Research Article Details
| Article ID: | A02579 |
| PMID: | 34324263 |
| Source: | Diabetes Obes Metab |
| Title: | Non-alcoholic fatty liver disease-related risk of cardiovascular disease and other cardiac complications. |
| Abstract: | BACKGROUND/AIM: Non-alcoholic fatty liver disease (NAFLD) affects approximately 25% of the global adult population. The aim of this narrative review is to describe the associations between NAFLD and cardiovascular disease (CVD), arrhythmias, cardiac conduction defects, myocardial remodelling and heart failure. We also discuss the potential mechanisms that mediate or attenuate the strength of these associations, and briefly summarize the effect of treatments that both ameliorate NAFLD and decrease risk of CVD. METHODS: Searches of PubMed were performed by the two authors using the terms listed in Appendix. We limited the timeframe to the last decade due to the vast amount of research in the field (up to April 2021) for meta-analyses, reviews and original papers. Only articles published in English were considered. RESULTS: NAFLD is associated with an increased risk of fatal/non-fatal CVD events and other cardiac and arrhythmic complications (left ventricular hypertrophy, aortic-valve sclerosis and certain arrhythmias), independently of common CVD risk factors. There are probably several underlying mechanisms, including hepatic/systemic insulin resistance, atherogenic dyslipidaemia, hypertension and pro-atherogenic, pro-coagulant and pro-inflammatory mediators released from the steatotic/inflamed liver that may be involved. Some genetic polymorphisms, such as PNPLA3 (rs738409 C>G) and TM6SF2 (rs58542926 C>T), may worsen the liver disease, but also attenuate the strength of the association between NAFLD and CVD, possibly via their effects on lipoprotein metabolism. Of the currently tested drugs for treating NAFLD that also benefit the vasculature, pioglitazone and GLP-1 receptor agonists are the most promising. CONCLUSIONS: The complex interplay between the liver and cardiometabolic risk factors contributes to CVD, arrhythmias and cardiac disease in NAFLD. There is an urgent need for a multidisciplinary approach to manage both liver disease and cardiometabolic risk, and to test the cardiovascular and cardiac effects of new drugs for NAFLD. |
| DOI: | 10.1111/dom.14484 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I12 | 10763 | Hypertension | An artery disease characterized by chronic elevated blood pressure in the arteries. https://en.wikipedia.org/wiki/Hypertension, https://www.ncbi.nlm.nih.gov/pubmed/24352797 | disease of anatomical entity/ cardiovascular system disease/vascular disease/ artery disease | Details |
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D248 | Obeticholic Acid | Chemical drug | DB05990 | NR1H4 activator; NR1H4 agonist; FXR agonist | Enhance lipid metabolism | Approval rejected | Details |
| D545 | Pig placenta extract | Biological extract | -- | -- | -- | Under clinical trials | Details |
| D275 | Pioglitazone | Chemical drug | DB01132 | PPARG agonist | Improve insulin resistance | Advanced in clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |