Cardiovascular risk factors in non‐alcoholic fatty liver disease

Hagström, Hannes; Nasr, Patrik; Ekstedt, Mattias; Hammar, Ulf; Stål, Per; Askling, Johan; Hultcrantz, Rolf; Kechagias, Stergios

doi:10.1111/liv.13973

Cited by 82 publications

(69 citation statements)

References 27 publications

(58 reference statements)

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“…One possible explanation for this finding is that patients with ASCVD ≥7.5% already have an increased risk for cardiac-specific mortality and so the presence of advanced fibrosis does not seem to add additional risks. Our finding is supported by a recent study by Hagstrom et al (40) , which evaluated liver histology and traditional cardiovascular risk factors as a predictor of CVD outcomes in patients with biopsy-proven NAFLD. This study concluded that when CVD risk factors were taken into account, the presence of nonalcoholic steatohepatitis or advanced fibrosis was not associated with incident CVD risk in patients with NAFLD.…”

Section: Discussionsupporting

confidence: 88%

Mortality Risk Detected by Atherosclerotic Cardiovascular Disease Score in Patients With Nonalcoholic Fatty Liver Disease

et al. 2019

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Cardiovascular diseases (CVDs) are the leading cause of mortality in patients with nonalcoholic fatty liver disease (NAFLD). Our aim was to assess the association of atherosclerotic cardiovascular disease (ASCVD) risk scores with overall and cardiac‐specific mortality among patients with NAFLD. We used the National Health and Nutrition Examination Survey III with the National Death Index‐linked mortality files. NAFLD was defined by ultrasound as presence of steatosis in the absence of secondary causes of liver disease. High risk for CVD was defined as a 10‐year ASCVD score ≥7.5%. Hazard ratios (HRs) and population‐attributable fractions (PAFs) of high risk for CVD were calculated. Among 1,262 subjects with NAFLD (47.9% men; 41.2% white; mean age, 56.3 years), the prevalence of high risk for CVD was 55.9% and 4.8% had advanced fibrosis. After a median follow‐up of 17.7 years, 482 subjects (38.2%) died of overall causes, of whom 382 (79.3%) had a high risk for CVD. The unadjusted overall and cardiac‐specific mortality were higher for patients with NAFLD who had a high risk for CVD compared to subjects with NAFLD with a low risk for CVD (57.3% vs. 16.8% for overall mortality; 16.4% vs. 3.5% for cardiovascular mortality). After controlling for risk factors associated with mortality, high risk for CVD was associated with a 42% higher overall mortality rate (adjusted HR [aHR], 1.42; 95% confidence interval [CI], 1.05‐1.91) and twice the risk of cardiovascular mortality (aHR, 2.02; 95% CI, 1.12‐3.65). Adjusted PAFs were 11.4% for overall mortality and 44.9% for cardiovascular mortality. Conclusion: Among patients with NAFLD, ASCVD score ≥7.5% was associated with a higher risk of overall and cardiac‐specific mortality.

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Section: Discussionsupporting

confidence: 88%

Mortality Risk Detected by Atherosclerotic Cardiovascular Disease Score in Patients With Nonalcoholic Fatty Liver Disease

et al. 2019

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“…115 A recent Swedish cohort study in liver biopsy-diagnosed NAFLD with the longest documented follow-up time (of over 18 years) supported these findings by showing that patients with NAFLD are at an increased risk for CVD. 116 Although more studies are needed to confirm a causal relationship between NAFLD and CVD, these findings highlight Meta-analysis showing an association of NAFLD with major adverse CVD events 34 studies with a total of 164,494 participants were included; specifically, 21 crosssectional studies and 13 cohort studies were examined in this meta-analysis NAFLD was not associated with overall mortality and CVD mortality but was, however, associated with an increased risk of prevalence and incidence of CVD Hagström et al…”

Section: Cardiovascular Outcomes and Mortality In Nafldmentioning

confidence: 99%

Pathogenesis of Insulin Resistance and Atherogenic Dyslipidemia in Nonalcoholic Fatty Liver Disease

Akhtar¹,

Iqbal²,

Vazquez‐Montesino³

et al. 2019

Journal of Clinical and Translational Hepatology

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Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the developed world, with a global prevalence of around 25%. NAFLD is considered to be the hepatic manifestation of metabolic syndrome and is strongly associated with obesity, insulin resistance and dyslipidemia. Insulin resistance plays a pivotal role in the development of NAFLD-related dyslipidemia, which ultimately increases the risk of premature cardiovascular diseases, a leading cause of morbidity and mortality in patients with NAFLD. Insulin affects hepatic glucose and lipid metabolism by hepatic or extrahepatic pathways. Aside from insulin resistance, several other factors also contribute to the pathogenesis of atherogenic dyslipidemia in patients with NAFLD. These include diet composition, gut microbiota and genetic factors, to name a few. The identification of potentially modifiable risk factors of NAFLD is of importance, so as to target those who may benefit from lifestyle changes and to help develop targeted therapies that decrease the risk of cardiovascular diseases in patients with NAFLD. Citation of this article: Akhtar DH, Iqbal U, Vazquez-Montesino LM, Dennis BB, Ahmed A. Pathogenesis of insulin resistance and atherogenic dyslipidemia in nonalcoholic fatty liver disease.Abbreviations: DNL, de novo lipogenesis; NAFLD, nonalcoholic fatty liver disease; SIBO, small intestinal bacterial overgrowth.

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“…Other studies, like the one in the aforementioned meta‐analysis, have identified fibrosis as the best predictor of long‐term survival, with increased cardiovascular mortality in patients with advanced fibrosis . Yet, data on the relationship between fibrosis and CVD have also been inconsistent, and many of these prior studies were limited by either a retrospective design, a small number with advanced fibrosis, or inclusion of individuals with pre‐existing CVD . Furthermore, nearly all of these studies assessed cardiovascular mortality; few evaluated the development of incident fatal and nonfatal CVD as an outcome.…”

Section: Introductionmentioning

confidence: 99%

“…2,3,5 Yet, data on the relationship between fibrosis and CVD have also been inconsistent, and many of these prior studies were limited by either a retrospective design, a small number with advanced fibrosis, or inclusion of individuals with pre-existing CVD. 13,14 Furthermore, nearly all of these studies assessed cardiovascular mortality; few evaluated the development of incident fatal and nonfatal CVD as an outcome.…”

Section: Introductionmentioning

confidence: 99%

Advanced fibrosis is associated with incident cardiovascular disease in patients with non‐alcoholic fatty liver disease

Henson

Simon

Kaplan

et al. 2020

Aliment Pharmacol Ther

111

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Summary Background Non‐alcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiovascular disease. It is not well understood, however, which individuals with NAFLD are at highest risk for cardiovascular disease. Aims To determine the factors associated with incident cardiovascular events in a prospective cohort of individuals with biopsy‐proven NAFLD without pre‐existing cardiovascular disease. Methods From 2011 to 2018, adults with biopsy‐proven NAFLD without cardiovascular disease were enrolled in a tissue repository and were followed prospectively to the first recorded date of incident cardiovascular disease, death or the end of follow‐up (11/1/2018). Competing risks analysis was performed to identify predictors of incident cardiovascular disease. Results After a median follow‐up time of 5.2 years, 26/285 (9.1%) individuals experienced an incident cardiovascular event. Advanced fibrosis (stage 3‐4) on biopsy was a significant predictor of incident cardiovascular disease, and this persisted on multivariable analysis (SHR 2.86, 95% CI 1.36–6.04) after considering relevant covariates, including cardiovascular risk scores, which were not independent predictors. Of the non‐invasive indicators of fibrosis, the NAFLD fibrosis score was the only independent predictor of cardiovascular disease. Other histologic features, including steatohepatitis, were not associated with incident cardiovascular disease. Conclusions In adults with biopsy‐proven NAFLD, advanced fibrosis on biopsy and higher NAFLD fibrosis score were significant and independent predictors of incident cardiovascular disease, even after considering traditional risk factors and cardiovascular risk scores. These findings should be considered when evaluating NAFLD patients for primary prevention of cardiovascular disease, and further evaluation into the link between advanced fibrosis and cardiovascular disease is needed.

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Cardiovascular risk factors in non‐alcoholic fatty liver disease

Cited by 82 publications

References 27 publications

Mortality Risk Detected by Atherosclerotic Cardiovascular Disease Score in Patients With Nonalcoholic Fatty Liver Disease

Mortality Risk Detected by Atherosclerotic Cardiovascular Disease Score in Patients With Nonalcoholic Fatty Liver Disease

Pathogenesis of Insulin Resistance and Atherogenic Dyslipidemia in Nonalcoholic Fatty Liver Disease

Advanced fibrosis is associated with incident cardiovascular disease in patients with non‐alcoholic fatty liver disease

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