Non-alcoholic fatty liver disease biomarkers estimate cardiovascular risk based on coronary artery calcium score in type 2 diabetes: a cross-sectional study with two independent cohorts.
Cardiovascular diabetology
BACKGROUND:Studies have demonstrated that coronary artery calcification on one hand and non-alcoholic fatty liver disease (NAFLD) on the other hand are strongly associated with cardiovascular events. However, it remains unclear whether NAFLD biomarkers could help estimate cardiovascular risk in individuals with type 2 diabetes (T2D). The primary objective of the present study was to investigate whether the biomarkers of NAFLD included in the FibroMax® panels are associated with the degree of coronary artery calcification in patients with T2D. METHODS:A total of 157 and 460 patients with T2D were included from the DIACART and ACCoDiab cohorts, respectively. The coronary artery calcium score (CACS) was measured in both cohorts using computed tomography. FibroMax® panels (i.e., SteatoTest®, FibroTest®, NashTest®, and ActiTest®) were determined from blood samples as scores and stages in the DIACART cohort and as stages in the ACCoDiab cohort. RESULTS:CACS significantly increased with the FibroTest® stages in both the DIACART and ACCoDiab cohorts (p-value for trend = 0.0009 and 0.0001, respectively). In DIACART, the FibroTest® score was positively correlated with CACS in univariate analysis (r = 0.293, p = 0.0002) and remained associated with CACS independently of the traditional cardiovascular risk factors included in the SCORE2-Diabetes model [β = 941 ± 425 (estimate ± standard error), p = 0.028]. In the ACCoDiab cohort, the FibroTest® F3-F4 stage was positively correlated with CACS in point-biserial analysis (r = 0.104, p = 0.024) and remained associated with CACS after adjustment for the traditional cardiovascular risk factors included in the SCORE2-Diabetes model (β = 234 ± 97, p = 0.016). Finally, the prediction of CACS was improved by adding FibroTest® to the traditional cardiovascular risk factors included in the SCORE2-Diabetes model (goodness-of-fit of prediction models multiplied by 4.1 and 6.7 in the DIACART and ACCoDiab cohorts, respectively). In contrast, no significant relationship was found between FibroMax® panels other than FibroTest® and CACS in either cohort. CONCLUSIONS:FibroTest® is independently and positively associated with the degree of coronary artery calcification in patients with T2D, suggesting that FibroTest® could be a relevant biomarker of coronary calcification and cardiovascular risk. TRIAL REGISTRATION:ClinicalTrials.gov identifiers NCT02431234 and NCT03920683.
10.1186/s12933-024-02161-x
Association of Liver Fibrosis With Cardiovascular Diseases in the General Population: The Multi-Ethnic Study of Atherosclerosis (MESA).
Circulation. Cardiovascular imaging
BACKGROUND:The association of cardiovascular diseases (CVD) with liver fibrosis is poorly understood. We aim to assess the association of liver fibrosis by T1-mapping magnetic resonance imaging and CVD in MESA (Multi-Ethnic Study of Atherosclerosis). METHODS AND RESULTS:MESA enrolled 6814 participants free of clinical CVD at baseline (2000-2002). A subsample of participants underwent T1-mapping magnetic resonance imaging 10 years after the baseline (Y10 MESA exam, 2010-2012). Liver T1 maps were generated avoiding vessels and biliary ducts from which native T1 (n=2087) and extracellular volume fraction (ECV, n=1234) were determined. Higher ECV and native T1 were indicators of liver fibrosis. Linear regression analysis evaluated the cross-sectional relationship between liver native T1 and ECV at Y10 MESA exam with a history of CVD events (atrial fibrillation, heart failure, and coronary heart disease [CHD]). Of the 2087 participants (68.7±9.1 years; 46% females), 153 had prior CVD events (78 atrial fibrillation, 25 heart failure, and 78 CHD). History of CVD events was associated with 18.5 ms higher liver native T1 (<0.001) and 1.4% greater ECV (=0.06). Prior atrial fibrillation was related to higher liver native T1 (β=21.1; =0.001) and greater ECV (β=2.2; =0.02), whereas previous heart failure was associated with greater liver ECV (β=4.1; =0.02). There was also a relationship of prior CHD with liver native T1 (β=13; =0.05) and ECV (β=1.9; =0.05), which was attenuated by adjustment for coronary artery calcium score (β=7.1 and 1.6; =0.37 and 0.13, respectively). CONCLUSIONS:Liver fibrosis by T1-mapping magnetic resonance imaging is associated with history of heart failure, atrial fibrillation, and CHD in a multiethnic cohort. The association of liver fibrosis and CHD is at least in part mediated by atherosclerosis.
10.1161/CIRCIMAGING.117.007241
Association between non-alcoholic fatty liver disease and subclinical coronary atherosclerosis: An observational cohort study.
Lee Seung Bum,Park Gyung-Min,Lee Jong-Young,Lee Byung Uk,Park Jae Ho,Kim Byung Gyu,Jung Seok Won,Jeong In Du,Bang Sung-Jo,Shin Jung Woo,Park Neung Hwa,Yang Dong Hyun,Kang Joon-Won,Lim Tae-Hwan,Kim Hong-Kyu,Choe Jaewon,Lee Han Chu
Journal of hepatology
BACKGROUND & AIMS:There are limited data on the association between non-alcoholic fatty liver disease (NAFLD) and subclinical coronary atherosclerosis. This study investigated the influence of NAFLD on subclinical coronary atherosclerosis as detected by coronary computed tomography angiography (CCTA) in an asymptomatic population. METHODS:A total of 5,121 consecutive asymptomatic individuals with no prior history of coronary artery disease or significant alcohol intake voluntarily underwent abdominal ultrasonography and CCTA as part of a general health examination. Fatty liver was assessed by ultrasonography examination. The fatty liver index and NAFLD fibrosis score were also calculated. Coronary atherosclerotic plaques on CCTA were evaluated. The association between NAFLD and subclinical coronary atherosclerosis was determined by logistic regression analysis. RESULTS:Of the study participants, 1,979 (38.6%) had ultrasonography-diagnosed NAFLD. After adjustment for cardiovascular risk factors, there were no statistically significant differences in the adjusted odds ratios of NAFLD for calcified plaque (1.03; 95% CI 0.89-1.20; p = 0.673) and mixed plaque (1.15; 95% CI 0.93-1.42; p = 0.214). However, adjusted odds ratios for any atherosclerotic plaque (1.18; 95% CI 1.03-1.35; p = 0.016) and non-calcified plaque (1.27; 95% CI 1.08-1.48; p = 0.003) were significantly higher in NAFLD. In addition, there was a significant association of fatty liver index ≥30 with non-calcified plaque (1.37; 95% CI 1.14-1.65; p = 0.001) and NAFLD fibrosis score ≥-1.455 with non-calcified plaque (1.20; 95% CI 1.08-1.42; p = 0.030). CONCLUSIONS:In this large cross-sectional study of asymptomatic individuals undergoing CCTA, NAFLD was consistently associated with non-calcified plaque, suggesting an increased cardiovascular risk. LAY SUMMARY:In asymptomatic individuals, non-alcoholic fatty liver disease (NAFLD) was an independent risk factor for non-calcified plaque, which has been known as a vulnerable plaque associated with sudden and unexpected cardiac events. Therefore, appropriate medical therapy for NAFLD was required to reduce future cardiac events.
10.1016/j.jhep.2017.12.012
Liver Fibrosis Scoring Systems as Novel Tools for Predicting Cardiovascular Outcomes in Patients Following Elective Percutaneous Coronary Intervention.
Liu Hui-Hui,Cao Ye-Xuan,Jin Jing-Lu,Hua Qi,Li Yan-Fang,Guo Yuan-Lin,Zhu Cheng-Gang,Wu Na-Qiong,Gao Run-Lin,Li Jian-Jun
Journal of the American Heart Association
Background Previous studies have suggested a strong association of liver fibrosis scores (LFSs) with cardiovascular outcomes in patients with different cardiovascular diseases. Nonetheless, it is basically blank regarding the prognostic significance of LFSs in patients following percutaneous coronary intervention (PCI). This study sought to examine the potential role of LFSs in predicting long-term outcomes in a large cohort of patients with stable coronary artery disease after elective PCI. Methods and Results In this multicenter, prospective study, we consecutively enrolled 4003 patients with stable coronary artery disease undergoing PCI. Eight currently available noninvasive LFSs were assessed for each subject. All patients were followed up for the occurrence of cardiovascular events including cardiovascular death, nonfatal myocardial infarction, and stroke. During an average follow-up of 5.0±1.6 years, 315 (7.87%) major cardiovascular events were recorded. Subjects who developed cardiovascular events were more likely to have intermediate or high LFSs, including nonalcoholic fatty liver disease fibrosis score; fibrosis-4 score; body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes mellitus score (BARD); and aspartate aminotransferase/alanine aminotransferase ratio. Furthermore, compared with subjects with low scores, those with intermediate plus high score levels had significantly increased risk of cardiovascular events (adjusted hazard ratios ranging 1.57-1.92). Moreover, the addition of non-alcoholic fatty liver disease fibrosis score; fibrosis-4 score; or body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes mellitus score into a model with established cardiovascular risk factors significantly improved the prediction ability. Conclusions High LFSs levels might be useful for predicting adverse prognosis in patients with stable coronary artery disease following PCI, suggesting the possibility of the application of LFSs in the risk stratification before elective PCI.
10.1161/JAHA.120.018869
Performance of nonalcoholic fatty liver fibrosis score in estimating atherosclerotic cardiovascular disease risk.
Nutrition, metabolism, and cardiovascular diseases : NMCD
BACKGROUND AND AIMS:It is currently unclear whether the nonalcoholic fatty liver disease (NAFLD) fibrosis score, when compared to major anthropometric indices, is useful in estimating the risk of atherosclerotic cardiovascular disease (ASCVD). METHODS AND RESULTS:This study included 3886 adults undergoing a health checkup. An elevated risk of ASCVD was determined as a 10-year ASCVD risk ≥7.5% using Pooled Cohort Equations. NAFLD was diagnosed with abdominal ultrasonography. Receiver operating characteristic curves were used to evaluate the performance of estimating an elevated ASCVD risk. Among study participants, 521 (13.4%) had an elevated ASCVD risk and 1473 (37.9%) had NAFLD. Subjects with NAFLD had a significantly higher rate of ASCVD risk ≥7.5% (p < 0.001) compared to those without NAFLD. After adjusting for cardiometabolic risk factors, NAFLD (OR = 1.49, 95% CI: 1.10-2.00, p = 0.009) in all participants and NAFLD fibrosis score >0.676 (OR = 1.95, 95% CI: 1.30-2.92, p = 0.001) in individuals with NAFLD were significantly associated with an elevated risk of ASCVD. When compared to different anthropometric indices, NAFLD fibrosis score exhibited the largest area under the curve (AUC) in individuals with NAFLD (AUC = 0.750) in estimating an elevated ASCVD risk. Furthermore, NAFLD fibrosis score displayed the best predictive performance for identifying an elevated ASCVD risk in male participants with NAFLD (AUC = 0.737). CONCLUSION:NAFLD was a significant risk factor for elevated ASCVD risk. NAFLD fibrosis score >0.676 was associated with increased ASCVD risk in individuals with NAFLD. Compared with anthropometric indices, NAFLD fibrosis score demonstrated the best performance in estimating elevated ASCVD risk among those with NAFLD.
10.1016/j.numecd.2023.08.005
Prognostic value of coronary artery calcium score for the prediction of atherosclerotic cardiovascular disease in participants with suspected nonalcoholic hepatic steatosis: Results from the multi-ethnic study of atherosclerosis.
American heart journal
BACKGROUND:Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD) events; thus, a diagnostic approach to help identify NAFLD patients at high risk is needed. In this study, we hypothesized that coronary artery calcium (CAC) screening could help stratify the risk of ASCVD events in participants with suspected nonalcoholic hepatic steatosis. METHODS:A total of 713 participants with suspected nonalcoholic hepatic steatosis without previous cardiovascular events from the Multi-Ethnic Study of Atherosclerosis (MESA) were followed for the occurrence of incident ASCVD. Nonalcoholic hepatic steatosis was defined using nonenhanced computed tomography and liver/spleen attenuation ratio <1. Cox proportional hazards regression models were used to estimate hazard ratios (HR). C-statistics and areas under the time-dependent receiver operating characteristic curves (tAUC) were used to compare incremental contributions of CAC score when added to the clinical risk factors. RESULTS:In multivariable analyses, CAC score was found to be independently associated with incident ASCVD (HR = 1.33, 95% CI = 1.22-1.44, P < .001). The addition of CAC score to clinical risk factors increased the C-statistic from 0.677 to 0.739 (P < .001) and tAUC at 10 years from 0.668 to 0.771, respectively. In subgroup analyses, the incremental prognostic value of CAC score was more significant in participants with low/borderline- (<7.5%) and intermediate- (7.5%-20%) 10-year ASCVD risk scores. CONCLUSIONS:The inclusion of CAC score in global risk assessment was found to significantly improve the classification of incident ASCVD events in participants with suspected nonalcoholic hepatic steatosis, indicating a potential role for CAC screening in risk assessment.
10.1016/j.ahj.2023.07.008
The association of the steatosis severity in fatty liver disease with coronary plaque pattern in general population.
Hsu Pai-Feng,Wang Ying-Wen,Lin Chung-Chi,Wang Yuan-Jen,Ding Yaw-Zon,Liou Teh-Ling,Huang Shao-Sung,Lu Tse-Min,Chan Wan-Leong,Lin Shing-Jong,Leu Hsin-Bang
Liver international : official journal of the International Association for the Study of the Liver
BACKGROUND AND AIMS:Nonalcoholic fatty liver disease (NAFLD) is commonly observed in patients with cardiovascular disease (CVD). However, whether the steatosis severity of NAFLD is independently associated with coronary artery atherosclerosis is still controversial. METHODS:Consecutive Taiwanese individuals (1502) who received coronary computed tomography angiography (CCTA) and abdominal sonography as part of a general routine health evaluation were enrolled. The association between steatosis severity, coronary atherosclerosis involvement and various plaque patterns were analysed. RESULTS:Compared with non-steatosis, NAFLD subjects had more cardiovascular risk factors that correlated with the severity of steatosis (P for the trend <.05). The presence of atherosclerotic plaques correlated with the severity of steatosis (none: 53%, mild: 64.1%, and moderate to severe: 66.9%; P for the trend <.001). Parameters of coronary atherosclerosis, including atheroma burden obstructive score (ABOS), segment involvement score (SIS) and segment stenosis score (SSS), were higher in the moderate to severe steatosis group. After adjusting for major confounding factors, the severity of steatosis still correlated with the mixed plaque pattern (P = .043). Subgroup analysis of the risk of the presence of overall coronary and mixed plaques showed a significant association with increasing severity of steatosis, especially among these who were <65 years old, male, without metabolic syndrome, and with lower low-density lipoprotein choleseterol values. CONCLUSION:In this general population, steatosis severity of NAFLD is associated with coronary artery atherosclerosis burden. Furthermore, steatosis severity correlated with the risk of the presence of coronary plaques, especially high-risk plaques, and was independent of traditional risk factors.
10.1111/liv.14637
Alcoholic and non-alcoholic fatty liver disease and associations with coronary artery calcification: evidence from the Kangbuk Samsung Health Study.
Chang Yoosoo,Ryu Seungho,Sung Ki-Chul,Cho Yong Kyun,Sung Eunju,Kim Han-Na,Jung Hyun-Suk,Yun Kyung Eun,Ahn Jiin,Shin Hocheol,Wild Sarah Helen,Byrne Christopher D
Gut
OBJECTIVE:Recent evidence suggests that alcoholic fatty liver disease (AFLD) and non-alcoholic fatty liver disease (NAFLD) may differentially affect risk of cardiovascular mortality. To investigate whether early liver disease due to AFLD or NAFLD have similar or dissimilar effects on risk of early coronary artery atherosclerosis, we have investigated the associations between AFLD and NAFLD and coronary artery calcium (CAC). DESIGN:A cross-sectional study was performed in 105 328 Korean adults who attended a health check-up programme. CAC score was assessed using CT, daily alcohol intake was recorded as grams/day and liver fat by ultrasound. Logistic regression model was used to calculate ORs with 95% CIs for prevalent CAC. RESULTS:Both NAFLD and AFLD were positively associated with CAC score. After adjusting for potential confounders, multivariable-adjusted OR (95% CIs) for CAC >0 comparing NAFLD and AFLD to the reference (absence of both excessive alcohol use and fatty liver disease) were 1.10 (95% CI 1.05 to 1.16) and 1.20 (95% CI 1.11 to 1.30), respectively. In post hoc analysis, OR (95% CI) for detectable CAC comparing AFLD to NAFLD was 1.09 (95% CI 1.01 to 1.17). Associations of NAFLD and AFLD with CAC scores were similar in both non-obese and obese individuals without significant interaction by obesity (p for interaction=0.088). After adjusting for homeostasis model assessment of insulin resistance and high-sensitivity C reactive protein, the associations between fatty liver disease and CAC scores remained statistically significant. CONCLUSION:In this large sample of young and middle-aged individuals, early liver disease due to NAFLD and AFLD were both significantly associated with the presence of coronary artery calcification.
10.1136/gutjnl-2018-317666
Predictive value of liver fibrosis scores in cardiovascular diseases among hypertensive population.
Journal of hypertension
PURPOSE:To explore the predictive value of liver fibrosis scores [fibrosis-4, AST/platelet ratio index, BAAT score (BMI Age ALT TG), and BARD score (BMI AST/ALT Ratio Diabetes)] for the risk of cardiovascular disease (CVD) in a hypertensive population. METHODS:A total of 4164 hypertensive participants without history of CVD were enrolled in the follow-up. Four liver fibrosis scores (LFSs) were used, including the fibrosis-4 (FIB-4), APRI, BAAT score, and BARD score. The endpoint was CVD incidence which was defined as stroke or coronary heart disease (CHD) during the follow-up period. Cox regression analyses were used to calculate hazard ratios between LFSs and CVD. Kaplan-Meier curve was used to show the probability of CVD in different levels of LFSs. Restricted cubic spline further explored whether the relationship between LFSs and CVD was linear. Finally, we assessed the discriminatory ability of each LFS for CVD was assessed using C -statistics, net reclassification index (NRI), and integrated discrimination improvement (IDI). RESULTS:During a median follow-up time of 4.66 years, 282 hypertensive participants had CVD. Kaplan-Meier curve showed that four LFSs were associated with CVD and high levels of LFSs significantly increase the probability of CVD in hypertensive population. In the multivariate Cox regression analysis, the adjusted hazard ratios for four LFSs were 3.13 in FIB-4, 1.66 in APRI, 1.47 in BAAT score, and 1.36 in BARD score. Moreover, after adding LFSs to original risk prediction model, we find that all four new models have higher C -statistics of CVD than the traditional model. Furthermore, the results of both NRI and IDI were positive, indicating that LFSs enhanced the effect on the prediction of CVD. CONCLUSIONS:Our study showed that LFSs were associated with CVD in hypertensive populations in northeastern China. Furthermore, it suggested that LFSs could be a new tool for identifying patients at high risk of primary CVD in a hypertensive population.
10.1097/HJH.0000000000003394