Liver Fat Is Associated With Markers of Inflammation and Oxidative Stress in Analysis of Data From the Framingham Heart Study

Fricker, Zachary; Pedley, Alison; Massaro, Joseph M.; Vasan, Ramachandran S.; Hoffmann, Udo; Benjamin, Emelia J.; Long, Michelle T.

doi:10.1016/j.cgh.2018.11.037

Cited by 75 publications

(75 citation statements)

References 70 publications

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“…Thus, to date, it remains unproven whether NAFLD is simply a marker of cardiac and arrhythmic complications or is causally implicated in the pathogenesis of these complications. Increasing evidence suggests that NAFLD (especially in its more severe histologic forms) exacerbates systemic/hepatic insulin resistance and causes the release of a variety of pro‐inflammatory, pro‐fibrogenic, pro‐oxidant and vasoactive mediators that may promote the development and progression of AF, cardiomyopathy (mainly left ventricular diastolic dysfunction, left atrial enlargement and increased cardiac mass) and ischaemic heart disease . Further supporting a role for pro‐inflammatory cytokines as potential triggers of AF, a meta‐analysis has shown that increased levels of proinflammatory biomarkers (such as plasma interleukin‐6 and C‐reactive protein concentrations) are strongly associated with an increased risk of incident AF both in the general population and in patients undergoing coronary artery bypass grafting .…”

Section: Discussionmentioning

confidence: 99%

Association between non‐alcoholic fatty liver disease and risk of atrial fibrillation in adult individuals: An updated meta‐analysis

Mantovani

Dauriz

Sandri

et al. 2019

Liver International

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Background & Aims Recent studies examined the association between non‐alcoholic fatty liver disease (NAFLD) and risk of atrial fibrillation (AF) in adults, but the findings have been inconsistent. We provided a quantitative estimate of the magnitude of the association between NAFLD and risk of AF. Methods We searched publication databases using predefined keywords to identify observational studies (published up to December 14, 2018), in which NAFLD was diagnosed by biopsy, imaging or biochemistry and AF was diagnosed by medical history and electrocardiograms. Data from selected studies were extracted and meta‐analysis was performed using random‐effects modelling. Results Nine cross‐sectional and longitudinal studies were included in the final analysis (n = 364 919 individuals). Meta‐analysis of data from 5 cross‐sectional studies showed that NAFLD was associated with an increased risk of prevalent AF (random‐effects odds ratio 2.07, 95% CI 1.38‐3.10; I2 = 54.7%), independent of age, sex, body mass index, hypertension and other common AF risk factors. This risk was particularly high among patients with established diabetes (n = 1 study; random‐effects odds ratio 5.17, 95% CI 2.05‐13.02). Meta‐analysis of data from 4 longitudinal studies showed that NAFLD was independently associated with a 10‐year increased risk of incident AF only in type 2 diabetic patients (n = 1 study; random‐effects hazard ratio 4.96, 95% CI 1.42‐17.28). Sensitivity analyses did not modify these findings. Funnel plots did not reveal significant publication bias. Conclusions NAFLD is associated with an increased risk of AF in middle‐aged and elderly individuals (especially in those with type 2 diabetes). However, the observational design of the eligible studies does not allow for proving causality.

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Section: Discussionmentioning

confidence: 99%

Association between non‐alcoholic fatty liver disease and risk of atrial fibrillation in adult individuals: An updated meta‐analysis

Mantovani

Dauriz

Sandri

et al. 2019

Liver International

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“…A link between dyslipidaemia and hepatic inflammation has also been suggested by recent data showing that proprotein convertase subtilisin/kexin type-7 (PCSK7) gene variations correlate with severity of liver disease in human NAFLD [55]. Furthermore, the presence of liver fat has also been linked to plasma inflammatory biomarkers in the Framingham Heart Study [56]. Extracellular vesicles released by steatotic hepatocytes are also able to drive endothelial inflammation and atherogenesis [57].…”

Section: Multiple Sources Of Cytokines Drive Liver Inflammation and Ementioning

confidence: 92%

NAFLD and increased risk of cardiovascular disease: clinical associations, pathophysiological mechanisms and pharmacological implications

Targher

Byrne

Tilg

2020

Gut

497

365

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Non-alcoholic fatty liver disease (NAFLD) is a public health problem, affecting up to a third of the world’s adult population. Several cohort studies have consistently documented that NAFLD (especially in its more advanced forms) is associated with a higher risk of all-cause mortality and that the leading causes of death among patients with NAFLD are cardiovascular diseases (CVDs), followed by extrahepatic malignancies and liver-related complications. A growing body of evidence also indicates that NAFLD is strongly associated with an increased risk of major CVD events and other cardiac complications (ie, cardiomyopathy, cardiac valvular calcification and cardiac arrhythmias), independently of traditional cardiovascular risk factors. This narrative review provides an overview of the literature on: (1) the evidence for an association between NAFLD and increased risk of cardiovascular, cardiac and arrhythmic complications, (2) the putative pathophysiological mechanisms linking NAFLD to CVD and other cardiac complications and (3) the current pharmacological treatments for NAFLD that might also benefit or adversely affect risk of CVD.

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“…Liver steatosis promotes atherogenic dyslipidemia [increased small, dense low-density lipoprotein (LDL) particles, triglycerides, and decreased high-density lipoprotein (HDL) cholesterol] (Amor et al, 2017), activates intrahepatic and systemic inflammation [increased C-reactive protein (CRP), interleukin 6 (IL-6), tumor necrosis factor (TNF), intercellular adhesion molecule 1, and P-selectin] (Feldstein et al, 2004; Fricker et al, 2019) and the renin-angiotensin-aldosterone system (RAS) (Oikonomou et al, 2018), and disturbs the coagulation mechanism (increased fibrinogen, factor VII, and PAI-1) (Verrijken et al, 2014). All the NAFLD-related pathogenic mechanisms mentioned above may contribute to the increased risks of diabetic macrovascular and microvascular complications ( Figure 1 ).…”

Section: Nafld Increases Risks Of T2dmentioning

confidence: 99%

NAFLD and Diabetes: Two Sides of the Same Coin? Rationale for Gene-Based Personalized NAFLD Treatment

2019

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The prevalence of non-alcoholic fatty liver disease (NAFLD) has been increasing rapidly and at the forefront of worldwide concern. Characterized by excessive fat accumulation in the liver, NAFLD regularly coexists with metabolic disorders, including type 2 diabetes, obesity, and cardiovascular disease. It has been well established that the presence of NAFLD increases the incidence of type 2 diabetes, while diabetes aggravates NAFLD to more severe forms of steatohepatitis, cirrhosis, and hepatocellular carcinoma. However, recent progress on the genotype/phenotype relationships in NAFLD patients indicates the development of NAFLD with a relative conservation of glucose metabolism in individuals with specific gene variants, such as the patatin-like phospholipase domain-containing 3 (PNPLA3) and transmembrane 6 superfamily member 2 protein (TM6SF2) variants. This review will focus on the clinical and pathophysiological connections between NAFLD and type 2 diabetes and will also discuss a disproportionate progression of NAFLD and diabetes, and the different responses to lifestyle and drug intervention in NAFLD patients with specific gene variants that may give insight into personalized treatment for NAFLD.

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Liver Fat Is Associated With Markers of Inflammation and Oxidative Stress in Analysis of Data From the Framingham Heart Study

Cited by 75 publications

References 70 publications

Association between non‐alcoholic fatty liver disease and risk of atrial fibrillation in adult individuals: An updated meta‐analysis

Association between non‐alcoholic fatty liver disease and risk of atrial fibrillation in adult individuals: An updated meta‐analysis

NAFLD and increased risk of cardiovascular disease: clinical associations, pathophysiological mechanisms and pharmacological implications

NAFLD and Diabetes: Two Sides of the Same Coin? Rationale for Gene-Based Personalized NAFLD Treatment

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