Coronary Artery Disease is More Severe in Patients with Non-Alcoholic Steatohepatitis than Fatty Liver

Niikura, Toshihiro; Imajo, Kento; Ozaki, Anna; Kobayashi, Takashi; Iwaki, Michihiro; Honda, Yoshihiro; Kessoku, Takaomi; Ogawa, Yasuhiro; Yoneda, Masato; Kohno, Hiroyuki; Saito, Satoru; Nakajima, Atsushi

doi:10.3390/diagnostics10030129

Cited by 24 publications

(25 citation statements)

References 35 publications

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“…The association between hepatic fibrosis and the risk of CVD in patients with NAFLD has been reported in several studies 9,11,25‐28 . NASH‐related fibrosis is associated with increased small dense low‐density lipoprotein and oxidised phospholipids leading to oxidative stress and mitochondrial damage, which may also increase the risk of atherosclerosis 29,30 .…”

Section: Discussionmentioning

confidence: 91%

“…Most clinical studies have demonstrated this association using non‐invasive assessment for fibrosis based on indirect serum biomarkers, such as NFS and FIB‐4 index 25,26 . Only a few studies have demonstrated an association of hepatic fibrosis with the risk of CVD in patients with biopsy‐proven NAFLD 9,11,27 . To the best of our knowledge, this is the first study to evaluate the association of CAC with MRE‐determined liver stiffness in patients with NAFLD.…”

Section: Discussionmentioning

confidence: 94%

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Liver stiffness by magnetic resonance elastography is associated with increased risk of cardiovascular disease in patients with non‐alcoholic fatty liver disease

Park

Jung

Verma

et al. 2021

Aliment Pharmacol Ther

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SummaryBackgroundMagnetic resonance elastography (MRE) is a reliable non‐invasive alternative to liver biopsy for assessing liver fibrosis. There are limited data regarding an association between liver fibrosis by MRE and risk of cardiovascular disease (CVD).AimTo investigate the association of high‐risk CVD phenotype determined by coronary artery calcification (CAC) with liver fibrosis by MRE in patients with non‐alcoholic fatty liver disease (NAFLD).MethodThis was a cross‐sectional analysis of well‐characterised, prospective cohorts including 105 patients with NAFLD (MR imaging‐derived proton density fat fraction ≥ 5%) with contemporaneous cardiac computed tomography (CT) and MRE. Patients were assessed using MRE for liver stiffness, and cardiac CT for the presence of CAC (defined as coronary artery calcium score > 0). Odds of presence of CAC were analysed using logistic regression analysis.ResultsThe average age and body mass index were 54.9 years and 32.9 kg/m2 respectively. In this cohort, 49.5% of patients had CAC and 35.2% had significant liver fibrosis (defined as MRE ≥2.97 kPa). Compared to patients without CAC, those with CAC were older (50.0 [39.0‐59.0] vs 63.0 [55.5‐67.5], P < 0.001) and had higher Framingham risk score (FRS, 1.0 [0.5‐3.5] vs 6.0 [2.0‐12.0], P < 0.001). In multivariable‐adjusted analysis, liver stiffness as a continuous trait on MRE was independently associated with the presence of CAC in a sex and age‐adjusted model (adjusted odd ratios [aOR] = 2.23, 95% confidence interval [CI] = 1.31‐4.34, P = 0.007) as well as in a FRS‐adjusted model (aOR = 2.16, 95% CI = 1.29‐4.09, P = 0.008). When analysed as a dichotomous trait, significant fibrosis (MRE‐stiffness ≥2.97 kPa) remained independently associated with the presence of CAC in both FRS‐adjusted model and sex and age‐adjusted model (aOR = 3.21‐3.53, P = 0.013‐0.017). In addition, CAC was more prevalent in patients with significant fibrosis than those without as determined by MRE (67.6% vs 39.7%, P = 0.012).ConclusionLiver stiffness determined by MRE is an independent predictor for the presence of CAC in patients with NAFLD. Patients with NAFLD and significant fibrosis by MRE should be considered for further cardiovascular risk assessment, regardless of their FRS.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 94%

Liver stiffness by magnetic resonance elastography is associated with increased risk of cardiovascular disease in patients with non‐alcoholic fatty liver disease

Park

Jung

Verma

et al. 2021

Aliment Pharmacol Ther

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“…Our study finding could partially explain that few studies analyzing the relationship between NAFLD and CAD, and they present controversial results, which may be due to different spectrums of NAFLD severity [ 26 ]. As for the mechanism underlying the positive relationship between severe NAFLD and CAD, abnormal insulin resistance, inflammation with oxidative stress and endothelial dysfunction may play an important pathway for the development of atherosclerosis with a potential dose–response relationship [ 5 , 6 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

Severe, but not mild to moderate, non-alcoholic fatty liver disease associated with increased risk of subclinical coronary atherosclerosis

Hsiao

Teng

et al. 2021

BMC Cardiovasc Disord

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Background Non-alcoholic fatty liver disease (NAFLD) is associated with high risk of cardiovascular disease. The prevalence is increasing to 45–65% in the general population with routine health check-up, and most subjects have the mild degree NAFLD in recent years. Moreover, there are no studies on the association between NAFLD severity and coronary atherosclerosis in the real-world setting by ultrasonography. Methods The aim of this study was to determine the relationship between the severity of NAFLD and subclinical coronary atherosclerosis. Overall, 817 subjects meet criteria for NAFLD were enrolled in the retrospective cohort study (155 subjects were excluded). The severity of NAFLD was divided into the normal, mild, moderate and severe degree based on the finding of abdominal ultrasonography. The assessment of coronary atherosclerosis was based on CAC scan/coronary CT angiography finding in terms of CAC score ≧ 100, CAC score ≧ 400, CAD-RADS ≧ 3 and presence of vulnerable plaque(s). Results A significant linear trend was observed between the severity of NAFLD and subclinical coronary atherosclerosis. Compared with the reference group (including normal, mild, and moderate NAFLD), severe degree NAFLD was the independently associated risk of subclinical coronary atherosclerosis in term of CAC score ≧ 100, CAC score ≧ 400, CAD-RADS ≧ 3 and presence of vulnerable plaque(s) based on binary logistic regression after adjustment for FRS score and body fat percentage. Conclusions Severe degree, but not mild to moderate, was associated with high risk of subclinical coronary atherosclerosis, independently of FRS score and body-fat percentage.

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“…In this analysis of 10 studies, the initial definition of CVD varied by author. Zheng, et al defined CV disease as carotid intima media thickening > 0.8 mm along with post-exercise brachial-ankle pulse wave velocity as surrogates for clinical cardiovascular disease [20]. Yun, et al, Harring, et al and Hwang, et al defined cardiovascular mortality via ICD 10 codes.…”

Section: Discussionmentioning

confidence: 99%

“…NAFLD is a multifactorial disease that develops from the interactions of genetics, diet, and lifestyle [5,6,20,21]. NAFLD and CVD both have significant similarities in terms of risk factors, genetic predispositions, and pathophysiology.…”

Section: Incidence and Prevalence Of Cardiovascular Events And Mortalitymentioning

confidence: 99%

Increased Incidence and Prevalence of Cardiovascular Events and Mortality in Female Patients with NAFLD: A Meta-Analysis and Meta-Regression

Yaser¹,

Neethi²,

Herman³

et al. 2020

Int J Clin Cardiol

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Background: Non-alcoholic fatty liver disease (NAFLD) and cardiovascular diseases (CVD) share similar risk factors. Recent studies have focused on obesity and insulin-resistance, but the link between NAFLD and CVD persists regardless of traditional risk factors. Despite the increased incidence and prevalence of NAFLD worldwide , there has been no thorough investigation of gender disparities nor a closer look taken into investigating the role gender may play in increased cardiovascular (CV) mortality incidence and prevalence in patients with NAFLD. Objective: We assessed incidence and prevalence of CV events and mortality based on gender in patients with NA-FLD, at any stage of fibrosis. A meta-regression was conducted to further analyze the impact of age on both genders. Methods: An aggregate analysis was performed on ten studies with NAFLD patients. A random-effects model was used to pool the overall incidence and prevalence rates of CV events and mortality as well as all-cause mortality to examine any gender disparity. We also performed a meta-regression analysis to evaluate the effect of age on mortality for men versus women with NAFLD and CV events and mortality. Summary odds ratios (OR) and 95% confidence intervals (CI) were estimated using a random-effects model. Results: In 259,598 patients with NAFLD, of which 44% were females and 56% were males, all-cause mortality was 1.5 × higher in women compared to men (OR 1.65, 95% CI 1.12-2.43, p < 0.012). CV events and mortality were also 2 × higher in women compared to men (OR 2.12 95% CI 1.65-2.73, p < 0.001). On meta-regression, females had higher mortality with advancing age starting at age 42 (coefficient = 0.0518, p = 0.00001). Conclusion: For patients with NAFLD, women had a markedly higher incidence and prevalence of CV events, CV mortality and all-cause mortality when compared to men. Meta-regression showed increased mortality among women with advancing age. As the incidence and prevalence of NAFLD and concomitant CV events increases worldwide, we urge the medical community to increase surveillance and perform rigorous cardiovascular risk assessments for women, especially beginning at age 42. Additionally, we recommend heterogenous surveys of gender disparities, increased focus on gender as a decisive factor for downstream CV events, the relationship between NAFLD severity and gender-based mortality differences, and larger studies representing equivalent male and female populations.

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Coronary Artery Disease is More Severe in Patients with Non-Alcoholic Steatohepatitis than Fatty Liver

Cited by 24 publications

References 35 publications

Liver stiffness by magnetic resonance elastography is associated with increased risk of cardiovascular disease in patients with non‐alcoholic fatty liver disease

Liver stiffness by magnetic resonance elastography is associated with increased risk of cardiovascular disease in patients with non‐alcoholic fatty liver disease

Severe, but not mild to moderate, non-alcoholic fatty liver disease associated with increased risk of subclinical coronary atherosclerosis

Increased Incidence and Prevalence of Cardiovascular Events and Mortality in Female Patients with NAFLD: A Meta-Analysis and Meta-Regression

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