021

                Medicine
                statins,older,primary prevention,myocardial infarction,mortality,stroke
                Medicine
                statins, older, primary prevention, myocardial infarction, mortality, stroke

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