NAFLD and cardiovascular diseases: a clinical review.
01 Jul 2021-Clinical Research in Cardiology (Springer Berlin Heidelberg)-Vol. 110, Iss: 7, pp 921-937
TL;DR: The underlying pathophysiological mechanisms linking NAFLD and CVD are described, the role ofNAFLD as a metabolic dysfunction associated cardiovascular risk factor is discussed, and common cardiovascular manifestations in NAFLd patients are focused on.
Abstract: Non-alcoholic fatty liver DISEASE (NAFLD) is the most common chronic liver disease in Western countries and affects approximately 25% of the adult population. Since NAFLD is frequently associated with further metabolic comorbidities such as obesity, type 2 diabetes mellitus, or dyslipidemia, it is generally considered as the hepatic manifestation of the metabolic syndrome. In addition to its potential to cause liver-related morbidity and mortality, NAFLD is also associated with subclinical and clinical cardiovascular disease (CVD). Growing evidence indicates that patients with NAFLD are at substantial risk for the development of hypertension, coronary heart disease, cardiomyopathy, and cardiac arrhythmias, which clinically result in increased cardiovascular morbidity and mortality. The natural history of NAFLD is variable and the vast majority of patients will not progress from simple steatosis to fibrosis and end stage liver disease. However, patients with progressive forms of NAFLD, including non-alcoholic steatohepatitis (NASH) and/or advanced fibrosis, as well as NAFLD patients with concomitant types 2 diabetes are at highest risk for CVD. This review describes the underlying pathophysiological mechanisms linking NAFLD and CVD, discusses the role of NAFLD as a metabolic dysfunction associated cardiovascular risk factor, and focuses on common cardiovascular manifestations in NAFLD patients.
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01 Aug 2018
TL;DR: In this paper, the authors describe long-term outcomes and evaluate the effects of clinical and histologic parameters on disease progression in patients with advanced nonalcoholic fatty liver disease (NAFLD) with bridging fibrosis.
Abstract: Background & Aims Little is known about the natural course of nonalcoholic fatty liver disease (NAFLD) with advanced fibrosis. We describe long-term outcomes and evaluate the effects of clinical and histologic parameters on disease progression in patients with advanced NAFLD. Methods We conducted a multi-national study of 458 patients with biopsy-confirmed NAFLD with bridging fibrosis (F3, n = 159) or compensated cirrhosis (222 patients with Child-Turcotte-Pugh scores of A5 and 77 patients with scores of A6), evaluated from April 1995 through November 2013 and followed until December 2016, death, or liver transplantation at hepatology centers in Spain, Australia, Hong Kong, and Cuba. Biopsies were re-evaluated and scored; demographic, clinical, laboratory, and pathology data for each patient were collected from the time of liver biopsy collection. Cox proportional and competing risk models were used to estimate rates of transplantation-free survival and major clinical events and to identify factors associated with outcomes. Results During a mean follow-up time of 5.5 years (range, 2.7–8.2 years), 37 patients died, 37 received liver transplants, 88 had initial hepatic decompensation events, 41 developed hepatocellular carcinoma, 14 had vascular events, and 30 developed nonhepatic cancers. A higher proportion of patients with F3 fibrosis survived transplantation-free for 10 years (94%; 95% confidence interval [CI], 86%–99%) than of patients with cirrhosis and Child-Turcotte-Pugh A5 (74%; 95% CI, 61%–89%) or Child-Turcotte-Pugh A6 (17%; 95% CI, 6%–29%). Patients with cirrhosis were more likely than patients with F3 fibrosis to have hepatic decompensation (44%; 95% CI, 32%–60% vs 6%, 95% CI, 2%–13%) or hepatocellular carcinoma (17%; 95% CI, 8%–31% vs 2.3%, 95% CI, 1%–12%). The cumulative incidence of vascular events was higher in patients with F3 fibrosis (7%; 95% CI, 3%–18%) than cirrhosis (2%; 95% CI, 0%–6%). The cumulative incidence of nonhepatic malignancies was higher in patients with F3 fibrosis (14%; 95% CI, 7%–23%) than cirrhosis (6%; 95% CI, 2%–15%). Death or transplantation, decompensation, and hepatocellular carcinoma were independently associated with baseline cirrhosis and mild ( Conclusions Patients with NAFLD cirrhosis have predominantly liver-related events, whereas those with bridging fibrosis have predominantly nonhepatic cancers and vascular events.
338 citations
01 Jan 2017
TL;DR: The Grading of Recommendations, Assessment Development, and Evaluation (GRADE) system as discussed by the authors provides a data-supported approach to the diagnostic, therapeutic, and preventive aspects of NAFLD care.
Abstract: This guidance provides a data-supported approach to the diagnostic, therapeutic, and preventive aspects of NAFLD care. A "Guidance" document is different from a "Guideline." Guidelines are developed by a multidisciplinary panel of experts and rate the quality (level) of the evidence and the strength of each recommendation using the Grading of Recommendations, Assessment Development, and Evaluation (GRADE) system. A guidance document is developed by a panel of experts in the topic, and guidance statements, not recommendations, are put forward to help clinicians understand and implement the most recent evidence. This article is protected by copyright. All rights reserved.
86 citations
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TL;DR: In this article , Steinberg et al. provide an overview of the physiological and pathological roles of the core DNL enzymes and assess strategies and agents currently in development to therapeutically target them, including citrate/isocitrate carrier (CIC), ATP-citrate lyase (ACLY), acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS).
Abstract: Fatty acids are essential for survival, acting as bioenergetic substrates, structural components and signalling molecules. Given their vital role, cells have evolved mechanisms to generate fatty acids from alternative carbon sources, through a process known as de novo lipogenesis (DNL). Despite the importance of DNL, aberrant upregulation is associated with a wide variety of pathologies. Inhibiting core enzymes of DNL, including citrate/isocitrate carrier (CIC), ATP-citrate lyase (ACLY), acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), represents an attractive therapeutic strategy. Despite challenges related to efficacy, selectivity and safety, several new classes of synthetic DNL inhibitors have entered clinical-stage development and may become the foundation for a new class of therapeutics. De novo lipogenesis (DNL) is vital for the maintenance of whole-body and cellular homeostasis, but aberrant upregulation of the pathway is associated with a broad range of conditions, including cardiovascular disease, metabolic disorders and cancers. Here, Steinberg and colleagues provide an overview of the physiological and pathological roles of the core DNL enzymes and assess strategies and agents currently in development to therapeutically target them.
78 citations
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TL;DR: In this article, the authors describe decades of research aimed at identifying key molecules and cellular players involved in each main aspect of hepatic cholesterol metabolism and summarize the recent advances regarding the biological processes of liver cholesterol transport and its role in NAFLD and atherosclerosis.
54 citations
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TL;DR: In this paper, Steatosis was found to be related with coronary heart disease involvement, with moderate to severe steatosis related to clinical coronary artery disease (CAD) and 24 subclinical CAD.
37 citations
References
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Theo Vos1, Amanuel Alemu Abajobir, Kalkidan Hassen Abate2, Cristiana Abbafati3 +775 more•Institutions (305)
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016.
10,401 citations
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TL;DR: All-cause age-standardised YLD rates decreased by 3·9% from 1990 to 2017; however, the all-age YLD rate increased by 7·2% while the total sum of global YLDs increased from 562 million (421–723) to 853 million (642–1100).
7,419 citations
"NAFLD and cardiovascular diseases: ..." refers background in this paper
...According to current World Health Organization (WHO) estimates, approximately 54% of all strokes and 47% of all cases of ischemic heart disease are a direct consequence of high blood pressure [93, 94]....
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TL;DR: As the global epidemic of obesity fuels metabolic conditions, the clinical and economic burden of NAFLD will become enormous, and random‐effects models were used to provide point estimates of prevalence, incidence, mortality and incidence rate ratios.
6,746 citations
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TL;DR: This guidance provides a data-supported approach to the diagnostic, therapeutic, and preventive aspects of NAFLD care.
4,431 citations
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TL;DR: Key guidelines in the Physical Activity Guidelines for Americans, 2nd edition, provide information and guidance on the types and amounts of physical activity that provide substantial health benefits and emphasize that moving more and sitting less will benefit nearly everyone.
Abstract: Importance Approximately 80% of US adults and adolescents are insufficiently active. Physical activity fosters normal growth and development and can make people feel, function, and sleep better and reduce risk of many chronic diseases. Objective To summarize key guidelines in thePhysical Activity Guidelines for Americans, 2nd edition (PAG). Process and Evidence Synthesis The 2018 Physical Activity Guidelines Advisory Committee conducted a systematic review of the science supporting physical activity and health. The committee addressed 38 questions and 104 subquestions and graded the evidence based on consistency and quality of the research. Evidence graded as strong or moderate was the basis of the key guidelines. The Department of Health and Human Services (HHS) based the PAG on the2018 Physical Activity Guidelines Advisory Committee Scientific Report. Recommendations The PAG provides information and guidance on the types and amounts of physical activity to improve a variety of health outcomes for multiple population groups. Preschool-aged children (3 through 5 years) should be physically active throughout the day to enhance growth and development. Children and adolescents aged 6 through 17 years should do 60 minutes or more of moderate-to-vigorous physical activity daily. Adults should do at least 150 minutes to 300 minutes a week of moderate-intensity, or 75 minutes to 150 minutes a week of vigorous-intensity aerobic physical activity, or an equivalent combination of moderate- and vigorous-intensity aerobic activity. They should also do muscle-strengthening activities on 2 or more days a week. Older adults should do multicomponent physical activity that includes balance training as well as aerobic and muscle-strengthening activities. Pregnant and postpartum women should do at least 150 minutes of moderate-intensity aerobic activity a week. Adults with chronic conditions or disabilities, who are able, should follow the key guidelines for adults and do both aerobic and muscle-strengthening activities. Recommendations emphasize that moving more and sitting less will benefit nearly everyone. Individuals performing the least physical activity benefit most by even modest increases in moderate-to-vigorous physical activity. Additional benefits occur with more physical activity. Both aerobic and muscle-strengthening physical activity are beneficial. Conclusions and Relevance ThePhysical Activity Guidelines for Americans, 2nd edition, provides information and guidance on the types and amounts of physical activity that provide substantial health benefits. Health professionals and policy makers should facilitate awareness of the guidelines and promote the health benefits of physical activity and support efforts to implement programs, practices, and policies to facilitate increased physical activity and to improve the health of the US population.
4,280 citations
Additional excerpts
...This is in line with general physical exercise recommendations for improved cardiometabolic health and reduced cardiovascular morbidity in adults, namely 150–300 min of moderate-intensity or 75–150 min of vigorous-intensity activity weekly, supplemented by two sessions of muscle-building exercise and less sedentary time [141, 142]....
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