Risk of Heart Failure in Patients With Nonalcoholic Fatty Liver Disease

Non-Alcoholic Fatty Liver Disease and Risk of Macro- and Microvascular Complications in Patients with Type 2 Diabetes

“…In this regard, for instance, in a 2022 systematic review of randomised controlled trials testing the efficacy of peroxisome proliferator-activated receptor (PPAR) agonists, GLP-1 receptor agonists and SGLT-2 inhibitors for treating NAFLD in adults with or without type 2 diabetes, our research group found that pioglitazone (a PPAR-γ agonist), lanifibranor (a pan-PPAR agonist) and GLP1-R agonists (e.g., liraglutide and semaglutide) are able to obtain the resolution of NASH without worsening of fibrosis, whereas SGLT-2 inhibitors (e.g., empagliflozin and dapagliflozin) are able to reduce liver fat content, as detected by magnetic resonance-based techniques [87]. Given the strong relationship between NAFLD and macro-and microvascular complications, it is possible to speculate that these agents may exert a beneficial effect not only on the hepatic disease, but also in reducing the risk of developing cardiovascular and renal diseases [25,[86][87][88]. However, herein it is important to note that pioglitazone is contraindicated in patients with symptomatic heart failure or in patients with a high risk of heart failure [25].…”

“…Given the strong relationship between NAFLD and macro-and microvascular complications, it is possible to speculate that these agents may exert a beneficial effect not only on the hepatic disease, but also in reducing the risk of developing cardiovascular and renal diseases [25,[86][87][88]. However, herein it is important to note that pioglitazone is contraindicated in patients with symptomatic heart failure or in patients with a high risk of heart failure [25]. Seeing the multiple pathways implicated in the pathogenesis of NAFLD and its complications, as well as the single response from single-agent therapies across RCTs available so far, it is also reasonable to hypothesize that the combination of different therapies (e.g., GLP-1 receptor agonists plus SGLT-2 inhibitors) will be more appropriate for treating NAFLD patients [86,87,89].…”

“…In particular, the synthesis of lipids, including DAG, may also contribute to the hepatic production of inflammatory cytokines and pro-coagulant factors [13,[20][21][22]; (c) the bidirectional relationship between NAFLD and hypertension [23]. Several observational studies and some meta-analyses have reported that patients with NAFLD have an increased risk of developing hypertension [24], thus suggesting that this association may partly mediate the relationship between NAFLD and cardiac complications and that that NAFLD may be a consequence, but also a cause of hypertension [23]; (d) patients with NAFLD have early changes in myocardial substrate metabolism inducing cardiac functional disturbances, probably conditioning a higher risk of heart failure [25] and arrhythmias [22,26]; (e) chronic hyperglycemia induces an inflammatory and osteoblastic phenotype in valvular interstitial cells in experimental models of aortic valve sclerosis [27]. Increased valvular inflammation, through a systemic inflammatory state, could also mediate the increased cardiac valve sclerosis in NAFLD patients, independent of the presence of T2DM; (f) experimental data also indicate that NAFLD, mainly when advanced stages occur, may contribute to the activation of multiple pathways involved in the pathophysiology of CKD [10,28].…”

“…Another 2021 meta-analysis confirmed that NAFLD (as detected by imaging techniques, ICD codes or liver biopsy) was independently associated with increased risk of myocardial infarction (random-effects odds ratio 1.66, 95% confidence interval 1.39-1.99), ischemic stroke (random-effects odds ratio 1.41, 95% confidence interval 1.29-1.55) and heart failure (random-effects odds ratio 1.62, 95% confidence interval 1.43-1.84) [26]. In this regard, it is important to underline that the magnitude of cardiovascular risk is strongly related to the severity of NAFLD [25,[80][81][82]. For instance, in a nationwide, matched cohort study of 10,568 Swedish individuals with biopsy-confirmed NAFLD (11% with T2DM at baseline) who were followed for a median period of 14 years, Simon et al reported that, when compared to 49,925 adults of the general population (3% with established T2DM at baseline), mortality rates from CVD were significantly elevated in patients with simple steatosis (adjusted-hazard ratio 1.25, 95% confidence interval 1.16-1.35), and that these risks progressively increased in patients with NASH without fibrosis (adjusted-hazard ratio 1.66, 95% confidence interval 1.38-2.01), in those with non-cirrhotic fibrosis (adjusted-hazard ratio 1.40, 95% confidence interval 1.17-1.69) and also in those with cirrhosis (adjusted-hazard ratio 2.11, 95% confidence interval 1.63-2.73) [80].…”

Non-Alcoholic Fatty Liver Disease Defined by Fatty Liver Index and Incidence of Heart Failure in the Korean Population: A Nationwide Cohort Study

“…In Korea, the prevalence of NAFLD was about 27% in the general population [9] and was 16.1% (21.6% in men, 11.2% in women) when diagnosed with ultrasnography [10]. NAFLD is a risk factor for major adverse cardiovascular events (MACE) and is a multisystem disease [11]. The gold standard diagnosis for NAFLD and non-alcoholic steatohepatitis (NASH) is biopsy, but being an invasive technique [12], various non-invasive indices have been developed especially for the purposes of public health check-up studies [13].…”