NAFLD and Cardiovascular Diseases: Epidemiological, Mechanistic and Therapeutic Considerations

Abstract

Overwhelming evidence suggests an association of cardiovascular disease (CVD) with non-alcoholic fatty liver disease (NAFLD); however, the underlying mechanisms remain largely speculative. It is, however, likely that common mechanisms contribute to the development of CVD and NAFLD, with lifestyle factors such as smoking, sedentary lifestyle with poor nutrition habits and physical inactivity being major candidates. These behavioral factors, on a predisposing genetic background, trigger changes in gut microbiota, inflammation, dyslipidemia and oxidative stress, leading to metabolic syndrome, diabetes and obesity as well as atherosclerosis. Treatment options to counteract both the progression and development of CVD and NAFLD include lifestyle interventions, optimal medical therapy of comorbid conditions and, as final possibility, bariatric surgery. As no causal pharmacotherapy of NAFLD is available, further research is urgently needed to address the unmet need of a growing population with NAFLD and CVD.

Differences between current clinical guidelines for screening, diagnosis and management of nonalcoholic fatty liver disease and real-world practice: a targeted literature review

“…It is also noteworthy that most of the trials of antidiabetic drugs that are considered potentially beneficial in managing NAFLD, in particular glucagon-like peptide I receptor antagonists (GLP-1 RAs) and sodiumglucose cotransporter 2 (SGLT-2) inhibitors, were ongoing and unpublished when the guidelines under consideration were being developed [47]. Although not suitably indicated, GLP-1 RAs are favorably viewed for evaluation as pharmacotherapy in NAFLD, due to their combined effects on markers of steatosis, weight, and cardiometabolic parameters [16,47,48]. SGLT-2 inhibitors also show promise, although the risk of urinary tract infections may limit their use [16].…”

“…Although not suitably indicated, GLP-1 RAs are favorably viewed for evaluation as pharmacotherapy in NAFLD, due to their combined effects on markers of steatosis, weight, and cardiometabolic parameters [16,47,48]. SGLT-2 inhibitors also show promise, although the risk of urinary tract infections may limit their use [16]. Both classes of antidiabetic appear to have better benefit-risk profiles than pioglitazone, which features in NAFLD guidelines from EASL [26], NICE [31] and the AASLD [16,27].…”

“…SGLT-2 inhibitors also show promise, although the risk of urinary tract infections may limit their use [16]. Both classes of antidiabetic appear to have better benefit-risk profiles than pioglitazone, which features in NAFLD guidelines from EASL [26], NICE [31] and the AASLD [16,27]. Other, novel agents with mechanisms of action that target metabolic, inflammatory, or fibrotic processes have also been studied, some in late-phase trials, but development has stalled due to benefit-risk profiles perceived as inadequately favorable [49,50].…”

“…Although adults are most commonly affected by NAFLD, with occurrence increasing with age, rates of childhood NAFLD are increasing, particularly in association with the occurrence of obesity [1,8,11,12]. Cardiometabolic comorbidities share epidemiological, pathophysiological and behavioral/lifestyle features with NAFLD, suggesting a close association with aspects of metabolic syndrome and insulin resistance [1,8,[13][14][15][16]. Management of cardiometabolic conditions such as type 2 diabetes mellitus (T2DM) and metabolic syndrome using lifestyle modification and pharmacotherapy is a key component of NAFLD care [6,16,17].…”

Mitochondrial Lipid Homeostasis at the Crossroads of Liver and Heart Diseases

“…Results of many cross-sectional studies, meta-analyses and systematic reviews suggest that NAFLD increases the risk of atherosclerosis and favours the development of unstable plaques [10][11][12][13]. In addition, genetic evidence suggests that NAFLD-mediated dyslipidemia is a crucial factor of elevated CVD risk [14].…”