Endothelial dysfunction and cardiovascular risk in non-alcoholic fatty liver disease – a systematic review and meta-analysis
Bibliographic record
Abstract
Abstract Background Nonalcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder that has been associated with an increased risk of cardiovascular diseases. Endothelial dysfunction, characterized by impaired flow-mediated dilation (FMD) of the brachial artery, is a known predictor of cardiovascular risk. However, the relationship between NAFLD and endothelial dysfunction, as well as the impact of NAFLD on clinical cardiovascular events, remains unclear. Objective The aim of this systematic literature review was to determine the association between endothelial dysfunction, as measured by FMD of the brachial artery, and NAFLD. Additionally, we aimed to investigate the relationship between NAFLD and clinical cardiovascular events (CVE). Methods A systematic search was conducted in PubMed, Scopus, ScienceDirect, and Google Scholar for articles published between 2000 and July 2023. The reference lists of the included studies were also searched to retrieve possible additional studies. Original studies published in English focusing on adults with NAFLD and endothelial dysfunction are included. Editorials, commentaries, letters and studies focusing on pediatric populations and non-NAFLD liver diseases were excluded. The quality of included studies was appraised using the Newcastle–Ottawa scale. Meta-analyses were performed using Review Manager 5.4 software. Results The initial search yielded a total of 1792 articles and ultimately only 20 studies met the criteria. A total 6396 NAFLD patients were studied. Meta-analysis showed that individuals diagnosed with NAFLD had significantly lower brachial FMD values compared to their respective control groups (standardized mean difference: -4.63, 95% confidence interval: -5.68 to -3.58, p < 0.0001). Furthermore, NAFLD patients exhibited a significantly higher risk of clinical cardiovascular events compared to controls (odds ratio: 2.61; 95% CI: 1.41–4.83, p < 0.002). Subgroup analysis of studies focusing on non-alcoholic steatohepatitis (NASH) versus pure steatosis demonstrated that individuals with NASH had even lower FMD values than those with pure steatosis (standardized mean difference: -3.84, 95% confidence interval: -7.56 to -0.13, p = 0.03, I2 = 66%). Limitations, bias and heterogeneity The review included studies published in English language, over last 23 years and specified database resulted in language bias and might have missed older pertinent studies from another important database. The overall heterogeneity is attributed to variations in study populations, outcome measurements, differences in methodological approaches among included studies, and diverse diagnostic criteria for NAFLD. Conclusion Individuals with NAFLD exhibited impaired brachial FMD, indicating compromised endothelial function. Furthermore, NAFLD patients had an elevated risk of clinical cardiovascular events.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.009 | 0.021 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.017 | 0.027 |
| Bibliometrics | 0.006 | 0.008 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".