Jul 2026· Metabolism: Clinical and Experimental· Vol 183, pp.
156692
· 0 citations· 59 references
Medicine
TL;DR
Individuals with MASLD who experience a CVD event have a higher subsequent risk of long-term LREs, and the value of targeted liver monitoring for high-risk individuals after CVD and integrated heart-liver co-management is underscored.
Abstract
Background
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a risk factor for cardiovascular disease (CVD). However, the risk of liver-related events (LREs) after CVD is often overlooked. We investigated the association between incident CVD and subsequent long-term LRE risk among individuals with MASLD.
Methods
We used UK Biobank data to examine whether incident CVD (coronary heart disease [CHD], myocardial infarction [MI], heart failure [HF], or atrial fibrillation [AF]) was associated with subsequent long-term LREs (cirrhosis, decompensation, hepatocellular carcinoma, or liver-related death) in MASLD. Semi-Markov multi-state and time-dependent Cox regression models estimated transition rates and adjusted hazard ratios (aHRs). Imaging and proteomic data explored biological mechanisms.
Results
Among 142,454 individuals with MASLD, 22,630 (15.9%) developed incident CVD, and 2635 (1.8%) developed subsequent LREs over a median of 15.1 years. The transition rate from CVD to LREs was higher than the direct progression from MASLD to LREs (3.56 vs. 1.08 per 1000 person-years). Time-dependent Cox regression showed that incident CVD was associated with a higher risk of subsequent LREs (aHR 1.93, 95%CI 1.73-2.14). The risk varied by CVD subtypes, with HF highest, followed by AF, CHD, and MI (all P < 0.001). Exploratory integrated multi-omics analyses revealed associations between cardiac dysfunction and hepatic parameters, and identified a shared proteomic signature enriched in immune and fibrotic pathways.
Conclusions
Individuals with MASLD who experience a CVD event have a higher subsequent risk of long-term LREs. These findings underscore the value of targeted liver monitoring for high-risk individuals after CVD and integrated heart-liver co-management.
Background: Atherosclerotic cardiovascular disease (ASCVD) is a major cause of morbidity and mortality in metabolic dysfunction–associated steatotic liver disease (MASLD). We investigated whether fibrosis severity assessed using guideline-recommended noninvasive liver fibrosis pathways was associated with incident ASCVD across different glycemic states. Methods: This retrospective cohort study included subjects with MASLD. Fibrosis severity was classified using the Korean Association for the Study of the Liver/European Association for the Study of the Liver (KASL/EASL) and American Gastroenterological Association (AGA) sequential pathways, based on fibrosis-4 followed by vibration-controlled transient elastography. Incident ASCVD was analyzed using Fine-Gray subdistribution hazard models, with death treated as a competing event. Results: Among 6519 subjects with MASLD who had both fibrosis-4 and vibration-controlled transient elastography data, 3243 had normoglycemia, 2369 had prediabetes, and 907 had diabetes; 3221 were included in the survival analysis cohort. Baseline 10-year ASCVD risk increased with worsening glycemic status. In the longitudinal analysis, the association between fibrosis severity and incident ASCVD differed by glycemic status. In patients with prediabetes, the highest fibrosis tier was associated with higher incident ASCVD risk (adjusted subdistribution hazard ratio: 2.62, p=0.024). This association was also more apparent in younger individuals. In patients with diabetes, 5-year cumulative ASCVD incidence was high across fibrosis tiers (15.2%–18.5%), without a significant increase by fibrosis severity. Conclusions: Higher liver fibrosis severity assessed by noninvasive tests was associated with incident ASCVD outcomes in selected MASLD subgroups, particularly patients with prediabetes and younger individuals. Fibrosis assessment may help identify patients who warrant closer cardiometabolic evaluation when interpreted alongside established ASCVD risk prediction tools.
Jaehong Jeong, J. Hong, Dong Yun Kim et al.· Hepatology Communications· 0 citations
OBJECTIVE
To examine the association of metabolic dysfunction-associated steatotic liver disease (MASLD) with cardiovascular disease (CVD) mortality in adults with cardiovascular-kidney-metabolic (CKM) syndrome and to explore the possible roles of insulin resistance and inflammation.
METHODS
We analyzed 2009-2018 NHANES data including 10,061 adults with CKM staging (8340 at stages 0-2). MASLD was defined by the United States Fatty Liver Index (USFLI). We used restricted cubic spline models, Kaplan-Meier analysis, multivariable Cox regression, sensitivity analyses and mediation analysis to test the dose-response relationship, survival disparities and mediating effects.
RESULTS
MASLD prevalence rose with CKM stage progression. In CKM stages 0-2, USFLI scores linearly correlated with CVD mortality risk (P < 0.001). Participants with MASLD had poorer survival and a higher hazard of CVD mortality than those without MASLD (HR = 4.03, 95 % CI 1.55-10.48). Insulin resistance and inflammation partially mediated the observed association.
CONCLUSIONS
In early CKM syndrome, MASLD was associated with higher CVD mortality risk. Insulin resistance and inflammation may partly explain this association. These results support the potential value of integrating MASLD screening into early CKM syndrome risk stratification and management.
Zhuoxing Li, Qianyu Yang, Li Zang et al.· Diabetes Research and Clinic...· 0 citations
Cardiovascular-kidney-metabolic (CKM) syndrome integrates metabolic abnormalities, chronic kidney disease, and cardiovascular disease (CVD), with stages 0–3 representing a critical window for primary prevention. Whether the Chinese visceral adiposity index (CVAI) adds predictive value for CVD in this population remains uncertain.
Using data from the China Health and Retirement Longitudinal Study (CHARLS), a nationwide prospective cohort, we included 7,539 participants with CKM stages 0–3. Incident CVD (heart disease or stroke) was the primary outcome. Cox proportional hazards models and restricted cubic splines assessed the association and dose-response relationship, and discrimination was evaluated with the AUC and censoring-adjusted time-dependent AUC, with comparisons against BMI, waist circumference, VAI, and TyG.
Over a median follow-up of 8.0 years, 1,718 incident CVD events were recorded. Each SD increase in CVAI was associated with a 19.5% higher CVD risk (HR, 1.195; 95% CI, 1.135–1.259), with a graded quartile effect (Q4 vs. Q1 HR, 1.585; 95% CI, 1.359–1.848;
P
for trend < 0.001) and a continuous dose-response relationship (
P
for nonlinearity = 0.931). Adding CVAI modestly improved discrimination (AUC, 0.640 to 0.646; DeLong
P
= 0.039), but its AUC was not superior to BMI (0.647) or waist circumference (0.646). Primary CVAI findings remained consistent across subgroup and sensitivity analyses and in competing-risk models, whereas VAI showed no significant independent association.
CVAI is independently and continuously associated with incident CVD in CKM stages 0–3 and may serve as a practical adjunctive tool for early CVD risk stratification.
Long Feng, Geng Yang, He-Song Zeng et al.· Cardiovascular Diabetology· 0 citations
AIMS
To examine the associations between cardiovascular-kidney-metabolic syndrome (CKM) stages and the risk of cardiovascular disease (CVD), including atherosclerotic CVD (ASCVD), and all-cause mortality (ACM), stratified by sex.
METHODS AND RESULTS
Using a population-based cohort, CoLaus|PsyCoLaus, we categorized participants into CKM stages: 0 (no CKM factors), 1 (excess/dysfunctional adiposity), 2 (metabolic risk factors and/moderate- to high-risk CKD), 3 (very high predicted CVD risk per SCORE2/very high-risk CKD), and 4 (clinical CVD). Associations were assessed using generalized ordered logistic regression, Cox proportional hazards models, and population attributable fractions (PAFs). Among 5,752 participants (53.2% women; mean age: women 53.1 ± 10.7, men 52.3 ± 10.7 years), 580 CVD events (381 ASCVD), and 723 deaths occurred over 14.3 years. CKM stage distribution differed by sex (men vs women): 0 (9.9 vs 26.1%), 1 (13.3 vs 13.7%), 2 (62.6 vs 56.8%), 3 (9.4 vs 1.7%), 4 (4.8 vs 1.7%). Risk of CVD and ASCVD rose with higher CKM stage (vs stage 0), with HRs of 5.16 (95% CI, 2.61-10.19) and 3.82 (1.76-8.27) for stage 3 in men, compared with 1.92 (0.91-4.04) and 1.95 (0.79-4.81) in women. For all-cause mortality, risk peaked at stage 3 in women (3.43 [1.92-6.10]) and at stage 4 in men (2.42 [1.27-4.64]). Incremental PAFs peaked at stage 2.
CONCLUSION
CKM stages were associated with a stepwise increase in risk of CVD and all-cause mortality, with important sex-specific differences observed particularly for all-cause mortality. These findings support the relevance of CKM staging for cardiovascular risk stratification and prevention in the general population.
N. Ahanchi, R. de la Harpe, B. Delabays et al.· European Journal of Preventi...· 0 citations
BACKGROUND
Patients with atherosclerotic cardiovascular disease (ASCVD) have a high risk of recurrent major adverse cardiovascular events (MACE) and chronic kidney disease (CKD). Although Life's Essential 8 (LE8) has been studied for cardiovascular outcomes in secondary prevention, systematic evaluations of its association with cardiorenal events remain lacking.
OBJECTIVES
To evaluate whether optimal cardiovascular health (CVH) was associated with lower risks of MACE and CKD in ASCVD patients.
METHODS
This study included 10,253 UK Biobank participants with ASCVD, categorized into low (<50), moderate (50‒79), and high (≥80) CVH groups by LE8 score. Associations with MACE and CKD were assessed using Fine-Gray regression models, population-attributable fractions (PAF), and 1:2 propensity-matched analyses versus 16,545 non-ASCVD participants.
RESULTS
During a median 13.3 years follow-up, 2,069 MACE and 1,290 CKD events occurred. Compared with high CVH, low CVH was associated with higher risks of MACE (subdistribution HR [sHR] 2.68, 95% CI 2.02-3.56, p <0.001) and CKD (sHR 2.34, 95% CI 1.57-3.48, p <0.001). Glucose control contributed the largest PAF to both MACE (10.5%) and CKD (15.1%), followed by smoking cessation (6.9% for MACE and 11.1% for CKD). Compared with matched non-ASCVD participants, ASCVD patients with high LE8 attenuated MACE (sHR 0.83, 95% CI 0.58-1.20; p = 0.33) and CKD (sHR 0.69, 95% CI 0.42-1.13; p = 0.14) risks.
CONCLUSIONS
Higher LE8 scores were associated with lower risks of MACE and CKD in ASCVD patients. Glucose control and smoking were key modifiable contributors. High LE8 achievement may attenuate risks toward non-ASCVD levels.
BACKGROUND
While metabolic dysfunction-associated steatotic liver disease (MASLD) has been consistently associated with increased cardiovascular risk in the general population, its association with cardiovascular disease (CVD) mortality in adults with established cardiometabolic risk factor (including obesity, hypertension, diabetes mellitus, or dyslipidemia) remains inconsistent. We aimed to determine whether frailty confounds the MASLD-CVD mortality association.
METHODS
We analyzed 10,413 US NHANES III adults with ≥ 1 cardiometabolic risk factor. Frailty was quantified using a 49-item frailty index (FI, ranging from 0 [maximal robustness] to 1 [severe frailty]) and categorized into quartiles. Associations between MASLD and CVD mortality were assessed using multivariable Cox proportional hazards models with and without frailty adjustment. Interaction and mediation analyses were also performed.
RESULTS
Over a mean follow-up of 23.36 years, 1,375 (13.20%) CVD deaths occurred. Frailty was significantly associated with both MASLD and CVD mortality. There was no evidence of interaction between MASLD and frailty, and mediation analysis showed no indirect effect of MASLD on CVD mortality through frailty. In absence of frailty adjustment, MASLD was not associated with CVD mortality (HR = 0.92, 95% CI: 0.78-1.10). After adjustment for frailty, MASLD was independently associated with higher CVD mortality (HR = 1.19, 95% CI: 1.07-1.32). Stratified by FI quartiles, significant associations were observed only in the higher frailty quartiles (Q3: HR = 1.35, 95% CI: 1.03-1.77; Q4: HR = 1.70, 95% CI: 1.07-2.69). The population attributable fraction of MASLD for CVD mortality was 10.1-12.5% after frailty adjustment.
CONCLUSIONS
Frailty may confound the MASLD-CVD mortality relationship in people with cardiometabolic risk factors. The association between MASLD and CVD mortality is detected only when frailty is adjusted for.
Ruoting Wang, Wenli Li, J. Lazarus et al.· Cardiovascular Diabetology· 0 citations
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