Nonalcoholic Fatty Liver Disease and the Heart

Stahl, Eric; Dhindsa, Devinder S.; Lee, Suegene K.; Sandesara, Pratik B.; Chalasani, Naga; Sperling, Laurence

doi:10.1016/j.jacc.2018.11.050

Cited by 303 publications

(342 citation statements)

References 163 publications

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“…21 These mechanisms provide some plausibility for the observation that NAFLD is closely linked to subclinical atherosclerosis. 22 Pancreatic fat ( Fig. 1A3) has been linked to b cell dysfunction 23 and concomitant postprandial and fasting hyperglycemia.…”

Section: An Integrative View On Atherosclerosismentioning

confidence: 99%

“…Inflammatory processes at the endothelial layer of the arterial wall play a fundamental role in the initiation, progression, and in particular, the clinical complications of 9 Ectopic fat is a major driver of atherosclerosis and its acute complications: epicardial fat (A1) has been linked to AF, accelerated coronary atherosclerosis, and left ventricular diastolic dysfunction 20 ; hepatic fat (NAFLD) (A2) causally contributes to atherogenic dyslipidemia and is closely linked to subclinical atherosclerosis 22 ; and pancreatic fat (A3) has been linked to beta-cell dysfunction 23 and concomitant postprandial and fasting hyperglycemia. Chronically elevated serum glucose levels, and postprandial glucose spikes in particular, promote oxidative stress/chronic inflammation, endothelial dysfunction, and sympathetic hyperactivity, and result in the formation of AGEs.…”

Section: Nonresolving Inflammation and Plaque Phenotypementioning

confidence: 99%

“…At any given BMI, an elevated waist circumference is predictive of visceral adiposity. 13 Using waist circumference as a proxy, increased ectopic and hepatic fat 22 in particular, is an independent risk factor for high-risk atherosclerosis 9,10 and coronary artery disease and death in prospective studies. 45 Mendelian randomization analyses indicate that triglyceride-related risk is causal in ASCVD and considering triglyceride levels along with waist circumference improves risk prediction.…”

Section: Hypertriglyceridemic Waistmentioning

confidence: 99%

See 2 more Smart Citations

High-Risk Atherosclerosis and Metabolic Phenotype: The Roles of Ectopic Adiposity, Atherogenic Dyslipidemia, and Inflammation

Lechner

McKenzie²,

Kränkel

et al. 2020

Metabolic Syndrome and Related Disorders

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Current algorithms for assessing risk of atherosclerotic cardiovascular disease (ASCVD) and, in particular, the reliance on low-density lipoprotein (LDL) cholesterol in conditions where this measurement is discordant with apoB and LDL-particle concentrations fail to identify a sizeable part of the population at high risk for adverse cardiovascular events. This results in missed opportunities for ASCVD prevention, most notably in those with metabolic syndrome, prediabetes, and diabetes. There is substantial evidence that accumulation of ectopic fat and associated metabolic traits are markers for and pathogenic components of high-risk atherosclerosis. Conceptually, the subset of advanced lesions in high-risk atherosclerosis that triggers vascular complications is closely related to a set of coordinated high-risk traits clustering around a distinct metabolic phenotype. A key feature of this phenotype is accumulation of ectopic fat, which, coupled with age-related muscle loss, creates a milieu conducive for the development of ASCVD: atherogenic dyslipidemia, nonresolving inflammation, endothelial dysfunction, hyperinsulinemia, and impaired fibrinolysis. Sustained vascular inflammation, a hallmark of high-risk atherosclerosis, impairs plaque stabilization in this phenotype. This review describes how metabolic and inflammatory processes that are promoted in large measure by ectopic adiposity, as opposed to subcutaneous adipose tissue, relate to the pathogenesis of high-risk atherosclerosis. Clinical biomarkers indicative of these processes provide incremental information to standard risk factor algorithms and advanced lipid testing identifies atherogenic lipoprotein patterns that are below the discrimination level of standard lipid testing. This has the potential to enable improved identification of high-risk patients who are candidates for therapeutic interventions aimed at prevention of ASCVD.

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Section: An Integrative View On Atherosclerosismentioning

confidence: 99%

Section: Nonresolving Inflammation and Plaque Phenotypementioning

confidence: 99%

Section: Hypertriglyceridemic Waistmentioning

confidence: 99%

See 1 more Smart Citation

High-Risk Atherosclerosis and Metabolic Phenotype: The Roles of Ectopic Adiposity, Atherogenic Dyslipidemia, and Inflammation

Lechner

McKenzie²,

Kränkel

et al. 2020

Metabolic Syndrome and Related Disorders

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show abstract

“…two pathways: one by which cardiovascular events occur via traditional risk factors and another through a more direct linkage, including endothelial dysfunction, systemic inflammation, altered lipid metabolism, insulin resistance, oxidative stress, fetuin-A and a prothrombotic state, which likely contribute in a complex, interrelated manner [23][24][25]. The lack of a relationship between steatohepatitis and CVD in our cohort might suggest that drivers or products of fibrogenesis may play a more important role in promoting CVD; however, it is also possible that the cardiovascular consequences of systemic inflammation do not clinically manifest until it has existed long enough to promote the development of advanced fibrosis.…”

mentioning

confidence: 99%

Advanced fibrosis is associated with incident cardiovascular disease in patients with non‐alcoholic fatty liver disease

Henson

Simon

Kaplan

et al. 2020

Aliment Pharmacol Ther

118

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Summary Background Non‐alcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiovascular disease. It is not well understood, however, which individuals with NAFLD are at highest risk for cardiovascular disease. Aims To determine the factors associated with incident cardiovascular events in a prospective cohort of individuals with biopsy‐proven NAFLD without pre‐existing cardiovascular disease. Methods From 2011 to 2018, adults with biopsy‐proven NAFLD without cardiovascular disease were enrolled in a tissue repository and were followed prospectively to the first recorded date of incident cardiovascular disease, death or the end of follow‐up (11/1/2018). Competing risks analysis was performed to identify predictors of incident cardiovascular disease. Results After a median follow‐up time of 5.2 years, 26/285 (9.1%) individuals experienced an incident cardiovascular event. Advanced fibrosis (stage 3‐4) on biopsy was a significant predictor of incident cardiovascular disease, and this persisted on multivariable analysis (SHR 2.86, 95% CI 1.36–6.04) after considering relevant covariates, including cardiovascular risk scores, which were not independent predictors. Of the non‐invasive indicators of fibrosis, the NAFLD fibrosis score was the only independent predictor of cardiovascular disease. Other histologic features, including steatohepatitis, were not associated with incident cardiovascular disease. Conclusions In adults with biopsy‐proven NAFLD, advanced fibrosis on biopsy and higher NAFLD fibrosis score were significant and independent predictors of incident cardiovascular disease, even after considering traditional risk factors and cardiovascular risk scores. These findings should be considered when evaluating NAFLD patients for primary prevention of cardiovascular disease, and further evaluation into the link between advanced fibrosis and cardiovascular disease is needed.

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“…Management of type 2 diabetes mellitus, dyslipidemia and metabolic syndrome according to available guidelines is of paramount importance to reduce the associated cardiovascular risk. Apart from the lipid lowering effects and cardiovascular risk reduction, statins have shown benefits in improving liver histology including fibrosis (68). Statins are safe to be used in patients with less than 3 fold elevation of transaminases, however routine prescription is not recommended in patients with decompensated cirrhosis and acute liver failure (69) (70).…”

Section: Management Of Risk Factors and Associationsmentioning

confidence: 99%

Non-alcoholic fatty liver disease – 2019

in-chief

2019

Sri Lanka J. Diabetes Endocrinol. Metab.

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Nonalcoholic Fatty Liver Disease and the Heart

Cited by 303 publications

References 163 publications

High-Risk Atherosclerosis and Metabolic Phenotype: The Roles of Ectopic Adiposity, Atherogenic Dyslipidemia, and Inflammation

High-Risk Atherosclerosis and Metabolic Phenotype: The Roles of Ectopic Adiposity, Atherogenic Dyslipidemia, and Inflammation

Advanced fibrosis is associated with incident cardiovascular disease in patients with non‐alcoholic fatty liver disease

Non-alcoholic fatty liver disease – 2019

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