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FIB‐4 liver fibrosis index correlates with aortic valve sclerosis in non‐alcoholic population
Abstract
Aim
Hepatic fibrosis, a progressive scarring of liver tissue, is commonly caused by non‐alcoholic fatty liver disease (NAFLD), which increases the risk of cardiovascular disease. The Fibrosis‐4 (FIB‐4) index is a non‐invasive tool used to assess liver fibrosis in patients with NAFLD. Aortic valve sclerosis (AVS), a degenerative disorder characterized by thickening and calcification of valve leaflets, is prevalent in the elderly and associated with increased cardiovascular morbidity and mortality. Recent studies have suggested that AVS may also be linked to other systemic diseases such as liver fibrosis. This study aimed to investigate the relationship between the FIB‐4 index and AVS in a non‐alcoholic population, with the hypothesis that the FIB‐4 index could serve as a potential marker for AVS.
Method
A total of 92 patients were included in this study. AVS was detected using transthoracic echocardiography, and patients were divided into groups according to the presence of AVS. The FIB‐4 index was calculated for all patients and compared between the groups.
Results
A total of 17 (18.4%) patients were diagnosed AVS. Patients with AVS had higher rates of diabetes mellitus, older age, hypertension, angiotensin‐converting enzyme inhibitor use, higher systolic blood pressure (BP) and diastolic BP in the office, coronary artery disease prevalence, left atrial volume index (LAVI), left ventricular mass index (LVMI), and late diastolic peak flow velocity (A) compared to those without AVS. Moreover, AVS patients had significantly higher creatinine levels and lower estimated glomerular filtration rate. Remarkably, the FIB‐4 index was significantly higher in patients with AVS. In univariate and multivariate analyses, higher systolic BP in the office (OR, 1.044; 95% CI 1.002–1.080, p = .024) and higher FIB‐4 index (1.46 ± .6 vs. .91 ± .46, p < .001) were independently associated with AVS.
Conclusion
Our findings suggest that the FIB‐4 index is associated with AVS in non‐alcoholic individuals. Our results highlight the potential utility of the FIB‐4 index as a non‐invasive tool for identifying individuals at an increased risk of developing AVS.
... Figure 1 illustrates the principal Figure 1. Spectrum of cardio-nephro-metabolic and vascular manifestations of MASLD [32][33][34][35][36] . AF: atrial fibrillation; CVD: cardiovascular disease; HF: heart failure; HTN: arterial hypertension; MASLD: metabolic dysfunction-associated steatotic liver disease. ...
... AF: atrial fibrillation; CVD: cardiovascular disease; HF: heart failure; HTN: arterial hypertension; MASLD: metabolic dysfunction-associated steatotic liver disease. cardiometabolic outcomes spanning from the full-blown metabolic syndrome to its individual components (arterial hypertension, diabetes, and prediabetes) and from major cardiovascular events (MACE) (both fatal and non-fatal) to atrial fibrillation, heart failure, and chronic kidney disease [32,33] . Further to these, heart valve calcifications (predominantly aortic valve sclerosis), left ventricular diastolic dysfunction and hypertrophy have also been reportedly associated with MASLD [34][35][36] . ...
... The putative pathomechanisms associating MASLD with the various cardiovascular manifestations named above are incompletely defined and the succession of such mechanisms, postulated to act in parallel, remains speculative [33] . Interestingly, cardiovascular manifestations of MASLD tend to worsen in parallel with increasing liver fat content, the progression from simple steatosis to steatohepatitis and more advanced stages of liver fibrosis [33,[40][41][42][43] . ...
Metabolic dysfunction-associated steatotic liver disease (MASLD) stands as an independent risk factor for cardiovascular disease (CVD), which is the leading cause of mortality among MASLD patients. The diverse spectrum of cardio-nephro-metabolic and vascular manifestations inherent in MASLD highlights the complex profile of CVD risk associated with this condition. However, current approaches to assessing CVD risk in MASLD lack specificity, predominantly relying on traditional markers. Although it is widely accepted that patients with advanced fibrosis are more prone to CVD risk, recent evidence suggests that this isolated focus may overlook the remarkable phenotypic variability of this CVD risk across the entire MASLD population. Emerging data indicate a progressive escalation of CVD risk in parallel with the severity of MASLD, highlighting the need for precise disease staging to inform accurate risk assessment. To address this challenge, we propose a novel sequential approach to CVD risk assessment in MASLD. While traditional CVD risk factors remain essential, incorporating liver-specific parameters enhances risk stratification and guides targeted interventions to mitigate the substantial burden of cardiovascular disease in this vulnerable population. This approach involves initial screening using FIB-4 and NAFLD fibrosis score, followed by assessment of liver fibrosis with imaging-based non-invasive techniques in individuals at intermediate-high risk for advanced fibrosis and liver fat quantification in low-risk individuals. Future prospective investigations should focus on the simultaneous use of liver biomarkers and imaging modalities to evaluate, in a sex-specific manner, the efficacy of the proposed approach and to determine optimal thresholds of liver fibrosis and steatosis for optimal CVD risk assessment.
Background:
Arterial hypertension is associated with cardiovascular morbidity and mortality. It was previously shown that left atrium volume increase associated with mortality and atherosclerotic heart disease. The aim of the present study was to demonstrate the value of endothelial dysfunction in predicting left atrium volume increase in newly diagnosed hypertension patients.
Methods:
This study included 96 consecutive newly diagnosed hypertensive patients. Left atrium volume and left ventricular ejection fraction were calculated. Pulse wave velocity and brachial artery flow-mediated dilation measurements were obtained from each patient.
Results:
Left Ventricle Mass Index (114 ± 29 g/m, 91 ± 17 g/m, P < 001), left ventricular septum (P < 0.001) and posterior wall thickness (P = 0.001), left ventricular end diastolic diameter (P = 0.016) were significantly higher in patients with higher left atrial volume index. FMD% was lower in patients with higher left atrial volume index those without (9.7 ± 3.5 vs. 13.31 ± 6.01, P = 0.004). Lateral wall E wave velocity was significantly lower (8.68 ± 2.8, 10.2 ± 2.8; P = 0.009), while isovolumetric relaxation time (101.9 ± 19.9 ms, 85.7 ± 15.2 ms; P < 0.001), and ejection time was longer (101.9 ± 19.9 ms, 85.7 ± 15.2 ms; P = 0.077) and Mitral E/ lateral wall E ratio (E/E relation) was significantly higher (P = 0.031) in patients with higher left atrial volume index.
Conclusion:
The rate of isovolumetric relaxation time, FMD% and E/E' ratio independently predicted left atrial volume index increase in newly diagnosed hypertension patients.
Non-alcoholic fatty liver disease (NAFLD) has a global prevalence of about 25%. Incidence is increasing with rising levels of obesity, type 2 diabetes and the metabolic syndrome, and NAFLD is predicted to become the leading cause of cirrhosis requiring liver transplantation in the next decade. However, the cardiovascular disease is the most common cause of death and only a minority will develop fibrosis and liver-related complications. Therefore, it is imperative to identify patients with advanced disease using non-invasive markers of fibrosis, which include serology-based tests (eg NAFLD Fibrosis Score and ELF test) and imaging (eg transient elastography). This targets appropriate patients for referral to secondary care for additional investigations such as liver biopsy and specialist care. Lifestyle modification and weight loss remains the cornerstone of management, but we are about to enter a new era of promising pharmacotherapies for NASH and fibrosis.
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in developed countries and is associated with obesity, dyslipidaemia, diabetes, and metabolic syndrome. Atherosclerosis and cardiovascular diseases are also highly prevalent in this group of patients, due to the presence of shared risk factors. The incidences of coronary artery calcification, hypertension, aortic valve sclerosis, diastolic dysfunction, atherosclerotic plaques, and increased carotid intima-media thickness were more common in patients with NAFLD than in those without. The present paper reviews the medical literature concerning the association between NAFLD and cardiovascular events.
Background:
Recent studies have associated non-alcoholic fatty liver disease (NAFLD) with increased risk of cardiovascular disease, using tests of subclinical atherosclerosis.
Aim:
To evaluate the influence of NAFLD on subclinical atherosclerosis and coronary artery disease (CAD).
Methods:
We reviewed Pubmed and EMBASE. According to inclusion and exclusion criteria, we selected 14 studies and were classified in two groups. Ten studies aimed the presence of subclinical atherosclerosis and four studies the presence of coronary artery disease. To assess subclinical atherosclerosis, we selected studies with pathological carotid intima-media thickness (CIMT) and with presence of carotid plaques. We considered coronary artery disease when patients showed at least 50% stenosis at one or more major coronary arteries. NAFLD was assessed by ultrasound (US) and liver biopsy.
Results:
NAFLD showed a higher prevalence of pathological CIMT [35.1% (351/999) vs. 21.8% (207/948); p < 0.0001], with OR 2.04 (95% CI: 1.65-2.51). Similarly, the presence of carotid plaques was higher in NAFLD diagnosed by US [34.2% (101/295) vs. 12.9% (51/394); p < 0.0001] [OR 2.82 (95% CI: 1.87-4.27)] and diagnosed by liver biopsy [64.8% (70/108) vs. 31.3% (59/188); p < 0.0001] [OR 4.41 (95% CI: 2.63-7.40)]. On the other hand, four studies assessed CAD in patients underwent coronary angiogram. Subjects with NAFLD showed 80.4% (492/612) of CAD, while it was detected in 60.7% (356/586) (p < 0.0001) in patients without NAFLD. Therefore, NAFLD was associated with a remarkably higher likelihood of CAD, using random effects model [OR 3.31 (95% CI: 2.21-4.95)] or fixed effects model [OR 3.13 (95% CI: 2.36-4.16)].
Conclusions:
NAFLD increases the risk of subclinical atherosclerosis and coronary artery disease. The right management of these patients could modify the natural history both liver and cardiovascular disease.
Non-alcoholic fatty liver disease is marked by hepatic fat accumulation not due to alcohol abuse. Several studies have demonstrated that NAFLD is associated with insulin resistance leading to a resistance in the antilipolytic effect of insulin in the adipose tissue with an increase of free fatty acids (FFAs). The increase of FFAs induces mitochondrial dysfunction and development of lipotoxicity. Moreover, in subjects with NAFLD, ectopic fat also accumulates as cardiac and pancreatic fat. In this review we analyzed the mechanisms that relate NAFLD with metabolic syndrome and dyslipidemia and its association with the development and progression of cardiovascular disease.
Nonalcoholic fatty liver disease (NAFLD) is an increasingly common condition that is believed to affect >25% of adults worldwide. Unless specific testing is done to identify NAFLD, the condition is typically silent until advanced and potentially irreversible liver impairment occurs. For this reason, the majority of patients with NAFLD are unaware of having this serious condition. Hepatic complications from NAFLD include nonalcoholic steatohepatitis, hepatic cirrhosis, and hepatocellular carcinoma. In addition to these serious complications, NAFLD is a risk factor for atherosclerotic cardiovascular disease, which is the principal cause of death in patients with NAFLD. Accordingly, the purpose of this scientific statement is to review the underlying risk factors and pathophysiology of NAFLD, the associations with atherosclerotic cardiovascular disease, diagnostic and screening strategies, and potential interventions.
This review evaluates the ability of the fibrosis index based on four factors (FIB-4) identifying fibrosis stages, long-time prognosis in chronic liver disease, and short-time outcomes in acute liver injury. FIB-4 was accurate in predicting the absence or presence of advanced fibrosis with cut-offs of 1.0 and 2.65 for viral hepatitis B, 1.45 and 3.25 for viral hepatitis C, 1.30 (<65 years), 2.0 (≥65 years), and 2.67 for non-alcoholic fatty liver disease (NAFLD), respectively, but had a low-to-moderate accuracy in alcoholic liver disease (ALD) and autoimmune hepatitis. It performed better in excluding fibrosis, so we built an algorithm for identifying advanced fibrosis by combined methods and giving work-up and follow-up suggestions. High FIB-4 in viral hepatitis, NAFLD, and ALD was associated with significantly high hepatocellular carcinoma incidence and mortality. Additionally, FIB-4 showed the ability to predict high-risk varices with cut-offs of 2.87 and 3.91 in cirrhosis patients and predict long-term survival in hepatocellular carcinoma patients after hepatectomy. In acute liver injury caused by COVID-19, FIB-4 had a predictive value for mechanical ventilation and 30-day mortality. Finally, FIB-4 may act as a screening tool in the secondary prevention of NAFLD in the high-risk population.
Non-alcoholic fatty liver disease (NAFLD) is a public health problem worldwide. This narrative Review provides an overview of the current literature to support the notion that NAFLD is a multisystem disease. Convincing evidence shows a strong association between NAFLD and the risk of developing multiple extrahepatic complications such as type 2 diabetes, cardiovascular disease (ie, the predominant cause of mortality in people with NAFLD), chronic kidney disease, and some types of extrahepatic malignancies. The magnitude of this risk parallels the severity of NAFLD (especially the stage of liver fibrosis). There are probably multiple underlying mechanisms by which NAFLD might increase the risk of cardiovascular disease, type 2 diabetes, and extrahepatic complications. Addressing the growing burden of NAFLD will require setting up a multidisciplinary working group and framework to progress and embrace novel collaborative ways of working to deliver holistic, person-centred care and management of people with NAFLD.
Non-alcoholic fatty liver disease (NAFLD) is a public health problem, affecting up to a third of the world’s adult population. Several cohort studies have consistently documented that NAFLD (especially in its more advanced forms) is associated with a higher risk of all-cause mortality and that the leading causes of death among patients with NAFLD are cardiovascular diseases (CVDs), followed by extrahepatic malignancies and liver-related complications. A growing body of evidence also indicates that NAFLD is strongly associated with an increased risk of major CVD events and other cardiac complications (ie, cardiomyopathy, cardiac valvular calcification and cardiac arrhythmias), independently of traditional cardiovascular risk factors. This narrative review provides an overview of the literature on: (1) the evidence for an association between NAFLD and increased risk of cardiovascular, cardiac and arrhythmic complications, (2) the putative pathophysiological mechanisms linking NAFLD to CVD and other cardiac complications and (3) the current pharmacological treatments for NAFLD that might also benefit or adversely affect risk of CVD.
Purpose of review:
Over the past decade, imaging modalities and serological tests have emerged as important tools in the evaluation of liver diseases, in many cases supplanting the use of liver biopsy and histological examination. Nonetheless, the accuracy and diagnostic value of these methods may not always be conclusive and the assessment of liver histology often remains the gold standard for diagnostic evaluation. The purpose of this review is to summarize the current role of liver biopsy in contemporary hepatology practice.
Recent findings:
Technical factors were found to influence the diagnostic value of liver biopsy and histological examination of the liver, including specimen number and size (preferably ≥3 nonfragmented specimens of >20 mm in length), needle diameter (1.6 mm Menghini), number of passes (mean 2.5), imaging-guidance, and operator experience. Liver biopsy was demonstrated to be diagnostically valuable in the evaluation of persistently abnormal liver tests of unclear cause, with histology pointing to a specific diagnosis in 84% of patients. Although coagulation abnormalities continue to be an important concern when performing liver biopsy, their influence on complication risk remains unclear. Implementation of less stringent preprocedural coagulation thresholds decreased preprocedural transfusions without increasing the bleeding rate. Serious complications associated with percutaneous liver-biopsy (PLB) and transjugular liver-biopsy are similar, but pain appears to be more common with PLB.
Summary:
Histopathological evaluation continues to be fundamentally important in assessing hepatic disease, and liver histology remains the most accurate approach to assess fibrosis and assign prognosis.
Nonalcoholic fatty liver disease (NAFLD) is a common, progressive liver disease that affects up to one-quarter of the adult population worldwide. The clinical and economic burden of NAFLD is mainly due to liver-related morbidity and mortality (nonalcoholic steatohepatitis, cirrhosis or hepatocellular carcinoma) and an increased risk of developing fatal and nonfatal cardiovascular disease, chronic kidney disease and certain types of extrahepatic cancers (for example, colorectal cancer and breast cancer). Additionally, there is now accumulating evidence that NAFLD adversely affects not only the coronary arteries (promoting accelerated coronary atherosclerosis) but also all other anatomical structures of the heart, conferring an increased risk of cardiomyopathy (mainly left ventricular diastolic dysfunction and hypertrophy, leading to the development of congestive heart failure), cardiac valvular calcification (mainly aortic-valve sclerosis), cardiac arrhythmias (mainly atrial fibrillation) and some cardiac conduction defects. This Review focuses on the association between NAFLD and non-ischaemia-related cardiac disease, discusses the putative pathophysiological mechanisms and briefly summarizes current treatment options for NAFLD that might also beneficially affect cardiac disease.
Aims:
The association between aortic valve sclerosis (AVSc) and cardiovascular (CV) events is not consistent among different studies. We have performed a meta-analysis evaluating the association between AVSc and fatal and/or non-fatal CV and cerebrovascular events.
Methods and results:
A systematic search was performed in the electronic databases (PubMed, Web of Science, Scopus, EMBASE). Studies evaluating coronary artery disease (CAD), stroke and CV mortality in AVSc patients and controls were included. Differences among cases and controls were expressed as Odds Ratio (OR) with pertinent 95% Confidence Intervals (CI). Thirty-one studies on 10,537 AVSc patients and 25,005 controls were included in the final analysis. The absolute risk of CAD was 45.8% (95% CI: 32.9-59.3) in AVSc patients and 29.4% (95% CI: 21.8-38.5) in controls with an OR of 2.02 (95% CI: 1.67-2.44) and an attributable risk of 35.8%. Moreover, stroke was reported in 11.8% (95% CI: 4.4-27.7) of AVSc patients and 7.9% (95% CI: 2.5-22.7) of controls (OR: 1.41, 95% CI: 1.16-1.71) with an attributable risk of 33.0%. CV mortality was 6.2% (95% CI: 2.7-13.5) in AVSc patients and 2.0% (95% CI: 0.5-7.9) in controls (OR: 2.70, 95% CI: 1.45-5.01), with an attributable risk of 67.7%. Results were confirmed when pooling together ORs for CAD, stroke and CV mortality obtained by means of multivariate analysis.
Conclusions:
AVSc is associated with CAD, stroke and CV mortality. Taken together, these data suggest that patients with AVSc may benefit from a stricter CV risk monitoring and that AVSc screening may be included in the frame of CV risk stratification protocols.
Aims:
This European Association Cardiovascular Imaging (EACVI) Expert Consensus document aims at defining the main quantitative information on cardiac structure and function that needs to be included in standard echocardiographic report following recent ASE/EACVI chamber quantification, diastolic function, and heart valve disease recommendations. The document focuses on general reporting and specific pathological conditions such as heart failure, coronary artery and valvular heart disease, cardiomyopathies, and systemic diseases.
Methods and results:
Demographic data (age, body surface area, blood pressure, and heart rhythm and rate), type (vendor and model) of ultrasound system used and image quality need to be reported. In addition, measurements should be normalized for body size. Reference normal values, derived by ASE/EACVI recommendations, shall always be reported to differentiate normal from pathological conditions. This Expert Consensus document suggests avoiding the surveillance of specific variable using different ultrasound techniques (e.g. in echo labs with high expertise in left ventricular ejection fraction by 3D and not by 2D echocardiography). The report should be also tailored in relation with different cardiac pathologies, quality of images, and needs of the caregivers.
Conclusion:
The conclusion should be concise reflecting the status of left ventricular structure and function, the presence of left atrial and/or aortic dilation, right ventricular dysfunction, and pulmonary hypertension, leading to an objective communication with the patient health caregiver. Variation over time should be considered carefully, taking always into account the consistency of the parameters used for comparison.
Key physiological functions of the liver, including glucose and lipid metabolism, become disturbed in the setting of non-alcoholic fatty liver disease (NAFLD) and may be associated with a systemic inflammatory ‘milieu’ initiated in part by liver-secreted cytokines and molecules. Consequently, the pathophysiological effects of NAFLD extend beyond the liver with a large body of clinical evidence demonstrating NAFLD to be independently associated with both prevalent and incident cardiovascular disease (CVD), chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). The magnitude of risk of developing these extrahepatic diseases parallels the underlying severity of NAFLD, such that patients with non-alcoholic steatohepatitis (NASH) appear to be at greater risk of incident CVD, CKD and T2DM than those with simple steatosis. Other modifiers of risk may include genetic variants (eg, patatin-like phospholipase domain-containing 3 and trans-membrane 6 superfamily member 2 polymorphisms), visceral adipose tissue accumulation, dietary intake and the gut microbiome. Emerging data also suggest that NAFLD may be a risk factor for colonic neoplasia and reduced bone mineral density, especially among men. Importantly, improvement/resolution of NAFLD is associated with a reduced incidence of T2DM and improved kidney function, adding weight to causality and suggesting liver focused treatments may reduce risk of extrahepatic complications. Awareness of these associations is important for the clinicians such that CVD risk factor management, screening for T2DM and CKD are part of the routine management of patients with NAFLD.
Objective:
Growing evidence suggested an association between aortic valve sclerosis (AVSc) and cardiovascular (CV) events. However, little is known about the association of AVSc with major markers of subclinical atherosclerosis. We performed a meta-analysis of literature studies to address this issue.
Methods:
Studies on the relationship between AVSc and common carotid artery intima-media thickness (IMT), prevalence of carotid plaques (CPs), flow-mediated dilation (FMD), aortic pulse wave velocity (PWV) and augmentation index (AIx) were systematically searched in electronic databases. Thirteen studies enrolling 1086 AVSc patients and 2124 controls were included.
Results:
Compared to controls, AVSc patients showed higher IMT (MD: 0.32mm; 95%CI: 0.07, 0.58; p=0.014), and higher prevalence of CPs (OR: 4.06; 95%CI: 2.38, 6.93; p<0.001). Moreover, lower FMD (MD: -4.48%; 95%CI: -7.23, -1.74; p=0.001) and higher PWV (MD: 0.96%; 95%CI: 0.11, 1.81; p=0.027) were found in AVSc subjects than in controls, with no differences in AIx (MD: 0.76%; 95%CI: -0.97, 2.49; p=0.389). In meta-regression analyses, body mass index and triglyceride levels have an impact on the difference in IMT between cases and controls, while male gender and smoking habit were associated with the difference in the prevalence of CPs between the two groups.
Conclusions:
AVSc is significantly associated with altered markers of subclinical atherosclerosis, thus supporting the concept that AVSc and atherosclerosis share common etiopathological mechanism and/or risk factors.
Background:
Nowadays, aortic valve sclerosis (AVSc) might be considered an atherosclerosis-like process due to significant association with age, male gender and some major features of metabolic syndrome. Nonalcoholic fatty liver disease (NAFLD) has been recognized as a clinical expression of the metabolic syndrome and as a predictor of cardiovascular events. We aim, with this meta-analysis, to evaluate the correlation between NAFLD and AVSc; this finding might suggest new insights and interactions among NAFLD, AVSc and the atherosclerotic process.
Methods and results:
A detailed search was conducted according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines to identify all studies providing data about the association between AVSc and NAFLD. 3 studies enrolling a total of 1172 patients with NAFLD and 1467 controls without NAFLD were included in the meta-analysis. The prevalence of AVSc was 41.3% (95% CI: 32.0%, 51.4%) in NAFLD patients and 24.6% (18.4%, 32.0%) in subjects without NAFLD with a corresponding OR of 2.28 (95% CI: 1.21, 4.28, p=0.01, I(2): 77.6%, p=0.011). A meta-regression analysis showed that age, prevalence of male gender, hypertension, body mass index, and dyslipidemia were directly and significantly associated with the difference in the prevalence of AVSc between patients with NAFLD and those without.
Conclusions:
In conclusion, our meta-analysis shows a significant association between NAFLD and AVSc. However, further evidence is needed to validate these findings and find out if there is a real link or just a mere association.
Background:
Non-alcoholic fatty liver disease (NAFLD)-related advanced hepatic fibrosis is associated with liver and cardiovascular morbidity and mortality. This study aims to compare the FIB4 index, NAFLD fibrosis score (NFS) and BARD score for prediction of advanced liver fibrosis.
Methods:
Pooled sensitivity, specificity, diagnostic odds ratio (DOR), summary receiver operating characteristic (SROC) curves and Spearman's correlation were used to examine the accuracy of each noninvasive scoring system for predicting NAFLD-related advanced fibrosis.
Results:
Four studies with 1,038 adult patients were included in this meta-analysis. A total of 135 patients (13.0%) had advanced fibrosis. In the FIB4 index group, pooled sensitivity and specificity with 95% CI, and the area under the ROC curve (AUROC) were 0.844 (0.772-0.901), 0.685 (0.654-0.716) and 0.8496 ± 0.0680, respectively, at a cut-off of 1.30. At a threshold of 3.25, the same parameters were 0.38 (0.30-0.47), 0.96 (0.95-0.98), and 0.8445 ± 0.0981. At a cut-off of -1.455, values were 0.77 (0.69-0.84), 0.70 (0.67-0.73), and 0.8355 ± 0.0667, respectively. At a 0.676 cut-off, pooled sensitivity and specificity with 95% CI were 0.27 (0.19-0.35) and 0.98 (0.96-0.98), respectively; and the AUROC was 0.647 ± 0.2208. In the BARD score group, pooled sensitivity and specificity with 95% CI were 0.74 (0.66-0.81) and 0.66 (0.63-0.69), respectively; and the AUROC was 0.7625 ± 0.0285.
Conclusions:
FIB4 index with a 1.30 cut-off has better diagnostic accuracy than the FIB4 index with a 3.25 cut-off, NFS and BARD score, despite showing its limited value for predicting NAFLD-related advanced fibrosis. This article is protected by copyright. All rights reserved.
Purpose
Aortic valve sclerosis (AVS) and mitral annulus calcification (MAC) are two powerful predictors of adverse cardiovascular outcomes in patients with type 2 diabetes, but the etiology of valvular calcification is uncertain. Nonalcoholic fatty liver disease (NAFLD) is an emerging cardiovascular risk factor and is very common in type 2 diabetes, but whether NAFLD is associated with valvular calcification in this group of patients is presently unknown.
Methods
We undertook a cross-sectional study of 247 consecutive type 2 diabetic outpatients with no previous history of heart failure, valvular heart diseases (aortic stenosis, mitral stenosis, moderate or severe aortic and mitral regurgitation) or hepatic diseases. Presence of MAC and AVS was detected by echocardiography. NAFLD was diagnosed by ultrasonography.
Results
Overall, 139 (56.3%) patients had no heart valve calcification (HVC-0), 65 (26.3%) patients had one valve affected (HVC-1) and 43 (17.4%) patients had both valves affected (HVC-2). 175 (70.8%) patients had NAFLD and the prevalence of this disease markedly increased in patients with HVC-2 compared with either HVC-1 or HVC-0 (86.1% vs. 83.1% vs. 60.4%, respectively; p < 0.001). NAFLD was significantly associated with AVS and/or MAC (unadjusted-odds ratio 3.51, 95% CI 1.89–6.51, p < 0.001). Adjustments for age, sex, waist circumference, smoking, blood pressure, hemoglobin A1c, LDL-cholesterol, kidney function parameters, medication use and echocardiographic variables did not appreciably weaken this association (adjusted-odds ratio 2.70, 95% CI 1.23–7.38, p < 0.01).
Conclusions
Our results show that NAFLD is an independent predictor of cardiac calcification in both the aortic and mitral valves in patients with type 2 diabetes.
Several similarities exist between atherosclerosis in the vasculature and chronic degenerative changes in valvular structures. It has been suggested that aortic valve sclerosis (AVS) and mitral annulus calcification (MAC) are manifestations of a generalized atherosclerosis, have similar pathogenesis, share common risk factors and are observed with higher prevalence in patients with different forms of atherosclerotic vascular disease. Moreover, recent studies have shown a close relation of MAC and AVS with adverse cardiovascular and cerebrovascular outcomes. However, many patients with AVS or MAC do not have coexisting peripheral vascular atherosclerosis and vice versa. Lipid-reducing therapy has been uniformly unsuccessful in slowing valvular calcification. Thus, whether valve calcifications are the result of a more generalized atherosclerosis, or reflect a primary degenerative process, progressing with advancing age, still remains. From a clinical point of view, it is of great importance to identify common links between valve calcification and vascular atherosclerosis with a view to assess whether the detection of AVS, MAC or both are indicative of subclinical atherosclerosis and predicts cardiovascular or cerebrovascular events. Thus, in this article, the authors review current evidence regarding the association between AVS and MAC with vascular atherosclerosis.
The presence of aortic valve sclerosis has been suggested as a marker of increased cardiovascular risk, including increased mortality. However, it remains unclear whether aortic valve sclerosis is independently associated with risk or merely a marker of coexistent cardiovascular risk factors. Aortic valve sclerosis is usually diagnosed on transthoracic echocardiography, the most widely used imaging modality in observational and natural history studies of aortic valve disease. Defining aortic valve sclerosis has remained challenging due to the variable and qualitative nature of its description by ultrasound techniques. Importantly, artifacts common to ultrasound imaging and awareness of demographic and clinical history information may bias the diagnosis of aortic valve sclerosis. Because clinicians may alter treatment recommendations or follow-up based on echocardiographic reporting of aortic valve sclerosis, highlighting pitfalls of the subjective nature by which aortic valve sclerosis is identified and establishing diagnostic criteria are necessary. This review describes the diagnostic criteria for aortic valve sclerosis used in outcome studies, summarizes the epidemiological findings reporting the relationship between aortic valve sclerosis and clinical outcome, and proposes a definition of aortic valve sclerosis based on the literature.
Although aortic-valve stenosis is clearly associated with adverse cardiovascular outcomes, it is unclear whether valve sclerosis increases the risk of cardiovascular events.
We assessed echocardiograms obtained at base line from 5621 men and women 65 years of age or older who were enrolled in a population-based prospective study. On echocardiography, the aortic valve was normal in 70 percent (3919 subjects), sclerotic without outflow obstruction in 29 percent (1610), and stenotic in 2 percent (92). The subjects were followed for a mean of 5.0 years to assess the risk of death from any cause and of death from cardiovascular causes. Cardiovascular morbidity was defined as new episodes of myocardial infarction, angina pectoris, congestive heart failure, or stroke.
There was a stepwise increase in deaths from any cause (P for trend, <0.001) and deaths from cardiovascular causes (P for trend, <0.001) with increasing aortic-valve abnormality; the respective rates were 14.9 and 6.1 percent in the group with normal aortic valves, 21.9 and 10.1 percent in the group with aortic sclerosis, and 41.3 and 19.6 percent in the group with aortic stenosis. The relative risk of death from cardiovascular causes among subjects without coronary heart disease at base line was 1.66 (95 percent confidence interval, 1.23 to 2.23) for those with sclerotic valves as compared with those with normal valves, after adjustment for age and sex. The relative risk remained elevated after further adjustment for clinical factors associated with sclerosis (relative risk, 1.52; 95 percent confidence interval, 1.12 to 2.05). The relative risk of myocardial infarction was 1.40 (95 percent confidence interval, 1.07 to 1.83) among subjects with aortic sclerosis, as compared with those with normal aortic valves.
Aortic sclerosis is common in the elderly and is associated with an increase of approximately 50 percent in the risk of death from cardiovascular causes and the risk of myocardial infarction, even in the absence of hemodynamically significant obstruction of left ventricular outflow.