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      Exploring the link between cardiovascular risk factors and manifestations in latent tuberculosis infection: a comprehensive literature review

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          Abstract

          Background

          The global burden of tuberculosis (TB) and cardiovascular disease (CVD) is overt, and the prevalence of this double burden disease remains steadily rising, particularly in low- and middle-income countries. This review aims to explore the association between latent tuberculosis infection (LTBI) and the development of cardiovascular diseases and risk factors. Furthermore, we elucidated the underlying pathophysiological mechanisms that contribute to this relationship.

          Main body

          Approximately 25% of the global population carries a dormant form of tuberculosis (TB) infection. During this latent stage, certain subsets of mycobacteria actively reproduce, and recent research suggests that latent TB infection (LTBI) is connected to persistent, long-term low-grade inflammation that can potentially contribute to the development of atherosclerosis and cardiovascular disease (CVD). The presence of LTBI can be confirmed through a positive result on either a tuberculin skin test (TST) or an interferon-gamma release assay (IGRA). Several plausible explanations for the association between LTBI and CVD include increased inflammation, autoimmunity related to heat shock proteins (HSP), and the presence of pathogens within the developing atherosclerotic plaque. The most commonly observed cardiovascular events and risk factors associated with LTBI are acute myocardial infarction, coronary artery stenosis, diabetes mellitus, and hypertension.

          Conclusions

          This article highlights the critical role of LTBI in perpetuating the tuberculosis disease cycle and its association with cardiovascular risk factors. Chronic and persistent low inflammation underlined the association. Identifying high-risk LTBI patients and providing targeted preventive medication are crucial strategies for global TB eradication and interrupting transmission chains.

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          Most cited references34

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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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            The Global Burden of Latent Tuberculosis Infection: A Re-estimation Using Mathematical Modelling

            Background The existing estimate of the global burden of latent TB infection (LTBI) as “one-third” of the world population is nearly 20 y old. Given the importance of controlling LTBI as part of the End TB Strategy for eliminating TB by 2050, changes in demography and scientific understanding, and progress in TB control, it is important to re-assess the global burden of LTBI. Methods and Findings We constructed trends in annual risk in infection (ARI) for countries between 1934 and 2014 using a combination of direct estimates of ARI from LTBI surveys (131 surveys from 1950 to 2011) and indirect estimates of ARI calculated from World Health Organisation (WHO) estimates of smear positive TB prevalence from 1990 to 2014. Gaussian process regression was used to generate ARIs for country-years without data and to represent uncertainty. Estimated ARI time-series were applied to the demography in each country to calculate the number and proportions of individuals infected, recently infected (infected within 2 y), and recently infected with isoniazid (INH)-resistant strains. Resulting estimates were aggregated by WHO region. We estimated the contribution of existing infections to TB incidence in 2035 and 2050. In 2014, the global burden of LTBI was 23.0% (95% uncertainty interval [UI]: 20.4%–26.4%), amounting to approximately 1.7 billion people. WHO South-East Asia, Western-Pacific, and Africa regions had the highest prevalence and accounted for around 80% of those with LTBI. Prevalence of recent infection was 0.8% (95% UI: 0.7%–0.9%) of the global population, amounting to 55.5 (95% UI: 48.2–63.8) million individuals currently at high risk of TB disease, of which 10.9% (95% UI:10.2%–11.8%) was isoniazid-resistant. Current LTBI alone, assuming no additional infections from 2015 onwards, would be expected to generate TB incidences in the region of 16.5 per 100,000 per year in 2035 and 8.3 per 100,000 per year in 2050. Limitations included the quantity and methodological heterogeneity of direct ARI data, and limited evidence to inform on potential clearance of LTBI. Conclusions We estimate that approximately 1.7 billion individuals were latently infected with Mycobacterium tuberculosis (M.tb) globally in 2014, just under a quarter of the global population. Investment in new tools to improve diagnosis and treatment of those with LTBI at risk of progressing to disease is urgently needed to address this latent reservoir if the 2050 target of eliminating TB is to be reached.
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              Incipient and Subclinical Tuberculosis: a Clinical Review of Early Stages and Progression of Infection.

              SUMMARYTuberculosis (TB) is the leading infectious cause of mortality worldwide, due in part to a limited understanding of its clinical pathogenic spectrum of infection and disease. Historically, scientific research, diagnostic testing, and drug treatment have focused on addressing one of two disease states: latent TB infection or active TB disease. Recent research has clearly demonstrated that human TB infection, from latent infection to active disease, exists within a continuous spectrum of metabolic bacterial activity and antagonistic immunological responses. This revised understanding leads us to propose two additional clinical states: incipient and subclinical TB. The recognition of incipient and subclinical TB, which helps divide latent and active TB along the clinical disease spectrum, provides opportunities for the development of diagnostic and therapeutic interventions to prevent progression to active TB disease and transmission of TB bacilli. In this report, we review the current understanding of the pathogenesis, immunology, clinical epidemiology, diagnosis, treatment, and prevention of both incipient and subclinical TB, two emerging clinical states of an ancient bacterium.
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                Author and article information

                Contributors
                irawatydjaharuddin@unhas.ac.id
                dr.muzakkir@gmail.com
                myaqanitha@gmail.com
                Journal
                Egypt Heart J
                Egypt Heart J
                The Egyptian Heart Journal
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                1110-2608
                2090-911X
                30 May 2023
                30 May 2023
                December 2023
                : 75
                : 43
                Affiliations
                [1 ]GRID grid.412001.6, ISNI 0000 0000 8544 230X, Department of Pulmonology and Respirology Medicine, Faculty of Medicine, , Universitas Hasanuddin, ; Makassar, 90245 Indonesia
                [2 ]GRID grid.412001.6, ISNI 0000 0000 8544 230X, Department of Cardiology and Vascular Medicine, Faculty of Medicine, , Universitas Hasanuddin, ; Jl. Perintis Kemerdekaan Km. 10, Makassar, 90245 South Sulawesi Indonesia
                [3 ]GRID grid.412001.6, ISNI 0000 0000 8544 230X, Department of Physiology, Faculty of Medicine, , Universitas Hasanuddin, ; Makassar, 90245 Indonesia
                [4 ]GRID grid.412001.6, ISNI 0000 0000 8544 230X, Doctoral Study Program, Faculty of Medicine, , Universitas Hasanuddin, ; Makassar, 90245 Indonesia
                Author information
                http://orcid.org/0000-0002-5240-4950
                http://orcid.org/0000-0002-4914-3542
                http://orcid.org/0000-0003-2420-0560
                Article
                370
                10.1186/s43044-023-00370-5
                10229520
                37249745
                f0ef16e1-d260-4924-94a0-26d4d6119a9c
                © The Author(s) 2023

                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 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/.

                History
                : 10 March 2023
                : 20 May 2023
                Categories
                Review
                Custom metadata
                © Egyptian Society of Cardiology 2023

                cardiovascular disease,myocardial infarction,ltbi,tuberculosis

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