Steatotic liver disease (SLD) is the new nomenclature that acknowledges the combined impact of metabolic dysfunction and alcohol consumption [
1]. SLD is a substantial public health concern, with an estimated 72 million adults in the United States (US) [
2]. Individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) often present with unfavorable metabolic conditions, such as obesity, type 2 diabetes, and dyslipidemia, that significantly increase the risk of cardiovascular disease (CVD) and atherosclerotic cardiovascular disease (ASCVD). Alcohol-related liver disease (ALD), which refers to individuals with significant alcohol intake, can increase the risk of CVD. Metabolic dysfunction and alcohol-related liver disease (MetALD) represents the coexistence of metabolic abnormalities and moderate alcohol intake, resulting in a higher risk of cardiovascular complications beyond those noted in MASLD alone. Therefore, evaluating the current burden of CVD in individuals with metabolic dysfunction and alcohol intake may be critical in reducing the risk of cardiovascular complications. These heterogeneous conditions, sharing a common feature of SLD and resulting fibrosis, may be linked with an increased risk of cardiovascular events and mortality. Beyond corroborating prior associations, we aimed to provide contemporary, nationally representative estimates of the distribution of predicted 10-year CVD and ASCVD risk categories across the newly defined SLD subtypes and to examine how Fibroscan-defined significant fibrosis impacts these distributions.
We used the National Health and Nutrition Examination Survey (NHANES) dataset, spanning 2017–2023, employing complex, clustered, stratified, and multistage sampling to obtain a representative sample of the adult US population. In mobile examination centers, 10,250 eligible participants aged 20 and older were identified, excluding those without data on alcohol consumption or transient elastography. The detailed methodology for defining SLD and fibrosis through transient elastography has been previously described [
2]. SLD is defined as a controlled attenuation parameter (CAP) score of 285 dB/m or higher (optimizing sensitivity and specificity criteria), determined by Fibroscan model 502 V2 (Echosens, Waltham, MA, USA) [
2,
3]. The detailed methodology for defining subtypes of SLD is described in
Supplementary Methods. A liver stiffness value ≥8 kPa (≥F2) was defined as significant fibrosis across the three SLD subtypes [
4].
The predicted 10-year CVD/ASCVD risk category was estimated using the Framingham risk score (FRS) [
5], the pooled cohort equation (PCE) [
6], and the predicting risk of CVD EVENTs equation (PREVENT) [
7], each with its respective risk variables: FRS included sex, age, smoking, lipids, blood pressure, antihypertensives, and diabetes; PCE added black/white race; PREVENT removed race and added estimated glomerular filtration rate (eGFR, based on the CKD-EPI equation), body mass index, and statin use. Risk categories: low (<5%), borderline (5.0–7.4%), intermediate (7.5–19.9%), and high (≥20%). Sample weights accounted for the survey design. We used direct standardization to the 2020 US Census adult population to obtain weighted, age-standardized proportions of predicted 10-year CVD/ASCVD risk categories for all subgroup comparisons, including by fibrosis status. Participants were evaluated for predicted 10‑year CVD/ASCVD risk categories across MASLD, MetALD, and ALD status, as well as according to the presence or absence of significant fibrosis. Among comparison groups, we present weighted age-adjusted proportions with 95% confidence interval (CI) and compare groups using the weighted Rao-Scott chi-square test, adjusting for weights, stratification, and clustering.
The weighted age-standardized prevalence for the various subtypes of SLD was 32.5% (95% CI, 31.0–33.9) for MASLD, 2.3% (95% CI, 1.91–2.75) for MetALD, and 0.82% (95% CI, 0.56–1.09) for ALD. When evaluating the predicted 10‑year CVD/ASCVD risk categories in the general population not affected by SLD (
Fig. 1), the age-standardized proportions of individuals with low, borderline, intermediate, and high predicted 10‑year CVD/ASCVD risk categories (using the PREVENT equations) were 8.6% (95% CI, 7.8–9.5), 19.8% (95% CI, 18.9–20.8), and 9.9% (95% CI, 9.3–10.6), respectively. In the MASLD group, these rates were higher: 10.6% (95% CI, 9.0–12.5), 23.6% (95% CI, 22.3–25.1), and 11.6% (95% CI, 10.6–12.7), respectively. Among those with MetALD, the corresponding proportions were 8.7% (95% CI, 5.9–12.5), 22.8% (95% CI, 17.9–28.7), and 7.3% (95% CI, 4.0–13.2). Individuals with MASLD or MetALD were statistically more likely to fall into higher predicted 10-year CVD risk categories compared to those without SLD. These findings were consistent across other cardiovascular risk-scoring systems, except for the PREVENT 10-year ASCVD risk for MetALD. Notably, the rates of intermediate and high risk in the ALD subgroup were higher than in those without SLD; however, these increases did not reach statistical significance, except for the FRS score, mainly due to wider CIs from the small sample size in ALD. Analysis of the three subtypes of SLD showed no statistically significant differences in predicted 10-year CVD/ASCVD risk categories among individuals with MASLD, MetALD, or ALD. In age‑standardized analyses and in age-stratified comparisons (
Supplementary Figs. 1,
2), those with significant fibrosis across all subtypes, MASLD, MetALD, and ALD, had higher proportions in intermediate/high predicted 10‑year CVD/ASCVD risk categories.
In this nationally representative study, we found that individuals with MASLD and MetALD had significantly higher predicted 10-year CVD/ASCVD risk categories, as assessed by multiple cardiovascular risk scores, compared to those without these conditions.
Epidemiological research has demonstrated a strong link between MASLD and CVD, independent of traditional CVD risk factors [
8]. Recent research indicates that CVD is a leading cause of mortality, accounting for approximately onethird of the deaths among individuals with MASLD [
9]. The prevalence of MetALD in the general population ranges from 1.7% to 4.5%, notably lower than that of MASLD [
10]. Recent US population-based studies indicate that individuals with MetALD face higher all-cause and cancer-related mortality compared to those with MASLD [
11]. Similarly, a Veterans Health Administration cohort study reported modestly higher all-cause mortality risks in MetALD compared to MASLD, with comparable rates for major CVD events [
12]. A meta-analysis of over 5.2 million participants found no significant difference in the risk of CVD between MetALD and MASLD [
13], consistent with our findings of similar predicted 10‑year CVD/ASCVD risk categories.
The risk of cardiovascular-related complications in individuals with hepatic fibrosis in the setting of MASLD, MetALD, and ALD is significant and interrelated with metabolic dysfunction and alcohol consumption. In MASLD, liver fibrosis severity is a strong predictor of CVD risk and overall prognosis, with advanced fibrosis linked to higher rates of CVD events and CVD-related mortality [
14]. We noted individuals with MetALD and ALD have comparable predicted 10‑year CVD risk categories as those with MASLD and more pronounced predicted 10‑year CVD risk categories among those with significant fibrosis. Noninvasive fibrosis scores, such as Fibrosis-4 (FIB-4) index, may help predict CVD outcomes in subtypes of SLD, highlighting the importance of fibrosis assessment for cardiovascular risk stratification across subtypes of SLD.
Over the past two decades, numerous models have been developed to estimate CVD risk. The FRS was among the first to predict 10-year risks for myocardial infarction and coronary heart disease-related death,5 but has limited accuracy across diverse populations, as it was developed by utilizing data from White participants from a single region [
15]. In 2013, the American Heart Association and American College of Cardiology introduced the PCE, which expanded the scope of outcomes and risk factors but tended to overestimate risk [
15]. To more accurately estimate risk, the PREVENT equations were developed in late 2023, incorporating traditional and kidney-metabolic measures, excluding race, and providing more accurate 10- and 30-year predictions for ASCVD and total CVD using nationally representative US data [
7]. Our application of PREVENT, a raceneutral, kidney-metabolic-integrated risk tool, alongside PCE and FRS offers the first national estimates of predicted 10-year CVD/ASCVD risk category distributions in MASLD, MetALD, and ALD. The largely concordant patterns across equations and the marked upward shift with significant fibrosis provide actionable insights for integrated hepatology‑cardiometabolic patient care plans.
In this study, we used NHANES 2017–2023 data to evaluate the contemporary burden of CVD and ASCVD among individuals with and without the three subtypes of SLD. Subtypes of SLD and significant fibrosis were determined using CAP values and liver stiffness measurements rather than noninvasive diagnostic panels. The limitations of our study are as follows. First, alcohol consumption was evaluated via self-reported questionnaires rather than laboratory-based metabolite testing. Second, although current standardized cut-offs for CAP and liver stiffness are lacking, we used validated thresholds from prior studies [
2-
4]. Third, age is a major determinant of all three equations and is also associated with fibrosis; although we report age-standardized estimates and provide age-stratified comparisons, residual confounding due to age and other factors may persist, and we are unable to isolate an age-independent effect of fibrosis from these model-based outcomes. Fourth, the ALD subgroup was small in this study, yielding wide CIs and limited statistical power. Therefore, ALD-specific comparisons should be interpreted cautiously. Finally, the outcomes are model-based predicted 10-year CVD/ASCVD risk categories, not observed cardiovascular events; therefore, the results reflect differences in predicted risk category distributions in a cross-sectional dataset and may not establish causality or event risk.
SLD is a growing health burden, encompassing subtypes such as MASLD, MetALD, and ALD, all of which contribute significantly to higher predicted 10-year CVD/ASCVD risk categories, particularly when significant fibrosis is present. Therefore, it may be prudent to develop clinical management pathways that prioritize early assessment and staging of hepatic fibrosis in individuals with SLD. Early identification of significant hepatic fibrosis in individuals with SLD may provide opportunities for preventative interventions.
FOOTNOTES
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Authors’ contribution
Donghee Kim and Aijaz Ahmed were responsible for the study concept and design, data acquisition, statistical analysis, interpretation of data, drafting the manuscript, critical revision of the manuscript for important intellectual content, and approval of the final manuscript. Pojsakorn Danpanichkul and Karn Wijarnpreecha were responsible for the interpretation and presentation of the data, critical revision of the manuscript for important intellectual content, and approval of the final manuscript.
-
Conflicts of Interest
The authors declare that there is no conflict of interest in preparing this manuscript, including financial and/or material support.
SUPPLEMENTARY MATERIAL
Supplementary material is available at Clinical and Molecular Hepatology website (
http://www.e-cmh.org).
Supplementary Figure 1.
Current prevalence of predicted 10-year cardiovascular disease (CVD) and atherosclerotic cardiovascular disease (ASCVD) risk categories among individuals with MASLD, MetALD, and ALD based on presence or absence of significant fibrosis. (A) Comparison of predicted 10-year CVD and ASCVD risk categories estimated by the predicting risk of CVD EVENTs equations (PREVENT) among individuals with MASLD based on the presence or absence of significant fibrosis. (B) Comparison of predicted 10-year CVD and ASCVD risk categories estimated by PREVENT equations among individuals with MetALD based on the presence or absence of significant fibrosis. (C) Comparison of predicted 10-year CVD and ASCVD risk categories estimated by PREVENT equations among individuals with ALD based on the presence or absence of significant fibrosis. P-value means comparison between significant fibrosis and no significant fibrosis. MASLD, metabolic dysfunction-associated steatotic liver disease; MetALD, metabolic dysfunction and alcoholrelated liver disease; ALD, alcohol-related liver disease.
Supplementary Figure 2.
Current prevalence of predicted 10-year cardiovascular disease (CVD) and atherosclerotic cardiovascular disease (ASCVD) risk categories among individuals with MASLD based on presence or absence of significant fibrosis stratified by age. (A) Comparison of predicted 10-year CVD and ASCVD risk categories estimated by the predicting risk of CVD EVENTs equations (PREVENT) among individuals with MASLD based on the presence or absence of significant fibrosis among individuals aged 20 to 54 years old. (B) Comparison of predicted 10-year CVD and ASCVD risk categories estimated by the PREVENT equations among individuals with MASLD based on the presence or absence of significant fibrosis among individuals aged 55 years or older. MASLD, metabolic dysfunction- associated steatotic liver disease.
Figure 1.Current prevalence of predicted 10-year cardiovascular disease (CVD) and atherosclerotic cardiovascular disease (ASCVD) risk categories among individuals without and with steatotic liver disease (SLD) based on the subtype of SLD. (A) Comparison of predicted 10-year CVD risk categories estimated by the predicting risk of CVD EVENTs equations (PREVENT) across subtypes of SLD. (B) Comparison of predicted 10-year ASCVD risk categories estimated by the PREVENT equations across subtypes of SLD. (C) Comparison of predicted 10-year ASCVD risk categories estimated by the pooled cohort equation (PCE) across subtypes of SLD. (D) Comparison of predicted 10-year CVD risk categories estimated by the Framingham risk score (FRS) across subtypes of SLD. P-value compared to no SLD. MASLD, metabolic dysfunction-associated steatotic liver disease; MetALD, metabolic dysfunction and alcohol-related liver disease; ALD, alcohol-related liver disease.
Abbreviations
alcohol-related liver disease
atherosclerotic cardiovascular disease
controlled attenuation parameter
metabolic dysfunction-associated steatotic liver disease
metabolic dysfunction and alcohol-related liver disease
National Health and Nutrition Examination Survey
predicting risk of CVD EVENTs equation
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