Relationship of Nonalcoholic Fatty Liver Disease and Heart Failure With Preserved Ejection Fraction

Salah, Husam M.; Soloveva, A.; Abdelmalek, Manal F.; Diehl, Anna Mae; Moylan, Cynthia A.; Wegermann, Kara; Rao, Vishal N.; Hernandez, Adrian F.; Tedford, Ryan J.; Parikh, Kishan S.; Mentz, Robert J.; McGarrah, Robert W.; Fudim, Marat

doi:10.1016/j.jacbts.2021.07.010

Cited by 64 publications

(52 citation statements)

References 116 publications

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“…This more pathogenic form of NAFLD progresses to fibrosis in approximately 35% of patients, significantly raising the risk for development of hepatocellular carcinoma (HCC), cirrhosis, and acute liver failure. Advanced NAFLD is also a significant risk factor for development of type 2 diabetes and cardiovascular diseases (CVD) (2,3).…”

Section: Introductionmentioning

confidence: 99%

Altered branched-chain α-keto acid metabolism is a feature of NAFLD in individuals with severe obesity

Grenier-Larouche¹,

Kwee²,

Deleye³

et al. 2022

JCI Insight

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Hepatic de novo lipogenesis is influenced by the branched-chain α-keto acid dehydrogenase (BCKDH) kinase (BCKDK). We aimed to determine whether circulating levels of the immediate substrates of BCKDH, the branched-chain α-ketoacids (BCKAs) and hepatic BCKDK expression are associated with the presence and severity of non-alcoholic fatty liver disease (NAFLD).Eighty metabolites (3 BCKA, 14 amino acids, 43 acylcarnitines, 20 ceramides) were quantified in plasma from 288 bariatric surgery patients with severe obesity (BMI > 35 kg/m 2 ) with scored liver biopsy samples. Metabolite principal component analysis (PCA) factors, BCKA, branchedchain amino acids (BCAA), and the BCKA:BCAA ratio were tested for associations with steatosis grade and presence of non-alcoholic steatohepatitis (NASH). Of all analytes tested, only the valine-derived BCKA, α-ketoisovalerate, and the BCKA:BCAA ratio were associated with both steatosis grade and NASH. Gene expression analysis in liver samples from two independent bariatric surgery cohorts showed that hepatic BCKDK mRNA expression correlates with steatosis, ballooning, and levels of the lipogenic transcription factor SREBP1. Experiments in AML12 hepatocytes showed that SREBP1 inhibition lowers BCKDK mRNA expression.These findings demonstrate that higher plasma levels of BCKA and hepatic expression of BCKDK are features of human NAFLD/NASH and identify SREBP1 as a transcriptional regulator of BCKDK.

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Section: Introductionmentioning

confidence: 99%

Altered branched-chain α-keto acid metabolism is a feature of NAFLD in individuals with severe obesity

Grenier-Larouche¹,

Kwee²,

Deleye³

et al. 2022

JCI Insight

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“…A heart-liver axis, that was drafted by in ammatory reactants from the heart and the liver, placed a new spotlight on the crosstalk of organs in disease development 22,44 . In the phenomapping analysis of HFpEF, one of phenogroups demonstrated high proin ammatory biomarkers including tumor necrosis factor-alpha-mediated in ammation, liver brosis, and tissue remodeling 45 .…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have revealed the correlation of elevated UA level with adverse outcomes of HFpEF [18][19][20] . Moreover, renal dysfunction 21 and liver diseases, such as nonalcoholic fatty liver disease 22 and liver stiffness 23 , were clinical co-morbidities for HFpEF. However, diagnostic scoring systems for HFpEF do not contain the in ammatory markers and markers for liver and renal dysfunction.…”

Section: Introductionmentioning

confidence: 99%

Development and validation of a diagnostic prediction model reminiscent of systemic inflammation and organ interaction in heart failure preserved ejection fraction (HFpEF) patients

Zhou

Xia

et al. 2022

Preprint

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Purpose Systemic inflammation and reciprocal organ interactions are associated with the pathophysiology of heart failure with preserved ejection fraction (HFpEF). Herein, we proposed a simple diagnostic model with markers from complete routine blood test as well as liver and renal dysfunction for HFpEF. Patients and methods: This is a hospital-based single-center, cross-sectional observation study. 1808 eligible patients with documented cardiovascular diseases were enrolled. HFpEF was diagnosed independently by two expert cardiologists according to the clinical manifestation, echocardiography and the N-Terminal pro B-type natriuretic peptide. A diagnostic model for HFpEF was developed by logistic regression and assessed by ROC and Brier score. Then, the model was validated by the 10-fold cross-validation and presented as nomogram and a web-based online risk calculator as well. Results Patients with HFpEF account for 47.23% in development data. Univariate, multivariate and LASSO regression analysis revealed that age, Hb, NLR, AST/ALT ratio, Cr, UA, atrial fibrillation, and pulmonary arterial hypertension were associated with HFpEF. The predictive model exhibited reasonably accurate discrimination (ROC, 0.753, 95% CI, 0.732 to 0.772) and calibration (Brier score was 0.200). Subsequent internal validation showed good discrimination and calibration (AUC = 0.750, Brier score was 0.202). Conclusion Our new diagnostic model incorporating markers of inflammation, liver-heart and kidney-heart interactions has the predictive ability for HFpEF, and may be helpful for timely diagnosis of patients with HFpEF.

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“…Indeed, some HFpEF phenotypes seem to be cardiac manifestations of NAFLD, thus supporting the novel concept of a pathophysiological continuum between NAFLD and HFpEF. Such a view is supported by multiple shared pathophysiological mechanisms that rely on increased systemic inflammation [ 67 ] and contribute to the associated endothelial dysfunction [ 67 ]. Indeed, NAFLD and nonalcoholic steatohepatitis (NASH) favor the accumulation of epicardial fat secreting proinflammatory adipocytokines, thus causing microvessel dysfunction and adjacent myocardium fibrosis.…”

Section: Key Summary Pointsmentioning

confidence: 99%

Heart Failure with Preserved Ejection Fraction and Obstructive Sleep Apnea: A Novel Paradigm for Additional Cardiovascular Benefit of SGLT2 Inhibitors in Subjects With or Without Type 2 Diabetes

Monda¹,

Gentile

Porcellati

et al. 2022

Adv Ther

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After examining the complex interplay between heart failure (HF) in its various clinical forms, metabolic disorders like nonalcoholic fatty liver disease (NAFLD), and obstructive sleep apnea (OSA) syndrome, in this mini-review we described possible favorable effects of sodium-glucose cotransporter 2 inhibitors (SGLT2is) on HF with preserved (i.e., C 50%) ejection fraction (HFpEF) through enhanced cardiorenal function and visceral-subcutaneous body fat redistribution. In greater detail, on the basis of pathophysiological mechanisms underlying OSA onset and the direct positive SGLT2i effect on renal function benefiting chronic kidney disease, we emphasized the promising role of SGLT2is in prevention, rehabilitation, and treatment of patients with OSA regardless of coexisting type 2 diabetes (T2DM). Indeed, SGLT2is enhance lipolysis and fatty acid beta-oxidation. These phenomena might prevent OSA by reducing the size of visceral and subcutaneous

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Relationship of Nonalcoholic Fatty Liver Disease and Heart Failure With Preserved Ejection Fraction

Cited by 64 publications

References 116 publications

Altered branched-chain α-keto acid metabolism is a feature of NAFLD in individuals with severe obesity

Altered branched-chain α-keto acid metabolism is a feature of NAFLD in individuals with severe obesity

Development and validation of a diagnostic prediction model reminiscent of systemic inflammation and organ interaction in heart failure preserved ejection fraction (HFpEF) patients

Heart Failure with Preserved Ejection Fraction and Obstructive Sleep Apnea: A Novel Paradigm for Additional Cardiovascular Benefit of SGLT2 Inhibitors in Subjects With or Without Type 2 Diabetes

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