Review
NAFLD, and cardiovascular and cardiac diseases: Factors influencing risk, prediction and treatment

https://doi.org/10.1016/j.diabet.2020.101215Get rights and content

Abstract

Background and aim

Non-alcoholic fatty liver disease (NAFLD), affecting up to around 30% of the world’s adult population, causes considerable liver-related and extrahepatic morbidity and mortality. Strong evidence indicates that NAFLD (especially its more severe forms) is associated with a greater risk of all-cause mortality, and the predominant cause of mortality in this patient population is cardiovascular disease (CVD). This narrative review aims to discuss the strong association between NAFLD and increased risk of cardiovascular, cardiac and arrhythmic complications. Also discussed are the putative mechanisms linking NAFLD to CVD and other cardiac/arrhythmic complications, with a brief summary of CVD risk prediction/stratification and management of the increased CVD risk observed in patients with NAFLD.

Results

NAFLD is associated with an increased risk of CVD events and other cardiac complications (left ventricular hypertrophy, valvular calcification, certain arrhythmias) independently of traditional CVD risk factors. The magnitude of risk of CVD and other cardiac/arrhythmic complications parallels the severity of NAFLD (especially liver fibrosis severity). There are most likely multiple underlying mechanisms through which NAFLD may increase risk of CVD and cardiac/arrhythmic complications. Indeed, NAFLD exacerbates hepatic and systemic insulin resistance, promotes atherogenic dyslipidaemia, induces hypertension, and triggers synthesis of proatherogenic, procoagulant and proinflammatory mediators that may contribute to the development of CVD and other cardiac/arrhythmic complications.

Conclusion

Careful assessment of CVD risk is mandatory in patients with NAFLD for primary prevention of CVD, together with pharmacological treatment for coexisting CVD risk factors.

Introduction

Non-alcoholic fatty liver disease (NAFLD) is a worldwide public-health problem (affecting up to one-third of adults in Western countries), and its prevalence is expected to further increase in the near future at rates similar to those of the obesity and type 2 diabetes mellitus (T2DM) epidemics [1], [2]. The clinical and economic burden of this common metabolic liver disorder is not only due to its liver-related complications [non-alcoholic steatohepatitis (NASH), cirrhosis, hepatocellular carcinoma], but also the increased risk of cardiovascular disease (CVD) and other extrahepatic diseases (such as T2DM, chronic kidney disease and some extrahepatic cancers) that have a considerable impact on health outcomes and healthcare-related expenditures [2], [3], [4], [5].

It is accepted that CVD is the leading cause of mortality amongst patients with NAFLD (accounting for about 40% of total deaths), followed by extrahepatic cancers and liver-related complications [2], [3], [4]. Over the past decade, it has also become evident that NAFLD is a ‘multisystem’ disease [6] that not only increases the risk of developing CVD, T2DM and/or chronic kidney disease [2], [7], but also results in other cardiac and arrhythmic complications (Fig. 1) [8].

This narrative review focuses on the strong association between NAFLD and increased risk of CVD and other cardiac/arrhythmic complications, discusses the potential underlying mechanisms through which NAFLD contributes to the development of these complications, and summarizes CVD risk prediction/stratification and its management when associated with NAFLD.

Section snippets

Risk of CVD

As has been previously reported, CVD is the leading cause of death in NAFLD [2], [3], [4]. Using mortality data from the US National Vital Statistics System (NVSS) multiple-cause mortality data, Paik et al. [9] recently confirmed that CVD is indeed one of the most important causes of death amongst NAFLD patients. Convincing evidence associates NAFLD with an increased prevalence and incidence of CVD even after adjusting for common CVD risk factors [2], [4], [10]. Table 1 quantifies the excess

Putative mechanisms

NAFLD and T2DM are frequently concomitant and share the same cardiometabolic risk factors: for example, both conditions are strongly associated with risk factors linked to MetS, including increased abdominal adiposity and insulin resistance [40]. However, while the increased risk of T2DM with NAFLD is independent of potential confounders [41], it is more difficult to prove that the association between NAFLD and CVD is independent of the cardiometabolic risk factors shared with T2DM.

CVD risk assessment

For the primary prevention of CVD in adults with NAFLD, determining the patient’s risk of future CVD events is essential for successfully implementing CVD risk reduction [71]. Several algorithms are commonly used in the general population to estimate future risk of CVD events and may be applied to adults with NAFLD. These include the Framingham Risk Score (FRS) and Atherosclerotic Cardiovascular Disease (ASCVD) score [109]. The FRS incorporates age, blood pressure, total cholesterol, HDL-C,

Conclusion

At this time, the available evidence strongly supports the notion that NAFLD is a ‘multisystem’ disease that adversely affects many extrahepatic organ systems, including the cardiovascular system [10]. NAFLD independently increases the risk of coronary atherosclerosis, cardiomyopathy and certain arrhythmias, which clinically result in increased CVD morbidity and mortality, and also parallels the severity of NAFLD (especially the stage of liver fibrosis). Although further studies are still

Conflicts of interest statement

None of the authors has any conflicts of interest to disclose in relation to this paper.

Funding sources

G.T. is supported in part by grants from the School of Medicine, University of Verona, Verona, Italy. C.D.B. is supported in part by the Southampton NIHR Biomedical Research Centre (IS-BRC-20004) in Southampton, UK.

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    All three authors contributed equally to this manuscript.

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